Wednesday, September 5, 2012

Hemorrhaging



 Hemorrhaging is also known as bleeding or abnormal bleeding as a result of blood loss due to internal.external leaking from blood vessels or through the skin.

 I. Classifications of Hemorrhaging
According to the classification from the American College of Surgeons' Advanced Trauma Life Support (ATLS), Hemorrhaging is divided into 4 classes, depending to the volumes of blood loss and other factors

Classification of hemorrhage

Class


ParameterIIIIIIIV
Blood loss (ml)<750750–15001500–2000>2000
Blood loss (%)<15%15–30%30–40%>40%
Pulse rate (beats/min)<100>100>120>140
Blood pressureNormalDecreasedDecreasedDecreased
Respiratory rate (breaths/min)14–2020–3030–40>35
Urine output (ml/hour)>3020–305–15Negligible
CNS symptomsNormalAnxiousConfusedLethargic
Modified from Committee on Trauma. CNS = central nervous system(1a).


II.  Types of hemorrhaging 
A. Mouth
A.1. Hematemesis 
Hematemesis is defined as a condition of either upper gastrointestinal tract fresh blood vomiting or altered blood vomiting due to acid on the blood.
1. Causes
There are many causes of  Hematemesis, including 
1.1. Mallory-Weiss syndrome: 
There is  records of 29 patients with Mallory-Weiss tears diagnosed by endoscopy. Ingestion of alcohol was a chief cause of bleeding. Single tears were the largest in number and 68% of the lacerations were seen just distal to the esophago-cardial junction(1).

1.2. Irritation of the lining of the esophagus or stomach 
Prolonged inflammation and allergic reaction or erosion as a result of irritant(s) can lead to damage to the cells of the lining of the esophagus or stomach.

1.3. Vomiting as a result of bleeding of the oral cavity, nose or throat
Vomiting of blood due to bleeding of the oral cavity, nose or throat

1.4. Vascular malfunctions
Vascular malformations, also known as congenital vascular malformations (CVMs) are defined as a condition of abnormalities in the formation of blood vessels of the gastrointestinal tract, including ulcer,  bleeding due dilated submucosal veins in the stomach and intestines.

1.5. Tumors of the stomach or esophagus
Abnormal cell growth such as tumors of the stomach or esophagus can cause internal bleeding as a result of tumor causes of breaking off the blood veins and capillaries.

1.6. Acute and chronic radiation syndrome
a. Acute radiation syndrome is a defined as a condition of radiation poisoning as a result of the exposure to high amounts of ionizing radiation that affects gastrointestinal track. leading to  infection and bleeding.
b. Chronic radiation syndrome
there is a  report describes a 73-yr-old man who developed uncontrollable hematemesis due to a primary aortoduodenal fistula in the fourth portion of the duodenum approximately 20 yr after radiotherapy and para-aortic lymph node dissection for seminoma(2).

1.7. Influenza virus
There is a report of Seven children who presented during the influenza A(H1N1) epidemic of 1988 are described. After a typical influenzal illness, they developed haematemesis of varying severity. Endoscopy revealed haemorrhagic gastritis(3).

1.8.The viral haemorrhagic fevers
There are reviews of the viral haemorrhagic fevers that infect man, namely smallpox, chikungunya fever, dengue fever, Rift Valley fever, yellow fever, Crimean haemorrhagic fever, Kyasanur Forest disease, Omsk haemorrhagic fever, Argentinian haemorrhagic fever (Junin virus), Bolivian haemorrhagic fever (Machupo virus), Lassa fever, haemorrhagic fever with renal syndrome, and Marburg and Ebola virus diseases(4).

1.9. Gastroenteritis 
Gastroenteritis is defined as a condition of inflammation of the upper gastrointestinal track of that can lead to diarrhea, vomiting, and abdominal pain and cramping(5). In severe case, it can cause blood vomiting.

1.9. Gastritis 
Gastritis is defined as a condition of an inflammation of the lining of the stomach as a result of excessive alcohol drinking and medication intake such as aspirin, ibuprofen, etc. over a prolonged period of time. there is a report of the case of 40-year-old woman who presented 6 weeks after intentional ingestion of hydrochloric acid with abdominal pain and haematemesis. Gastroscopy showed a necrosed and ulcerated stomach with pyloric stricture(6).

1.10. Peptic ulcer 
Dr. Thon K, and Dr.Röher HD.in the study of [Hemorrhaging peptic ulcer--Therapy? When? Which?] indicated that a close correlation between the risk and incidence of recurrent bleeding and the primary bleeding status during emergency endoscopy let us to design a new concept of a more aggressive surgical strategy. The dominating criteria for choice of treatment based on instant endoscopical classification of bleeding type and activity(7).

1.11. Chronic liver disease
Chronic liver disease and its sequelae (often long-term results of viral hepatitis) are commonplace. Haematemesis and hepatocellular failure are usually very difficult to manage due to a lack of sophisticated support techniques in developing countries. Invasive hepatic amoebiasis usually responds well to medical management; however, spontaneous perforation can occur and the consequences of this are serious(8).

1.12. Intestinal Schistosomiasis 
Intestinal schistosomiasis, caused by the trematodes Schistosoma mansoni and S. japonicum, is found over a wide area of Africa, the Middle East, in the Orient, South America, and parts of the Caribbean. In the article of Progress report Intestinal schistosomiasis, showed that Intestinal Schistosomiasis can lead to liver diseases and Haematological Changes, as Patients suffering from intestinal schistosomiasis are frequently anaemic. In Puerto Rico Ramos-Morales14 found that 58 % of 1,547 untreated patients had a haemoglobin concentration of less than 13 g/100 ml with 4% less than 1Og/100 ml. Seventy-six per cent of these patients were aged 15 years or less and some had hookworm infection which could have contributed to blood loss(9).


1.13. History of Smoking 
In a study of A total of 240 patients representing 18.7% of all patients (i.e. 1292) who had fibreoptic upper GI endoscopy during the study period were studied. Males outnumbered female by a ratio of 2.1:1. Their median age was 37 years and most of patients (60.0%) were aged 40 years and below. The vast majority of the patients (80.4%) presented with haematemesis alone followed by malaena alone in 9.2% of cases. The use of non-steroidal anti-inflammatory drugs, alcohol and smoking prior to the onset of bleeding was recorded in 7.9%, 51.7% and 38.3% of cases respectively. Previous history of peptic ulcer disease was reported in 22(9.2%) patients. Nine (3.8%) patients were HIV positive. The source of bleeding was accurately identified in 97.7% of patients(10).

1.14. Etc.

2. Symptoms
In the study of one hundred and seven consecutive patients with hematemesis and/or melena and a diagnosis of duodenal, gastric, or esophageal ulcers were interviewed immediately before or after endoscopy about the use of non-steroid anti-inflammatory drugs (NSAIDs) and symptoms before the hemorrhage, showed that if the patients admitted no symptoms of abdominal pain or discomfort, nausea, vomiting, or heartburn, they were classified as having no ulcer symptoms before the hemorrhage. Patients who had not taken NSAIDs during the last 48 h before the hemorrhage were classified as not having taken NSAIDs. Significantly fewer patients had ulcer symptoms in the group that had used NSAIDs than in the other group (p less than 0.01)(11).

2. Management and treatments
2.1. Severe blood blood and life threatening
In the study of treatment of hematemesis and hematochezia in elderly patients by Department of Internal Medicine (III) Asahikawa Medical College, hematemesis and hematochezia (melena) in elderly patients are serious symptoms which should be carefully handled since they can lead to death without suitable treatment. In elderly patients the advance of arteriosclerotic changes throughout the body decreases blood flow and function in various organs. When these arteriosclerotic changes become prominent in the gastric vascular structure, bleeding from gastric ulcers tends to easily occur and it can be difficult to stop. A large amount of bleeding can cause irreversible shock due to the decreased cardiopulmonary function, and diminished hepatorenal capacity would also be a decisive factor in determining the outcome of the state of shock(11). In this case, Fluids and/or blood is administered, preferably by central venous catheter, and the patient is prepared for emergency endoscopy, which is typically done in theatres. Surgical opinion is usually sought in case the source of bleeding cannot be identified endoscopically, and laparotomy is necessary. Securing the airway is a top priority in hematemesis patients, especially those with a disturbed conscious level (hepatic encephalopathy in oesophageal varices patient.) A cuffed endotracheal tube could be a life saving choice(12).

2.2. Blood loss but not life threatening
In this case, certain medication such as Proton-pump inhibitors (PPIs) to reduce gastric acid production and blood transfusion depending to levels of hemoglobin, no eating until endoscopy can be arranged.


Sources
(1a) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1065003/table/T1/
(1) http://www.ncbi.nlm.nih.gov/pubmed/7222121
(2) http://www.ncbi.nlm.nih.gov/pubmed/7611215
(3) http://www.ncbi.nlm.nih.gov/pubmed/1988788
(4) http://www.ncbi.nlm.nih.gov/pubmed/310725
(5) http://www.ebmedicine.net/topics.php?paction=showTopic&topic_id=229
(6) http://www.ncbi.nlm.nih.gov/pubmed/22140409
(7) http://www.ncbi.nlm.nih.gov/pubmed/4058204
(8) http://www.ncbi.nlm.nih.gov/pubmed/1764626
(9) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1411755/pdf/gut00657-0069.pdf
(10) http://www.ncbi.nlm.nih.gov/pubmed/22537571
(11) http://www.ncbi.nlm.nih.gov/pubmed/3879376
(12) http://en.wikipedia.org/wiki/Hematemesis

A.2. Hemoptysis
 Hemoptysis is defined as a condition of coughing up blood from the bronchi, larynx, trachea, or lungs.

1. Symptoms
Symptoms of Hemoptysis can be as a result of bronchial infection or a sign of a more serious illness such as tumor and cancer
1.1 Chest pain
Chest pain us one of most common dymptoms of patient with Hemoptysism. It may be a result of the diseases have affected the nerve cells  in the check area, including infection and tumor.

1.2. Dyspnea or shortness of breath (SOB)
This mau be the result of the disease has affected the lung in the absorption of oxygen, including tumor and infectiob There is a report of a 26-year-old Chinese man, presenting with hemoptysis in the emergency room, was hospitalized because of dyspnea. The X-ray examination revealed a tumor in the right chest cavity(1).

1.3. Fever
As a result of infection of the respiratory system.

1.4. Nausea and Vomiting
It is a result of bloods accumulation in the chest area needed to be cough out for the better function of the respiratory system.

1.5. Tachypnea (rapid breathing)
Top provide enough oxygen for the body

1.7. Etc.

2. Causes
2.1. Cystic fibrosis (23%), bronchiectasis (13%), tuberculosis sequelae (8%), chronic obstructive pulmonary disease (COPD)(6%)
According to the study of researchers at the Università degli Studi di Milano. Ospedale San Paolo, the causes of haemoptysis was as follows: cystic fibrosis (23%), bronchiectasis (13%), tuberculosis sequelae (8%), chronic obstructive pulmonary disease (COPD) (6%) and no apparent cause (21%). Major complications were recorded in 3/477 (0.6%): stroke (n=1), transient ischaemic attack (TIA) (n=1) and transient quadriplegia (n=1). Minor complications were recorded in 143/477 (30%): chest pain 86/143 (60%) and dysphagia 29/143 (20%). During a mean follow-up period of 14 (8-36) months, haemoptysis recurrence was observed in 42/110 cases (38%) of cystic fibrosis and in 77/367 cases of other diseases (21%)(2).

2.2. Thrombasthenia is a rare disorder of blood platelets, which results in easy bruising and nosebleeds.

2.3. Blood clot in the lung 
Blood clot in the lung due to Venous thrombosis, as a result of  blood clot formed in a vein breaks off and transported to the right side of the heart into the lungs. must be coughed out for the normal function of the lung. There is a report of a young woman diagnosed as having microscopic polyangiitis (MPO) presenting with diffuse alveolar hemorrhage (DAH). DAH is a rare, but life-threatening disorder. The patients presented with dyspnea, cough, hemoptysis (not constant). The radiographic features are very characteristic and reveal the signs of diffuse, bilateral alveolar filling in chest HRCT especially in middle and lower zones(3).

2.4. Bronchiectasis and Tuberculosis
There is a report of a 39-year-old woman presented with chronic cough, haemoptysis and hoarseness of voice. She had left recurrent laryngeal nerve palsy and high inflammatory markers on investigation. CT thorax revealed aortic wall thickening and traction bronchiectasis. 2 D echocardiogram revealed grade 1 aortic regurgitation compatible with aortitis(4). Other researchers in the study of 154 patients admitted for life-threatening hemoptysis (LTH) over 3 consecutive years. Bronchoscopy and arteriography procedures were performed, as prescribed by the attending physician. Patient evolution was followed 5 years post-event, wrote that teading causes of life-threatening hemoptysis (LTH) were bronchiectasis and tuberculosis. While bronchoscopy during a hemoptysis episode was effective in identifying the source of the bleeding, artery embolization was more effective in stabilizing the patient both at the short and long term(4a).

2.5.  Pulmonary edema 
Pulmonary edema has been reported in SCUBA divers, apnea divers, and long-distance swimmers. Researchers at the  University Boulevard, in the study of Immersion pulmonary edema in female triathletes, showed that Contributing factors include hemodynamic changes due to water immersion, cold exposure, and exertion which elevate cardiac output, causing pulmonary capillary stress failure, resulting in extravasation of fluid into the airspace of the lung(5).

2.6. Cystic fibrosis 
Cystic fibrosis (CF) is a recessive genetic disease characterized by dehydration of the airway surface liquid and impaired mucociliary clearance and Hemoptysis and pneumothorax are complications commonly reported in patients with cystic fibrosis(6).

2. 7. Esophageal and Lung cancer
If the tumor in the lung and Esophagus cause the break off of the blood vessels, it can cause coughing of blood to protect the respiratory system.

2.8. Esophageal and/or laryngeal candidiasis
Esophageal and/or laryngeal candidiasis can cause signs and symptoms of  hemoptysis(7).

2.9. Pneumonia 
There is a report of a 37-year-old man with hemoptysis, fever, and shortness of breath. The clinical and laboratory examinations revealed that the patient had pseudohemoptysis due to S. marcescens pneumonia, on an immunocompromised pattern, because of the coexistence of sarcoidosis, accoring to the study by General Hospital, Aristotle University of Thessaloniki(8).

2.10. Others
In the study of Hemoptysis: an uncommun case by Serviços de Medicina Interna e de Pneumologia, Hospital de Sousa Martin, researchers indicated that hemoptysis is a symptom that suggests a variety of pathologies that can be more or less benign and even fatal, a life threatening for the person who suffers it. Between the most common causes we have bronchitis, bronchiectasis and bronchopulmonary neoplasia. Less frequent causes are: Goodpasture's syndrome, Wegener's granulomatosis, systemic lupus erythematosus, between others(9).

3. Diagnosis 
3.1. Bronchoscopy
Bronchoscopy is a diagnostic technique to visualize inside the airway with insertion of bronchoscope into the airways. In the study to evaluated the diagnostic accuracy of results from fiberoptic bronchoscopy (FOB) and high-resolution computed tomography (HRCT) in 126 patients at Gangnam Severance Hospital (Seoul, Korea) who were suspected of having pulmonary tuberculosis (PTB), found that FOB is a useful tool in the rapid diagnosis of active PTB with a high sensitivity, specificity, PPV and NPV in sputum smear-negative PTB-suspected patients. HRCT improves the sensitivity of FOB when used in combination with FOB in sputum smear-negative patients suspected of having PTB(10).

3.2. Laryngoscopy
Laryngoscopy is a medical procedure to look at the back of the throat, including the voice box (larynx) and vocal cords.
 
3.3. Lung biopsy
Lung biopsy is the removal of a sample from the lung tissue through the wall of your chest for examination.
 
3.4. Mediastinoscopy
Mediastinoscopy is a surgical examination of the inside of the upper chest between and in front of the lung,, if your doctor suspected that the  Hemoptysis is caused by lung cancer.

3.5. Spirometry
Spirometry is test to measure the pulmonary function, including the volume and flow of air that can be inhaled and exhaled.

3.6. Tonsillectomy
Tonsillectomy is a surgical procedure to remove the tonsils from either side of the tonsillar fossa, if they are the cause of Hemoptysis.

3.7. Upper airway biopsy
It is a surgical removal of a sample from the upper airway (nose, mouth, throat) for examination.

3.8. Etc.
3. Management 
Researchers at the University of Wisconsin Medical School, Milwaukee, in the study of diagnosis and management of Hemoptysis, indicated that patient's history should help determine the amount of blood and differentiate between hemoptysis, pseudohemoptysis, and hematemesis. A focused physical examination can lead to the diagnosis in most cases. In children, lower respiratory tract infection and foreign body aspiration are common causes. In adults, bronchitis, bronchogenic carcinoma, and pneumonia are the major causes. Chest radiographs often aid in diagnosis and assist in using two complementary diagnostic procedures, fiberoptic bronchoscopy and high-resolution computed tomography, which are useful in difficult cases and when malignancy is suspected. The goals of management are threefold: bleeding cessation, aspiration prevention, and treatment of the underlying cause. Mild hemoptysis often is caused by an infection that can be managed on an outpatient basis with dose monitoring. If hemoptysis persists, consulting with a pulmonologist should be considered. Patients with risk factors for malignancy or recurrent hemoptysis also require further evaluation with fiberoptic bronchoscopy or high-resolution computed tomography(11). Other researchers suggested that the etiology of hemoptysis is best categorized from the various system or site of bleeding. The management of hemoptysis begins with an initial assessment of gas exchange and hemodynamic stability followed by an identification of the cause by means of fiberoptic bronchoscopy, and chest imaging studies to attain cessation of bleeding and to prevent future recurrence(12).

Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/22791000
(2) http://www.nejm.org/doi/full/10.1056/NEJMcpc0708507
(3) http://www.ncbi.nlm.nih.gov/pubmed/22335144
(4) http://www.ncbi.nlm.nih.gov/pubmed/22905814
(4a) http://www.ncbi.nlm.nih.gov/pubmed/22704276
(5) http://www.ncbi.nlm.nih.gov/pubmed/21660230
(6) http://www.ncbi.nlm.nih.gov/pubmed/20675678
(7) http://www.ncbi.nlm.nih.gov/pubmed/7422428
(8) http://www.ncbi.nlm.nih.gov/pubmed/21941452
(9) http://www.ncbi.nlm.nih.gov/pubmed/18282444
(10) http://www.ncbi.nlm.nih.gov/pubmed/22726571
(11) http://www.ncbi.nlm.nih.gov/pubmed/16225028
(12) http://www.ncbi.nlm.nih.gov/pubmed/20043609


B. Hematochezia (rectal bleeding)
Hematochezia is defined as a condition of the passage of bright red, bloody stool. In most cases it is an indication of hemorrhoids (swollen veins in and around the rectum) or diverticulitis, a common digestive disease particularly found in the large intestine, as a result of infection or inflammation.

1. Symptoms
1.1. Abdominal cramping and distention
In the some case the passing of large amount of  blood is accompanied with abdominal cramping and distention as a result of colitis (inflammation of the large intestine).

1.2. Constipation
It is a result of severe rectal pain.

1.3. Dizziness and Fatigue
These may be result of the influence of the blood loss causing not enough oxygen to be transported.

1.4. Fever
This can be a result of inflammation or infection of the large intestine.

 1.5. Body weakness
It is a result of not enough blood to transport nutrients and oxygen to the cells and organ needed.

1.7. Fainting or sudden changes in the level of consciousness
This is an result due to  large volume of blood loss and considered to be life threatening.

1.8. Etc.

2. Causes
2.1. Ectopic pregnancy
There is a report of case of severe rectal bleeding due to an ectopic pregnancy in the wall of the cecum is reported. The usual preoperative studies for rectal bleeding were performed but did not yield a definitive diagnosis. At laparotomy the right side of the uterus was found to be adherent to the cecum(1).

2.2. Abdominal colic and major gastrointestinal haemorrhage
There is a report of a case of massive rectal bleeding resulting from the placental attachment of an abdominal pregnancy to the sigmoid colon is reported. Both mother and infant survived this rare complication which should be considered when abdominal colic and major gastrointestinal haemorrhage occur in a pregnant patient(2). Other researchers also report of a case of an unusual case of massive bleeding per rectum caused by erosion into the caecum of placental tissue from an ectopic pregnancy is presented. Despite its rarity, abdominal pregnancies may have to be considered in sexually active fertile women presenting with difficult torrential bleeding from the lower gastrointestinal tract(3).

2.3. Angiodysplastic lesions (vascular lesions of the gastrointestinal tract)
In the study of a single angiodysplasias demonstrated by preoperative angiography in four patients and the review of the literature on intestinal angiodysplastic lesions, found that the relative frequency of angiodysplasias in the right side of the colon is noted. Visceral angiography is an important investigation in cases where there is persistent or recurrent bleeding from the gastrointestinal tract, especially when barium studies and laparatomy have been negative(4).

2.4. Coagulation disorder 
In the study of Rectal bleeding, deep venous thrombosis, and coagulopathy in a patient with Klippel-Trénaunay syndrome, reserachers indicated that this report validates the use of endorectal resection for venous malformation of the rectum in patients with KTS and highlights the difficult balance of controlling bleeding by correction of a consumptive coagulopathy and the increased risk of thromboembolic complications(5).

2.5. Hemostatic disorders
In the report of a 79-year-old woman (weight, 69 kg) was hospitalized in a gastroenterology unit for severe rectal bleeding. She had been treated for 2 months with dabigatran etexilate 110 mg twice daily for chronic atrial fibrillation. On admission, her creatinine clearance (CrCl) was 20.7 mL/min/1.73 m(2), prothrombin time (PT) less than 10% (reference range 70-130%), and international normalized ratio (INR) 14.5 (venous blood). Eleven days after admission, hematologic and renal function were normalized and rectal bleeding stopped. An 84-year-old man (weight, 71 kg) was admitted for rectal bleeding with acute renal failure and dehydration that began while he was treated with dabigatran etexilate 110 mg twice daily for atrial fibrillation. On admission, CrCl was 33.5 mL/min/1.73 m(2), PT 13%, and INR 7.53 (venous blood). Dabigatran etexilate was stopped on admission. At the end of the hospitalization, CrCl was 66.5 mL/min/1.73 m(2), PT 54%, and INR 1.53. In both cases, an objective causality assessment revealed that those adverse reactions were probably related to dabigatran etexilate(6).

2.6. Colon cancer
It can be with or without pain. In the study of 604 patients and 22 (3.6%, 95% confidence interval [CI] = 2.0% to 5.2%) were diagnosed with colorectal cancer. Significant predictors of colorectal cancer were found to be age (<50 years: odds ratio [OR] = 1; 50-69 years: OR = 5.1, 95% CI = 1.4 to 18.6; > or = 70 years: OR = 8.2, 95% CI = 2.1 to 31.8) and blood mixed with the stool (Likelihood ratio [LR] 1.5; adjusted OR = 3.8; 95% CI = 1.4 to 10.5). Presence of haemorrhoids associated with bright red bleeding not mixed with stool reduced the likelihood of cancer (OR = 0.4, 95% CI = 0.1 to 1.2) but did not eliminate it--a cancer was present in 2% of patients with these symptoms(7).

2.7. Colorectal polyps
In the conduction of two studies, the first in 1989, the second in 1991, in which we invited Danish general practitioners to register 3-4 patients aged 40 and over presenting with rectal bleeding, researchers found that study 1 among 208 patients aged 40 and over and presenting with a first episode of rectal bleeding, colorectal cancer and polyps were present in 15.4 and 7.7%, respectively. In Study 2 among 209 patients aged 40 and over and presenting with overt rectal bleeding, 156 reported a first bleeding episode or a change in their usual bleeding pattern, and in this group colorectal cancer and polyps were diagnosed in 14.1 and 11.5%, respectively. In the group with unchanged bleeding the cancer polyp prevalence was 6.7% (P < 0.05). The patients in both studies were followed through a yearly letter to the GP for at least 32 and 22 months, respectively(8).

2.8. Hemorrhoids
There is a report of within a period of 18 months, 387 patients were referred to the Proctologic Service at the Chaim Sheba Medical Center because of recurrent rectal bleeding. Hemorrhoids were found in 194 of these patients and further investigation showed that 45 of the 194 patients (23.2%) had other coexisting colonic pathology (12 cancers, 28 polyps, 4 inflammatory bowel diseases and 1 angiodysplasia). Sixteen of 40 patients with diverticulosis and 13 of 30 patients with hemoglobin less than 11 g/dl had additional colonic pathology(9).

2.9. Etc.

3. Risk Factors
3.1. Aging
Risk of rectal bleeding increase with age as  the result of weakened intestinal blood vessels. In the study of the group consisted of 102 patients (50 years of age or less)  with a flexible endoscope and an anoscopethat presented for evaluation of rectal bleeding, showed that six patients had colitis; all but one of these patients were less than 40 years of age. Flexible endoscopy and anoscopy provide complimentary information in middle-aged adults with rectal bleeding(10)

3.2. Family history of gastrointestinal disease
People with the family of ulcerative colitis and Crohn’s disease, are at increased risk of rectal bleeding

3.3. Others, according to American Journal of Gastroenterology (1998) 93, 2179–2183; doi:10.1111/j.1572-0241.1998.00530.x
FROM: Self-reported rectal bleeding in a United States community: prevalence, risk factors, and health care seeking by Nicholas J Talley and Michael Jones(11)

Table 1. Association of Rectal Bleeding With Potential Risk Factors Based on Univariate Logistic Regression

Figure and tables index

Any Rectal BleedingBlood Coating the StoolsBlood on Toilet PaperDark Blood Viewed in Stools

OR95% CIOR95% CIOR95% CIOR95% CI
  Age greater than or equal to 45 yr0.54* 0.41–0.721.190.67–2.121.640.43–6.230.600.29–1.23
  Sex (male)0.950.72–1.260.560.32–0.981.300.40–4.221.100.58–2.11
  Marital status0.820.55–1.223.0* 1.11–8.113.260.92–11.510.430.19–0.98
  Employment (yes vs no)0.550.31–0.960.590.16–2.180.550.06–4.721.670.50–5.63
  Education (< HS vs HS + tertiary)1.190.93–1.521.140.69–1.872.460.86–7.060.330.18–0.62
  Aspirin (none, some)1.080.82–1.421.060.61–1.841.520.47–4.940.750.39–1.44
  Ulcer history (yes)1.120.72–2.021.610.62–4.180.420.09–2.091.470.50–4.32
  Gastric surgery1.580.89–2.791.640.55–4.920.290.06–1.482.360.75–7.41
  IBS (yes)1.48* 1.04–2.101.060.54–2.051.070.28–4.151.650.78–3.50
  Constipation (yes)3.09* 2.33–4.101.510.86–2.670.240.05–1.142.30* 1.14–4.65
  Diarrhea (yes)2.08* 1.51–2.850.710.38–1.332.080.44–9.754.12* 2.10–8.11
  Urgency (yes)1.55* 1.11–2.151.240.66–2.350.940.25–3.603.25* 1.68–6.48
  Dyspepsia (yes)1.310.83–2.041.480.63–3.470.590.12–2.861.290.49–3.45
  Smoking (never vs current)0.960.67–1.390.410.18–0.970.740.18–3.093.67* 1.65–8.12
  Alcohol (0–6 vsgreater than or equal to 7 drinks wk)1.340.92–1.931.020.49–2.110.550.14–2.153.511.67–7.38
  Bowel surgery1.030.60–1.761.170.42–3.300.810.10–6.731.360.42–4.42
  Physician visits (bowel trouble)5.26* 3.19–8.651.170.53–2.570.820.17–3.932.93* 1.30–6.61
*  p < 0.05.
 HS = high school; IBS = irritable bowel syndrome; CI = confidence interval; OR = odds ratio.



4. Diagnosis
4.1. Colonoscopy and arteriography
In the study of Diagnosis and treatment of hematochezia: guideline for clinical practice, DR. Wandono H. at the Department of Internal Medicine, Hajj Hospital Surabaya wrote that there are difficulties in clinical practice to find the cause and making the diagnosis and therapy for hematochezia. Fortunately, the progress and development in medical technology, especially colonoscopy and arteriography, has assisted in clinical practice(12).

4.2. Blood test
The aim of blood test is to determine the hemoglobin concentration, coagulation and and tests of liver and renal function are useful in checking for factors that may exacerbate bleeding.

4.3. In stable patients
a. In younger patients
If the physical examination or anoscopy reveals a bleeding hemorrhoid or other cause of local anal pathology, no other test is necessary as the possibility of colon cancer is fewer than 1% in those younger than age 30 years.
b. In older patients
80% of colorectal malignancies are found in patients older than the age of 50 years. Even if a local lesion such as a hemorrhoid is discovered. Twenty-seven percent of patients with carcinoma of the rectum and 10% of those with carcinoma of the sigmoid have been noted to have coincidental hemorrhoids. Most patients older than the age of 40 years with rectal bleeding are candidates for colonoscopy.
4.2, 4.3,(13)

4.5. Computed tomography (CT) angiography
CT angiography is an accurate, cost-effective tool in the diagnosis of acute GI bleeding and can show the precise location of bleeding, thereby directing further management, according to the study by  Shanghai Jiao Tong University School of Medicine(14).
4.6. Etc.

5. Treatment and management
5.1. Severe hematochezia
In the study to  evaluate (a) the diagnosis and treatment of 80 consecutive patients with severe, ongoing hematochezia from unknown source and (b) the effectiveness and safety of urgent colonoscopy after oral purge, researcher wrote that because of ongoing severe hematochezia in the intensive care unit, urgent diagnosis and treatment was recommended by the attending physicians and surgeons. Emergency panendoscopy was performed before purge. Urgent colonoscopy was performed in the intensive care unit after patients received oral purge and their gut was cleared of blood, clots, and stool. The final diagnosis in these patients was 74% colonic lesions (30% angiomata, 17% diverticulosis, 11% polyps or cancer, 9% focal ulcers, 7% other), 11% upper gastrointestinal lesions, and 9% presumed small bowel lesions. No lesion site was identified in 6%. Clinically significant fluid retention (medically controlled) occurred in 4% of patients after purge. Sixty-four percent of patients had intervention for control of bleeding: 39% had therapeutic endoscopy, 24% surgery, and 1% therapeutic angiography. For 22 patients who also had emergency visceral angiography, the diagnostic yield was 14% and the complication rate was 9%. and suggested that (a) Oral purge was effective and safe for cleansing the colon of stool, clots, and blood. Sulfate purge appeared to be safer than saline purge. (b) Before urgent colonoscopy and purge, emergency panendoscopy was indicated to exclude an upper gastrointestinal bleeding source. (c) Urgent colonoscopy after purge was effective, safe, and often diagnostic. (d) Compared with urgent colonoscopy, urgent visceral angiography was often nondiagnostic. However, the examinations may be complementary. (e) Hemostasis via colonoscopy has a definitive role in the treatment of some focal colonic lesions such as bleeding angiomata(15).

5.2. In Stable patients 
In the study of to examine 58 patients, presenting with clinical signs of lower GI hemorrhage,  through a 24-month period. Preliminary endoscopy was either negative or unfeasible. Images were obtained with a four-detector row CT with an arterial (4 x 1 mm collimation, 0.8 mm increment, 1.25 mm slice width, 120 kV, 165 mAs) and portal venous series (4 x 2,5 mm collimation, 2 mm increment, 3 mm slice width, 120 kV, 165 mAs). Time interval between endoscopy and CT varied between 30 minutes and 3 hours. The results of the multi-phase Multi-Slice-Computertomography (MSCT) were correlated with clinical course and surgical or endoscopical treatment(16).

Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/309659
(2) http://www.ncbi.nlm.nih.gov/pubmed/3875846  
(3) http://www.ncbi.nlm.nih.gov/pubmed/1295424
(4) http://www.ncbi.nlm.nih.gov/pubmed/4544790
(5) http://www.ncbi.nlm.nih.gov/pubmed/22424361
(6) http://www.ncbi.nlm.nih.gov/pubmed/22669799
(7) http://www.ncbi.nlm.nih.gov/pubmed/17007706
(8) http://www.ncbi.nlm.nih.gov/pubmed/8732328
(9) http://www.ncbi.nlm.nih.gov/pubmed/3872288
(10) http://www.ncbi.nlm.nih.gov/pubmed/7628276
(11) http://www.nature.com/ajg/journal/v93/n11/fig_tab/ajg1998500t1.html#figure-title
(12) http://www.ncbi.nlm.nih.gov/pubmed/18046067
(13) http://www.dermaamin.com/site/images/stories/fruit/Primarycaremedicine/sid436397.html 
(14) http://www.ncbi.nlm.nih.gov/pubmed/20712058
(15) http://www.ncbi.nlm.nih.gov/pubmed/3263294
(16) http://www.ncbi.nlm.nih.gov/pubmed/16333787


C. Hematuria
Hematuria is defined as a medical condition with the presence of blood in the urine.

C.1 Causes and Risk factors
C.1. Causes
1. According to to the study at the University of Texas Southwestern Medical Center at Dallas,  bladder cancer based on > or = 10 years of smoking or environmental exposure with microscopic hematuria are rarely evaluated thoroughly and only 12.8% were referred for urologic evaluation. Further studies are needed to evaluate both the utilization and effectiveness of guidelines for hematuria(1).

2. Kidney cancer
Tumor compresses onto capillary ot blood vessel can cause blood in the urine.

3. Inflammation 
In the study of 82 of 1209 patients (6.8%), follow-up evaluation was available for 43 of 85 (50.6%) findings by histologic diagnosis (n = 9), imaging evaluation (n = 31), or clinical information (n = 3). There were 11 (0.9%) examinations with acute findings, of which acute inflammation of the gastrointestinal tract and pancreaticobiliary system were the most common. Seventy-two (5.9%) examinations revealed 74 nonacute but important findings(2).

4. Sickle cell disease
There is a report of a case of recurrent gross hematuria, sickle cell trait and von Willebrand's disease is reported. The gross hematuria abated promptly after the institution of cryoprecipitate therapy(3).

5. Oral anticoagulation (OA)
Oral anticoagulation (OA) is a common treatment with a known risk of fatal or major bleeding, but also minor bleeding symptoms and menorrhagia can cause substantial discomfort and necessitate medical or surgical interventions(4).

6. Vigorous exercise
There is a report of during a 6-month Amphibious Task Force deployment to the Mediterranean Sea, five sailors and Marines were admitted to the ship's ward with severe upper extremity pain, elevated serum muscle enzymes, and a urinalysis dip positive for blood in the absence of microscopic hematuria-a finding highly suggestive of myoglobinuria(5).

7. Sexual activity
In the study to assess the relationship between sexual behaviour, urinary symptoms, urinalysis and bacteriuria in men attending STD clinics of 704 patients had had sexual intercourse (SI) within 14 days of testing, 424 had urinary symptoms and 122 had pyuria. All 13 patients with positive culture had SI < 14 days before testing, urinary symptoms and pyuria. No association was found between sexual orientation, type of SI, number of sexual partners, condom usage and bacteriuria(6).

8. Hemorrhagic cystitis 
In the study to evaluate the association between the prevalence of viral infections and hemorrhagic cystitis in pretransplant and posttransplant recipients and donors, showed that detection of single and multiple infections of BK virus, adenovirus, and cytomegalovirus in blood and/or urine samples of hematopoietic stem cell transplant recipients, in combination with 1 or more inducing factors of hemorrhagic cystitis were enforced on the important role these risk factors play in the cause of hemorrhagic cystitis(7).

9. Etc.

C.2. Risk factors 
1. Family history 
PKD1 gene abnormality is responsible for 85% of cases of ADPKD, patients with PKD2 mutations typically present later and progress more slowly. Patients with ADPKD can present with a positive family history, hypertension, flank pain, haematuria, renal insufficiency or proteinuria(8). 

2. Other risk factors
In the study to determine the prevalence of urological pathology in a retrospective and prospective study of patients with microscopic haematuria attending a haematuria clinic, between January 1998 and May 2001, 781 patients attended the haematuria clinic; of these, 368 (47%; median age 60 years, range 18-90) had a history of microscopic haematuria, as detected by urine dipstick testing, showed that Urine cytology showed no malignant cells in any patient with a history of microscopic haematuria. In 143 patients (39%), urine cytology showed no red blood cells and all other investigations were normal. Of the remaining 225 patients, IVU showed a tumour in one (bladder), renal stones in 15 and an enlarged prostate in two. Renal ultrasonography detected no additional pathology. Urine analysis showed one urinary tract infection. Flexible cystoscopy detected five patients with a bladder tumour (all G1pTa), two urethral strictures, five bladder stones and enlarged prostates, six enlarged prostates only, and nine red patches in the bladder, showing one patient with carcinoma in situ. No PSA levels were suggestive of prostate cancer(9).


3. Etc.

C.2. Symptoms and signs
1. There is a report of healthy 60-year-old man presented with urinary urgency and microhematuria, The workup revealed no urothelial lesions, but did suggest a calcified intraperitoneal mass causing extrinsic compression of the bladder. Laparoscopic exploration revealed a glistening, spherical mass attached by a stalk to the sigmoid colon. Removal and histologic examination of the mass revealed calcified fat necrosis, most likely due to the spontaneous torsion and calcification of an appendix epiploicae(10).

2. Blood clots
 Massive hematuria of renal origin was diagnosed in 4 dogs. In all dogs, blood and blood clots were clearly visible in the urine, according to study by Stone EA and researcher team(11).

3. Burning sensation 
It may be result of inflammation or infection of the urinary track.
4. Pain when urinating (dysuria)
Telephone and clinic interviews identified 21 patients (36%) with symptoms of the dysuria and hematuria syndrome. The most common symptoms were hematuria (71%) and bladder or suprapubic pain (76%). Of the patients 18 (86%) ranked the severity of symptoms as mild to moderate and 3 (14%) ranked them as severe, according to the study by the University of Washington(12).

5. Fever  
As a result of infection or inflammation

6. Weight loss and flank pain
There is a report of 37-year-old man with a history of bladder augmentation presented with gross hematuria, weight loss and flank pain, according to thye study of Department of Clinical Urology, University of Southern California Keck School of Medicine

7.  Etc.

C.3. Diagnosis(13)
In the review of 1502 study participants, routine urinalysis was performed in 73.2% and 164 (14.9%) subjects had documented hematuria (>3 red blood cells / high-power field) before inclusion, found that  42.1% had no further evaluation. Additional testing included 
1. Repeat urinalysis (36%),
The aim of urtnalysis, including  physical, chemical, and microscopic examinations, is to diagnose of urologic conditions such as calculi, urinary tract infection (UTI), and malignancy(14).

2. Urine culture (15.2%)
The mid stream urinary test to check for bacteria and germs in the urine. the aim is to test for urinary track infection.

3. Cytology (10.4%)
The aim of the test is to detect the irregular cells growth in the urinary track.

4. Imaging (22.6% overall
The aim of the test is to  evaluate the urinary tract including the kidneys, ureters, bladder, prostate, or urethra.
4.1.15.9% Computed tomography
The best choice to evaluate the kidneys and ureters.
4.2. 4.3% intravenous pyelography
Similar in analyzing the kidneys and ureters
4.3.  2.4% magnetic resonance imaging, and
Similar in analyzing the kidneys and ureters 
4.4. Cystoscopy (12.8%).
The best choice to examine the bladder with the use of a thin, flexible cystoscope which is insert in to the bladder via the urethra


C.4. Treatment
Treatments are depending to the diagnosis of the diseases, including
1. Kidney stones
If the diagnosis found that Hematuria is the result of kidney stone, under normal condition, you are asked to drink plenty water to washout the stone and take pain control medicine. In some conditions, extracorporeal shock wave lithotripsy may be necessary to crush the stones to smaller piece to allow them to pass through via the urinary track. Other case, if the stone is found in the ureter, cystoscopy may help to it.
2. Urinary tract infection:
Urinary track infection is the result of invasion of bacteria, antibiotics will be taken over a certain period depending to types of bacteria.

3. Benign prostate enlargement
In case of hematuria is caused by benign prostate enlargement then alpha blockers and 5α-reductase inhibitors may be taken.

4. Medications: If a medication is the causes of hematuria, then the medication may be replaced with other with the same effectiveness but with no side effect of urinary bleeding, if one can be found. If not, you doctor may weight the benefits and risk of the medicine.

5. Urinary tract blockage: if the disease is caused by a blockage, the surgery may be become necessary generally to correct or remove the block.

6. Etc.

Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/20564400
(2) http://www.ncbi.nlm.nih.gov/pubmed/22915402
(3) http://www.ncbi.nlm.nih.gov/pubmed/313457 
(4) http://www.ncbi.nlm.nih.gov/pubmed/17260163
(5) http://www.ncbi.nlm.nih.gov/pubmed/7816216
(6) http://www.ncbi.nlm.nih.gov/pubmed/8976831
(7) http://www.ncbi.nlm.nih.gov/pubmed/22142049
(8) http://www.ncbi.nlm.nih.gov/pubmed/22497104
(9) http://www.ncbi.nlm.nih.gov/pubmed/12175388
(10) http://www.ncbi.nlm.nih.gov/pubmed/11880093
(11) http://www.ncbi.nlm.nih.gov/pubmed/6629996
(12) http://www.ncbi.nlm.nih.gov/pubmed/8326629
(13) http://www.ncbi.nlm.nih.gov/pubmed/20564400
(14) http://www.aafp.org/afp/2005/0315/p1153.html
 

D. Upper head hemorrhaging
D.1.  Intracranial hemorrhage
 Intracranial hemorrhage is defined as condition of bleeding within the skull.
D.1.1. Types of Intracranial hemorrhage
In the study to evaluate the sensitivity and specificity of head ultrasound (HUS) in the detection of intracranial hemorrhage in premature neonates compared with brain MRI using susceptibility-weighted imaging (SWI), showed that Ultrasound (US) and MRI scans of the brain using SWI in premature neonates were retrospectively evaluated for grade I-III germinal matrix hemorrhage (GMH), periventricular hemorrhagic infarction (PVHI), intra-axial hemorrhage other than PVHI, extra-axial hemorrhage in each cerebral hemisphere and cerebellar hemorrhage in each cerebellar hemisphere(1).
1. Intra-axial hemorrhage (cerebral hemorrhage)
Intra-axial hemorrhage is defined as a condition of  bleeding in the brain itself, including bleeding of the brain tissues and ventricles,

2. Extra-axial hemorrhage
Extra-axial hemorrhage is defined as a condition of skull bleeding outside of the brain

D.1.2. Causes and Rick factors
1. Causes 
a. Malignant melanoma
There is a report of a41-year-old female presented with repeated pontine hemorrhage. Histological examination showed malignant melanoma cells. No cutaneous lesion was found and positron emission tomography found no abnormalities. Our presumptive diagnosis was primary intra-axial brainstem malignant melanoma. The possibility of malignant melanoma should be considered in patients with intra-axial brainstem lesion associated with repeated hemorrhages(2).

b.  Head trauma
Patients receiving warfarin or clopidogrel are considered at increased risk for traumatic intracranial hemorrhage after blunt head trauma. In a study of a total of 1,064 patients were enrolled (768 warfarin patients [72.2%] and 296 clopidogrel patients [27.8%]). There were 364 patients (34.2%) from Level I or II trauma centers and 700 patients (65.8%) from community hospitals. One thousand patients received a cranial CT scan in the ED. Both warfarin and clopidogrel groups had similar demographic and clinical characteristics, although concomitant aspirin use was more prevalent among patients receiving clopidogrel. The prevalence of immediate traumatic intracranial hemorrhage was higher in patients receiving clopidogrel (33/276, 12.0%; 95% confidence interval [CI] 8.4% to 16.4%) than patients receiving warfarin (37/724, 5.1%; 95% CI 3.6% to 7.0%), relative risk 2.31 (95% CI 1.48 to 3.63). Delayed traumatic intracranial hemorrhage was identified in 4 of 687 (0.6%; 95% CI 0.2% to 1.5%) patients receiving warfarin and 0 of 243 (0%; 95% CI 0% to 1.5%) patients receiving clopidogrel(3).


c. High blood pressure
 In a cohort of patients with spontaneous ICH, we obtained ICP values from nursing documentation of hourly vital signs and reviewed charts to rule out spurious ICP recordings, showed that among 243 patients, 57 (24 %) underwent ICP monitoring, of whom 40 (70 %; 95 % CI 57-82 %) had an episode of ICP > 20 mmHg. Intracranial hypertension was less likely in older patients (OR per decade 0.6, 95 % CI 0.3-0.9) and after infratentorial hemorrhage (OR 0.1, 95 % CI 0-0.7). Intracranial hypertension was not independently associated with mRS scores (OR 0.8, 95 % CI 0.3-2.3); this remained true for a threshold of >25 mmHg (OR 0.5, 95 % CI 0.2-1.5), number of elevations (OR 0.98 per elevation, 95 % CI 0.96-1.00), or area under the curve (OR 1.00 per mmHg × h, 95 % CI 0.99-1.01)(4).

d. Cerebral Aneurysms
  Cerebral aneurysm is defined as a cerebrovascular disorder causes of the blood vessel to bulge or balloon out of the wall of a blood vessel as a result of the weaken of blood vessels and veins and occurred mostly at the bifurcations and branches of the large arteries located at the Circle of Willis. It can burst and cause bleeding into the brain(5) leading to Intracranial hemorrhage(5). 

e. Brain Arteriovenous malformations
 Brain Arteriovenous malformations is defined as a condition of abnormal connection between veins and arteries, with a high rate of bleeding into the brain usually congenital.

f. Cerebral Amyloid angiopathy
Cerebral Amyloid angiopathy is defined as a condition of  amyloid build up on the walls of  the blood vessel walls in the brain. Cerebral amyloid angiopathy (CAA) is one of the main causes of intracerebral hemorrhage (ICH), a subtypes of  Intracranial hemorrhage in the elderly, according to the study by the Institut de Recerca, Universitat Autònoma de Barcelona(6).

g. Blood or bleeding disorders.
In the study to analyze the association of the initial platelet count with mortality and progression of intracranial hemorrhage (ICH) in blunt traumatic brain injured (TBI) patients, showed that Of 626 TBI patients, 310 (49.5%) had a minimum of two brain computed tomography scans and were able to have ICH progression evaluated. Patients with platelets <175,000/mm3 had a significantly increased risk for ICH progression (OR [95% CI]: 2.09 [1.07-4.37]; adjusted p = 0.043). ICH progression was associated with increased need for craniotomy (OR [95% CI]: 3.27 [1.28-8.33]; adjusted p = 0.013) and mortality (OR [95% CI]: 3.41 [1.11-10.53]; adjusted p = 0.033). A platelet count <100,000/m3 was an independent predictor for mortality (OR [95% CI]: 9.5 [1.3-71.4]; adjusted p = 0.029)(7).

h. Neurosarcoidosis
Neurosarcoidosis, a complication of sarcoidosis in which inflammation occurs in the nervous system are related intracranial haemorrhage, according to the study by the incorporating the National Children's Hospital, Trinity College(8).

g. Liver disease 
Intracranial hemorrhages and late hemorrhagic disease associated cholestatic liver disease, according to the study of 11 infants with cholestatic liver disease with different etiologies exhibiting intracranial hemorrhage (ICH) to researchers at the  Erciyes University, Erciyesevler Mahallesi(9).

h. Brain tumors
There is a report of  three cases of metastatic brain tumors which began with the symptoms of vascular accident and were demonstrated as high density area by CT scan. Two of them are metastasis of lung cancer and another, hepatoma. Characteristic CT findings are as follow: 1) atypical location 2) non-homogeneous high density area extending from the margin of the tumor (sometimes ring-like appearance) 3) surrounding massive edema 4) positive contrast enhancement 5) multiple lesions(10).

i. Stroke and oral anticoagulants
Use of intravenous tissue-type plasminogen activator (IV tPA) for acute ischemic stroke is restricted to patients with an international normalized ratio (INR) less than 1.7. However, a recent study showed increased risk of symptomatic intracranial hemorrhage after IV tPA use in patients with oral anticoagulants (OAC) even with an INR less than 1.7(11).

j. Etc.

2. Risk factors 
1. According to the study of Risk factors for intracranial hemorrhage and nonhemorrhagic stroke after fibrinolytic therapy (from the GUSTO-i trial), showed that Of 592 patients in the Global Utilization of Streptokinase and tPA for Occluded Arteries-I trial who had a stroke during initial hospitalization, the risk for intracranial hemorrhage was significantly greater in those with recent facial or head trauma (odds ratio 13.0, 95% confidence interval 3.4 to 85.5); dementia was additionally associated with an increased risk for intracranial hemorrhage (odds ratio 3.4, 95% confidence interval 1.2 to 10.2). Because facial or head trauma may greatly influence treatment decisions, this risk factor should be incorporated into models designed to estimate the risks and benefits of fibrinolytic therapy(12).

D.1.2. Symptoms
1.  Intracranial pressure
Intracranial pressure as a result of a traumatic brain injuries can cause large mass which puts pressure on the brain(13).

2. Severe headache followed by vomiting is one of the more common symptoms of intracerebral hemorrhage, a sub types of Intracranial hemorrhage(14).

3. Seizures with no previous history of seizures
In the study to determine the outcome and prognostic factors in those patients with severe AVM-ICH, showed that there were seven males and nine females with a mean age of 32 years (range 6-66). All had Glasgow coma score 8 or less and most exhibited motor posturing and/or dilated pupils. Fifteen patients had intraprenchymal, ten had intraventricular, and four had subarachnoid hemorrhage (SAH). Twelve patients underwent hematoma evacuation with concomitant decompressive craniectomy in 11 and external ventricular drainage (EVD) in six. EVD was the only treatment offered to four patients. AVM excision was not routinely attempted in the acute phase. Three patients died from extensive bihemispheric infarction and refractory intracranial pressure. All 13 survivors improved neurologically and 12 had an acceptable functional outcome (modified Rankin scale ≤ 4) after a mean follow-up of 10 months (range 1-49). Among all clinical, radiological, and operative variables, only cisternal SAH (P = 0.007) and early seizures (P = 0.018) were significantly associated with death(15).

3. Other symptoms as a result of central nervous system has been affect by intracranial hemorrhage, such as weakness in an arm or leg, decreased alertness, tingling or numbness, difficulty writing or reading, loss of motor tremors, loss of balance, etc.

D.1.3. Diagnosis
After a complete physical and history examination, the tests which your doctor may order include
1. Computed tomography (CT)
Computed tomography (CT) is the standard diagnostic tool uses X-rays to make detailed pictures of structures inside the skull to check for fractures and bleeding, specially in case of trauma. Scheduled repeat head computed tomography after mild traumatic brain injury has been shown to have limited use for predicting the need for an intervention. We hypothesized that repeat computed tomography in persons with intracranial hemorrhage and a Glasgow Coma Scale (GCS) score of 13 to 15, without clinical progression of neurologic symptoms, does not impact the need for neurosurgical intervention or discharge GCS scores, according to the study by The University of Texas-Southwestern Medical Center(16).

2.  Lumbar puncture 
If the CT is negative for bleeding, lumbar puncture or a spinal tap may be necessary to collect a sample of cerebrospinal fluid (CSF) to check for the presence of blood. There is a report of two cases of spinal epidural hematoma and two cases of intracranial subdural hematoma after lumbar puncture (LP) are reported in children receiving chemotherapy for acute lymphoblastic leukemia and non-Hodgkin lymphoma. The bleeding was asymptomatic but interfered with treatment in one case, and caused either severe backache or headache but no neurological deficit in the other three patients(17).

3. Magnetic resonance imaging (MRI) can be helpful  in detecting structural abnormalities of the body to determine the extent of injury to the brain. 

4. Arteriography
In case a ruptured aneurysm is suspected, arteriography, a medical imaging technique used to visualize the inside, or lumen, of blood vessels to pinpoint the location of the ruptured aneurysm. 

5. Other tests may be necessary, depending to conditions of the patient and suspection of the doctor.
Some researchers suggested (in case of ttrauma and absence of trauma) that ICH is diagnosed through history, physical examination, and, most commonly, noncontrast CT examination of the brain, which discloses the anatomic bleeding location. Trauma is a common cause. In the absence of trauma, spontaneous intraparenchymal hemorrhage is a common cause associated with hypertension when found in the deep locations such as the basal ganglia, pons, or caudate nucleus(18).

D.1.4. Treatments 
Treatments of Intracranial hemorrhage are completely depending to diseases of differentiation
1. Medication
a. Antihypertensive therapy
In the study of the efficacy of the American Heart Association/American Stroke Association guidelines for ultra-early, intentional antihypertensive therapy in intracerebral hemorrhage, showed that there are clinical benefits, by the prevention of subsequent HE, in maintaining a MAP level lower than that recommended by the the American Heart Association/American Stroke Association (AHA/ASA) (110 mm Hg) after hospitalization for patients who have intracerebral hemorrhage (ICH)(19).

b. Factor VII
Factor VII is a protein that causes blood to clot. Several studies have demonstrated successful correction of the international normalized ratio (INR) using prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa). To our knowledge, no study has directly compared these agents for treatment of warfarin-related ICH(20).

c. Mannitol and hypertonic saline
In the study to develop effective strategies for the medical treatment of ICP in cases of ICH, we evaluated the therapeutic efficacy of mannitol and hypertonic saline in a canine model of ICH, found that
hypertonic saline, in both 3 and 23.4% concentrations, is as effective as mannitol in the treatment of intracranial hypertension observed in association with ICH. Hypertonic saline may have a longer duration of action, particularly when used in 3% solution. None of three treatment regimens influence regional cerebral blood flow or cerebral metabolism(21).

d. Acetaminophen to relieve the symptoms of  headache and  body temperature.

e. Corticosteroids
Corticosteroids, a synthetic drug and closely resemble cortisol, which is produced by the adrenal glands may be used in case of hypertensives and swelling.

f. Etc.

2. Non medical treatments
a. In case of intracranial pressure, placement of intracranial pressure monitors (The intracranial pressure (ICP) is monitored and ICP also can be lowered by draining cerebral spinal fluid (CSF) out through the catheter) by non-neurosurgeons: Excellent outcomes can be achieved. Placement of ICP monitors may be performed safely by both neurosurgeons and non-neurosurgeons. This procedure should thus be considered a core skill for trauma surgeons and surgical residents alike, thereby allowing initiation of prompt medical treatment in both rural areas and trauma centers with inadequate neurosurgeon or fellow coverage, according to the study by Department of Trauma Services, Via Christi Hospital on Saint Francis (J.M.H.(22).

3. Surgery
"Currently, most neurosurgeons in the UK would operate on patients with a deteriorating conscious level and a worsening neurological deficit. In addition, haematomas between 20—80 ml in volume are more likely to be operated upon as are lobar/superficial haematomas. With cerebellar haemorrhage, although there are again no randomized controlled trials comparing surgical and conservative treatment, there seems to be greater agreement that hematomas greater than 3—4 cm should be operated upon, especially when there is concomitant clinical deterioration or hydrocephalus", according to the study of Surgical treatment of intracerebral haemorrhage by University of Newcastle upon Tyne, Newcastle upon Tyne, UK (23).

Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/22633043
(2) http://www.ncbi.nlm.nih.gov/pubmed/19029781
(3) http://www.ncbi.nlm.nih.gov/pubmed/22626015
(4) http://www.ncbi.nlm.nih.gov/pubmed/22833445
(5) http://diseases-researches.blogspot.ca/p/cerebral-aneurysm.html
(6) http://www.ncbi.nlm.nih.gov/pubmed/22261638
(7) http://www.ncbi.nlm.nih.gov/pubmed/20386283
(8) http://www.ncbi.nlm.nih.gov/pubmed/22681045
(9) http://www.ncbi.nlm.nih.gov/pubmed/22327309
(10) http://www.ncbi.nlm.nih.gov/pubmed/7279131
(11) http://www.ncbi.nlm.nih.gov/pubmed/21980194
(12) http://www.ajconline.org/article/S0002-9149%2803%2901581-9/abstract
(13) http://emedicine.medscape.com/article/247664-overview
(14) http://en.wikipedia.org/wiki/Cerebral_hemorrhage
(15) http://www.ncbi.nlm.nih.gov/pubmed/21234617
(16) http://www.ncbi.nlm.nih.gov/pubmed/22929497
(17) http://www.ncbi.nlm.nih.gov/pubmed/16155928
(18) http://www.ncbi.nlm.nih.gov/pubmed/22284061
(19) http://www.ncbi.nlm.nih.gov/pubmed/20541417?dopt=Abstract
(20) http://www.ncbi.nlm.nih.gov/pubmed/21492631
(21) http://www.ncbi.nlm.nih.gov/pubmed/10232539
(22) http://www.ncbi.nlm.nih.gov/pubmed/22929484
(23) http://bmb.oxfordjournals.org/content/56/2/444.full.pdf

D.2. Cerebral hemorrhage
Cerebral hemorrhage, a sub type of intracranial hemorrhage, is defined as a condition of  bleeding as a result of artery bursts in the brain, considered as one of the main cause of stroke, according to the research article of Endoscopic management of hypertensive intraventricular haemorrhage with obstructive hydrocephalus(1).

D.2.1. Causes and Rick factors
1. Causes
a.  Penetrating head trauma
Patients receiving warfarin or clopidogrel are considered at increased risk for traumatic intracranial hemorrhage after blunt head trauma. In a study of a total of 1,064 patients were enrolled (768 warfarin patients [72.2%] and 296 clopidogrel patients [27.8%]). There were 364 patients (34.2%) from Level I or II trauma centers and 700 patients (65.8%) from community hospitals. One thousand patients received a cranial CT scan in the ED. Both warfarin and clopidogrel groups had similar demographic and clinical characteristics, although concomitant aspirin use was more prevalent among patients receiving clopidogrel. The prevalence of immediate traumatic intracranial hemorrhage was higher in patients receiving clopidogrel (33/276, 12.0%; 95% confidence interval [CI] 8.4% to 16.4%) than patients receiving warfarin (37/724, 5.1%; 95% CI 3.6% to 7.0%), relative risk 2.31 (95% CI 1.48 to 3.63). Delayed traumatic intracranial hemorrhage was identified in 4 of 687 (0.6%; 95% CI 0.2% to 1.5%) patients receiving warfarin and 0 of 243 (0%; 95% CI 0% to 1.5%) patients receiving clopidogrel(2).

b. Amyloid angiopathy
In the review of neuropathologic studies suggestion of an association between cerebral amyloid angiopathy (CAA) and small ischemic infarctions as well as hemorrhages by analyzing MR images from 78 subjects with a diagnosis of probable CAA and a similar aged group of 55 subjects with Alzheimer disease or mild cognitive impairment (AD/MCI) for comparison. DWI and apparent diffusion coefficient (ADC) maps were inspected for acute or subacute infarcts, showed that MRI evidence of small subacute infarcts is present in a substantial proportion of living patients with advanced cerebral amyloid angiopathy (CAA). The presence of these lesions is associated with a higher burden of hemorrhages, but not with conventional vascular risk factors(3).

c. Cerebral venous sinus thrombosis
Cerebral venous sinus thrombosis is defined as a rare condition of stroke as a result  from thrombosis (a blood clot) of the dural venous sinuses. There is a report of a A 65-year-old man presented with right hemiparesis and loss of consciousness. Brain computed tomography showed a left frontoparietal hemorrhage. Angiographic studies with magnetic resonance imaging showed the presence of a partial superior saggital sinus thrombosis. With a diagnosis of CVST, intravenous heparin was administered. After 24 hours the patient had a symptomatic increase in ICH size, and 2 days later the patient developed a status epilepticus with new evidence of rebleeding. Anticoagulant treatment was stopped and the patient experienced neurological improvement, with no new episodes of rebleeding(4).

d. Infection of Streptococcus mutans
Infection with Streptococcus mutans expressing collagen-binding protein (CBP) is a potential risk factor for haemorrhagic stroke(5).


e. Fetal cytomegalovirus infection
There is a report of a 38-year-old gravida 3, para 2 at 16 weeks of gestation who underwent ultrasound examination for anomaly screening. The scan revealed an extensive irregular echogenic area in the fetal brain, especially at the level of lateral ventricles, suggestive of intraventricular and cerebral hemorrhage due to intrauterine cytomegalovirus (CMV) infection(6).

e. Cerebral Aneurysms
  Cerebral aneurysm is defined as a cerebrovascular disorder causes of the blood vessel to bulge or balloon out of the wall of a blood vessel as a result of the weaken of blood vessels and veins and occurred mostly at the bifurcations and branches of the large arteries located at the Circle of Willis. It can burst and cause bleeding into the brain(5) leading to Intracranial hemorrhage(7)


f. Brain Arteriovenous malformations
 Brain Arteriovenous malformations is defined as a condition of abnormal connection between veins and arteries, with a high rate of bleeding into the brain usually congenital.


g.  Etc.


2. Risk factors 
In the study of a total of 1714 patients with hemorrhagic stroke  participation in the Hemorrhagic Stroke Project (HSP), showed that of these, 217 cases met the criteria for primary ICH. Cases with primary ICH were matched to 419 controls. Independent risk factors for ICH included hypertension (adjusted odds ratio [OR], 5.71; 95% CI, 3.61 to 9.05), diabetes (adjusted OR, 2.40; 95% CI, 1.15 to 5.01), menopause (adjusted OR, 2.50; 95% CI, 1.06 to 5.88), current cigarette smoking (adjusted OR, 1.58; 95% CI, 1.02 to 2.44), alcoholic drinks≥2/day (adjusted OR, 2.23; 95% CI, 1.16 to 4.32), caffeinated drinks≥5/day (adjusted OR, 1.73; 95% CI, 1.08 to 2.79), and caffeine in drugs (adjusted OR, 3.55; 95% CI, 1.24 to 10.20)(8).

D.2.2. Symptoms 
1.  Intracranial pressure
Intracranial pressure as a result of a traumatic brain injuries can cause large mass which puts pressure on the brain(9).

2. Severe headache followed by vomiting is one of the more common symptoms of intracerebral hemorrhage, a sub types of Intracranial hemorrhage(10).

3. Seizures with no previous history of seizures
In the study to determine the outcome and prognostic factors in those patients with severe AVM-ICH, showed that there were seven males and nine females with a mean age of 32 years (range 6-66). All had Glasgow coma score 8 or less and most exhibited motor posturing and/or dilated pupils. Fifteen patients had intraprenchymal, ten had intraventricular, and four had subarachnoid hemorrhage (SAH). Twelve patients underwent hematoma evacuation with concomitant decompressive craniectomy in 11 and external ventricular drainage (EVD) in six. EVD was the only treatment offered to four patients. AVM excision was not routinely attempted in the acute phase. Three patients died from extensive bihemispheric infarction and refractory intracranial pressure. All 13 survivors improved neurologically and 12 had an acceptable functional outcome (modified Rankin scale ≤ 4) after a mean follow-up of 10 months (range 1-49). Among all clinical, radiological, and operative variables, only cisternal SAH (P = 0.007) and early seizures (P = 0.018) were significantly associated with death(11).

3. Other symptoms as a result of central nervous system has been affect by intracranial hemorrhage, such as weakness in an arm or leg, decreased alertness, tingling or numbness, difficulty writing or reading, loss of motor tremors, loss of balance, etc.

D.2.3. Diagnosis
1. Computed tomography (CT) scan
If your doctor suspects the bleeding is within the brain itself, then CT scan is the best choice. Computed tomography (CT) is the standard diagnostic tool uses X-rays to make detailed pictures of structures inside the skull to check for fractures and bleeding, specially in case of trauma. Scheduled repeat head computed tomography after mild traumatic brain injury has been shown to have limited use for predicting the need for an intervention. We hypothesized that repeat computed tomography in persons with intracranial hemorrhage and a Glasgow Coma Scale (GCS) score of 13 to 15, without clinical progression of neurologic symptoms, does not impact the need for neurosurgical intervention or discharge GCS scores, according to the study by The University of Texas-Southwestern Medical Center(12).

2. A Lumbar puncture
If CT scan can not identify the diagnosis, your doctor may suggest a lumbar puncture (spinal tap) to rule out subarachnoid hemorrhage. Lumbar puncture or a spinal tap may be necessary to collect a sample of cerebrospinal fluid (CSF) to check for the presence of blood. There is a report of two cases of spinal epidural hematoma and two cases of intracranial subdural hematoma after lumbar puncture (LP) are reported in children receiving chemotherapy for acute lymphoblastic leukemia and non-Hodgkin lymphoma. The bleeding was asymptomatic but interfered with treatment in one case, and caused either severe backache or headache but no neurological deficit in the other three patients(13).

3. Other tests such as
a Magnetic resonance imaging (MRI) can be helpful  in detecting structural abnormalities of the body to determine the extent of injury to the brain. 

b. Arteriography
In case a ruptured aneurysm is suspected, arteriography, a medical imaging technique used to visualize the inside, or lumen, of blood vessels to pinpoint the location of the ruptured aneurysm. 

4. Etc.

D.2.4. Treatments 
Depending on the underlying abnormality 
1. Medication
a. Antihypertensive therapy
In the study of the efficacy of the American Heart Association/American Stroke Association guidelines for ultra-early, intentional antihypertensive therapy in intracerebral hemorrhage, showed that there are clinical benefits, by the prevention of subsequent HE, in maintaining a MAP level lower than that recommended by the the American Heart Association/American Stroke Association (AHA/ASA) (110 mm Hg) after hospitalization for patients who have intracerebral hemorrhage (ICH)(14).

b. Factor VII
Factor VII is a protein that causes blood to clot. Several studies have demonstrated successful correction of the international normalized ratio (INR) using prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa). To our knowledge, no study has directly compared these agents for treatment of warfarin-related ICH(15).

c. Mannitol and hypertonic saline
In the study to develop effective strategies for the medical treatment of ICP in cases of ICH, we evaluated the therapeutic efficacy of mannitol and hypertonic saline in a canine model of ICH, found that
hypertonic saline, in both 3 and 23.4% concentrations, is as effective as mannitol in the treatment of intracranial hypertension observed in association with ICH. Hypertonic saline may have a longer duration of action, particularly when used in 3% solution. None of three treatment regimens influence regional cerebral blood flow or cerebral metabolism(16).

d. Acetaminophen to relieve the symptoms of  headache and  body temperature.

e. Corticosteroids
Corticosteroids, a synthetic drug and closely resemble cortisol, which is produced by the adrenal glands may be used in case of hypertensives and swelling.

f. Etc.

2. Non medical treatments
a. In case of intracranial pressure, placement of intracranial pressure monitors (The intracranial pressure (ICP) is monitored and ICP also can be lowered by draining cerebral spinal fluid (CSF) out through the catheter) by non-neurosurgeons: Excellent outcomes can be achieved. Placement of ICP monitors may be performed safely by both neurosurgeons and non-neurosurgeons. This procedure should thus be considered a core skill for trauma surgeons and surgical residents alike, thereby allowing initiation of prompt medical treatment in both rural areas and trauma centers with inadequate neurosurgeon or fellow coverage, according to the study by Department of Trauma Services, Via Christi Hospital on Saint Francis (J.M.H.(17).

3. Surgery
a. Non invasive treatment
Interventional radiology involves treatments that include passing a catheter to widen or to close off blood vessels in the brain without surgery(18).

b. Surgery
"Currently, most neurosurgeons in the UK would operate on patients with a deteriorating conscious level and a worsening neurological deficit. In addition, haematomas between 20—80 ml in volume are more likely to be operated upon as are lobar/superficial haematomas. With cerebellar haemorrhage, although there are again no randomized controlled trials comparing surgical and conservative treatment, there seems to be greater agreement that hematomas greater than 3—4 cm should be operated upon, especially when there is concomitant clinical deterioration or hydrocephalus", according to the study of Surgical treatment of intracerebral haemorrhage by University of Newcastle upon Tyne, Newcastle upon Tyne, UK (19).

Sources
(1) http://www.biomedcentral.com/1471-2377/7/1
(2) http://www.ncbi.nlm.nih.gov/pubmed/22626015
(3) http://www.ncbi.nlm.nih.gov/pubmed/19349602
(4) http://www.ncbi.nlm.nih.gov/pubmed/21712666
(5) http://www.ncbi.nlm.nih.gov/pubmed/21952219
(6) http://www.ncbi.nlm.nih.gov/pubmed/18417974
(7) http://diseases-researches.blogspot.ca/p/cerebral-aneurysm.html
(8) http://stroke.ahajournals.org/content/36/9/1881.abstract
(9) http://emedicine.medscape.com/article/247664-overview
(10) http://en.wikipedia.org/wiki/Cerebral_hemorrhage
(11) http://www.ncbi.nlm.nih.gov/pubmed/21234617
(12) http://www.ncbi.nlm.nih.gov/pubmed/22929497 
(13) http://www.ncbi.nlm.nih.gov/pubmed/16155928
(14) http://www.ncbi.nlm.nih.gov/pubmed/20541417?dopt=Abstract
(15) http://www.ncbi.nlm.nih.gov/pubmed/21492631
(16) http://www.ncbi.nlm.nih.gov/pubmed/10232539
(17) http://www.ncbi.nlm.nih.gov/pubmed/22929484
(18) http://www.cedars-sinai.edu/Patients/Programs-and-Services/Stroke-Program/Stroke-Resources/Cerebral-Hemorrhage.aspx
(19) http://bmb.oxfordjournals.org/content/56/2/444.full.pdf


D.4. Subarachnoid hemorrhage (SAH)
Subarachnoid hemorrhage (SAH) is defined as a condition of the presence of blood  within the subarachnoid space (the area between the brain and the thin tissues that cover the brain).

D.4.1. Causes and Rick factors
1. Causes
a. Bleeding from an arteriovenous malformation (AVM)
There is a report of nineteen additional cases of angiographic vasospasm after AVM rupture are reported in the literature. The mean age of these patients was 33 years; there was a 1.25:1 female to male predominance in this group. One-half of these patients had an intraparenchymal hemorrhage, and only 56% of them had SAH(1).

b. Bleeding from a cerebral aneurysm 
There is a report of a 59-year-old woman with type IIA von Willebrand's disease (VWD) presented with subarachnoid hemorrhage (SAH). Computed tomography showed SAH in the right sylvian fissure and intracranial hemorrhage in the right temporal lobe. Angiography demonstrated an aneurysm at the bifurcation of the right middle cerebral artery(2).

c. Coagulopathy
In the study carried out in an attempt to find out the association of coagulopathy and the development of delayed traumatic intracerebral hematoma (DTICH) in patients diagnosed with a traumatic subarachnoid hemorrhage (TSAH), found that on admission, peripheral blood samples for coagulation studies were taken within 6 hours after injury. All patients had subsequent CT scans performed within 24 hours of admission. Thirty (47.6%) of 63 patients exhibited radiological evidence of DTICH on their subsequent CT scans. There was a significant correlation between the increased value of serum fibrinogen degradation product (FDP > 40 micrograms/ml) and the development of DTICH(3).

d. Head injury
In the study of Coagulopathy in severe traumatic brain injury: a prospective study, found that the incidence of TBI coagulopathy in SHI is high, especially in penetrating injuries. Independent risk factors for coagulopathy in isolated head injuries include GCS score of <or=8, ISS >or=16, hypotension upon admission, cerebral edema, subarachnoid hemorrhage, and midline shift. The development of TBI coagulopathy is associated with longer ICU length of stay and an almost 10-fold increased risk of death(4).

f. Use of blood thinners
There is a repory of a 45-year-old woman with prosthetic valves replacement, was admitted with severe headache and vomiting one month after starting danazol treatment at 300 mg per day. She was receiving long-term anticoagulation with warfarin and dipyridamole, taking 3.5 mg and 300 mg per day respectively. The patient's thrombotest value was less than 6% at the time of admission. Cranial CT revealed subarachnoid hemorrhage(5).

g. Certain types of herb
If you are experience certain symptoms of Hemorrhaging, please consult with your doctor before taking any blood thinning herbal medicine. Moderate to severe adverse events, such as spinal epidural hematoma, spontaneous intracerebral hemorrhage, retrobulbar hemorrhage, subarachnoid hemorrhage, spontaneous hyphema, and postoperative bleeding, have occasionally been anecdotally associated with consumption of dietary supplements(6).


h.  Etc.

2. Risk factors
a, Gene defect
In the study to evaluate whether genes influencing coagulation are associated with the occurrence of aneurysmal subarachnoid hemorrhage (SAH) and with secondary cerebral ischemia and rebleeding in patients with aneurysmal SAH, showed that aneurysmal SAH patients are more often carriers of the subunit B His95Arg factor XIII polymorphism compared to controls. This suggests that carriers of the subunit B His95Arg factor XIII polymorphism have an increased risk of aneurysmal SAH(7).

b. von Willebrand's disease
von Willebrand's disease is associated with the onset of  subarachnoid hemorrhage (SAH)(8).

c. Vitamin K deficiency
Although late VKDB leads to significant morbidity and mortality, it can be avoided by providing vitamin K prophylaxis to all newborns. Administration of vitamin K (1 mg) at birth can prevent intracranial bleeding and other hemorrhagic manifestations, according to the study by Erciyes University, Talas, Kayseri, Turkey(9).

d. Factor XI deficiency
Aneurismal subarachnoid haemorrhage (SAH) is a devastating event affecting patients at a fairly young age and accounting for significant morbidity and mortality.  Researchers at the National and Kapodistrian University of Athensm reported a unique case of aneurismal SAH in a patient with underlying coagulation FXI deficiency which was incidentally identified after patient's admission, as routine blood tests revealed increased activated partial thromboplastin time. Despite early successful treatment with coiling, the patient had a second episode of SAH a few months after his discharge, due to aneurysm revascularization and rupture(10).


d. Etc.

D.4.2. Symptoms
1.  Thunderclap headache, neck stiffness, psychosocial consequences
 Classic signs and symptoms include sudden onset of 'thunderclap' headache but patients can present with atypical symptoms such as neck stiffness. For patients who survive SAH, the psychosocial consequences can be devastating and can affect their families or carers(11).

2.  Head ache and Meningeal signs 
In the study of 193 adult aSAH patients confirmed headache as well as meningeal signs as the most frequent symptom on presentation to the emergency department, and this was cited as the most common reason for seeking medical treatment(12).

3. Confusion, seizures.  impairment of language ability and vasospasm
eizures are a recognized complication of subarachnoid hemorrhage (SAH). They can increase the cerebral metabolic demands and lead to cardiopulmonary compromise. This could be detrimental in the setting of delayed cerebral ischemia (DCI), when the brain tissue is vulnerable to further reductions in oxygen delivery or increases in demand. An association between seizures and worsening ischemia could influence the decision to use antiepileptic drug (AED) prophylaxis in patients with vasospasm(13). 

4. Intracranial pressure (pressure inside the skull), drop of cerebral blood flowand Cushing reflex respons, brain edema formation, loss of hippocampal neurons, neurological dysfunction
SAH induced a sharp increase of intracranial pressure (ICP) from 5.1+/-1.2 to 78.5+/-9.3 mm Hg (mean+/-SD; p<0.05), a concomitant drop of cerebral blood flow (rCBF) by 81+/-4% (p<0.05), and a significant Cushing reflex response (p<0.05). rCBF measurements alone could not reliably detect SAH. SAH resulted in significant brain edema formation (brain water content increase at 72 h: 2.9+/-0.9%; p<0.05), loss of hippocampal neurons (CA1: -56%, CA2: -55%; CA3: -72%; 7 days; p<0.05), severe neurological dysfunction over 7 days, and a mortality of 30%.(14).

5. Other symptoms
There is a report of a 50-year-old male patient suffered from subarachnoid hemorrhage (SAH). No abnormal condition was found in intracranial vascular digital subtraction angiography (DSA). But, this patient presented with positive hantavirus-IgM and IgG, with typical clinical process, which lead to the diagnosis of EHF followed by SAH.  Meticulous assessment of EHF patients with a serious condition had one or more central nervous system (CNS) abnormalities, such as sudden headache, vomiting, confusion, meningismus, and convulsions, which is necessary for diagnosing and giving timely treatment to improve the prognosis(14a). 

D.4.3. Diagnosis
1. Computed tomography (CT) scan or multidetector CT angiography
If your doctor suspects the bleeding is within the brain itself, then CT scan is the best choice. Computed tomography (CT) is the standard diagnostic tool uses X-rays to make detailed pictures of structures inside the skull to check for fractures and bleeding, specially in case of trauma. Scheduled repeat head computed tomography after mild traumatic brain injury has been shown to have limited use for predicting the need for an intervention. CT scan has correctly identified over 95% of cases—especially on the first day after the onset of bleeding. Others suggested that multidetector CT angiography can be used as a primary examination tool in the diagnostic work-up of patients with SAH(15).

2. A Lumbar puncture
If CT scan can not identify the diagnosis, your doctor may suggest a lumbar puncture (spinal tap). In the study to evaluate the Differentiation of early subarachnoid hemorrhage from traumatic lumbar puncture, showed that the 0.3 to 7% hemolysis which occurred was relatively independent both of the time following SAH and of the number of red blood cells (rbc) in the cerebrospinal fluid (CSF). There was, on the other hand, a significant and time-dependent increase in CSF lactate concentration early after SAH, suggesting the potential clinical value of the detection of increased lactate with a relatively normal lactate/pyruvate ratio in hemorrhagic CSF. Until this can be evaluated in human subjects, however, determination of the rbc counts or total hemoglobin concentrations in serially collected samples of CSF remains the best clinical method(16).

3.  ECG
ECG is found to be important in differetiating of SAH. In the study to evaluate all patients admitted to a 31-bed department of intensive care between 1993 and 2000 with acute aneurysmal SAH documented by cerebral angiography or autops, indicated that of 159 patients (49.6 years [range: 20-75]) with acute SAH, 106 (66.7%) had abnormal ECGs (classified by an observer blinded to the patients' clinical course and outcome. Conduction abnormalities were present in 7.5%. Arrhythmias occurred in 30.2%. By univariate analysis, the presence of ST depression was related to outcome as assessed by the Glasgow Outcome Scale (GOS) (15% poor outcome [GOS 4-5] vs. 1% good outcome [GOS 1-3], p<0.05)(17).

4. Etc.

D.4.4. Complications and diseases associated with SAH
1. Changes in coagulative and fibrinolytic activities
Both coagulative and fibrinolytic activities were altered after the onset of SAH. These results demonstrate that the coagulative/fibrinolytic cascade might be activated via different mechanisms in different types of stroke(18).

2. Terson's Syndrome
TS was diagnosed in 20 of 155 SAH patients (30 eyes), and detected in 16 (14.16%) of 113 patients with aneurysmal SAH and four (9.52%) of 42 patients with traumatic SAH. No correlations were found between state-of-consciousness, GCS scores, and presence of TS in patients with traumatic SAH. Among patients suffering from aneurysmal SAH, however, significant relationships were observed between state-of-consciousness, GCS scores, Hunt-Hess grades, and incidence of TS (p < 0.01). No statistically significant difference was observed between men and women with regard to the incidence of TS (χ(2) = 0.821, p = 0.365)(19).

3. Fahr's Disease
there is a report of a case of an acute IBCG presentation in which the cause of the deterioration was an aneurysmal subarachnoid hemorrhage(20).

4. Hydrocephalus 
Hydrocephalus, also known as "water in the brain" is defined as complex and multifactorial neurological disorders of accumulation of cerebrospinal fluid (CSF) in the cavity of brain of that can lead to intracranial pressure inside the side, resulting of brain trauma, stroke, infection, tumor, etc. Acute hydrocephalus is present in 20% of patients with subarachnoid hemorrhage. One third of them may be asymptomatic on admission; 50% of those who have clinical hydrocephalus recover spontaneously within the first 24 h. The presence of acute hydrocephalus after subarachnoid hemorrhage is associated with additional morbidity and higher mortality secondary to rebleeding(21).

5. Etc.


D.4.4. Treatments 
1. Surgery
a. Clipping
In the study of the data of patients with SAH who underwent aneurysmal clipping at the Kartal Training and Research Hospital between 1999 and 200, showed that  early surgery is advantageous over late surgery in patients with SAH with lower post-operative vasospasm and mortality rates(22).

b. Coiling
In  the study of 15 patients with high-risk intracranial saccular aneurysms treated using electrolytically detachable coils introduced via an endovascular approach. The patients ranged in age from 21 to 69 years. The most frequent clinical presentation was subarachnoid hemorrhage (eight cases). Considerable thrombosis of the aneurysm (70% to 100%) was achieved in all 15 patients, and preservation of the parent artery was obtained in 14. Although temporary neurological deterioration due to the technique was recorded in one patient, no permanent neurological deficit was observed in this series and there were no deaths. It is believed that this new technology is a viable alternative in the management of patients with high-risk intracranial saccular aneurysms. It may also play an important role in the occlusion of aneurysms in the acute phase of subarachnoid hemorrhage(23).

c. Fenestration of the lamina terminalis and removal of cisternal clots
 In the study to investigate the effects of clot removal on multiple outcome variables following the clipping of ruptured anterior communicating aneurysms, showed that vasospasm affected 5 of 17 (29%) in group A and 8 of 13 (61.5%) in group B (p < 0.05). Endovascular treatment for vasospasm was required in one patient in group A (5.8% of 17, 20% of 5) and in five from group B (38.4% of 13, 62.5% of 8) (p < 0.05). Mortality was observed in one case in group A (5.8% of 17, 20% of 5) and in two cases in group B (15.3% of 13, 25% of 8) and was related to vasospasm after SAH. Ventriculoperitonal shunt (VPS) was required in one case in group A (5.8%) and in five cases in group B (38.4%). Conclusions: Fenestration of the lamina terminalis and removal of cisternal clots significantly decreased the incidence of post-SAH hydrocephalus and was associated with better outcomes(24).

2.  Other Treatments
The preference of medication with poor clinical evidence, such as magnesium sulfate, aspirin, statins, and anti-fibrinolytics was lower than 10%. The use of intravenous nimodipine and systemic glucocorticoids was as high as 31%. The availability of endovascular therapy was 69%. The indication for treatment of patients with unruptured intracranial aneurysms that required intervention was less than 13.8%. In patients with ruptured or unruptured intracranial aneurysms, coiling was the preferred method for exclusion, according to a a sample of members from the Colombian Association of Neurosurgery(25)

3. Etc.

Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/22381269
(2) http://www.ncbi.nlm.nih.gov/pubmed/16377951
(3) http://www.ncbi.nlm.nih.gov/pubmed/11260889
(4) http://www.ncbi.nlm.nih.gov/pubmed/19131806
(5)  http://www.ncbi.nlm.nih.gov/pubmed/1886315
(6) http://www.ncbi.nlm.nih.gov/pubmed/22300597
(7) http://www.ncbi.nlm.nih.gov/pubmed/19826759 
(8) http://www.ncbi.nlm.nih.gov/pubmed/16377951
(9) http://www.ncbi.nlm.nih.gov/pubmed/21928065 
(10) http://www.ncbi.nlm.nih.gov/pubmed/19367158
(11) http://www.ncbi.nlm.nih.gov/pubmed/20437757
(12) http://www.ncbi.nlm.nih.gov/pubmed/22578393
(13) http://www.ncbi.nlm.nih.gov/pubmed/21427775
(14) http://www.ncbi.nlm.nih.gov/pubmed/20457182
(14a) http://www.ncbi.nlm.nih.gov/pubmed/22135608
(15) http://www.ncbi.nlm.nih.gov/pubmed/20935079
(16) http://www.ncbi.nlm.nih.gov/pubmed/906062
(17) http://www.ncbi.nlm.nih.gov/pubmed/15301889
(18) http://www.ncbi.nlm.nih.gov/pubmed/16671428 
(19) http://www.ncbi.nlm.nih.gov/pubmed/22913767
(20) http://www.ncbi.nlm.nih.gov/pubmed/22754741
(21) http://www.ncbi.nlm.nih.gov/pubmed/9586937
(22) http://www.ncbi.nlm.nih.gov/pubmed/22368972 
(23) http://thejns.org/doi/abs/10.3171/jns.1991.75.1.0008
(24) http://www.ncbi.nlm.nih.gov/pubmed/22890652
(25) http://www.ncbi.nlm.nih.gov/pubmed/22059120


E. Pulmonary hemorrhage (P-Hem)
Pulmonary hemorrhage is defined  as a acute condition of lung bleeding from the from the upper respiratory tract or the endotracheal tube of the lung with the mortality of 30 to 40%.

E.1. Causes and Rick factors
A. Causes  
1. Pulmonary Embolism
In the study to determine the characteristics of the history, physical examination, chest radiograph, electrocardiogram, and the ventilation/perfusion lung scan probability in elderly patients with pulmonary embolism who present with the syndrome of pulmonary infarction or hemorrhage, found that although a few clinical features of the pulmonary hemorrhage/infarction syndrome of pulmonary embolism in elderly patients differ from patients less than 40 years of age, in general, the clinical characteristics are comparable to younger patients(1).

2. Bacteria infection
Enterovirus 71 (EV71) infection with pulmonary edema or pulmonary hemorrhage as a fulminant and often fatal illness(2). Others report a case of a 63-year-old woman treated by intensive chemotherapy for acute myeloid leukemia (AML) who presented while severely neutropenic and thrombocytopenic a Sm pulmonary infection with hemoptysis leading to death in 48 h, according to the study of Lethal pulmonary hemorrhage caused by a fulminant Stenotrophomonas maltophilia respiratory infection in an acute myeloid leukemia patient(3).

3. Lung cancer
In the study to investigate  the risk factors associated with fatal pulmonary hemorrhage (PH) in patients with locally advanced non-small cell lung cancer (NSCLC), treated with chemoradiotherapy, showed that f the 583 patients, 2.1% suffered a fatal PH. The numbers of patients with minimum, minor, and major cavitations were 13, 11, and 14, respectively. Among the 38 patients with tumor cavitation, all 3 patients who developed fatal PH had major cavitations. On multivariate analysis, the presence of baseline major cavitation (odds ratio, 17.878), and a squamous cell histology (odds ratio, 5.491) proved to be independent significant risk factors for fatal PH. Interestingly, all patients with fatal PH and baseline major cavitation were found to have tumors with squamous cell histology, and the occurrence of fatal PH in patients having both risk factors was 33.3%(4).

4. Pneumonia 
In the review of the epidemiological, clinical and diagnosis findings of pneumonia and pulmonary hemorrhage observed in patients with leptospirosis in the period January 2007 to October 2009. A 64% (20/31) of patients diagnosed with leptospirosis presented pneumonia. Fifteen of them (75%) had severe pneumonia, of which seven (35%) were pulmonary hemorrhage. In ten patients (32%) reason for consultation and clinical early stage was a secretory gastroenteritis with fever and abdominal pain. Jaundice was only expressed in eleven patients (35%)(5).

5. Etc.

B. Risk factors
1. Extreme Exercise
There is a report of Exercise-induced pulmonary hemorrhage (EIPH) occurs in horses that race at high speeds(6)

2. Hereditary hemorrhagic telangiectasia and others
Hereditary hemorrhagic telangiectasia (Osler-Weber- Rendu disease) is inherited as an autosomal dominant trait with an incidence as high as 1:2300, according to the study of Hereditary hemorrhagic telangiectasia with pulmonary arteriovenous malformations. Prematurity is the factor most commonly associated with P-Hem; other associated factors are those that predispose to perinatal asphyxia or bleeding disorders, including toxemia of pregnancy, maternal cocaine use, erythroblastosis fetalis, breech delivery, hypothermia, infection, Respiratory Distress Syndrome, administration of exogenous surfactant (in some studies) and ECMO(7).


3. Etc,

E.2. Symptoms
1. The onset of P-Hem is characterized by oozing of bloody fluid from the nose and mouth or endotracheal tube with associated rapid worsening of the respiratory status, cyanosis and, in severe cases, shock(7).

2. In the report of 3 cases of enterovirus 71 infection with pulmonary edema or pulmonary hemorrhage as the early clinical manifestation, found that pulmonary edema or pulmonary hemorrhage occurred in the 3 cases with EV71-infected infants. The initial presentation was often nonspecific with fever and vomiting, and sudden appearances of cyanosis, tachypnea, tachycardia, hypertension or hypotension, limb weakness may suggest pulmonary edema or hemorrhage. Excessive fluid resuscitation may deteriorate the illness, on the contrary, fluid restriction and inotropic agents, and early intubation with positive pressure mechanical ventilation may be the proper treatment(8).

3. Etc.

E.3. Diagnosis 
1. The computed tomography (CT) scans and chest radiograph
In the study of the computed tomography (CT) scans and chest radiograph of seven patients with bronchoscopic or pathologically proven cases of pulmonary hemorrhage to determine the appearance and value of each modality, showed that CT revealed the presence and location in all cases while chest radiographs were falsely negative in two cases. The CT pattern was always an alveolar pattern while the pattern was more variable on chest radiographs. By providing better pattern definition than the chest radiographs, CT is the study of choice in detecting the presence of a suspected pulmonary hemorrhage(9).

2. Bronchoalveolar lavage (BAL)
Bronchoalveolar lavage (BAL) is a medical procedure to collect and examine the lung fluid with the use of a bronchoscope, passing through the mouth or nose into the lungs. In the study to investigate the efficacy of bronchoalveolar lavage (BAL) in diagnosing pulmonary hemorrhage  in 51 immunosuppressed patients with new pulmonary infiltrates, showed that Severe pulmonary hemorrhage was ultimately diagnosed in 14 cases, and a mild degree of hemorrhage was found in an additional 19 cases. Thrombocytopenia and invasive fungal infections were statistically associated with severe hemorrhage, as was an increased percentage of alveolar macrophages in the BAL sample(10).

3.  CT-guided transthoracic lung biopsy
Higher rates of complications are significantly found with multiple punctures (pneumothorax risk multiplied by 7.4), longer intra-parenchymal needle tract (5 and 7% higher risk of pneumothorax and hemorrhage for every 1 mm increase in depth), and with smaller lesions (2 and 5% lower risk respectively for pneumothorax and hemorrhage for every 1 cm increase in lesion size). The presence of an interposing rib is associated with a higher rate of hemorrhage(11).

4. Etc.

E.4. Complication
1. Leptospirosis
 Leptospirosis is a widespread zooanthroponosis that is prevalent in tropical regions due to the
favorable environmental survival conditions of its etiologic agent (Leptospira)(12).

2. Fetomaternal complications
Antenatal diagnosis and treatment of women with hereditary hemorrhagic telangectasia and pulmonary arteriovenous malformations might prevent potentially lifethreatening fetomaternal complications(13).

3. Pulmonary infection and respiratory failure
 In the study of spinal cord injury (SCI) rats, pulmonary edema and hemorrhage were occurred in the early stage of SCI while the other organs were almost normal. And the location of lung edema and hemorrhage were the same as that of pulmonary infection(14).

4. Etc.


E.4. Treatments 
Treatments depend on the diagnosis of each patient, if the underlined cause is due to medication, then medicine has to be stopped.

1. Immediate treatment
According to the Intensive Care Nursery House Staff Manual immediate treatment of P-Hem should include tracheal suction, oxygen and positive pressure ventilation. To assist in decreasing P-Hem, mean
airway pressure should be increased, either by a relatively high PEEP (i.e., 6 to 10
cmH2O) or by high frequency ventilation(15). In the infants, reserachers at suggested that current management of PH in VLBW infants includes ventilatory support using high positive end expiratory pressure, transfusion of blood and blood products to support the circulation and correct any hemostatic or coagulation defects and evaluation and treatment for patent ductus arteriousus (PDA). These strategies are often ineffective in preventing a poor outcome. rFVIIa is effective in controlling life-threatening hemorrhage in patients with hemophilia A and B with inhibitors, and in nonhemophiliacs with a variety of inherited or acquired hemostatic defects including platelet disorders, liver disease and von Willebrand's disease.(15a)

 2. Embolization - Interventional treatment of pulmonary arteriovenous malformations
Acording to the study of Dr. Andersen PE and Dr. Kjeldsen AD. at the Odense University Hospital " Pulmonary arteriovenous malformations (PAVM) are congenital vascular communications in the lungs.  The generally accepted treatment strategy of first choice is embolization of the afferent arteries to the arteriovenous malformations. It is a minimally invasive procedure and at the same time a lung preserving treatment with a very high technical success, high effectiveness and low morbidity and mortality. Embolization prevents cerebral stroke and abscess as well as pulmonary haemorrhage and further raises the functional level. Embolization is a well-established method of treating PAVM, with a significant effect on oxygenation of the blood. Screening for PAVM in patients at risk is recommended, especially in patients with HHT(16).

3. Corticosteroids 
There is a report of a patient suffered from acute glomerulonephritis with modest renal impairment and life-threatening pulmonary hemorrhage. The pulmonary hemorrhage caused severe hypoxia that necessitated artificial ventilation. As a last resort, 1 g/day of methylprednisolone was administered intravenously. Rapid cessation of pulmonary hemorrhage ensued with clearing of the lungs fields. the suggestion of large doses of glucocorticosteroids should be administered to patients with life-threatening pulmonary hemorrhage before considering bilateral nephrectomy, especially if the renal function is still adequate. Bilateral nephrectomy is an irreversible approach and, as with massive doses of steroids, has yet to be proved to be a consistently effective mode of therapy(17).

4. Etc. 

Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/11416457
(2) http://www.ncbi.nlm.nih.gov/pubmed/19099810
(3) http://www.ncbi.nlm.nih.gov/pubmed/15360016 
(4) http://www.ncbi.nlm.nih.gov/pubmed/22260460
(5) http://www.ncbi.nlm.nih.gov/pubmed/21550928
(6) http://www.ker.com/library/proceedings/04/EIPH_p95.pdf 
(7) http://www.ucsfbenioffchildrens.org/pdf/manuals/29_PulmHemorrhage.pdf 
(8) http://www.ncbi.nlm.nih.gov/pubmed/19099810  
(9) http://www.sciencedirect.com/science/article/pii/089970719390021E
(10) http://www.ncbi.nlm.nih.gov/pubmed/3605828 
(11) http://www.ncbi.nlm.nih.gov/pubmed/22645895 
(12) http://saithan.net/pulmonary%20and%20sys%20disease/Pulmonary%20complications%20of%20leptospirosis.pdf 
(13) http://ape.med.miami.edu/Doc/Resident%20Web%20Site%20Articles/Other%20diseases/Hereditary%20Hemorrhagic%20Telangiectasias/OB%20article%20+%20pulmAVMs.pdf
(14) http://www.ncbi.nlm.nih.gov/pubmed/22683446 
(15) http://www.ucsfbenioffchildrens.org/pdf/manuals/29_PulmHemorrhage.pdf
(15a) http://www.nature.com/jp/journal/v22/n8/full/7210787a.html
(16) http://www.ncbi.nlm.nih.gov/pubmed/21160695 
(17) http://annals.org/article.aspx?articleid=689575 

F. Vaginal bleeding
Vaginal bleeding is defined a condition of abnormal vaginal bleeding or spotting between periods as a result of hormonal imbalances (abnormal uterine bleeding), pregnancy, menopause, diseases, bleeding disorders, medications, etc. Researchers at the 2nd Department of Obstetrics and Gynecology, University of Athensuggested that the occurrence of irregular, prolonged or heavy abnormal uterine bleeding is one of the most urgent gynecological problems in adolescence and the diagnosis of dysfunctional uterine bleeding should be used only when all other organic and structural causes of abnormal vaginal bleeding have been ruled out(1).

F.1. Causes and Risk factors
1. Causes
a. Hormonal imbalance  
Menstrual bleeding that falls outside the range of normal is often a cause of great concern, before treating with hormonal interventions or blood products, PCOS, should always be ruled out with clinical signs of hyperandrogenism, obesity, or insulin resistance. Attention must also be paid to signs or a family history of a bleeding disorder, as vWD is commonly associated with excessive uterine bleeding(2). Ovulatory abnormal uterine bleeding, or menorrhagia, may be caused by thyroid dysfunction, coagulation defects (most commonly von Willebrand disease), endometrial polyps, and submucosal fibroids. Transvaginal ultrasonography or saline infusion sonohysterography may be used to evaluate menorrhagia(2a).

b. Von Willebrand disease
Von Willebrand disease is defined as a hereditary condition of  coagulation abnormality. There is a report of a 17 year old woman presented with severe anaemia due to menorrhagia. On investigation, she was shown to have abnormalities of her haemostatic mechanism consistent with von Willebrand's disease Type I, although there was no family history of this disorder(3).

c. cervical cancer
In the study to determine the presentation, pathological findings, treatment, and outcome of patients with cervical sarcom, f 1804 patients in the study with cervical malignancies, 8 cervical sarcomas were identified. All patients presented with vaginal bleeding and discharge(4).

d. Birth control pill
The Pill normally is prescribed by your doctor to reduce the heavy period blood for woman as well as in treating of period pain, or for contraceptive purpose ( 21 days on and 7 days off). Oral contraception is the dominant method of contraception for women in the world wide, in Canada there is more than 43% of sexually active women use it. It is defined as medications taken by mouth to prevent unwanted pregnancy. Bleeding and spotting is normal for the first six months for women starting any oral contraceptive combination pill because our body needs time to adjust to the new medication(5).

e. Endometrial hyperplasia
Endometrial hyperplasia is a condition of over growth of endometrial cell causing too thick of the endometrium of that can lead to abnormal bleeding. Researchers at the Department of Pathology, Aarhus University Hospital found that the mean (+/-s.d.) endometrial thickness was significantly different in patients with hyperplasia 11.5 mm (+/-5.0), polyps 11.8 mm (+/-5.1), sub-mucous myomas 7.1 mm (+/-3.4) and in patients without these abnormalities(abnormal uterine bleeding) 8.37 (+/-3.9) (p<0.001)(6).

f. Intrauterine device (IUD)
Researchers at the School of Medicine, Zhejiang University, in the study of the expression of angiopoietin-1 and -2 in the endometrium of women with abnormal bleeding induced by an intra-uterine device, found that  Immunohistochemical analysis showed elevated Ang-2 protein levels in secretory phase endometrium from IUD patients compared with the control women. These results suggest that the angiopoietin/Tie-2 system promotes vascular remodelling in the endometrium and that changes in the expression of Ang-1, Ang-2 and Tie-2 may contribute to abnormal uterine bleeding in some IUD users(7).

h. Miscarriage or ectopic pregnancy
h.1. Miscarriage 
Miscarriage is defined as the loss of an embryo before the 20th week of pregnancy as it is incapable of surviving independently. In medical terminology, miscarriage is a type of abortion, as it refers to the pregnancy ends with the death and removal or expulsion of the fetus, regardless of whether it is spontaneous or medically induced abortion. In US alone, over 15% of pregnancy ends in miscarriage.
Most common symptoms of miscarriage. 50% of bleeding during 20 weeks of pregnancy ends in miscarriage(8).
  
h.2. Ectopic pregnancy
Ectopic pregancy is defined as a condition in which the fertilized implant in somewhere else other than in the uterus. In most case, ectopic pregnancy occurrs in the one of the Fallopian tube, causinf tubal pregnancy. Ectopic pregnancy will end up in miscarriage as the fertilized can not survive outside of uterus. Bleeding occurs between 6 - 8 weeks of pregnancy may be a sign of miscariage due to the implant egg inability to survive out side of uterus(9).

i. Amenorrhea, age, PID, fibroids and ovarian masses
In the document sonographically identifiable causes of vaginal bleeding in secondarily amenorrhoeic women of child bearing age, showed that 75(73.2%) patients had pregnancy-related conditions, 14(13.7%) had normal, non-pregnant uteri while the remaining 13 (12.8%) had other gynaecological conditions namely pelvic inflammatory disease (PID), uterine fibroids and ovarian masses. Though pregnancy-related conditions are the major causes of vaginal bleeding in amenorrhoeic women of childbearing age, PID, fibroids and ovarian masses are possible findings(10).

j. Polycystic ovary syndrome
Polycystic Ovarian Syndrome is defined as endocrinologic diseases caused by undeveloped follicles clumping on the ovaries that interferes with the function of the normal ovaries as resulting of enlarged ovaries, leading to hormone imbalance( excessive androgen), resulting in male pattern hair development, acne,irregular period or absence of period, weight gain and effecting fertility. It effects over 5% of women population or 1 in 20 women(11).

h. Etc.

2. Risk factors
a. Physical, psychological and environmental factors
questionnaire survey was conducted on 14,752 women by trained doctors, when pregnant women came for the first antenatal examination, including sociodemographic characteristics, prior adverse pregnancy outcomes, diseases history, life event stress, adverse environmental exposure and detailed information on VB(12).

b. Age
The rate of postmenopausal vaginal bleeding during the study period peaks at the age of 55-59 years (25.9/1000 postmenopausal women/year) and declines thereafter(13).

c. Medical conditions and medication
People who have had medical conditions such as thyroid and pituitary disorders, diabetes, cirrhosis of the liver, and systemic lupus erythematosus or taken certain medication such as steroids or blood thinnersare at incresed risk of vaginal bleeding(14)

d. Inherited bleeding disorders (IBDs) 
Inherited bleeding disorders (IBDs) are by definition life-long. Women with IBDs are more likely to suffer HMB, to be symptomatic, and to present with bleeding in association with gynaecological problems. Heavy and/or abnormal menstrual bleeding increases with age due increased anovulatory cycles and gynaecological pathologies in older women(15).

d.  Etc.


3. Symptoms 
a. Bleeding or spotting between periods
b. Bleeding after sex
In most case, it is caused by sexual transmitting diseases
c. Irregular menstruation (menstrual cycle less than 28 days (more common) or more than 35 days apart)
d. Variable menstrual flow ranging from scanty to profuse
e. Menopausal bleeding
f. Etc.

F.3. Diagnosis
After a complete physical exam, including pelvic examination and questions related to your general health, including episode of vaginal bleeding, last normal menstrual cycle, previous abnormal bleeding, use of birth control pill, numbers of sexual partners, history of abnormal bleeding, etc.


a. Bacteria culture
If you are experience vaginal bleeding, bacteria cultire may be the first that you doctor orders to rule out sexually transmitted diseases such as gonorrhea and chlamydia.

b. Pap smear
To rule out irregular cervicl cell growth cause of vaginal bleeding

c. Endometrial biopsy
If you doctor suspect that the bleeding is of result of endometrial cells overgrowth.

d. Pelvic ultrasound
Pelvic ultrasound allows your doctor to examine the structures and organs in the lower abdomen and pelvis with an aim to find the underlined causes of vaginal bleeding

e. Blood tests such as thyroid function tests, complete blood count
To rule out Ovulatory abnormal uterine bleeding caused by thyroid dysfunction, coagulation defects (most commonly von Willebrand disease.

f. Pregnancy test
the aim of the Pregnancy test is to rule out the bleeding caused by complication of pregnancy,

g. Etc..

F.4. Treatments
Treatments depends to the finding of the underlined causes of vaginal bleeding, such as
F4.1. Fibroids and uterine bleeding 
http://medicaladvisorjournals.blogspot.ca/2011/08/menstrual-conditionsirregularities.html

F.4.2. Endometriosis
http://medicaladvisorjournals.blogspot.ca/2011/12/endometriosis.html

F.4.3. Ectopic pregnancy
http://medicaladvisorjournals.blogspot.ca/2012/01/ectopic-pregnancy.html

F.4.4. Polycystic ovary syndrome
1. In Conventional Medicine Perspective
2.In Traditional Chinese Medicine Perspective 
3. In Weight Loss Perspective
4. Permanently Eliminate All Types of Ovarian Cysts and PCOs Within 2 Months for Only $4? 

F.4.5. Pelvic Inflammation Disease
1. In conventional medicine perspective
2. In Trsditional Chinese medicine Perspective
  Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/22846527
(2) http://www.ncbi.nlm.nih.gov/pubmed/22764555
(2a) http://www.ncbi.nlm.nih.gov/pubmed/22230306
(3) http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0014910/ 
(4) http://www.ncbi.nlm.nih.gov/pubmed/22740005
(5) http://medicaladvisorjournals.blogspot.ca/2012/01/oral-contraception-pill-combined-oral.html 
(6) http://www.ncbi.nlm.nih.gov/pubmed/11437723  
(7) http://www.ncbi.nlm.nih.gov/pubmed/20233519
(8) http://medicaladvisorjournals.blogspot.ca/2012/01/miscarriage.html
(9) http://medicaladvisorjournals.blogspot.ca/2012/01/ectopic-pregnancy.html  
(10) http://www.ncbi.nlm.nih.gov/pubmed/18923588 
(11) http://medicaladvisorjournals.blogspot.ca/2012/01/overcome-infertility-fertility-and_13.html
(12) http://www.ncbi.nlm.nih.gov/pubmed/22584214
(13) http://www.ncbi.nlm.nih.gov/pubmed/20424279
(14) http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0014910/
(15) http://www.ncbi.nlm.nih.gov/pubmed/22445218

G. Postpartum hemorrhage
Postpartum hemorrhage (PPH) is a loss of blood greater than 500 ml, following vaginal delivery, or 1000 ml,  following cesarean section.The mortility rate is of 1000 women per 100,000 live births as a result of Postpartum hemorrhage (PPH). In the evaluation of all  randomly assigned participants,active bleeding was controlled within 20 min with study treatment alone for 440 (90%) women given misoprostol and 468 (96%) given oxytocin (relative risk [RR] 0·94, 95% CI 0·91—0·98; crude difference 5·3%, 95% CI 2·6—8·6). Additional blood loss of 300 mL or greater after treatment occurred for 147 (30%) of women receiving misoprostol and 83 (17%) receiving oxytocin (RR 1·78, 95% CI 1·40—2·26). Shivering (229 [47%] vs 82 [17%]; RR 2·80, 95% CI 2·25—3·49) and fever (217 [44%] vs 27 [6%]; 8·07, 5·52—11·8) were significantly more common with misoprostol than with oxytocin. No women had hysterectomies or died(1).

G.1. Causes and Risk factors
1. Causes
Causes of Postpartum hemorrhage (PPH) are of result of uterine atony, trauma, retained placenta, and coagulopathy(4Ts)
a. Uterine atony
Uterine atony is a loss of functions of compression of the vessels to reduce blood flow after child birth. According to the study of Department of Obstetrics and Gynecology, Duke University School of Medicine, omen with severe PPH had a mean oxytocin area under the curve of 10,054 mU compared to 3762 mU in controls (P < .001). After controlling for race, body mass index, admission hematocrit, induction status, magnesium therapy, and chorioamnionitis using logistic regression, oxytocin area under the curve continued to predict severe PPH(2).

b. Trauma
Trauma due to a body wound or shock as a sudden physical injure such as car accidence are associated to the to the cause of Postpartum hemorrhage (PPH.Uncontrolled bleeding continues to be a major cause of mortality in trauma, cardiac surgery, postpartum hemorrhage and liver failure, according
 to the study of Use of Activated Recombinant Factor VII in Severe Bleeding - Evidence for Efficacy and Safety in Trauma, Postpartum Hemorrhage, Cardiac Surgery, and Gastrointestinal Bleeding(3).

c. Tissues
Blood clots or retained tissues after birth, including retained placenta accounts for 10% of PPH. The primary tissue-based etiology of PPH is retained placenta. In the study of intravenous sulprostone infusion in the treatment of retained placenta, showed that the placenta was successfully expelled in 39.7% of cases, whereas 60.3% of women underwent manual removal of placenta. Blood loss was significantly lower in women with successful placental expulsion than in women who had manual removal of the placenta (582 ± 431 ml vs. 1275 ± 721 ml, p < 0.0001). Sulprostone infusion did not cause adverse effects or significant postpartum morbidity(4).

d. Coagulopathy 
Coagulopathy is defined as a condition of  coagulation abnormalities in which blood clots fail to form. According to the study by the Duke University Medical Center, Durham, systemic bleeding at the time of postpartum hemorrhage (PPH) is usually the result of coagulopathy that has developed acutely as a result of massive hemorrhage after uterotonics and sutures have failed(5).

e. Etc.

2. Risk factors
a. In vaginal delivery
According to the study of University of Uruguay, Montevideo, Uruguay, moderate and severe postpartum hemorrhage occurred in 10.8% and 1.9% of deliveries, respectively. The risk factors more strongly associated and the incidence of moderate postpartum hemorrhage in women with each of these factors were: retained placenta (33.3%) (adjusted odds ratio [OR] 6.02, 95% confidence interval [CI] 3.50-10.36), multiple pregnancy (20.9%) (adjusted OR 4.67, CI 2.41-9.05), macrosomia (18.6%) (adjusted OR 2.36, CI 1.93-2.88), episiotomy (16.2%) (adjusted OR 1.70, CI 1.15-2.50), and need for perineal suture (15.0%) (adjusted OR 1.66, CI 1.11-2.49). Active management of the third stage of labor, multiparity, and low birth weight were found to be protective factors. Severe postpartum hemorrhage was associated with retained placenta (17.1%) (adjusted OR 16.04, CI 7.15-35.99), multiple pregnancy (4.7%) (adjusted OR 4.34, CI 1.46-12.87), macrosomia (4.9%) (adjusted OR 3.48, CI 2.27-5.36), induced labor (3.5%) (adjusted OR 2.00, CI 1.30-3.09), and need for perineal suture (2.5%) (adjusted OR 2.50, CI 1.87-3.36)(6).

b. In caesarean section
caesarean section is associated to increased risk of  recurrent massive uterine bleeding, according to the report of a 37 yr old patient suffered severe atonic bleeding requiring different operating procedures (Clipping of the uterine arteries) in combination with an uterotonic and haemostaseological medication as well as massive transfusion of blood components and recombinant factor VIIa. After a period of 17 days without any bleeding the patient presented to the emergency room with recurrent massive uterine bleeding(7).
 
c. Racial and ethnic disparities
Hispanic ethnicity and Asian/Pacific Islander race were associated with a statistically significant increased odds of atonic PPH in comparison with Caucasians, despite adjustment for potential mediators (adjusted odds ratio [OR] for Hispanics: 1.21, 99% confidence interval [1.18, 1.25]; for Asians/Pacific Islanders: 1.31 [1.25, 1.38], with Caucasians as reference)(8).

d. Others risk factors
According to the study of Risk Factors for Postpartum Hemorrhage: Can We Explain the Recent Temporal Increase?, major independent risk factors for PPH included primiparity, prior Caesarean section, placenta previa or low-lying placenta, marginal umbilical cord insertion in the placenta, transverse lie, labour induction and augmentation, uterine or cervical trauma at delivery, gestational age < 32 weeks, and birth weight ≥ 4500 g. An overall increase in rate of PPH over the study period (OR 1.029; 95% CI 1.024 to 1.034 per year) disappeared (OR 0.995; 95% CI 0.988 to 1.001 per year) after inclusion of maternal age, parity, prior Caesarean section, labour induction and augmentation, placenta previa or low-lying placenta, and abnormal placenta, with most of the reduction attributable to rises in previous Caesarean section and labour augmentation(9). Also according to  the length of the third stage of labor and the risk of postpartum hemorrhage, Obstet Gynecol.  2005;105:290–3 and Stones  RW, Paterson  CM, Saunders  NJ.  Risk factors for major obstetric haemorrhage.  Eur J Obstet Gynecol Reprod Biol.  1993;48:15–8., risk factors for postpartum hemorrhage also include a prolonged third stage of labor, multiple delivery, episiotomy, fetal macrosomia, and history of postpartum hemorrhage

G.3. Prevention and management
According to the article of Active versus expectant management in the third stage of labour (Review) by Prendiville WJ, Elbourne D, McDonald S, routine ’active management’ is superior to ’expectant management’ in terms of blood loss, post partum haemorrhage and other serious complications of the third stage of labour. Active management is, however, associated with an increased risk of unpleasant side effects (eg nausea and vomiting), and hypertension, where ergometrine is used. Active management should be the routine management of choice for women expecting to deliver a baby by vaginal delivery in amaternity hospital. The implications are less clear for other settings including domiciliary practice (in developing and industrialised countries)(10).
 
G.4. Diagnosis and Treatments 
1. Diagnosis
The aim of diagnosis is to determine the underlined causes of the disease, inmost cases , it is caused by 4Ts. Estimation of blood loss by calibrated bags has been shown to be significantly more accurate than visual estimation at vaginal delivery. Careful monitoring of the mother's vital signs, laboratory tests, in particular coagulation testing, and immediate diagnosis of the cause of PPH are important key factors to reduce maternal morbidity and mortality(11).

2. Treatments
According to the researchers at the Department of Obstetrics and Gynecology, Orbis Medical Centre, in the current treatment of severe PPH, first-line therapy includes transfusion of packed cells and fresh-frozen plasma in addition to uterotonic medical management and surgical interventions. In persistent PPH, tranexamic acid, fibrinogen, and coagulation factors are often administered. Secondary coagulopathy due to PPH or its treatment is often underestimated and therefore remains untreated, potentially causing progression to even more severe PPH. In most cases, medical and transfusion therapy is not based on the actual coagulation state because conventional laboratory test results are usually not available for 45 to 60 minutes. Thromboelastography and rotational thromboelastometry are point-of-care coagulation tests. A good correlation has been shown between thromboelastometric and conventional coagulation tests, and the use of these in massive bleeding in nonobstetric patients is widely practiced and it has been proven to be cost-effective. Fibrinogen seems to play a major role in the course of PPH and can be an early predictor of the severity of PPH. The FIBTEM values (in thromboelastometry, reagent specific for the fibrin polymerization process) decline even more rapidly than fibrinogen levels and can be useful for early guidance of interventions(12).

Sources
(1) http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2961924-3/abstract
(2) http://www.ncbi.nlm.nih.gov/pubmed/21047614
(3) http://www.ncbi.nlm.nih.gov/pubmed/22670132
(4) http://www.ncbi.nlm.nih.gov/pubmed/22862433
(5) http://www.ncbi.nlm.nih.gov/pubmed/22430921
(6) http://www.ncbi.nlm.nih.gov/pubmed/19461428
(7) http://www.ncbi.nlm.nih.gov/pubmed/22628026
(8) http://www.ncbi.nlm.nih.gov/pubmed/22886840
(9) http://jogc.com/abstracts/full/201108_Obstetrics_5.pdf
(10) http://apps.who.int/rhl/reviews/CD000007.pdf
(11) http://www.ncbi.nlm.nih.gov/pubmed/21332452
(12) http://www.ncbi.nlm.nih.gov/pubmed/22430921


H. Breakthrough bleeding 
Breakthrough bleeding is defined as a condition of an abnormal flow of blood from the uterus that occurs between menstrual periods especially due to irregular sloughing of the endometrium in women on contraceptive hormones(1).

H.1. Causes and Risk factors
1. Excessive thick uterine lining (edometrium) 
During the last stage of the menstrual cycle, normally a layer of endometriosis lining on the inside of the uterus is expelled, known as menstruation blood. In some women, excessive thick of uterine lining (edometrium) may cause breakthrough bleeding.

2. Hormonal fluctuations
Fluctuating hormones around ovulation may experience breakthrough bleeding.

3. Taking oral contraceptives
In the study of  dilated thin-walled blood and lymphatic vessels in human endometrium: a potential role for VEGF-D in progestin-induced break-through bleeding, researchers at the Department of Obstetrics and Gynaecology and Monash Institute for Medical Research, Monash University, wrote that using a NOD/scid mouse model with xenografted human endometrium we were able to show that progestin treatment causes decidualisation, VEGF-D production and endometrial vessel dilation. Our results lead to a novel hypothesis to explain BTB, with stromal cell decidualisation rather than progestin treatment per se being the proposed causative event, and VEGF-D being the proposed effector agent(2).

4.  Amenorrhea
In the study of The induction of amenorrhoea by Hipkin LJ. indicated that a survey has shown that many women favour eliminating menstruation and it has been suggested that therapeutic induction of amenorrhoea might be an advantage in female personnel mobilised for war, but it poses some side effects including bleeding and spotting, 2 kg weight gain, breast tenderness, depression, and headaches(3).

5. Progestin treatment
Clinicians routinely prescribe progestins along with estrogens during menopausal hormone therapy (HT) to block estrogen-dependent endometrial proliferationmay cause breakthrough bleeding.

6. Polyps
In teh study to determine the effectiveness of different treatments for abnormal uterine bleeding in women with known endometrial polyps, showed that  polypectomy and other treatments of women with abnormal uterine bleeding who had benign polyps detected by sonohysterography. Women with endometrial polyps diagnosed by sonohysterography between January 1997 and July 1998 were sent questionnaires on pretreatment and posttreatment uterine bleeding and satisfaction with their treatments(4).

7. Other causes
Stopping or missing estrogens or oral contraceptives, stress, weight gain or loss, diet change, displaced intra uterine device, vagina injury, taking anticoagulant medications, etc.(5)


H.3. Prevention 
1. Lose weight
Accumulation of fat in obese women can cause the increased risk of breakthrough bleeding due to ongoing production of estrogen.

2. Smoking
Smoking can interfere with menstrual control of oral contraceptive that can lead to breakthrough bleeding.

3. Reduce intake of enzyme inducers

4.  Mifepristone
in the study to determine if mifepristone would decrease BTB in new starters of DMPA. Twenty regularly cycling women who were new starters of DMPA were randomized to receive 50 mg of mifepristone or placebo every 2 weeks for 24 weeks, researchers at the University of Southern California Keck School of Medicine, showed that percent days of BTB and number of cycles with bleeding intervals > or =8 and > or =14 days were evaluated using daily bleeding diaries. Ovulation was determined by measuring thrice-weekly urinary metabolites of estrogen and progesterone. Endometrial concentrations of ER and PR were determined by immunohistochemistry. Mifepristone significantly decreased the percent days of BTB and the number of cycles with prolonged bleeding intervals when compared to placebo. No subject ovulated in either group. ER immunostaining increased and PR immunostaining decreased after mifepristone treatment. In conclusion, a 50 mg dose of mifepristone taken every 2 weeks decreases the incidence of BTB in new starters of DMPA. This effect may be due to modulation of endometrial estrogen and progesterone receptors(6).

5. Etc.

 
H.3. Treatment and Management
1. Ongoing study
In the study of to evaluate doxycycline, a common antibiotic used to treat infections and acne, as a possible treatment in preventing or stopping unexpected menstrual bleeding in women, tf the study shows the drug is successful in stopping "breakthrough bleeding," more women may turn to new continuous contraception options – options that allow women to effectively stop menstrual bleeding, said study investigator Bliss Kaneshiro, M.D.,instructor in obstetrics and gynecology, OHSU School of Medicine(7).
Treatment and Management depening to the unlined causes, include
2.  Excessive thick uterine lining (edometrium) 
First, certain tests must be taken to rule out the cause of endometrial cancer(8). The excessive thicken endometrium may be as a result of estrogenic stimulation, wrong use of oral contraceptives, medication such tamoxifen, obese cause of excess estrogen due to fat, etc.

3. Oral contraceptives(9)
If the breakthrough breeding is a result of the use of oral contraceptive, some researchers suggested
a. Missed pills, late pills, irregular taking. Probably the commonest cause of breakthrough bleeding
b. Breakthrough bleeding is more common in the first six months and will often settle.
c. Infectous diseases, especially chlamydia which not infrequently presents with a history of abnormal bleeding.
d. Drugs, especially enzyme inducers which increase the metabolic transformation
of the hormones as they pass through the liver thereby decreasing contraceptive blood levels.
e. Gastrointestinal upsets are well recognised as a cause of breakthrough bleeding due to impairment of absorption.
g. Some foods are enzyme inducers
h. The formulation may need changing but think of this last rather than first. Breakthrough bleeding is more common with the low oestrogen pills but may settle if given time. A triphasic formulation will often give good cycle control. Try changing the type of progestogen.


4. Amenorrhea
If breakthrough is a result of medication-induced Amenorrhea, then taking off medication,  normal menstruation resumes in the cycle after they are discontinued.

5.  Hormonal fluctuations
In this practice guideline, the management guidelines are limited to the treatment of bleeding from the endometrium. In most cases bleeding caused by hormonal fluctuations is self-limiting. However, symptomatic treatment with progestogens or sub-50 oral contraceptives is possible. NSAIDs taken during the first three days of menstruation are the second-choice treatment in women with excessive bleeding. Tranexamic acid or a levonorgestrel-releasing IUD are other possibilities. (10) 

5. Progestin treatment
Clinicians routinely prescribe progestins along with estrogens during menopausal hormone therapy (HT) to block estrogen-dependent endometrial proliferation. Breakthrough bleeding (BTB) can negate the utility of this treatment. Because progestin antagonists also inhibit estrogen-dependent endometrial proliferation in women and macaques, we used a menopausal macaque model to determine whether a potent progestin antagonist (ZK 230 211, Schering AG; ZK) combined with estrogen would provide a novel mode of HT(11) 

Sources
(1) http://www.merriam-webster.com/medical/breakthrough%20bleeding
(2) http://www.ncbi.nlm.nih.gov/pubmed/22383980
(3) http://www.ncbi.nlm.nih.gov/pubmed/1533675 
(4) http://www.ncbi.nlm.nih.gov/pubmed/11084172 
(5) http://www.targetwoman.com/articles/breakthrough-bleeding.html
(6) http://www.ncbi.nlm.nih.gov/pubmed/14668006
(7) http://www.ohsu.edu/xd/about/news_events/news/2007-news-archive/08-27-drug-may-hold-key-to-pre.cfm
(8) http://medicaladvisorjournals.blogspot.ca/2011/06/cancers-from-b-to-t-most-common-types_05.html.
(9) http://www.rnzcgp.org.nz/assets/documents/Publications/Archive-NZFP/Dec-2002-NZFP-Vol-29-No-6/Sparrow-December-02.pdf
(10) http://www.ncbi.nlm.nih.gov/pubmed/12467159
(11) http://www.ncbi.nlm.nih.gov/pubmed/16936297

I. Ovarian hemorrhage
Approximately 4% of women are admitted to hospitals because of ovarian cyst rupture, hemorrhage, or torsion.
In the a study of Ovarian hemorrhage after transvaginal ultrasonographically guided oocyte aspiration: a potentially catastrophic and not so rare complication among lean patients with polycystic ovary syndrome, researchers at the Department of Obstetrics and Gynecology, Shaare Zedek Medical Center found that although acute hemorrhage is a rare event after TVOA, lean patients with PCOS specifically are at much higher risk for this complication(1).
Others report of a case of an 18-year-old female with EBV-associated ITP, who developed a severe intra-abdominal bleed secondary to a hemorrhagic ovarian cyst. Females in this age group are in their early childbearing years and present a unique set of possible hemorrhagic complications not seen in younger patients(2).

Please check the following article for more information of ovarian bleeding 
1. Ovarian Cysts In Conventional Medicine Perspective
2. Ovarian Cysts In Traditional Chinese Medicine Perspective
3. Endometriomas - Chocolate Cysts - In Conventional Medicine Perspective
4. Endometriomas - Chocolate Cysts - In Traditional Chinese Medicine 

Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/19064264 
(2) http://www.ncbi.nlm.nih.gov/pubmed/17279009 
 

J. Upper gastrointestinal bleeding
Upper gastrointestinal bleeding (UGIB) is defined as hemorrhaging derived from a source proximal to the ligament of Treitz. It is life threatening and considered as medical emergency, which is followed by high mortality rate, ranging from 6 to 15% in spite of modern diagnostic methods and treatment.

J.1. Causes and risk factors
1. Causes
1.1. Esophageal causes of Upper gastrointestinal bleeding
Espophagus or gullet, an organ in vertebrates, is the tube that lead foods from the pharynx to the stomach.
a. Esophageal varices
In the study to investigate the effects of splenectomy and ligature of the left gastric vein on risk factors for bleeding of esophagogastric varices in patients with schistosomiasis mansoni, hepatosplenic form, with a history of upper gastrointestinal bleeding, showed that the variceal pressure has fallen from 22.3+/-2.6 mmHg before surgery to 16.0+/-3.0 mmHg in the immediate postoperative period (p<0.001), reaching 13.3+/- 2.6 mmHg in the sixth month of follow-up. A significant reduction of the frequency of the parameters associated with a greater risk of hemorrhage was observed between the preoperative period and six-month follow-up, when the proportion of large esophageal varices (p<0.05), varices extending to the upper esophagus (p<0.05), bluish varices (p<0.01), varices with red signs (p<0.01) and gastropathy (p<0.05) decreased(1)

b. Esophagitis 
there is a report of a case of recurrent, severe upper gastrointestinal bleeding due to hemorrhagic candidal esophagitis in a man with renal failure is described. Dysphagia, odynophagia, and retrosternal chest discomfort were all absent. Oral thrush was present only at the outset. Standard therapy for massive bleeding with blood products alone was not successful. Intravenous amphotericin eventually resulted in resolution, according to the study by University of Manitoba, Canada(2).

c. Esophageal cancer 
Esophageal cancer is not very uncommon and caused by malignant of the esophagus due to abnormal cell growth as a result of the DNA alternation of the cells that line the upper part of the esophagus or glandular cells that are present at the lower part of the esophagus that connected with the stomach.
The esophageal cancer tend to spread if it left untreated and starts from the lining of esophagus, then later penetrate in the the wall of the esophagus and spread to the lumph node around the bottom of the esophagus, stomach and the chest, then to the distant parts of the body. for more information, please visit
http://medicaladvisorjournals.blogspot.ca/2011/06/cancers-from-b-to-t-most-common-types_07.html

d. Esophageal ulcers 
there is a report of five cases in the upper GI tract due to insufflating large amounts of air through the endoscopes. All 5 patients needed an emergency upper endoscopy for acute presumed upper GI bleeding. In two cases both esophageal variceal bleeding and ulcer bleeding were detected; the fifth case presented with a bleeding due to gastric cancer(3).

e. Other causes
Other causes of UGI bleeding include Dieulafoy's lesion, Mallory-Weiss syndrome, and portal hypertensive enteropathy. The most common non-variceal endoscopic findings reported in patients with lower gastrointestinal bleeding are portal hypertensive colopathy and hemorrhoids(4). 

1.2. Gastric causes of Upper gastrointestinal bleedinga
a. Gastric ulcer 
There is a report iIn 16 patients (mean age, 59.4 years) with acute bleeding ulcers (13 gastric ulcers, 2 duodenal ulcers, 1 malignant ulcer), a metallic clip was placed via gastroscopy and this had been preceded by routine endoscopic treatment, according to the study of Chonbuk National University Medical School(5).

b. Gastric cancer 
Bleeding from the upper gastrointestinal system may be caused by gastrointestinal stromal tumors of the stomach, which are mainly characterized by occult bleeding, while profuse bleeding rarely occurs accompanied by hemorrhagic shock. Gastrointestinal stromal tumors of stomach are the most common mesenchimal tumors of the gastrointestinal tract(1). For more information of Stomach Cancer/Gastric Cancer, please visit http://medicaladvisorjournals.blogspot.ca/2011/06/cancers-from-b-to-t-most-common-types_30.html

c. Gastritis 
In a material of 4560 panendoscopic investigations carried out in an endoscopy laboratory haemorrhages from the upper gastrointestinal tract were found in 201 cases. In 49 cases the cause of blood loss was acute haemorrhagic gastritis. Among them males accounted for 41% (mean age 35.6 years) and females for 59% (mean age 41.8 years)(6).

d. Gastric varices 
Although most portal hypertensive bleeds result from the ruptured distal esophageal varices, bleeding from other sources such gastric varices, portal hypertensive gastropathy, and ectopic varices can lead to clinically significant bleeding. Variceal bleeding typically presents as massive gastrointestinal (GI) bleeding with hematemesis, melena or hematochezia(7).

e. Gastric antral vascular ectasia 
Gastric antral vascular ectasia (GAVE) syndrome, also known as watermelon stomach is a significant cause of acute or chronic gastrointestinal blood loss in the elderly. is characterized endoscopically by "watermelon stripes." Without cirrhosis, patients are 71% female, average age 73, presenting with occult blood loss leading to transfusion-dependent chronic iron-deficiency anemia, severe acute upper gastrointestinal bleeding, and nondescript abdominal pain(8).

f. Dieulafoy's lesions
Dieulafoy's lesions are considered uncommon causes of gastrointestinal bleeding and occur from pinpoint non-ulcerated arterial lesions(9).

g. Etc.

1.3. Duodenal causes of Upper gastrointestinal bleeding
The duodenum represents second place in frequency for the presence of diverticula in the digestive tract after the colon. Duodenal diverticulum as a cause of hemorrhage of the upper gastrointestinal (GI) tract has been described as an infrequent complication, although it must be considered in patients with digestive hemorrhage without evident cause at the esophagogastric level(10).

1.4. Etc.

2. Risk factors
a. Medication
Medication such as aspirin, NSAIDs, warfarin, corticosteroids and SSRIs are associated with increase risk of upper gastrointestinal bleeding. In the study assess the impact of increased use of low-dose aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs), warfarin, corticosteroids and selective serotonin re-uptake inhibitors (SSRIs) on the site and outcome of non-variceal gastrointestinal (GI) bleeds, researchers at the Lund University, Lund, Sweden, found that aspirin, warfarin and SSRI users tended to suffer more severe GI bleeds than non-users of these drugs. When comparing non-ulcer GI bleeds with PUBs, aspirin (OR 0.56, 95% CI 0.38-0.82) was more strongly associated with PUBs, whereas SSRIs (OR 3.71, 95% CI 1.39-12.9) and corticosteroids (OR 2.8, 95% CI 1.28-6.82) were more associated with non-ulcer GI bleeds after adjusting for age, gender and co-morbidity(11).

b. Acid reflux disease
Gastrointestinal (GI) complaints are common among athletes with rates in the range of 30% to 70%. Both the intensity of sport and the type of sporting activity have been shown to be contributing factors in the development of GI symptoms. Three important factors have been postulated as contributing to the pathophysiology of GI complaints in athletes: mechanical forces, altered GI blood flow, and neuroendocrine changes. As a result of those factors, gastroesophageal reflux disease (GERD), nausea, vomiting, gastritis, peptic ulcers, GI bleeding, or exercise-related transient abdominal pain (ETAP) may develop(12). For more information of gastroesophageal reflux disease (GERD), please visit
http://medicaladvisorjournals.blogspot.ca/2011/09/gastroesophageal-reflux-disease-gerd.html

c. Age
Upper GI bleeding was significantly correlated with age younger than 50 (P = .01) and male gender (P = .01; odds ratio, 3.13)(13).

d. Coagulopathy
Coagulopathy was prevalent in 16% of patients after nonvariceal upper gastrointestinal bleeding (NVUGIB). and independently associated with more than a fivefold increase in the odds of in-hospital mortality. Wide variation in plasma use exists indicates clinical uncertainty regarding optimal practice(14).

e. Etc.

J.2. Symptoms 
Acccordfing to the study of a total of 124 patients were eligible for inclusion, 71 (57%) of whom were male. A total of 63 (51%) presented with blood in stool and 53 (43%) with bloody emesis; 8 (6%) had blood in both emesis and stool. A total of 31 (25%) patients had a lower GI bleed, 88 (70%) had an upper, and 5 (4%) had both upper and lower bleeding sources. The mean BUN level was 24 mg/dL, the mean Cr level 1.03 mg/dL, and the mean BUN/Cr ratio was 24. The mean hemoglobin (Hb) level was 11.3 g/dL, the mean Hct was 32 g/dL, and 51% required transfusion. Upper GI bleeding was significantly correlated with age younger than 50 (P = .01) and male gender (P = .01; odds ratio, 3.13)(15).
1. Blood vomiting looks like coffee grounds(15).
2. Blood in stool
3.  Light head, Fatigue, Generalized weakness and fainting as a result of massive blood loss
4. Abdominal pain
5.  Constipation
6. Diarrhea
7. Gastroesophageal reflux disease (GERD)
8. Etc.

J.3. Diagnosis
According to the study by Georgia Health Sciences University,  Rapid assessment and resuscitation of upper gastrointestinal bleeding should precede the diagnostic evaluation in unstable patients with severe bleeding. Risk stratification is based on clinical assessment and endoscopic findings. Early upper endoscopy (within 24 hours of presentation) is recommended in most patients because it confirms the diagnosis and allows for targeted endoscopic treatment, including epinephrine injection, thermocoagulation, application of clips, and banding. Endoscopic therapy results in reduced morbidity, hospital stays, risk of recurrent bleeding, and need for surgery. Although administration of proton pump inhibitors does not decrease mortality, risk of rebleeding, or need for surgery, it reduces stigmata of recent hemorrhage and the need for endoscopic therapy(16).

 J.4. Prevention
1. Reduce stress
Stress-damage of upper gastro-intestinal tract (GIT) mucous membrane and gastro-intestinal hemorrhage (GIH)(17).

2. Cardiac surgery
GI bleeding events occurred approximately 10 days after cardiac surgery in patients with a complicated postoperative course. Improving the heart function is the best way to reduced risk of Upper gastrointestinal bleeding(18).

3. Drugs, alcohol and smoking
Chronic moderate alcohol consumption by itself does not seem to increase the liability to peptic ulceration. With highly concentrated alcoholic beverages, gastric bleeding from acute lesions may, however, be occasionally precipitated under certain circumstances, such as when unbuffered ASA is taken concomitantly. Smoking of cigarettes is associated, and perhaps causally related, with an increased incidence of gastric and duodenal ulcerations, impaired ulcer healing, and more frequent ulcer recurrences(19).

4. Avoid prolonged period intake of aspirin and medication which can induce Upper gastrointestinal bleeding (UGIB), such as Ibuprofen (Motrin, Advil)Naproxen (Anaprox, Naprosyn, Aleve)Ketoprofen (Orudis).

5. No extreme exercise
Gastrointestinal (GI) complaints are common among athletes with rates in the range of 30% to 70%. Both the intensity of sport and the type of sporting activity have been shown to be contributing factors in the development of GI symptoms. Three important factors have been postulated as contributing to the pathophysiology of GI complaints in athletes: mechanical forces, altered GI blood flow, and neuroendocrine changes. As a result of those factors, gastroesophageal reflux disease (GERD), nausea, vomiting, gastritis, peptic ulcers, GI bleeding, or exercise-related transient abdominal pain (ETAP) may develop(20).

6. Etc.


J.5. Treatments
Some researchers suggested that despite successful endoscopic therapy, rebleeding can occur in 10 to 20 percent of patients; a second attempt at endoscopic therapy is recommended in these patients. Arteriography with embolization or surgery may be needed if there is persistent and severe bleeding(16). Others indicated that Pre-endoscopic management (including use of scoring scales, nasogastric tube placement and blood pressure stabilization) is crucial for triage and optimal resuscitation of patients, and should include a multidisciplinary approach at an early stage. Unless the patient has specific comorbidities, transfusion should only be considered if their hemoglobin level is ≤70 g/l. Endoscopic therapy, the cornerstone of therapeutic management of high-risk lesions, should not be delayed for more than 24 h following admission. Several endoscopic techniques, mostly using clips or thermal methods, are available and new approaches are emerging. When endoscopy fails, surgery or arterial embolization should be considered. Although the efficacy of prokinetics and high-dose intravenous PPI prior to endoscopy is controversial, the use of an intravenous PPI following endoscopy is strongly recommended. Antiplatelet therapy should be suspended and resumed in 3-5 days. Finally, all patients should be tested for Helicobacter pylori by serology in the acute setting(21).

Natural Remedies for Dementia Memory Loss Reversal
Guarantee to Stop Progression and Reverse Memory Loss in Alzheimer and  Dementia  with step by step instructions through Scientific Studies  within 2 Months or your Money back

Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer

For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html


Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/22569978
(2) http://www.ncbi.nlm.nih.gov/pubmed/8202782
(3) http://www.ncbi.nlm.nih.gov/pubmed/22649332
(4) http://www.ncbi.nlm.nih.gov/pubmed/22661272
(5) http://www.ncbi.nlm.nih.gov/pubmed/21852908
(6) http://www.ncbi.nlm.nih.gov/pubmed/2623868
(7) http://www.ncbi.nlm.nih.gov/pubmed/22514572
(8) http://www.ncbi.nlm.nih.gov/pubmed/20740102
(9) http://www.ncbi.nlm.nih.gov/pubmed/20514835
(10) http://www.ncbi.nlm.nih.gov/pubmed/18492423
(11) http://www.ncbi.nlm.nih.gov/pubmed/20695720
(12) http://www.ncbi.nlm.nih.gov/pubmed/22897615
(13) http://www.ncbi.nlm.nih.gov/pubmed/9928705
(14) http://www.ncbi.nlm.nih.gov/pubmed/22897615
(15) http://www.ncbi.nlm.nih.gov/pubmed/9928705
(16) http://www.ncbi.nlm.nih.gov/pubmed/22534226
(17) http://www.ncbi.nlm.nih.gov/pubmed/22834289
(18) http://www.ncbi.nlm.nih.gov/pubmed/22720275
(19) http://www.ncbi.nlm.nih.gov/pubmed/6378444
(20) http://www.ncbi.nlm.nih.gov/pubmed/22410703
(21) http://www.ncbi.nlm.nih.gov/pubmed/22230903
(1) http://www.ncbi.nlm.nih.gov/pubmed/22924257


Friday, August 24, 2012

Hydrocephalus

Hydrocephalus, also known as "water in the brain" is defined as complex and multifactorial neurological disorders of accumulation of cerebrospinal fluid (CSF) in the cavity of brain of that can lead to intracranial pressure inside the side, resulting of brain trauma, stroke, infection, tumor, etc.

I. Types of Hydrocephalus
1. Congenital hydrocephalus
Congenital hydrocephalus is a condition presented at birth as a result of genetic defect or abnormal fetal development. In the study to illustrate the value of knockout mice in identifying genetic factors involved in the development of congenital hydrocephalus, showed that dysfunctional motile cilia represent the underlying pathogenetic mechanism in 8 of the 12 lines (Ulk4, Nme5, Nme7, Kif27, Stk36, Dpcd, Ak7, and Ak8)... characterization of mouse models can enhance understanding of important cell signaling and developmental pathways involved in the pathogenesis of hydrocephalus(1). At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development(2).

2. Acquired hydrocephalus
Acquired hydrocephalus is a condition developed after birth as a result of injure or diseases.

3. Communicating hydrocephalus or non-obstructive hydrocephalus,
Communicating hydrocephalus is defined as condition as the cerebrospinal fluid (CSF) can still flow between the ventricles.


4.  Non communicating hydrocephalus or obstructive hydrocephalus
Non communicating hydrocephalus is defined as a condition as the cerebrospinal fluid (CSF)  is blocked and can not flow between the ventricles.

II. Causes and risk factors
A. Causes
Although the actual causes of  Hydrocephalus is unknown, some researchers suggested that
1. Genetic defect
Congenital hydrocephalus id associated with dysfunctional motile cilia represent the underlying pathogenetic mechanism in 8 of the 12 lines (Ulk4, Nme5, Nme7, Kif27, Stk36, Dpcd, Ak7, and Ak8).(3). Other researchers suggested that Although hydrocephalus is usually a sporadic disorder, there exist some rare but well delineated syndroms, in which recurrence is to be expected. The here presented Bickers-Adams-Syndrome of sex-linked hydrocephalus is caused by congenital aqueductal stenosis(4).

2.  Meningitis
Hydrocephalus is associated with the complications of tuberculous meningitis (TBM) occurred in up to 85% of children with the disease. It is more severe in children than in adults. It could be either of the communicating type or the obstructive type with the former being more frequently seen(5).

3. Neural tube defect
Congenital hydrocephalus is a relatively uncommon abnormality in population malformation surveys accounting for between four and ten out of every 10,000 births. In the review of Sixty cases of  28 with NTD (group 1) and 32 without NTD (group 2). The groups were similar in terms of maternal and child variables at birth and hospitalization days during the 1st year of life. The mortality (including intrauterine deaths and deaths of babies with malformations incompatible with life that characterize a very poor prognosis) until 1 year of age was 36% in group 1 and 59% in group 2 (p = 0.077). The rate of cardiac malformations was higher in the group without NTD (p = 0.015). The length of hospital stay after birth (1st admission) was significantly higher in the group with NTD (p = 0.007)(6).

5. Intraventricular hemorrhage
Intraventricular hemorrhage and posthemorrhagic hydrocephalus are common causes of neonatal morbidity and mortality among preterm and low-birth weight infants (PT-LBWIs), but Intraventricular hemorrhage in PT-LBWIs remains a significant problem, particularly when it is associated with PHH leading to long-term neurological impairment and decreased survival rate(7).

6. PTB Deficiency
Polypyrimidine tract-binding protein (PTB) is a well-characterized RNA-binding protein and known to be preferentially expressed in neural stem cells (NSCs) in the central nervous system. Dr. Shibasaki T and the research team at the Center for Experimental Medicine and Systems Biology. showed that PTB depletion in the dorsal telencephalon is causally involved in the development of HC and that PTB is important for the maintenance of AJs in the NSCs of the dorsal telencephalon(8).

6.  Tumors
Tumor-associated hydrocephalus is common in primary pediatric brain tumors. In the study of a total of 56.7% of cases presented hydrocephalus, including hydrocephalus that occurred at tumor diagnosis (51.5%), and hydrocephalus developed after tumor diagnosis (5.1%). At tumor diagnosis, the hydrocephalus was mainly obstructive type (98%) and rarely communicating type (1.9%). Definite shunting procedures in this series comprised of ventriculoperitoneal (VP) shunt in 54.4%, endoscopic third ventriculostomy (ETV) in 10.9%, subduroperitoneal (SP) shunt in 4.8%, septostomy in 0.7%, lumboperitoneal shunt in 0.6%, and ventriculoatrial shunt in 0.1% of patients with hydrocephalus(9).

7. Traumatic head injury
Post-traumatic hydrocephalus (PTH) is considered a frequent complication after severe head injury (HI). External hydrocephalus is a well-established entity in infants which is benign and usually resolves without shunting [1, 2]. The term “External Hydrocephalus” has also been used to describe the presence of extra ventricular cerebrospinal fluid (CSF) collections accompanied by hydrocephalus, particularly in cases of adults suffering from aneurysmal subarachnoid hemorrhage and severe head injuries [3–6]. Several other terms have been used to describe this entity [7] which has lead to confusion about this disease(10).


8. Subarachnoid hemorrhage 
Acute hydrocephalus as a consequence of subarachnoid hemorrhage is a relatively frequent problem. Dr. Suarez-Rivera O. at the National Institute of Neurology and Neurosurgery, Mexico City, indicated that that acute hydrocephalus is present in 20% of patients with subarachnoid hemorrhage. One third of them may be asymptomatic on admission; 50% of those who have clinical hydrocephalus recover spontaneously within the first 24 h(11)

9. Etc.

B. Risk factors
1. Family history

Family studies suggested that the risk to siblings of a child with uncomplicated congenital hydrocephalus, where the anatomical site is not specified, is about 1 in 50 (1 in 40 for males, 1 in 80 for females). With aqueduct stenosis, the risk to brothers of affected boys is 1 in 22, to sisters only 1 in 50. The risks to siblings of sisters is less. Probably less than 2% of uncomplicated hydrocephalus has an X-linked basis and such an aetiology should be suspected if the special clinical features are present, there is more than one male sibling affected, or there are affected male relatives on the mother's side(12).

2. Nontumoral aqueductal stenosis, nontectal tumor and tectal glioma
Hydrocephalus was most commonly due to nontumoral aqueductal stenosis (43%), nontectal tumor (25%), or tectal glioma (13%). Five patients (16%) had multicystic/loculated hydrocephalus(13).

3. Preterm and low-birth weight infants
Preterm and low-birth weight infants are associated with increased risk of  intraventricular and/or periventricular hemorrhage (IVH and PVH, respectively) of that can lead to Hydrocephalus(14).

4. Other factors
Although the precise nature of the neuropsychological deficits in hydrocephalus are not completely known, several factors such as etiology, raised intracranial pressure, ventricular size, and changes in gray and white matter tissue composition as well as shunt treatment complications have been shown to influence cognition. In fact, the presence of complications and other brain abnormalities in addition to hydrocephalus such as infections, trauma, intraventricular hemorrhage, low birthweight, and asphyxia are important determinants of the ultimate cognitive status, placing the child at a high risk of cognitive impairment(15).

5. Etc.

III. Symptoms
A.  In infancy
1. Increase in head circumference or an unusually large head size
Fluid accumulated will result in Increase in head circumference or an unusually large head size in infant regardless to the types of hydrocephalus due to bulge of the fontanelle (soft spot), Dr. Bhasker B and the research team in the reports a new finding in two siblings with primary hypomagnesaemia as a result of renal magnesium wasting, namely, rapidly increasing head size. External hydrocephalus and brain shrinkage in primary hypomagnesaemia seen on computed tomography of the brain with reversibility after magnesium treatment has not been reported previously(16).


2. Rapid eye movement sleep
In the monitor of Intracranial pressure (ICP) for 24 h in 30 hydrocephalic patients (21 infants, 9 children) showed that during sleep related to a period of rapid eye movement (REM) fairly regular steep-rising waves of raised ICP recurred every 50-75 min, decreasing slowly to previous levels in 25-40 min(17).

3. Sleepiness, Irritability, Sunsetting of the eyes, Seizures are most common symptoms in infant(18)

4. Other symptoms
Dr. Kirkpatrick M and scientists at the Royal Hospital for Sick Children, in the study of Symptoms and signs of progressive hydrocephalus, showed that in the clinical features of 107 cases of children with hydrocephalus and measured raised intraventricular pressure were analysed retrospectively. Fifty one children had recently been diagnosed as having hydrocephalus, and the remainder had had shunts injected to direct the cerebrospinal fluid. The most common symptoms in the group were vomiting, behavioural changes, drowsiness, and headaches. The most common clinical signs were inappropriately increasing occipitofrontal head circumferences, tense anterior fontanelles, splayed sutures, and distension of the scalp veins. Half the infantile cases of hydrocephalus were without symptoms, and a quarter of the cases with cerebrospinal fluid shunts and measured raised intraventricular pressure were without signs. There were no fewer than 33 different clinical signs including several unusual ones, such as macular rash and sweating. We believe that the presentation of hydrocephalus with raised intraventricular pressure is sufficiently variable, unusual, or even absent to justify the direct measurement of intracranial pressure(19).


8. Etc.

B.  Children and adults
Beside some symptoms mentioned in the infant section, Children and adults with the disease may also be experience other symptoms because of the head can no longer expand to accommodated to the accumulation of the fluid
1. The most common symptoms in the group were vomiting, behavioural changes, drowsiness, and headaches. The most common clinical signs were inappropriately increasing occipitofrontal head circumferences, tense anterior fontanelles, splayed sutures, and distension of the scalp veins(19).

2. Diplopia, headaches, and papilledema
Hydrocephalus can also cause symptoms of diplopia, headaches, and papilledema, There is a report of a 48-year-old woman was admitted to the hospital because of diplopia, headaches, and papilledema. Imaging revealed cysts in the fourth ventricle and spinal canal(20)


3. Headache, hearing difficulty and blurred vision
Headache and blurred vision are also associated with symptoms of hydrocephalus. There is a report of a
patient of 25-year-old female, admitted to the department of otorhinolaryngology with complaints of hearing difficulty, headache and blurred vision(21).


4. Other symptoms
Dr. Kubo Y and research team at the Osaka University Graduate School of Medicine, in the study of Validation of grading scale for evaluating symptoms of idiopathic normal-pressure hydrocephalus, showed that the interrater reliability of this scale was high. The iNPHGS cognitive domain score significantly correlated with the cognitive test scores, including the Mini-Mental State Examination (MMSE), the gait domain score with the Up and Go Test and Gait Status Scale scores, and the urinary domain score with the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. The MMSE, Gait Status Scale and ICIQ-SF scores significantly improved in patients whose iNPHGS scores improved after CSF tapping but not in those whose iNPHGS scores did not improve after CSF tapping. Fourteen of the 38 patients received shunt operations. In these 14 patients, changes in the iNPHGS cognitive and urinary domains after CSF tapping were significantly associated with the changes after the shunt operation(22). Other found that the most frequently observed neuropsychiatric symptom in the iNPH patients was apathy followed by anxiety and aggression. No symptom was more prevalent or more severe in iNPH than in AD. The severity of cognitive impairment was correlated with both aberrant motor activity and apathy(23).

5. Etc.

IV. Diagnosis
A. Misdiagnosis
 Because some of these symptoms may also be experienced in other disorders, sometimes normal pressure hydrocephalus is  incorrectly diagnosed and never properly treated, including
1. Tuberculosis
Neurosarcoidosis, a complication of sarcoidosis in which inflammation occurs in the brain, spinal cord, and other areas of the nervous system is observed in approximately 5% of sarcoidosis. Its common manifestations are facial palsy (50% of patients with neurosarcoidosis) and optic neuritis. Hydrocephalus is a very uncommon reported finding. Although the typical presentation of sarcoidosis such as facial palsy is not a diagnostic dilemma, more atypical presentations such as hydrocephalus with altered mentality in a tuberculosis patient can lead to a misdiagnosis(24).

2. Alzheimer's disease
Dr. Silverberg GD and scientists at the Stanford University School of Medicine in the study of Alzheimer's disease and normal-pressure hydrocephalus, suggested that if all else being equal, the initially dominant physiological change determines whether CSF circulatory failure manifests as Alzheimer's disease (AD) or as normal-pressure hydrocephalus (NPH). If CSF production failure predominates, AD develops. However, if resistance to CSF outflow predominates, NPH results. Once either disease process takes hold, the risk of the other disorder may rise. In AD, increased deposition of Abeta in the meninges leads to greater resistance to CSF outflow. In NPH, raised CSF pressure causes lower CSF production and less clearance of Abeta(25).

3. Parkinson's disease
There are several reports of cases with the characteristic clinical manifestations of normal pressure hydrocephalus--progressive dementia, gait difficulty and urinary incontinence--have been published earlier, it was Adams and Hakim who emphasized the clinical triad and the effect of shunting the cerebrospinal fluid as a means of treatment. Messert and Baker stressed that the gait disturbance had a close resemblance to the freezing gait of parkinsonism but Dr. Lobo Antunes J, and the the research team suggested that recognition of the existence of both disorders in the same patients is important since appropriate treatment of each of them led to marked improvement of their symptoms(26).

4. Creutzfeldt-Jakob disease
There is a report of  two different dementing diseases, Creutzfeldt-Jakob disease and normal-pressure hydrocephalus in a single patient. The inefficacy of a shunt procedure in this particular case, and the need of a brain biopsy in patients with normal-pressure hydrocephalus before undergoing cerebrospinal fluid shunting are stressed. A purely coincidental occurrence, or a possible aetiopathogenic relationship between both diseases are postulated(27).

5. Etc.

B. Diagnosis(28)
According to Dr. Michael Kiefer and the research team, in the study of the Differential Diagnosis and Treatment of Normal-Pressure Hydrocephalus suggested that
B.1. Diagnosis according to patient impairement
1. For patient of Gait impairment, differential diagnosis include the Characteristics of Externally rotated posture of the feet, Particular difficulty turning on the body’s long axis and Absence of apraxia.

2. For patients with Cognitive deficits/dementia, aside from reactive depression (without depressive thought content), patients with NPH generally do not have any psychiatric abnormalities. Thus, changes of mood, personality, and behavior steer the differential diagnosis toward a neurodegenerative disorder of another type. An objective examination should be performed with the aid of specific psychometric tests for the assessment of subcortical frontal lobe deficits.
Some suitable tests of this type are :
2.1 The grooved pegboard test
2.2. The Stroop test
2.3. The digit span test
2.4. The trail-making A/B test
2.5. The Rey auditory-verbal learning test

3. For patients with Incontinence 
Disturbances of bladder function in NPH result from detrusor hyperactivity owing to the partial or total absence of central inhibitory control. Patients initially suffer from increased urinary frequency (e42e44); later developments are urge incontinence and, finally, permanent urinary incontinence. Fecal incontinence is rare in NPH (2) and should arouse suspicion of another type of neurodegenerative disease. If present in a patient with NPH, it implies severe frontal subcortical dysfunction.
CSF shunting can improve bladder dysfunction in as many as 80% of iNPH patients if performed early, but in no more than 50% to 60% if performed in an advanced stage of the disease (e15, e20, e45).

4. NPH and other neurodegenerative disorders
 Findings that make NPH less likely      
4.1. Asymmetrical findings    
4.2. Cortical deficits, e.g., aphasia, apraxia, paresis     
4.3. Progressive dementia without gait disturbance     
4.5. Lack of progression of symptoms

B.2. General Diagnosis and tests 
1.  Computerized tomography (CT) or magnetic resonance imaging (MRI)
Either computerized tomography (CT) or magnetic resonance imaging (MRI) of the brain is necessary—yet, alone, never sufficient to establish the diagnosis of NPH.

2. Invasive diagnostic testing
The aim of the tests is needed to raise the prognostic accuracy above 80%
2.1. Spinal tap test: lumbar puncture with the removal of 30 to 70 mL of CSF. This can be repeated on two or three consecutive days
2.2. Continuous spinal drainage of 150 to 200 mL of CSF per day for 2 to 7 days (1– 2)
If the number of steps taken in a 10 m gait test, and the time needed to walk 10 m, are reduced by at least 20%, and/or psychometric tests show an improvement of at least 10%.

3. Other invasive tests
Long-term ICP measurement for 24 to 72 hours is performed in no more than a few centers. Special pressure waves and brain pulse amplitudes are measured Such techniques are not recommended for routine use, both because their predictive value has not yet been sufficiently documented and because they require specialized equipment and expertise

VI. Preventions
Other than structures abnormalities caused by genetic defects, accidence, etc., most acquired hydrocephalus can be prevented by enhancing the immune system in fighting against forming of free radicals causes of irregular cells growth and foreign invasion such virus and bacteria and reduce the risk of diseases cause of Hydrocephalus, such as dementia.
A. Do's and Do Not's list
 1. Mediterranean diet
If you are typical American dieter, you are at increased to develop dementia when you get older as the diet is classified as one of the most unhealthy diet in the existence, as the study of ,researchers wrote in an older population of Southern Italy with a typical Mediterranean diet, high monounsaturated fatty acids energy intake appeared to be associated with a high protection against cognitive decline. In addition, dietary fat and energy in older people seem to be risk factors, while fish consumption and cereals are found to reduce the prevalence of AD in the European and North American countries(1). Also recent research supports the hypothesis that calorie intake, among other non-genetic factors, can influence the risk of clinical dementia.(29).

2. Yoga 
Yoga is believed to have beneficial effects on cognition, attenuation of emotional intensity and stress reduction. In  the study to evaluate the effects of yoga on memory and psychophysiological parameters related to stress, comparing yoga practice and conventional physical exercises in healthy men (previously yoga-naïve). Memory tests, salivary cortisol levels and stress, anxiety, and depression inventories were assessed before and after 6months of practice. Yoga practitioners showed improvement of the memory performance, as well as improvements in psychophysiological parameters(30). Other researchers at the G.J. Patel Ayurved College, showed that Mind and body are inseparable entities and influences each other until death. Many factors such as stress, anxiety, depression, negative thoughts, unhealthy life style, unwholesome diet etc., disturb mental and physical wellbeing. Senile dementia is the mental deterioration, i.e, loss of intellectual ability associated with old age. It causes progressive deterioration of mental faculties, e.g., memory, intellect, attention, thinking, comprehension and personality, with preservation of normal level of consciousness.(31). Other suggested that the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress(31a).

3. Aging of theory of mind
In the study to predict that educational level and cognitive processing are two factors influencing the pattern of the aging of ToM at Anhui Medical University, showed that  the younger group and the older group with equally high education outperformed the older group with less education in false-belief and faux-pas tasks. However, there was no significant difference between the two former groups. The three groups of participants performed equivalently in the eyes test as well as in control tasks (false-belief control question, faux-pas control question, faux-pas control story, and Eyes Test control task). The younger group outperformed the other two groups in the cognitive processing tasks(32)

3. Moderate alcohol drinking
Moderate alcohol drinking of less than 2 cups for men and 1 cups for women are said to offers possible health benefits(3), but Binge drinking in midlife is associated with an increased risk of dementia, according to the follow-up, 103 participants had developed dementia. Binge drinking (ie, alcohol exceeding the amount of 5 bottles of beer or a bottle of wine on 1 occasion at least monthly), as reported in 1975, was associated with a relative risk of 3.2 (95% confidence interval=1.2-8.6) for dementia. Passing out at least twice as a result of excessive alcohol use during the previous year, as reported in 1981, was associated with a relative risk of 10.5 (2.4-46) for dementia in drinkers.(33). Other in the study to evaluated how (1) the number of alcoholic drinks the subjects consumed per month and (2) the drinking cessation of certain subjects were associated with their relative and absolute T, B, CD4, and CD8 lymphocyte counts and immunoglobulin A (IgA), IgM, and IgG levels, indicated that indicated that measures of immune status differed among the drinking categories and that, generally, the differences changed after adjustment for covariates. These differences consisted, as alcohol consumption increased, of higher IgA and IgM levels, relative T and CD4 lymphocytes, and the ratio of CD4 to CD8 cells, and of lower IgG levels, relative B and CD8 lymphocytes, absolute lymphocyte, and lymphocyte subset counts after adjusting for other covariates(33a).

4.  Stop Smoking or never smoke before
Smoking is a risk factor for several life-threatening diseases, but its long-term association with dementia is controversial and somewhat understudied.In a studyof a total of 5367 people (25.4%) were diagnosed as having dementia (including 1136 cases of AD and 416 cases of VaD) during a mean follow-up period of 23 years. Results were adjusted for age, sex, education, race, marital status, hypertension, hyperlipidemia, body mass index, diabetes, heart disease, stroke, and alcohol use, Dr. Rusanen M, and the team at the University of Eastern Finland, said " heavy smoking in midlife was associated with a greater than 100% increase in risk of dementia, AD, and VaD more than 2 decades later. These results suggest that the brain is not immune to long-term consequences of heavy smoking"(34).

5. Drink you tea and coffee
Caffeine in tea and coffee may enhance cognitive function acutely. In Aging and Dementia (CAIDE) study, the findings of the previous studies are somewhat inconsistent, but most studies (3 out of 5) support coffee's favorable effects against cognitive decline, dementia or AD. In addition, two studies had combined coffee and tea drinking and indicated some positive effects on cognitive functioning. For tea drinking, protective effects against cognitive decline/dementia are still less evident. In the CAIDE study, coffee drinking of 3-5 cups per day at midlife was associated with a decreased risk of dementia/AD by about 65% at late-life. coffee(35). Others in the study of Immunomodulatory effects of decaffeinated green tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss), showed that decaffeinated green tea in lower doses of administration could be optimum to enhance the immunity of rainbow trout(36a).

6. Eat you fruits and veggies 
Fruits and veggies contains high amounts of antioxidant which enhance the immune system in fighting against forming of free radicals in which can cause damage to the brain cells of that lead to dementia. Researchers at The Johns Hopkins University indicated that use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD. Antioxidant supplements merit further study as agents for the primary prevention of AD(36).

7. Regular exercise and moderate exercise for elder
In the study to evaluate to the effects of regular exercise versus a single bout of exercise on cognition, anxiety, and mood were systematically examined in healthy, sedentary young adults who were genotyped to determine brain-derived neurotrophic factor (BDNF) allelic status, indicaed that altered activity-dependent release of BDNF in Met allele carriers may attenuate the cognitive benefits of exercise. Importantly, exercise-induced changes in cognition were not correlated with changes in mood/anxiety, suggesting that separate neural systems mediate these effects(37). Other indicated that Overall, in healthy older adults, regular, particularly aerobic, exercise appears to be a friend of the immune system, helping to offset diminished adaptive responses and chronic inflammation. The possibility exists that particularly strenuous exercise may cause acute immunologic changes, such as diminished NK cell activity, which could predispose to infection in certain individuals(37a)

8.  Avoid nutritional deficiency with balance diet
Beyond our believe, in the study to highlight how an excess of dietary carbohydrates, particularly fructose, alongside a relative deficiency in dietary fats and cholesterol, may lead to the development of Alzheimer's disease and a first step in the pathophysiology of the disease is represented by advanced glycation end-products in crucial plasma proteins concerned with fat, cholesterol, and oxygen transport.(38). Dr Pae M, and the research team at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, suggested that  the need for a more in-depth, wholestic approach to determining the optimal nutritional strategies that would maintain a healthy immune system in the elderly and promote their resistance to infection and other immune-related diseases(38a).

9. Avoid environment risk of dementia(39)
Certain environment toxins produced as a result of industrialization or naturally have been linked to cognitive degenerative diseases. Researchers at the University of British Columbia in the investugation of Novel environmental toxins: steryl glycosides as a potential etiological factor for age-related neurodegenerative diseases, showed that Mice fed washed cycad flour show signs that mimic ALS-PDC, which include progressive deficits in motor, cognitive, and olfactory functions associated with neuron loss in the spinal cord, nigrostriatal system, cortex, hippocampus, and olfactory bulb. Through a series of chemical extractions of washed cycad flour, we identified steryl glycoside molecules as bioactive molecules that are neurotoxic in culture and in mice. A detailed review of this class of molecule revealed that the molecules are abundant in the environment, particularly in plants and bacteria. Lipid analysis showed that some bacteria that are associated with some forms of neurodegenerative disorders have the capacity to synthesize steryl glycosides. Furthermore, certain steryl glycosides have been found to be a cell stress mediator and may have some immunomodulary effects. Others researchers showed that Parkinson disease (PD) and Alzheimer disease (AD), are of purely genetic origin in a minority of cases and appear in most instances to arise through interactions among genetic and environmental factors and early environmental origins of neurodegenerative disease in later life. Also environment toxins can reduce the immune function in protecting against other diseases.

10. No illicit drug, please(40)
Illicit drug used may cause nervous system impairment as a result of direct and indirect effects on the integrity and function of nervous system tissue and, potentially, through immune effects. HIV-1 infection poses an additional risk of impairment, and this risk may be decreased as a result of antiretroviral drug treatment. Others researchers suggested that injection drug use represents the primary risk factor for up to 40% of patients with HIV infection. Illicit drug also can effect the CNS and weaken the immune system.

11. Prevent prolonged period of using certain drug(41)
As aging, accumulation of toxins of certain medication used to treat certain diseases, such as antidepressants, sedatives, cardiovascular drugs and anti-anxiety medications may cause increased risk of cognitive dysfunction leading to produced dementia-like symptoms. Certain medication can suppress the immune system.

12. Etc.

B. Diet to prevent Hydrocephalus
The aims of the diet is to provide sufficient nutrients to body and enhance the immune function in fighting against inflammation and weakened immune system causes of Hydrocephalus
B.1. Black beans (Phaseolus)
1. Antioxidant effect
In the evaluation of the indigestible fraction (IF)of the cooked seeds of three pulses (black bean, chickpea and lentil) and their antioxidant effect found that Condensed tannins were retained to some extent in the IF that exhibited significant antioxidant capacity. The total IF of the three pulses produced short chain fatty acids (SCFA) after 24 h of in vitro fermentation by human colonic microflora. IF from black bean and lentil were best substrates for the fermentative production of butyric acid, according to "In vitro fermentability and antioxidant capacity of the indigestible fraction of cooked black beans (Phaseolus vulgaris L.), lentils (Lens culinaris L.) and chickpeas (Cicer arietinum L.)" by Hernández-Salazar M, Osorio-Diaz P, Loarca-Piña G, Reynoso-Camacho R, Tovar J, Bello-Pérez LA.(42)

2. Molybdenum
Molybdenum cofactor is vital for human enzymes, including xanthine oxidase, sulfite oxidase, and aldehyde oxidase, Deficiency may cause
a. Prenatal brain disruption, according to the study of "Prenatal brain disruption in molybdenum cofactor deficiency" by Carmi-Nawi N, Malinger G, Mandel H, Ichida K, Lerman-Sagie T, Lev D.(43)

3. Nervous system
Protein is essential for the brain in transmitting information between themselves and cells in the other parts of the body, thus reducing the blood sugar levels from rising too rapidly after a meal, reducing the risk of nervous symptoms cause of anxiety, stress and depression, etc., according to the study of "The planar polarity protein Scribble1 is essential for neuronal plasticity and brain function" by Moreau MM, Piguel N, Papouin T, Koehl M, Durand CM, Rubio ME, Loll F, Richard EM, Mazzocco C, Racca C, Oliet SH, Abrous DN, Montcouquiol M, Sans N, posted in PubMed (44)

B.2. Brown rice
1. Selenium
Oat contains trace minerals selenium which is essential for the healthy function of the thyroid and immune system as it increases the antioxidant defense system by fighting against the forming of free radicals and reduce the risk of irregular cells growth causes of tumor and cancer, according to the study of "Selenium in the immune system" by Arthur JR, McKenzie RC, Beckett GJ.(45)

2. Antioxidants
Beside containing high levels of magnesium which is necessary for the synthesis of fatty acids to produce energy for our body needs, it also is one of the important component of antioxidant enzyme of which increases the body in fighting against the forming of free radical, according to the study of "Analysis of antioxidant enzyme activity and magnesium level in chronic obstructive pulmonary disease (COPD)" by Kurys E, Kurys P, Kuźniar A, Kieszko R., posted in PubMed(46) 

B.3.  Asparagus 
1. Immunomodulatory activity
In the research of Roots of Asparagus racemosus Willd (Shatavari in vernacular) and its effect on immunostimulation found that asparagus racemosus root aqueous extract (ARE) also showed higher antibody titres and DTH responses. ARE, in combination with LPS, Con A or SRBC, produced a significant proliferation suggesting effect on activated lymphocytes and suggested that mixed Th1/Th2 activity of ARE supports its immunoadjuvant potential, according to "Immunomodulatory activity of Asparagus racemosus on systemic Th1/Th2 immunity: implications for immunoadjuvant potential" by Gautam M, Saha S, Bani S, Kaul A, Mishra S, Patil D, Satti NK, Suri KA, Gairola S, Suresh K, Jadhav S, Qazi GN, Patwardhan B.(47)  

2. Antioxidants
Asparagus contains some kinds of antioxidant that help to improve the immune system in fighting against the forming of radicals, thus promoting synthesis DNA and regulates cell division, according to "The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile" by Brambilla D, Mancuso C, Scuderi MR, Bosco P, Cantarella G, Lempereur L, Di Benedetto G, Pezzino S, Bernardini R.(48) 

B.4. Leek
1. Vitamin K
Since leak contains a measure amount of vitamin K, it helps to protect against aging diseases and the under layers of the skin, thus reducing the risk of wrinkle due to aging and enhances the absorption of calcium, thus promoting the formation of healthy bones, according to the study of "Vitamin K, osteoporosis and degenerative diseases of ageing" by Vermeer C, Theuwissen E., researchers found that According to the triage theory, long-term vitamin K inadequacy is an independent, but modifiable risk factor for the development of degenerative diseases of ageing including osteoporosis and atherosclerosis.(49)  

2. Antioxidant activities
In the investigation of the methanol extract of dried skin of Allium cepa and its isolation of quercetin-3'-O-beta-D-glucoside [1] found that the antioxidant activity of 1 was evaluated in the oxygen radical absorbance capacity assay; it showed 3.04 micromol Trolox equivalents/mmol. 1 was shown to be a promising ingredient that could be useful for treating hyperpigmentation and for protecting against oxidative stress, according to "Melanin biosynthesis inhibitory and antioxidant activities of quercetin-3'-O-beta-D-glucoside isolated from Allium cepa" by Arung ET, Furuta S, Ishikawa H, Tanaka H, Shimizu K, Kondo R.(50)

B.5. Etc. 

C. Photochemical to prevent Hydrocephalus 
C.1. Rosemarinol, is a phytochemical monophenols, found in essential oil of labiate herbs like Rosemary and also in variety of other plants.
1. Chemical stabilization of fish oil
In the study of fish oil undergoes multiple changes in its physical properties and its autoxidation occurred found that rosemary extract rich in carnosic acid to ternary blends of tocopherols, ascorbyl palmitate and lecithin or Citrem significantly retarded autoxidation, according to "Chemical stabilization of oils rich in long-chain polyunsaturated fatty acids during storage" by Pop F.

2. Anti-inflammatory effects
In the research of the extract of rosemary leaves from supercritical fluid extraction and its anti inflammatory effects found that the yield of 3.92% and total phenolics of 213.5 mg/g extract obtained from the most effective extraction conditions showed a high inhibitory effect on lipid peroxidation (IC(50) 33.4 μg/mL). Both the SC-CO(2) extract and CA markedly suppressed the LPS-induced production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), phosphorylated inhibitor-kappaB (P-IκB), and nuclear factor-kappaB (NF-κB)/p65 in a dose-dependent manner, according to the study of "Anti-inflammatory effects of supercritical carbon dioxide extract and its isolated carnosic acid from Rosmarinus officinalis leaves" by Kuo CF, Su JD, Chiu CH, Peng CC, Chang CH, Sung TY, Huang SH, Lee WC, Chyau CC.(51)

3. Supercritical fluid
In the investigation of rosemary extract could enhance antioxidant defenses and improve antioxidant status in aged rats found that rosemary extract produced a decrease in antioxidant enzyme activity, lipid peroxidation and ROS levels that was significant for catalase activity in heart and brain, NOS in heart, and LPO and ROS levels in different brain tissues. These observations suggest that the rosemary supplement improved the oxidative stress status in old rats, according to "Protective effect of supercritical fluid rosemary extract, Rosmarinus officinalis, on antioxidants of major organs of aged rats" by Posadas SJ, Caz V, Largo C, De la Gándara B, Matallanas B, Reglero G, De Miguel E.(52)

C.2. Gingerole
Gingerole, is also known as gingerol, a phytochemical of Flavonoids (polyphenols) found in fresh ginger. and in variety of other plants. The herb has been used to treat nausea and vomiting of pregnancy, motion sickness, rheumatoid arthritis, relieve migraine, etc.
1. Antioxidant and anti-inflammatory effects
In the investigation of the effectiveness of chemical constituents of Zingiber officinale Rosc. (Zingiberaceae)in treating oxidative stress found that compounds [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol of the herb scavenges of 1,1-diphenyl-2-picyrlhydrazyl (DPPH), superoxide and hydroxyl radicals, inhibitsof N-formyl-methionyl-leucyl-phenylalanine (f-MLP) induced reactive oxygen species (ROS) production in human polymorphonuclear neutrophils (PMN), lipopolysaccharide induced nitrite and prostaglandin E(2) production in RAW 264.7 cells, according to the study of "Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol" by Dugasani S, Pichika MR, Nadarajah VD, Balijepalli MK, Tandra S, Korlakunta JN(53)

2. Dementia
In the study of Ginger effectiveness in treating dementia in South Asia with A 70% aqueous/methanolic extract of dried ginger (Zo.Cr) was used. Zo.Cr tested positive for the presence of terpenoids, flavonoids, secondary amines, phenols, alkaloids and saponins found that
specific inhibition of butyrylcholinesterase (BuChE) rather than acetylcholinesterase enzyme. Different pure compounds of ginger also showed spasmolytic activity in stomach fundus, with 6-gingerol being the most potent. 6-Gingerol also showed a specific anti-BuChE effect, according to "Muscarinic, Ca(++) antagonist and specific butyrylcholinesterase inhibitory activity of dried ginger extract might explain its use in dementia" by Ghayur MN, Gilani AH, Ahmed T, Khalid A, Nawaz SA, Agbedahunsi JM, Choudhary MI, Houghton PJ.(54)

C.3.  Naringenin
Naringenin, a flavanone, belonging to the red, blue, purple pigments of Flavonoids (polyphenols) found predominantly in citrus fruits is considered as one of powerful antioxiant with many health benefits.
1. Antioxidant, radical scavenging and biomolecule activity
In the affirmation of the capacity of flavonoid naringenin and its glycoside naringin in the comparison of theirs antioxidant capacities, radical scavenging and biomolecule activities found that naringenin exhibited higher antioxidant capacity and hydroxyl and superoxide radical scavenger efficiency than naringin and both flavanones were equally effective in reducing DNA damage. However, they show no protective effect on oxidation of GSH, according to the study of "Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: a comparative study" by Cavia-Saiz M, Busto MD, Pilar-Izquierdo MC, Ortega N, Perez-Mateos M, Muñiz P.(55)

2. Anti-inflammatory effects
In the evaluation of the mechanisms of action of the effective compounds. Flavone, the isoflavones daidzein and genistein, the flavonols isorhamnetin, kaempferol and quercetin, the flavanone naringenin, and the anthocyanin pelargonidin amd theirs anti-inflammatory effects found that they inhibited iNOS protein and mRNA expression and also NO production in a dose-dependent manner, according to "Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages" by Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E.(56)

3. Immunity
In the unvestigation of Naringenin, a flavonoid in grapefruits and citrus fruits and its effec in immune system found that naringenin potently suppressed picryl chloride (PCl)-induced contact hypersensitivity by inhibiting the proliferation and activation of T lymphocytes. In vitro, both of the activated hapten-specific T cells and the T cells stimulated with anti-CD3/anti-CD28 showed growth arrest after naringenin treatment, according to "A novel regulatory mechanism of naringenin through inhibition of T lymphocyte function in contact hypersensitivity suppression" by Fang F, Tang Y, Gao Z, Xu Q.(57)

C.4.  Tangeritin
Tangeritin, one of the flavones, is found in tangerine and many citrus peels
1. Neuroprotective effects
In the evaluation of neuroprotective effects of a natural antioxidant tangeretin, a citrus flavonoid and its effect on Parkinson's disease found that tangeretin crosses the blood-brain barrier. The significant protection of striato-nigral integrity and functionality by tangeretin suggests its potential use as a neuroprotective agent, according to "Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease" by Datla KP, Christidou M, Widmer WW, Rooprai HK, Dexter DT.(58)

2. Antioxidants
In the comparison of hand-pressed juice of polymethoxylated flavones (PMFs) and flavanone glycosides (FGs) and the peeled fruit of 'Sainampueng' tangerines ( Citrus reticulata Blanco cv. Sainampueng) antioxidant effects found that hand-pressed juice of C. reticulata Blanco cv. Sainampueng serves as a rich source of PMFs, FGs, carotenoids, and antioxidants: 4-5 tangerine fruits ( approximately 80 g of each fruit) giving one glass of 200 mL hand-pressed juice would provide more than 5 mg of nobiletin and tangeretin and 36 mg of hesperidin, narirutin, and didymin, as well as 30 mg of ascorbic acid, >1 mg of provitamin A active beta-cryptoxanthin, and 200 microg of alpha-tocopherol, according to "Polymethoxylated flavones, flavanone glycosides, carotenoids, and antioxidants in different cultivation types of tangerines ( Citrus reticulata Blanco cv. Sainampueng) from Northern Thailand" by Stuetz W, Prapamontol T, Hongsibsong S, Biesalski HK.(59)

C.5. Etc.

D. Antioxidants to prevent Hydrocephalus(60)
D.1. Antioxidant enzymes
Antioxidant enzymes are chemical substances found in plants that can protect the body from damage of free radicals by terminating the chain reactions by removing free radical intermediates and inhibiting other oxidation reactions.
1. Catalase
Catalase is an enzyme, found in most living organisms that are exposed to oxygen helped to converse hydrogen peroxide (free radicals) to water and oxygen as a rate of 40 million molecules of hydrogen peroxide to water and oxygen each second, using either an iron or manganese cofactor.

2. Glutathione peroxidase
The function of glutathione peroxidase is to protect the organism from oxidative damage by reducing lipid hydroperoxides, an oxidation of lipid cell membranes which can easily break and form free radicals of the form RO and converting free hydrogen peroxide to oxygen and water.

3. Glutathione reductase
Glutathione reductase, an enzyme reduces pair of sulfur atoms glutathione to the a organosulfur compound form of antioxidant (consisting of three amino acids joined by peptide bonds) which helps to prevent damage of important cellular components caused by free radicals and peroxides.

4. Super oxide dismutase (both Cu-Zn and Mn)
Super oxide dismutase is an important antioxidant defense in nearly all cells exposed to oxygen by converting superoxide into oxygen and hydrogen peroxide depending on the metal cofactor such as both Cu-Zn and Mn.

D.2. Metals binding proteins 
1. Ceruloplasmin
Ceruloplasmin, the major copper-carrying protein in the blood plays a role in iron metabolism. It prevents the oxidation that leads to the forming of oxidation from Fe2+ (ferrous iron) into Fe3+ (ferric iron) by exhibiting a copper-dependent oxidase activity, causing mutations in the ceruloplasmin gene cause of iron overload in the brain, liver, pancreas, and retina.

2. Ferritin
Ferritin, the protein produced by almost all living organisms, acts as a component to fight against iron deficiency and iron overload, keep in a soluble and non-toxic form and transport it to the body needs, including organs. It enhances the immune system in the presence of an infection or cancer and prevent the infectious agent attempts to bind iron to become free radicals by migrating from the plasma to within cells.

3. Lactoferrin
Lactoferrin, a multifunctional protein of the transferrin family, is one of the components of the immune system of the body by fighting against foreign invasion of bacteria and virus and lipid oxidation by inhibiting oxidation in a concentration-dependent manner even at concentrations beyond its capacity.

4. Metallotheinein
Metallotheinein, a family of cysteine-rich, low molecular weight proteins helps to bind both physiological heavy metals through the organosulfur compound of its cysteine residues. It also captures harmful superoxide and hydroxyl radicals by liberating the metal ions which were bound to cysteine.

5. Transferrin
Transferrin is a glycoprotein that binds iron very tightly but reversibly. It enhance the immune system in fighting against infection, inflammation by creating an environment low in free iron that impedes bacteria survival and cell oxidation.

6. Hemoglobin
Hemoglobin is the protein molecule in red blood cells that enhances the carrying of oxygen from the lungs to the body's tissues and return CO2 from the tissues to the lungs.
During oxidate stress, the cell membrane is protected by intraerythrocytic hemoglobin from the forming of free radical.

7. Myoglobin
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates. The binding of oxygen by myoglobin is unaffected by the oxidation or chain of oxidative reaction in the surrounding tissue, thus reducing the free radicals damage caused by oxidate stress.

8. Etc.
 
VII. Treatment
A. In Conventional medicine perspective
A.1. Surgical treatment
In general, treatment of Hydrocephalus involves the placement of a tube made of silastic, into the cerebral ventricles to bypass the flow obstruction and drain the excess fluid into other body cavities, where the fluid can be reabsorbed. In the study of Lumboperitoneal shunts for the treatment of normal pressure hydrocephalus, Dr. Bloch O,  and Dr.McDermott MW. indicated that Studies have reported shunt complication rates up to 38%, with subdural hemorrhage rates as high as 10%. Lumboperitoneal (LP) shunts with horizontal-vertical valves (HVV) are an alternative for cerebrospinal fluid (CSF) diversion that avoids direct cerebral injury and may reduce the risk of overdrainage. They also showed that
 in 33 patients with LP-HVV shunts inserted for the treatment of iNPH from 1998 to 2009. Patients were evaluated for improvements in gait, urinary function, and dementia after shunt placement. All patients had evidence of ventriculomegaly and a positive response to pre-operative lumbar puncture or extended lumbar drainage. All 33 (100%) patients had pre-operative gait dysfunction, 28 (85%) had incontinence, and 20 (61%) had memory deficits. Mean follow-up time was 19 months. Following shunt placement, 33/33 (100%) patients demonstrated improved gait, 13/28 (46%) had improvement in incontinence, and 11/20 (55%) had improvement in memory. Shunt failures requiring revision occurred in nine patients (27%), with an average time to failure of 11 months. Infections occurred in two patients (6%). There were no neurologic complications, including no hemorrhages. Thus, LP-HVV shunt placement is a safe and effective alternative to ventriculoperitoneal shunting for iNPH, resulting in significant symptomatic improvement with a low risk of overdrainage. It should be considered as an option for the treatment of patients with iNPH who demonstrate clinical improvement following lumbar drainage(61).
Other cautioned of The incidence of infection and malfunction with an LP shunt is significantly lower than that with a VP shunt. An LP shunt is also indicated for pediatric patients, although a relatively higher incidence of malfunction is noted compared to adults(62)

A.2. Non Medical treatment
1. Occupational therapy and physical therapy
In the study to examine effectiveness of standardized occupational therapy and physical therapy assessments in detecting functional changes and predicting clinical improvement in patients with suspected normal pressure hydrocephalus undergoing cerebrospinal fluid drainage, indicated that specific occupational therapy and physical therapy assessments demonstrate sensitivity to change and predictive value with patients with suspected normal pressure hydrocephalus undergoing cerebrospinal fluid drainage(63).

2. Psycological and Speech therapy
In the review of the literature on psychic disturbance in normal pressure hydrocephalus, showed that in the 26 cases of CSF drainage, impairment of memory and concentration were always present in normal pressure hydrocephalus; behaviour disorders were very frequent and characterized by both types of frontal behaviour; the mental picture also comprised difficulties of calculation, writing, visuoconstructive praxis and, less frequently, impaired speech and reading ability. CSF drainage brought clinical improvement in 73% of the cases. Disorders of consciousness, mental function and behaviour regressed generally progressively as soon as the operation had been performed(64).

3. Etc.

B. In herbal medicine perspective 
There is no specific herbs formula or herbs 
According to the article of Hydrocephalus by Dherbs, Hydrocephalus is a result of the building up of toxins cause of accumulations of fluid on the brain as he provide each step
1. Toxins removal
a. Blood and Lymphatic with ECHINACEA ANGUSTIFOLIA, BEET ROOT, DRAGONS BLOOD, SPIRULINA, DANDELION, BURDOCK, MANJISTHA, BITTER MELON, RED CLOVER, CHICKWEED, SASSAFRAS, AMLA FRUIT, CLEAVERS, VIDANGA, INDIGO, POKE ROOT, NETTLE, IRON WEED, CAPSICUM, RED ROOT, YELLOW DOCK, PAU D’ARCO, ANANTAMUL, SOLOMON SEAL, OLIVE LEAF, GOLDENSEAL.

b.  Cardiovascular with GARLIC, CAPSICUM, HAWTHORN BERRIES, LILY OF THE VALLEY, ARJUNA, SIBERIAN GINSENG, REISHI MUSHROOM, MOTHERWORT, DANDELION LEAF, MYRRH, GINGER, BALA, PUNARNAVA, MISTLETOE, GINGKO BILOBA, PRICKLY ASH, MULBERRY.

c. Liver and Gallbladder with MANJISTHA ROOT, ANANTAMUL, SCHIZANDRA, BEET ROOT, DANDENLION, BHUMYAMALAKI, ARTICHOKE, ROSEMARY, TURMERIC, LICORICE, BUPLEURUM, AMALAKI FRUIT, PIPPALI FRUIT, MILK THISTLE SEEDS, PEONY ROOT, BHRINGARAJ, RHUBARB, FENUGREEK, GOLDENSEAL.


d. Lungs and Respiratory with GOKSHURA FRUIT, JUNIPER BERRY, GUDUCHI, CORN SILK, CORIANDER SEED, FENNEL SEED, PUNARNAVA, UVA URSI, ASPARAGUS, BUCHU, CRANBERRY, TRIBULUS, CLEAVERS, GOLDENROD, CELERY SEED, ANANTAMUL, PARSLEY LEAF, GRAVEL ROOT, PIPSISSEWA, HORSETAIL, NETTLE.

e. Colon and Digestive Tract with SENNA LEAVES AND PODS, OAT BRAN, BARLEY GRASS, SLIPPERLY ELM, BLACK PEPPER, CASCARA SAGRADA, CARBON (ACTIVATED CHARCOAL), BUCKTHORN, HARITAKI, TURMERIC, PSYLLIUM HUSK, IRISH MOSS, ALOE VERA, GINGER, CLAY BENTONITE, POKE ROOT, CAYENNE PEPPER, HINGVASTAK.

f. Carbon (also known as Activated Charcoal) is not a formula but the residue of burnt plant matter (Willow bark) that is carbon and copper-based and therefore ELECTRICAL

2. 10 DAYS ELECTRIC GREENS COMBO REGIMEN
 10-day Cleanse that helps cleanse, build, and nourish the body at the same time. It is a unique cleanse consisting of a mix of super green foods such as alfalfa, nettle, kamut grass, blue green algae, spirulina, chlorella, and wheat grass to name a few.

3. Soften and dissolve hardened, stubborn mucus and phlegm of which can cause toxins accumulation with LICORICE, CALENDULA, MULLEIN LEAVES, RED CLOVER, QUASSIA, PLANTAIN, FENUGREEK.

4. Enhance circulation with HAWTHORNE BERRY, CAYENNE (40,000), CINNAMON, AND GINGER.

5. Release fluid with UVA URSI, LILY OF THE VALLEY, DANDELION LEAF & ROOT, CORN SILK, BILBERRY, ANISE, CELERY, FENNEL, BLACK COHOSH, MULLEIN LEAF, ROSEMARY, QUEEN OF THE MEADOW, PARSLEY, AND BURDOCK ROOT.

6. Nourish, strengthen, and tone the veins and venous system with HORSE CHESTNUT, BILBERRY, ORANGE PEEL, BUTCHER’S BROOM, GOTU KOLA, MANJISTHA, CINNAMON, GINGER, HORSETAIL, WHITE OAK BARK, LEMON PEEL, AND CALENDULA.

7. Colon and intestinal complaints and helps to maintain overall colon and intestinal health and wellbeing! with SENNA LEAVES, CHAMOMILE, GINGER, PEPPERMINT, LICORICE, and STEVIA .

8. Etc.
For more information of DHerbssolution, please visit (65)


C. In Traditional Chinese medicine perspective
 According to the article of Hydrocephalus posted on Dicovery TCM, Hydrocephalusis a result of
1. Deficiency of the kidney qi
a. Main symptoms and signs 
Marked enlargement of skull, widened fontanel with separation of sutures,sluggish expression, dimness in the eyes, dropping eyeballs like "the setting sun", large anteverted head with thin neck, strabismus, vomiting and convulsion in severe cases, whitish complexion, poor appetite, loose stools, pale tongue with a little fur, weak pulse and bluish superficial venule of index finger. 
b. Therapeutic method   
Tonifying  the kidney and marrow. 
c. Prescription and drugs  The prescription used is the modified Bushen Dihuang Pill (Rehmannia Pill for Tonifying the kidney) composed of 10 g of Shudihuang ( Radix Rehmanniae Praeparata ), 10 g of Shanyao (Rhizoma Dioscoreae ), 10 g of Shanzhuyu ( Fructus Corni), 10 g of Fuling (Poria), 10 g of Zexie (Rhizoma Alismatis), 10 g of Mudanpi ( Cortex Moutan Radicis), 6 g of Niuxi (RadixAchyranthis Bidentatae), 6 g of Lujiaojiao (colla Comus Cervi) (melted) and 6 g of Danggui ( Radix Angelicae Sinensis ) 
Modification  For the patients with concurrent talantropia, strabismus or blurred vision, 10 g of Gouqizi (Fructus Lycii), 8 g of Tusizi (Semen Cuscutae), 10 g of Juemingzi ( Semen Cassiae ) and 10 g of Juhua ( Flos Chrysanthemi) are added.
2. Hyperactivity of the liver due to asthenia of the kidney
a. Main symptoms and signs  
Separation of skull sutures, large and wide anterior fontanel, dropping eyeballs with more white than black, brightless eyes, dry mouth, dysphoria, feverish palms and soles, muscular twitching and cramp, occasional scream, red tongue,deep, thready and rapid pulse and purplish superficial venule of index finger
b.Therapeutic methods  
Nourishing the kidney yin, calming the liver yang to stop wind. 
c. Prescription and drugs The prescription used is the modified Zhibai Dihuang Pill in combination with Sanjia Fumai Decoction composed of 6 g of Shudihuang (Radix Rehmanniae Praeparata), 10 g of Shanyao (Rhizoma Dioscoreae), 8 g of Shanzhuyu (Fructus Corni), 10 g of Fuling ( Poria ), 6 g of Zexie ( Rhizoma Alismatis ), 10 g of Guiban ( Plastrum Testudinis) ( to be decocted first), 6 g of Zhimu (Rhizoma Anemarrhenae), 3 g of Huangbai ( Cortex Phellodendri), 6 g of Ejiao ( Colla COrii Asini) and 12 g of Baishaoyao (Radix Paeoniae Alba ). 
Modification  For the patients with fever due to yin deficiency, 6 g of Yuzhu (Rhizoma Polygonati Odorati) and 6 g of Baiwei (Radix Cynanchi Atrati ) are added; for the patients with dysphoria, 3 g of Hupofen (powder of Succinum) (taken separately) and 15 g of Zhenzhumu (Concha Margaritifera Usta) (to be decocted first) are included; for patients with muscular twitching and cramp, or occasional scream, 6 g of Tianma ( Rhizoma Gastrodiae ), 10 g of Gouteng ( Bamulus Uncariae cum Uncis) (to be decocted later) and 10 g of Baijiangcan (Bombyx Batryticatus) are added.
3. Water retention due to asthenia of the spleen
a. Main symptoms and signs Wide and large fontanel, separation of fontanel sutures, whitish complexion,lassitude, poor appetite, loose stools, epigastric and abdominal distension, pale tongue with whitish and thin or whitish and greasy fur, thready and weak pulse and light red superficial venule of index finger.
b. Therapeutic method  
Warming the spleen to promote water metabolism.
c. Prescription and drugs  The prescription used is the modifided Fuzi Lizhong Decoction (Aconite Decoction for Regulating the Middle Energizer) in combination with Wuling Powder (Five-ingredient Powder with Poria) composed of 3 g of Renshen (Radix Ginseng), 10 g of Baizhu (Rhizoma Atractylodis Macrocephalae), 6 g of Ganjiang (Rhizoma Zingiberis), 3 g of Zhifuzi ( Radix Aconiti Praeparata) (to be decocted first), 10 g of Zhuling (Polygorus Umbellatus), 10 g of Fuling (Poria), 6 g of Zexie (Rhizoma Alismatis ) and 6 g of Guizhi ( Ramulus Cinnamomi )
Modification  For the patients with poor appetite, 10 g of Jiaoshanzha (carbonized Fructus Crataegi), 10 g of Jiaomaiya (carbonized Fructus Hordei Germinatus ) and 10 g of Jiaoshenqu (carbonized Massa Fermentata Medicinalis) are added; for the patients with loose stools,6 g of Cheqianzi ( Semen Plantaginis) (to be wrapped) and 10 g of Shanyao (Rhizoma Dioscoreae) are included; for the patients with vomiting, 6 g of Banxia (Rhizoma Pinelliae ) and 6 g of Zhuru ( Caulis Bambusae in Taeniam) are added; for the patients with yang deficiency of the spleen and kidney, poor appetite and loose stools,Kidney-regulating Powder may be applied. The powder is composed of 10 g of Shanyao (Rhizoma Dioscoreae), 3 g of Renshen (Radix Ginseng), 10 g of Baifuling (Poria), 10 g of Fushen (Poria cum Ligno Hospite ), 10 g of Baizhu (Rhizoma Atractylodis Macrocephalae), 12 g of Baishaoyao (Radix Paeoniae Alba ), 6 g of Shudihuang (Radix Rehmanniae Praeparata), 8 g of Danggui (Radix Angelicae Sinensis ), 10 g of Huangqi (Radix Astragall seu Hedysari), 6 g of Chuanxiong (Rhizoma Ligustici Chuanxiong) , 3 g of Zhigancao (Radix Glycyrrhizae Praeparata) and 10 g of Shichangpu ( Rhizoma Acori Graminei). The ingredients are ground into fine powder, 10 g of which is decocted with ginger and Chinese dates to be taken each time.
4. Stagnation of preponderant heat and toxin
a. Main symptoms and signs Gradual enlargement of skull, prominent and distending fontanel, closure of fontanel sutures with recurrent separation, dropping eyes, fever, short breath, dysphoria with cry and tantrum, flushed complexion with red lips or strabismus, spasm of limbs, dark and scanty and deep yellow urine, constipation, red tongue with yellowish fur, taut and rapid pulse, purple and sluggish superficial venule of index finger. 
b. Therapeutic methods   
Clearing away heat and removing toxin, removing blood stasis and dredging collaterals. 
c. Prescription and drugs The prescription used is the modified Xidi Qingluo Decoction (Decoction of Rhinoceros Horn and Rehmannia Root for Clearing away Heat from Collaterals) composed of 15g of Shuiniujiaopian (slices ofcornu Bubali) (to be decocted first), 10 g of Shengdihuang ( Radix Rehmanniae ), 10 g of Lianqiao ( Fructus Forsythiae ), 3 g of Dengxincao ( Medulla Junci), 10 g of Mudanpi ( Cortex Moutan Radicis ),10 g of Chishaoyao ( Radix Paeoniae Rubra ), 6 g of Taoren (Semen Persicae ) and 10 g of Baimaogen (Rhizoma Imperatae ) . 
Modification For the patients with stagnation of phlegm and heat, chest distress with nausea, red tongue with yellowish fur, 6 g of Danxing (Arisaema cum Bile), 10 g of Shichangpu ( Rhizoma Acori Graminei ) ,6 g of Dilong ( Lumbricus ) and 10 g of Tianzhuhuang (concretio silicea Bambusae ) are added; for the patients with clonic convulsion, 6 g of Quanxie (Scorpio), 10 g of Gouteng (Bamulus Uncariae cure Uncis) (to be decocted later) and 12 g of Baishaoyao (Radix Paeoniae Alba) are included. For enlargement of skull, separation of fontanel sutures without closure, visible local bluish superficial venules, tongue with ecchymosis, or deafness and dumbness, hypophrenia and paralysis of limbs resulted from the fact that blood stasis obstructs cerebral collaterals, constricts cerebral marrow and blocks cerebral orifices, the therapeutic method is removing blood stasis to eliminate obstructive orifices. The prescription used is the modified Tongqiao Huoxue Decoction (Decoction for Removing Obstruction from Orifices and Activating Blood Circulation) composed of 10 g of Danggui (Radix Angelicae Sinensis ), 8 g of Chuanxiong ( Rhizoma Ligustici Chuanxiong), 10 g of Chishaoyao (Radix Paeoniae Rubra), 6 g of Taoren ( Semen Persicae), 6 g of Honghua (Flos Carthami ), 10 g of Danshen ( Radix Salviae Miltiorrhizea), 8 g of Dilong (Lumbricus), O. 05 g of Shexiang (artificial Moschus) (to be infused separately),8 g of Niuxi (RadixAchyranthis Bidentatae) and 10 g of Fuling (Poria).
For more information of TCM in treating please visit  (66)
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/21746835
(2) http://www.ncbi.nlm.nih.gov/pubmed/16773266
(3) http://www.ncbi.nlm.nih.gov/pubmed/21746835
(4) http://www.ncbi.nlm.nih.gov/pubmed/3907171
(5) http://www.ncbi.nlm.nih.gov/pubmed/19770534
(6) http://www.ncbi.nlm.nih.gov/pubmed/17934294
(7) http://www.ncbi.nlm.nih.gov/pubmed/16256848
(8) http://www.ncbi.nlm.nih.gov/pubmed/22705452
(9) http://www.ncbi.nlm.nih.gov/pubmed/21928036
(10) http://www.hindawi.com/journals/crim/2010/743784/
(11) http://www.ncbi.nlm.nih.gov/pubmed/9586937
(12) http://www.ncbi.nlm.nih.gov/pubmed/6524107
(13) http://www.ncbi.nlm.nih.gov/pubmed/22702328
(14) http://www.ncbi.nlm.nih.gov/pubmed/22116446
(15) http://www.ncbi.nlm.nih.gov/pubmed/11883667
(16) http://www.ncbi.nlm.nih.gov/pubmed/10569968
(17) http://www.ncbi.nlm.nih.gov/pubmed/183936
(18) http://pediatrics.about.com/cs/conditions/a/hydrocephalus_2.htm
(19) http://www.ncbi.nlm.nih.gov/pubmed/2923462
(20) http://www.ncbi.nlm.nih.gov/pubmed/22591299
(21) http://www.ncbi.nlm.nih.gov/pubmed/2046855
(22) http://www.ncbi.nlm.nih.gov/pubmed/18025828
(23) http://www.ncbi.nlm.nih.gov/pubmed/19996513
(24) http://www.ncbi.nlm.nih.gov/pubmed/20717518
(25) http://www.ncbi.nlm.nih.gov/pubmed/12878439
(26) http://www.ncbi.nlm.nih.gov/pubmed/6583309
(27) http://www.ncbi.nlm.nih.gov/pubmed/6989174
(28) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265984/?tool=pubmed
(29) http://www.ncbi.nlm.nih.gov/pubmed/18466323
(30) http://www.ncbi.nlm.nih.gov/pubmed/22342535
(31) http://www.ncbi.nlm.nih.gov/pubmed/22408297
(31a) http://www.ncbi.nlm.nih.gov/pubmed/21829284
(32) http://www.ncbi.nlm.nih.gov/pubmed/22515730
(33) http://www.ncbi.nlm.nih.gov/pubmed/16222166
(33a) http://www.ncbi.nlm.nih.gov/pubmed/1356316
(34) http://www.ncbi.nlm.nih.gov/pubmed/20182054
(35) http://www.ncbi.nlm.nih.gov/pubmed/14732624
(36) http://www.ncbi.nlm.nih.gov/pubmed/22554780
(36a) http://www.ncbi.nlm.nih.gov/pubmed/21985858
(37) http://www.ncbi.nlm.nih.gov/pubmed/21402242
(37a) http://www.ncbi.nlm.nih.gov/pubmed/19001887
(38) http://healthyliving50over.blogspot.ca/2012/04/delay-dementia-causes-of-dementia.html
(38a) http://www.ncbi.nlm.nih.gov/pubmed/22500273
(39) http://healthyliving50over.blogspot.ca/2012/05/environment-toxin-causes-of-dementia.html
(40) http://healthyliving50over.blogspot.ca/2012/05/substance-abuse-causes-of-dementia.html
(41) http://healthyliving50over.blogspot.ca/2012/05/medication-causes-of-dementia.html
(42) http://www.ncbi.nlm.nih.gov/pubmed/20549791
(43) http://www.ncbi.nlm.nih.gov/pubmed/21285035
(44) http://www.ncbi.nlm.nih.gov/pubmed/20660256
(45) http://www.ncbi.nlm.nih.gov/pubmed/12730442
(46) http://www.ncbi.nlm.nih.gov/pubmed/11977322
(47) http://www.ncbi.nlm.nih.gov/pubmed/19038322
(48) http://www.ncbi.nlm.nih.gov/pubmed/18826565 
(49) http://www.ncbi.nlm.nih.gov/pubmed/21427421
(50) http://www.ncbi.nlm.nih.gov/pubmed/21812337
(51) http://www.ncbi.nlm.nih.gov/pubmed/21375325
(52) http://www.ncbi.nlm.nih.gov/pubmed/19289162
(53) http://www.ncbi.nlm.nih.gov/pubmed/19833188
(54) http://www.ncbi.nlm.nih.gov/pubmed/18812031
(55) http://www.ncbi.nlm.nih.gov/pubmed/20394007
(56) http://www.ncbi.nlm.nih.gov/pubmed/18274639
(57) http://www.ncbi.nlm.nih.gov/pubmed/20471963
(58) http://www.ncbi.nlm.nih.gov/pubmed/11726811
(59) http://www.ncbi.nlm.nih.gov/pubmed/20420369 
(60) http://medicaladvisorjournals.blogspot.ca/2012/05/dementia-preventions-antioxidants.html
(61) http://www.ncbi.nlm.nih.gov/pubmed/22705135
(62) http://www.ncbi.nlm.nih.gov/pubmed/2362678
(63) http://www.ncbi.nlm.nih.gov/pubmed/18843422
(64) http://www.ncbi.nlm.nih.gov/pubmed/749513
(65) http://dherbs.com/articles/hydrocephalus-439.html
(66) http://tcmdiscovery.com/TCMDisease/Paediatrics/info/D-Treatment/20081010_231.html