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Cerebral Vascular Disease
Subarachnoid Hemorrhage (SAH)
A SAH occurs when blood leaks into the membranes that surround the brain. The underlying causes for SAH include ruptured aneurysm (a ballooning of the arterial wall) and vascular malformations. Symptoms of SAH include:
- Sudden onset of severe headache
- Nausea or vomiting
- Stiff neck
- Light intolerance
- Total or partial loss of consciousness
After an aneurysm ruptures, a blood clot forms over the affected area. If the clot is disturbed, rebleeding occurs. Rebleeding is the leading cause of death among SAH patients. It is critical that patients with the symptoms of SAH seek immediate medical attention.
Risk Factors
Risk factors for SAH include hypertension, cigarette smoking, and family history of a primary relative with a SAH (4% risk). Other risk factors include age, gender, race, and alcohol use. The risk of rupture depends on the size of the aneurysm.
The incidence of SAH increases throughout middle age and peaks between the ages of 40 and 60. SAH affects women in 60% of all cases. African Americans have nearly twice the risk as Caucasians. Cigarettes and alcohol abuse have been shown to increase aneurysm rupture. People with a family history of aneurysm-induced SAH are at higher risk because certain types of aneurysms appear to run in families.
Diagnosis
The most common diagnostic procedures for determining the cause of hemorrhagic stroke are CT scan, MRI, and cerebral angiogram. These procedures are used to determine the type of stroke and the specific area of the brain that has been affected. Treatment of the stroke is based on the findings of these procedures.
Additional Risk Factors
Can Cholesterol Levels Be Too Low?
Cholesterol has obtained such a bad reputation, that some people may be inadvertently harming themselves by intentionally keeping their serum cholesterol too low.
At the American Heart Association's Annual Stroke Conference (February 1999), a report was presented showing that people with cholesterol levels under 180 doubled their risk of hemorrhagic stroke compared to those with cholesterol levels of 230. Hemorrhagic stroke occurs when a blood vessel in the brain breaks open and is different from the more common thrombotic stroke caused by an abnormal blood clot. This study also showed that the risk of thrombotic stroke was twice as likely in those with cholesterol levels over 280 compared to those at 230. The report concluded that the optimal cholesterol level for overall stroke prevention was around 200.
An article in the journal Neuroepidemiology found that the proportion of intracerebral hemorrhage (ICH) cases with low cholesterol was significantly greater than in controls. The authors concluded that an increased risk for primary ICH was associated with low cholesterol, a relationship that may apply specifically to hemorrhages from hypertensive vasculopathy (Segal et al. 1999).
Some Foundation members have pushed their cholesterol levels far below 180. In the few reports of hemorrhagic stroke experienced by Foundation members, their cholesterol levels have all been far below 180 mg/dL. The Life Extension Foundation recommends that cholesterol levels be monitored regularly and medication or supplement doses regulated to maintain a range of between 180-200 mg/dL.
Drugs that May Increase Bleeding Risk
Phenylpropanolamine (PPA). PPA is a popular ingredient in dozens of over-the-counter and prescription diet aids and cough and cold remedies. A case-control study found that the use of PPA significantly increased the risk of hemorrhagic stroke in women. The FDA has requested that drug companies stop marketing products containing PPA (Kernan et al. 2000; Mersfelder 2001).
Coumadin. Intracranial hemorrhage is one of the known side effects of Coumadin (warfarin). Coumadin is the drug of choice for thrombosis prophylaxis (prevention). Its uses include prophylaxis for myocardial infarction, stroke, arterial thromboembolism, and deep venous thrombosis. Coumadin is used in patients with prosthetic (artificial) heart valves and is sometimes used in combination with aspirin to thin the blood.
Coumadin interferes with the synthesis of vitamin K which forms several essential coagulation factors. It prolongs prothrombin time (PT) and thromboplastin time (APTT). Prothrombin time is the time measured in seconds for a fibrin clot to form. Thromboplastin time measures in seconds the ability of blood to clot normally. Both tests are closely related and are often ordered together. The universal standard coagulation blood test for Coumadin patients is called the INR or International Normalization Ratio.
Bleeding is the primary side effect of Coumadin therapy. Minor bleeding often occurs in the mucous membranes, particularly around the eyes and nose (causing nosebleeds). Of particular concern is easy bruising and ecchymoses (purple patches on the skin). Another side effect is "purple toe syndrome," referring to drastically reduced blood flow to the feet.
Coumadin (warfarin) has an extremely long list of contraindications and drug interactions (see below page 521 ). Of particular concern is its use in elderly patients because they are more susceptible to the effects of anticoagulants and have an increased possibility of hemorrhage.
- Coumadin is contraindicated in alcoholism, aneurysm, breast-feeding, the elderly, endocarditis, hemophilia, hemorrhage, hepatic disease, hypertension, intramuscular injections, leukemia, lumbar puncture, peptic ulcer disease, pericardial effusion, polycythemia vera, pregnancy, protein C deficiency, protein S deficiency, psychosis, surgery, vasculitis, vitamin C deficiency, and vitamin K deficiency.
- Coumadin interacts with a large number of common drugs, including acetaminophen, aspirin, barbiturates, some antibiotics, estrogens, ethanol, heparin, influenza virus vaccine, lovastatin, NSAIDs, oral contraceptives, thrombolytic agents, and thyroid hormones. Your physician must be informed of all prescription and over-the-counter medications you are taking before beginning Coumadin therapy.
- Adverse side effects to Coumadin include agranulocytosis, alopecia (hair loss), anorexia, bleeding, chondrodysplasia punctata, cleft palate, diarrhea, exfoliative dermatitis, fetal abortion, intracranial hemorrhage, intraocular hemorrhage, leukopenia, nausea/vomiting, pruritus (itching), purple-toe syndrome, skin necrosis, and urticaria.
Those currently on anticoagulant therapy with Coumadin and aspirin should closely monitor their PT and INR and take the clinical symptoms of hemorrhage seriously. Particular attention should be given to nosebleeds. Even minor symptoms of bleeding should be cause for alarm, particularly in the elderly and those on multiple medications.
There are several natural blood-thinners that may be used in conjunction with Coumadin and aspirin. See the Thrombosis Prevention and Thrombotic Stroke protocols for more information.
Conventional Treatments
Treatment of hemorrhagic stroke is based on the underlying cause of the hemorrhage and the extent of damage to the brain: treatment includes medication and surgical intervention. In patients with hypertension-induced ICH, initial treatment involves the use of antihypertensive agents. However, lowering blood pressure in ICH remains controversial. Studies have shown that one third of ICHs expand in the first 24 hours (Brott et al. 1997). Some physicians have therefore concluded that a need to lower blood pressure exists in managing acute ICH. No trial has demonstrated the effectiveness of lowering blood pressure. Furthermore, there is significant concern about reducing cerebral blood perfusion pressures in patients with elevated intracranial pressure.
The American Heart Association guidelines recommend that mean arterial blood pressure be kept lower than 130 mmHg in patients with a history of hypertension (Broderick et al. 1997). If the hemorrhage results from the use of anticoagulants, such as Coumadin or Heparin, these medications are discontinued immediately. Protamine and vitamin K may be given to reduce bleeding in patients with anticoagulant-induced bleeding.
In patients with ruptured aneurysms, surgical intervention is the method of treatment and includes placing a clip across the aneurysm or embolization if the damaged area is difficult to approach. During embolization, a wire-packed catheter is threaded through the blood vessels until it reaches the damaged area; the wires are then detached so that they form coils that attract blood cells to promote clot formation. Patients with ICH may benefit from a surgical evacuation of the hematoma. Surgical intervention is contraindicated in patients who are 75 years old or older, who have significant pre-existing disease, or who arrive at the hospital in very poor condition.
Innovative Drug Strategies
Hydergine
Hydergine, an antioxidant medication that helps to protect brain cells, may be beneficial for the treatment of hemorrhagic shock. In Europe , Hydergine is administered on an acute-care basis for the prevention of brain damage following stroke. The recommended dosage of Hydergine in an acute situation is 10 mg administered sublingually and 10 mg given orally. Because the FDA has not approved Hydergine for use in the treatment of stroke, emergency room physicians may not be willing to administer this medication. Patients or their surrogates can, however, request that this medication be used. Hydergine has been approved in the treatment of other diseases, so it is available through the hospital pharmacy.
Piracetam
Piracetam, a nootropic medication similar to pyroglutamate (an amino acid), may be useful in the treatment of hemorrhagic stroke. Piracetam appears to protect brain cells from injury and death during stroke, thereby lessening the potential for permanent neurological damage. The recommended dosage for piracetam is 4800 mg a day taken orally. A Belgian study indicated that piracetam may be very beneficial if administered within 7 hours after the onset of stroke (De Deyn et al. 1997). Piracetam is not currently available in the United States .
Any disruption of blood flow to the brain causes massive free radical damage that induces much of the reperfusion injury to brain cells characteristic of stroke. When blood flow is interrupted and subsequently restored (reperfused), tissues release iron that provides a catalyst for the formation of free radicals that often permanently damage brain cells. The Life Extension Foundation has spent millions of dollars conducting research that involves developing methods of protecting the brain cells from injury caused by blood flow disruption. The use of antioxidant nutrients, drugs, and hormones, along with specific calcium-channel blockers and cell membrane-stabilizing agents, provide enormous protection to brain cells.
To learn more about therapies that may restore neurological function following hemorrhagic stroke, refer to the Foundation's protocol for Age-Associated Mental Impairment.
Supplements
CDP-Choline
CDP-choline (citicholine) is a unique form of choline that readily passes through the blood-brain barrier directly into the brain. Choline is essential for proper brain and neuron function. It is used to make acetylcholine, one of the major neurotransmitters. Choline also aids the movement of fats in and out of cells. Brain tissue is composed almost entirely of fats.
An article in the journal Stroke described a study of citicholine sodium (cytidine-5'-diphosphocholine) in an experimental model of ICH using Swiss albino mice. Treatment with citi choline significantly improved neurological functional outcome and reduced the volume of ischemic injury surrounding the hematoma (Clark et al. 1998).
CDP-Choline has been approved in Europe and Japan to treat stroke, head injuries, and other neurological impairments. Its effectiveness in treating stroke has not been substantiated in more recent clinical trials, so CDP should be considered an adjuvant therapy at best.
Vitamin C
Vitamin C is well known for its health benefits. Humans, unfortunately, are not able to produce ascorbic acid. We therefore rely upon dietary sources. Pauling earned his second Nobel Prize by proposing that vitamin C deficiency was a major cause of atherosclerosis and cardiovascular disease.
A study in the journal Stroke measured the levels of vitamin C in 13 patients with intracranial hemorrhage and 15 patients with head trauma. Compared with 40 healthy controls, ascorbic acid (vitamin C) levels were significantly lower and inversely correlated with the severity of neurologic impairment (Polidori et al. 2001).
An article in the journal Stroke described a 20-year study in Japan that examined vitamin C levels and the risk of stroke (Yokoyama et al. 2000). High concentrations of vitamin C strongly predicted lower risks of cerebral infarction and hemorrhagic stroke. Those who had a dietary intake of vegetables 6-7 times per week had half the sex- and age-adjusted risks of all stroke and cerebral infarction than those consuming vegetables 0-2 times a week. The authors noted that the effects of vitamin C on stroke could not be explained by the antioxidant theory alone because an inverse association of serum vitamin C concentration was observed not only with cerebral infarction, but also with hemorrhagic stroke. The authors proposed several mechanisms by which vitamin C may protect against stroke:
- Vitamin C levels are inversely correlated with blood pressure. High blood pressure is a well known risk factor for stroke.
- Ascorbic acid promotes endothelial prostacyclin which decreases vascular tone and inhibits platelet aggregation (Srivastava 1985; Toivanen 1987; Lefer 1990).
- Oxidized LDL-induced increases in leukocyte-platelet aggregation may be prevented by ascorbic acid (Lehr et al. 1995).
Those at risk of a stroke or victims recovering from stroke may have increased demands for vitamin C. High amounts of vitamin C should not be acutely administered during the period when one is actually having a stroke. This recommendation is based on Life Extension Foundation-sponsored research indicating that during an acute ischemic event to the brain, too much vitamin C may promote iron-induced oxidative stress. This type of oxidative stress does not occur during periods of normal blood flow when other antioxidants (such as tocopherols) are available to balance the catalyzing effects of vitamin C, and iron is not being abnormally released from the tissues due to re-perfusion injury.
Whenever vitamin C supplements are used, it is important to consume antioxidants such as alpha-lipoic acid, the tocopherols-tocotrienols, and N-acetyl-L-cysteine to protect the vitamin C itself from turning into an oxidizing agent. |