Health Salon

Diagnosis, Treatment, and Prevention Overview - from Life Extension Foundation

Many people are familiar with the dramatic portrayal of strokes in movies. While strokes are clearly a medical emergency, most strokes are far less dramatic. In fact, the symptoms of most strokes are so mild that they are often dismissed as unimportant. The critical time for strokes is immediately after they occur.

The symptoms of thrombotic strokes include nausea and dizziness; sudden, severe headaches; weakness, numbness; paralysis, particularly to one side of the body; partial or total loss of sight in one eye.
Diagnostic procedures for thrombotic strokes include ultrasound, CT scan, and MRI.

Treatment of thrombotic strokes consists of medication, natural supplements, and surgical interventions, based on the underlying cause. Controlling hypertension is essential prevention in the occurrence of ischemic strokes.

Silent strokes commonly occur after thrombotic strokes and may cause damage weeks or months after the initial stroke.
Ischemic stroke is a medical emergency. Time to treatment of this brain attack is important, concerning what is done once in the emergency room.

Tissue plasminogen activator is of great importance immediately after a stroke has occurred to help dissolve blood clots before they thrombose.
Heparin is sometimes used in critical care settings and should be requested by stroke victims.
Warfarin is the drug of choice to prevent strokes. Unfortunately, warfarin has a large number of contraindications and drug interactions with many commonly used medications.
Low-dose aspirin is widely recommended to help thin the blood and prevent strokes. One 81-mg tablet of aspirin a day with a heavy meal is recommended for its anticlotting and anti-inflammatory effects.
Ticlopidine may be recommended as a substitute for aspirin.
Mevacor, a statin drug (HMG-reductase inhibitor), is being investigated for use in reducing the risk of stroke, primarily because of its effect on cholesterol.
The following drug strategies should be considered in stroke prevention, treatment, and rehabilitation.

Hydergine, an antioxidant medication that protects brain cells, may be given in an acute situation. The recommended dosage is 10 mg given sublingually and 10 mg administered orally. Because the FDA has not approved Hydergine for this purpose, the patient or patient’s advocate should request that the medication be given.
Piracetam, a nootropic medication, may be useful in the prevention of thrombotic strokes because it appears to protect brain cells from injury during the stroke event. The recommended dosage for piracetam is 4800 mg a day, administered orally.
Nimodipine is a prescription medication that dramatically increases cerebral blood flow by acting as a calcium channel blocker. Nimodipine may be of clinical benefit in acute stroke. The recommended dose is 30 mg 3 times a day, although up to 60 mg 4 times a day have been used in studies.
Aminoguanidine, a medication that prevents glycosylation of proteins and helps prevent mental decline in the elderly, may be useful in preventing thrombotic strokes. The recommended dose is 300 mg once a day with food. This dose should not be exceeded.
An aggressive program for stroke prevention begins by addressing the known risk factors for stroke. The risk factors for ischemic strokes are hypertension, arteriosclerosis, and blood that has a propensity to clot abnormally inside vessels. Blood components that increase the risk of abnormal arterial clotting include elevated levels of LDL cholesterol, homocysteine, C-reactive protein, and/or fibrinogen. Drug and alcohol abuse, age, gender, and race are also factors.

Conventional medicine often recommends several drugs to cover some of these risk factors, including antihypertensives, cholesterol-lowering drugs (statins), and anticoagulants, such as Coumadin and aspirin. Each of these drugs has side effects and may interact with each other, particularly with Coumadin. Bleeding is of primary concern with anticoagulant therapy as it dramatically increases the risk of hemorrhagic stroke.

Natural supplements can be used as an adjunct to conventional drugs. Proper testing is required to monitor the effectiveness of both drug and nutritional supplement programs. Recommended blood tests include total cholesterol, HDL, LDL, triglycerides, glucose, prothrombin time, homocysteine, C-reactive protein, fibrinogen, and template bleeding time. Further, the Life Extension Foundation highly recommends using optimal levels, instead of the standard reference ranges, for these laboratory tests. The primary objective of using the following nutrients is to help restore function to injured brain cells.

CDP-Choline has been shown to be effective and is currently in clinical trials in the United States for treating strokes. CDP - Choline Caps contain 250 mg of pharma c t eutical grade cytidine-5′-diphosphocholine. One capsule a day is recommended for healthy people over the age of 40. Those with neurological impairment should take two capsules daily under the care of a physician.
Ginkgo biloba has been shown to be very effective as an antioxidant and in treating cerebral vascular deficiency, including stroke. Super Ginkgo Extract contains 120 mg of standardized ginkgo leaf powder. One capsule daily is recommended. Use ginkgo with caution when taking anticoagulants.
Essential fatty acids, including alpha-linolenic acid ( ALA ) and docosahexaenoic acid (DHA) from fish oils are recommended. Essential fatty acids are necessary to control inflammation leading to elevated levels of C-reactive protein and to lower fibrinogen levels. Super GLA/DHA provides high potency anti-inflammatory fatty acids. Six 1000-mg capsules a day are recommended. Perilla oil provides high potencies of precursors to EPA and DHA. Six 1000-mg capsules a day are recommended.
Vitamin C is recommended as a daily supplement for healthy people and may also be of benefit in stroke; 1000-4000 mg of high-quality vitamin C may be taken daily. Vitamin C should be taken with cofactor lysine for maximum benefit.
Vitamin E is an antioxidant and blood-thinner. The recommended dose for most people is 400-500 IU of alpha tocopherol, 200 mg of gamma tocop o herol, and at least 50 mg of the tocotrienols. Vitamin E should be used with caution with warfarin because it thins the blood.
Alpha-lipoic acid may also be considered. Super Alpha Lipoic Acid with Biotin contains 250 mg of pharmaceutical-grade alpha-lipoic acid and 3000 mcg of biotin. One to two capsules daily are suggested for healthy people. Up to 4 capsules can be taken for therapeutic effect. Alpha-lipoic acid should be taken with vitamin B12 because it may cause a worsening of symptoms in those with a vitamin B12 deficiency.
Minerals, including calcium, magnesium, potassium, and selenium should be considered based on the results of serum electrolytes (although serum levels may not represent mineral stores in the body). Thiazide and loop diuretics deplete potassium and coffee increases excretion. Magnesium is needed for the absorption of potassium.
The Mineral Formula for Men contains four different forms of magnesium, two forms of calcium, potassium, and manganese. One to four capsules daily are recommended as a booster to the minerals contained in the Life Extension Mix.
The Mineral Formula for Women contains more calcium, which reflects the greater need by women. One to four capsules daily are recommended as a booster to the minerals contained in the Life Extension Mix.
Calcium and magnesium are available separately in several forms, including calcium citrate with vitamin D3, calcium carbonate powder, calcium/magnesium powder, magnesium, magnesium citrate, and magnesium oxide powder.

Super Selenium Complex contains three different forms of selenium in capsule form. One capsule per day is recommended. Selenium drops are also available. One to five drops are suggested daily. Lower doses of selenium are recommended when taking Life Extension Mix.

Vitamin B6, vitamin B12, folic acid, and trimethylglycine should be considered if homocysteine levels are elevated (see the Cardiovascular Disease protocol for more information).
TMG t T ablets contain 500 mg of trimethylglycine. One to five tablets are recommended daily for healthy people. Up to 12 tablets can be taken daily if high levels of homocysteine persist.
Vitamin B6 may be taken at doses up to 800 mg daily to reduce homocysteine levels though high doses of 100-250 mg daily are usually adequate.
Vitamin B12, 300-1500 mcg daily.
Folic acid, 800 mcg daily.

Elevated fibrinogen leads to the formation of blood clots. Many of the recommended supplements to control homocysteine and lower cholesterol levels will work synergistically in keeping fibrinogen levels in the normal range. The following supplements may also be considered:
Green tea extract, 350 mg daily.
Vitamin A, 20,000 IU in a liquid base.
Beta carotene, one 25,000-IU softgel daily.
Bromelain, one 500-mg tablet at the beginning of each meal.
Niacin, 1500-3000 mg daily. Niacin should be monitored to avoid liver toxicity at doses above 1000 mg daily. Flush-free niacin may be taken to avoid the red face and flushing sensation of regular niacin.
SAMe may be considered, particularly if there is related depression. SAMe tablets contain 200 or 400 mg of pharmaceutical-grade S-adenosyl-methionine. The recommended total daily dose is 400-1600 mg. SAMe is best taken without food, unless GI upset occurs.
Policosanol has been shown to have a dramatic effect on lowering cholesterol, reducing platelet aggreg r ation and decreasing the size of experimentally induced thrombus. Policosanol tabs contain 10 mg of policosanol. The ideal cholesterol range is between 180-200 mg/dL. The average person uses 10 mg a day to achieve optimal cholesterol levels. Some people may only need 5 mg a day, while others may require 20 mg a day. Cholesterol levels should be monitored regularly because levels below 150 may be dangerous.
Garlic extract, 1000-6000 mg daily, may help lower cholesterol levels. (See the Cardiovascular Disease protocol for more information.) Garlic is available in two effective forms. One is the aged garlic extract under the Kyolic brand name. Use the formula that provides 1000 mg of Kyolic odorless garlic in each caplet. Pure-Gar Caps provide a high-allicin garlic that is not odor-free (900 mg garlic powder), and Pure-Gar with EDTA (a chelating agent).
Melatonin readily crosses the blood-brain barrier and may help protect against further free radical-induced brain cell injury. Melatonin is to be taken before bed as a sleep-enhancer, 300 mcg-10 mg nightly is recommended.
Hormones play a clear role in neuronal functioning and repair. Blood testing is recommended for all people over 40 to determine hormonal deficiencies.
Pregnenolone is synthesized from cholesterol. It acts as a memory enhancer and converts to progesterone and DHEA. One 50-mg capsule, 1-4 times daily.
DHEA improves brain cell activity and suppresses overproduction of the adrenal hormone, cortisol. The usual dose for men is 50 mg daily. For women the usual dose is 15-25 mg early in the day. See the DHEA Replacement protocol for additional information and warnings.
Testosterone and estrogen replacement are determined by blood testing. These hormones must be prescribed by a physician.
Arginine, vitamin B2, vitamin B3, and folic acid may be considered as a way to naturally increase nitric oxide synthesis. L-Arginine c C aps contain 900 mg of pure L-Arginine HCl. Arginine should be used with caution in diabetics and those with psychosis.
Carnosine may be useful in protecting the brain from neurological damage. Super Carnosine contains 500 mg of pure carnosine. One capsule 2-3 times a day is recommended.

Vinpocetine has been shown to have a positive effect on brain metabolism and to protect against excitotoxicity and may be of benefit in stroke recovery. Take 10 mg 3 times daily. For additional protection against excitotoxicity, consider a sublingual vitamin B12 lozenge called methylcobalamin in the dose of 5-40 mg a day.

Theanine, an amino acid found in green tea, produces a tranquilizing effect on the brain by increasing production of GABA, an inhibitory neurotransmitter. Theanine may also prevent ischemic damage to neurons. Up to four 100-mg capsules can be taken daily.
Dietary measures to lower stroke risk include high amounts of fresh fruits and vegetables every day and several servings of fish a week.
To learn about therapies that may protect arteries prior to a thrombotic stroke, or to reduce the risk of further disease or stroke attacks, refer to the protocols on Cardiovascular Disease and Thrombosis Prevention. To learn more about therapies that may restore neurological function following thrombotic stroke, refer to the protocol for Age-Associated Mental Impairment.

Hemorrhagic Stroke

For those who have experienced a hemorrhagic stroke or who have a cerebral vascular disease, such as cerebral aneurysm, it is suggested that nutrients that help build collagen and elastin be taken to help rebuild the endothelial lining of the cardiovascular arterial system. Nutrient supplements have also been reported to help reduce the risk of or damage caused by aneurysm or hemorrhage.

Of all patients diagnosed with an aneurysm or cerebral hemorrhage, 50% have hypertension. Cerebral atherosclerosis is also an underlying risk factor for cerebral vascular disease.

Although hemorrhagic strokes account for only 15% of all strokes, hemorrhagic strokes have a much higher mortality rate. There are two subcategories of hemorrhagic stroke: intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Although ICH and SAH are very similar, they generally result from different causes.

Intracerebral Hemorrhage (ICH)
ICH is defined as the rupturing of cranial blood vessels, resulting in the leakage of blood into brain tissues. Symptoms of ICH include:

Partial or total loss of consciousness
Vomiting or severe nausea
Weakness, numbness, or paralysis, especially on one side of the body
Sudden, severe headache
Severe vertigo (unable to walk or stand)
If these symptoms occur, it is essential to receive immediate medical attention.

ICH rarely occurs in people under the age of 45; however, the risk for developing ICH doubles every 10 years thereafter. ICH accounts for 11% of stroke deaths. ICH occurs more frequently in men, and African-Americans are more likely to be affected than are Caucasians.

Risk Factors
Risk factors for intracranial hemorrhage include:

Untreated hypertension, 50%
Amyloid angiopathy, 17%
Anticoagulation treatment (Warfarin), 10%
Brain tumors, 5-10%
Smoking, 5%
Drug abuse, especially crack cocaine and amphetamines, 5%. (This is the most common cause of ICH for people in their 20s and 30s.)
The most common risk factor for ICH is chronic hypertension. Hypertension causes arteries and arterioles to become weakened, resulting in leakage. A Chinese study noted that there was considerable increased risk for ICH in hypertensive patients who did not regularly take their medications (Hsiang et al. 1996).

Anticoagulants, such as Coumadin or Heparin, are prescribed for a variety of conditions, including ischemic stroke, myocardial infarction, and deep vein thrombosis. Proper monitoring of these medications is essential because they increase the risk of ICH.

Aspirin has also been shown to increase the risk of ICH in elderly patients (Wong et al. 2000). An article in the journal Stroke identified epistaxis (nosebleed) as a risk factor for ICH in middle-aged and elderly people, both independently and combined with the use of aspirin. The authors proposed that nosebleeds may be a warning sign for increased risk of ICH in people using aspirin (Saloheimo et al. 2001).

Hepatitis C virus infection has been identified as a risk factor for ICH. ICH patients with hepatitis C infections were also found to have lower cholesterol levels, lower platelet counts, and longer prothrombin times than ICH patients without hepatitis C, although most of the values were within normal range (Karibe et al. 2001).

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.

Strengthening Cerebral Vasculature
The skin of thick-skinned berries such as cherries and grapes, the seeds of grapes, and the skin, leaf, and flower of the Hawthorne tree are all naturally rich sources of a potent antioxidant called oligomeric proanthocyan a i dins (OPC). These naturally occurring antioxidant flavonoids are tissue specific for strengthening the walls of arteries and thereby reducing the risk of recurring aneurysms and hemorrhagic strokes. In addition to antioxidant protection, OPCs also support collagen and help maintain elastin throughout the entire body. These two critical proteins are major components of all our connective tissues and organs. They are responsible for maintaining structural integrity as well as the elasticity of all the tissues throughout your body. This includes joints, blood vessels, skin, ligaments, tendons, muscles, and even the heart.

By maintaining healthy levels of structural collagen and elastin, our bodies are able to continue to function more efficiently and maintain their youthful strength and flexibility longer. OPCs attach to “reactive sites” on collagen molecules and protect them from free radical attack. This is one of the reasons they are so protective and so valuable for the circulatory system (Laperra et al. 1977; Thebaut et al. 1985; Blazso et al. 1997; Rohdewald 1998; Packer et al. 1999). As noted earlier, oligomeric proanthocyan i a dins are found in grape seeds, Hawthorne tree skin, leaf, and flowers, thick-skinned berries, and the inner rind of citrus fruit.

Conclusion
Hemorrhagic stroke is a medical emergency. The two types of hemorrhages involved are ICH and SAH.

The primary risk factor for ICH is hypertension, because chronic hypertension weakens blood vessels. Other risk factors include drug and alcohol abuse, anticoagulant medications, age, gender, and race.
The underlying cause for SAH is cerebral aneurysm (an abnormal dilation of a blood vessel in the brain). Risk factors for SAH include family history of aneurysm, age, gender, and race.
Symptoms for both types of hemorrhagic stroke are similar and include sudden onset of severe headache, loss of consciousness, nausea and vomiting, and partial or total paralysis. Diagnosis of the underlying cause of hemorrhagic stroke is by CT scan, MRI, and angiography. Surgical evacuation of the hematoma may be necessary. For SAH, treatment includes clipping or embolization of the aneurysm.

The medications Hydergine and piracetam may be beneficial to patients with hemorrhagic shock. The FDA has not approved Hydergine for the treatment of stroke, but it should be available through the hospital pharmacy, and patients or their surrogates should request its use. Piracetam may be beneficial in preventing permanent neurological damage following stroke. Piracetam is not currently available in the United States .

There is little research on natural supplements for hemorrhagic stroke. CDP-Choline and vitamin C may be of some benefit in facilitating recovery and preventing future strokes. Supplements like vinpocetine and phosphatidylserine that enhance neuronal energy metabolism could also help in the rehabilitation process. See the section on Cerebral Aneurysm for recommendations on maintaining healthy blood vessels.

The symptoms of intracerebral hemorrhage (ICH) include nausea and vomiting; sudden, severe headache; weakness; numbness; paralysis, particularly to one side of the body; and partial or total loss of consciousness. The symptoms of subarachnoid hemorrhage (SAH) include sudden, severe headache; nausea and vomiting; stiff neck; light intolerance; and partial or total loss of consciousness.
Diagnostic procedures for hemorrhagic stroke include CT scan, MRI, and cerebral angiogram. Treatment of hemorrhagic stroke consists of medication and surgical interventions, based on the underlying cause of the hemorrhage:
For intracranial hemorrhage resulting from uncontrolled hypertension, the initial treatment is blood pressure control (see the Cardiovascular Disease protocol for more information about natural blood-pressure lowering supplements and the Hypertension protocol ).
Persons taking anticoagulants (Coumadin and aspirin) should exercise extreme care to prevent ICH. If signs of major hemorrhage are present, these medications should be immediately discontinued. For more information about Coumadin and natural blood-thinners, see the Thrombosis Prevention protocol and the Thrombotic Stroke section.
Smoking should be discontinued for those at risk of ICH. The detrimental effects of smoking on the cardiovascular system are well known.
Amyloidosis can be due to several diseases, including multiple myeloma (amyloid light chains) and Alzheimer’s disease (beta-amyloid). The Alzheimer’s Disease protocol contains information on several natural supplements that reduce beta-amyloid deposition.
Hydergine, an antioxidant medication that protects brain cells, may be given in an acute situation. The recommended dosage is 10 mg given sublingually and 10 mg administered orally. Because the FDA has not approved Hydergine for this purpose, the patient or patient’s advocate should request that the medication be given.
Piracetam, a nootropic medication, may be useful in the prevention of hemorrhagic stroke because it appears to protect brain cells from injury during the stroke event. The recommended dosage for piracetam is 4800 mg a day, administered orally.
CDP-choline may be useful in both preventing and reducing the neurological damage following hemorrhagic stroke. CDP-Choline Caps contain 250 mg of pharmaceutical grade cytidine-5′-diphosphocholine. One capsule a day is recommended for healthy people over the age of 40. Those with neurological impairment should take 2 capsules daily.
Vitamin C has been shown to both lower the risk of hemorrhagic stroke and reduce the neurological damage following hemorrhagic stroke. An appropriate dosage of vitamin C depends on the dietary intake. A prophylactic dose of 2.5-6 grams daily is recommended. Up to 15 grams a day may be taken therapeutically. Large doses should be consumed with meals. Do not take high doses of vitamin C during an acute stroke.
For further protection from free-radical induced brain injury, consider taking 300 mcg-10 mg of melatonin (at night) and 100-200 mg of palm-oil derived tocotrienols (vitamin E) a day.
Cerebral Aneurysm

Cerebral artery aneurysm, one of the cerebral vascular diseases, can be fatal. An aneurysm is a weakened portion of the heart or a blood vessel, usually an artery, that fills up with blood under pressure, causing it to balloon outward. Aneurysm can be caused by a hereditary weakness in the vessel wall, high blood pressure, atherosclerosis, direct injury, infection, and other diseases.

Approximately 30,000 people a year in the United States experience an aneurysm rupture, causing cerebral hemorrhage. It has been estimated that if five people were to experience a cerebral hemorrhage today, in 1 year: only one of those people would be alive and well; one would be disabled; and the other three would be dead.

Cerebral vascular hemorrhage may also produce delayed problems such as hydrocephalus (”fluid on the brain”) and narrowing of the blood vessels because of the irritation of the blood on the blood vessels (known as vasospasm). Rebleeding, hydrocephalus, and vasospasm can happen days to weeks after the initial bleed. Aneurysms can and do grow. If they reach a certain size, usually more than 25 mm (1 inch), they may start applying pressure on the surrounding brain tissue and cause additional problems.

Cerebral aneurysm is very uncommon in patients under 20 years of age and is increasingly common in older patients. In people over 65, cerebral aneurysm may be found in as high as 5% of the population. It appears cerebral aneurysm is related to an absence of a muscular layer that makes up part of the blood vessels; over time, it stretches and thins and creates the aneurysm. Smoking appears to markedly increase the chance that one will develop a cerebral aneurysm.

Indications of the presence of an aneurysm depend on the location of the aneurysm. Aneurysm generally exhibits few symptoms and is discovered by accident on x-ray films or imaging scans performed for some other reason.

The rupture or hemorrhage of an aneurysm usually produces severe pain. The location of the aneurysm usually determines the amount of bleeding, shock, loss of consciousness, or if death will occur. In some cases, the aneurysm may leak blood, causing warning pain without the rapid deterioration and damage characteristic of a rupture. The threat of aneurysm goes beyond the immediate site damage it can cause. Blood clots often form in an aneurysm, creating danger of embolisms and clotting in distant organs or vessels.

Cerebral hemorrhagic problems occur when an aneurysm ruptures, causing internal bleeding. For example, aneurysm affecting the arteries supplying the brain can occur at any age, but occurs most often in people 60 years of age with a history of hypertension. The aneurysm may rupture, causing hemorrhage and blood leakage into the membrane surrounding the brain. A cerebral artery aneurysm is particularly important because it can lead to fatal subarachnoid hemorrhage which occurs underneath one of the layers of tissue lining the brain. This aneurysm frequently occurs from inherited vascular defects at the branch points of cerebral arteries.

If your physician suspects an aneurysm or the possibility of hemorrhage, he or she will probably recommend ultrasound testing, computed tomography scanning (CT scan), magnetic resonance imaging (MRI), or angiography of the area to determine the size and severity and to predict the possibility of rupture and subsequent hemorrhage.

Conventional Treatment
If an aneurysm is large and the risk of rupture is significant, surgery may be necessary.

When an aneurysm ruptures, emergency surgery is necessary to stop the bleeding. Surgical intervention into cerebral aneurysm or hemorrhage may be difficult or impossible because of the constraints of access to the damaged or threatened areas of the brain.

Hypertensive drugs may also be prescribed in an attempt to lower blood pressure and reduce the chances of additional aneurysm or cerebral hemorrhage (see the Cardiovascular Disease protocol for more information on natural ways to reduce blood pressure).

Integrated or Alternative Therapies
Researchers speculated in a 1998 issue of Life Sciences Journal that “an acute systemic oxidative stress condition might influence the rupture of intracranial aneurysm.” Vitamin E was specifically identified by investigators to act as an antioxidant by scavenging free radicals and thus reducing the conditions that precipitate these cerebral vascular ruptures (Marzatico et al. 1998). We recommend taking 400-800 IU of vitamin E daily to reduce the risk of aneurysm ruptures. Vitamin C at 2000-5000 mg a day is suggested, along with 300 mg a day of the flavonoid proanthocyan i a din (from grape seed or pine bark) for further protection against underlying factors that cause cerebral vascular disease.

Magnesium is crucial for arterial structure, and it is suggested that 1500 mg a day of elemental magnesium be taken along with 1000 mg a day of calcium and 500 mg a day of potassium.

Mechanisms that regulate cerebral circulation have been intensively investigated in recent years, and this research is increasingly focused on the effects of nitric oxide. Nitric oxide is an important regulator of cerebral vascular tone. Nitric oxide maintains the cerebral vasculature in a dilated state. Arginine, a natural supplement, specifically enhances nitric oxide synthesis. Persons with cerebral vascular disease may consider taking 4-5 grams of arginine 3 times a day to better maintain the health of vessels.

Activation of potassium channels appears to be a major mechanism for dilatation of cerebral arteries. Agents that increase the intracellular concentration of cyclic adenosine monophosphate (cAMP) produce vasodilatation. Supplementation with 500 mg a day of potassium and 5-20 mg a day of Hydergine may enhance vasodilatation in cerebral vascular disease, helping to restore vessels to a healthier state.

Additionally, alcohol consumption poses a risk for development of hypertension (high blood pressure), strokes, and sudden death through the depletion of magnesium from the body. The dietary intake of magnesium modulates the hypertensive actions of alcohol (Altura et al. 1999). Experiments indicate that chronic ethanol ingestion results in the contraction of the cerebral arteries and capillaries, a contraction that causes increased cerebral vascular resistance. Chronic ethanol ingestion increases the reactivity of intact microvessels to vasoconstrictors and results in decreased reactivity to vasodilators. However, pretreatment of animals with magnesium prevents ethanol from inducing a stroke and prevents the adverse cerebral vascular changes from taking place. Magnesium influences the response of cerebral arteries to several other natural or synthetic stimulators (agonists) and has been shown to decrease cerebral vascular resistance. Contractility of cerebral arteries is dependent upon the actions and interactions of calcium and magnesium (Altura et al. 1994).

It is clear from published studies that magnesium can induce healthy vascular tone in all types of vascular smooth muscle. Magnesium appears to act on voltage-, receptor-, and leak-operated membrane channels in vascular smooth muscle. Standard channel blocker drugs do not have this uniform capability. Calcium channel-blocking drugs, however, can block calcium infiltration into brain cells, lower cerebral vascular resistance, relieve cerebral vasospasm, and lower arterial blood pressure.

Magnesium can also cause significant vasodilatation of intact cerebral arteries. Although magnesium is three to five orders of magnitude less potent than the standard calcium channel-blocking drugs, it possesses unique and potentially useful effects in maintaining healthy cerebral vascular circulation. Those with cerebral vascular disease, and especially those who consume alcohol, should take 1500 mg a day of elemental magnesium.

Nimotop (nimodipine) is an FDA-approved calcium channel-blocking drug specific to cerebral circulation and brain-cell activity. It has been shown to work better in the restoration of cerebral circulation than any other calcium channel-blocking drug yet tested. The normal dose is 30 mg of Nimotop taken 3 times a day.

Medical Device Advances the
Treatment of an Aneurysm
By using the device known as the Guglielmi coil, physicians can now correct an aneurysm that is not approachable surgically, either because of its position in the brain or because of other factors that present a high risk.

The coil is an extremely fine wire made from platinum–one of the softest metals–at the end of a longer stainless steel wire. Several coils, depending on the size of the aneurysm, are inserted inside the bubble-like aneurysm through a catheter (a long, narrow tube) threaded through the patient’s blood vessels. When the coil is in the correct position–verified by a blood vessel X-ray called an angiogram–it is given a positive electrical charge. The charge causes the steel wire to dissolve at the point of a junction with the platinum coil and the positively charged coil attracts blood cells to form a clot within the aneurysm.

The coils and resulting blood clot fill up the aneurysm, essentially sealing it off. Eventually, the lining of the blood vessel grows over the “neck” of the aneurysm and the aneurysm is essentially healed.

Conclusion
Cerebral vascular disease can be life - threatening. Aneurysm and the subsequent rupture-causing hemorrhage are caused by inherited vascular defects and may be unavoidable. Aneurysm is often precipitated by atherosclerosis and hypertension. High blood pressure increases the risk of aneurysm. Reduction of high blood pressure is imperative in reducing the risk of cerebral vascular disease. Natural supplements combined with lowered blood pressure can reduce the risk and/or damage caused by cerebral vascular disease.

Refer to the Age-Associated Mental Impairment protocol for additional suggestions about restoring cerebral circulation. See the Cardiovascular Disease protocol and the Hypertension protocol for more information on hypertension, cholesterol reduction, and atherosclerosis.

The following nutrients and drugs should be considered:

To maintain cerebral vasculature, thus lowering the risk of a cerebral aneurysm or hemorrhagic stroke, the following supplements should be considered:
Magnesium, 1500 mg daily.
Arginine, 4-5 grams daily.
Calcium, 1000 mg daily.
Grape-seed skin extract, two 200-mg capsules daily.
To enhance vasodilation and improve the health of vessels, consider the following:
Potassium, 500 mg daily.
Hydergine, 5-20 mg daily. (Hydergine may be obtained by prescription or from offshore pharmacies.)
Antioxidants scavenge free radicals and protect against underlying factors that lead to cerebral vascular disease:
Vitamin E containing tocopherols and toco - trienols provide the most broad spectrum protection, 1-2 softgels daily of Gamma E Tocopherol/Tocotrienols. (Provides 210 mg of gamma - tocopherol and full spectrum tocotrienols.)
Vitamin C, 2000-5000 mg daily.
For more information

Contact the National Institute of Neurological Disorders and Stroke, (800) 352-9424.

Product availability

Vinpocetine, low-dose aspirin, CDP-Choline Caps, Policosanol Tabs, Super Ginkgo Extract, vitamin E succinate, Gamma E Tocopherol/Tocotrienols, Super GLA/DHA, Mega EPA, alpha lipoic acid, selenium, green tea extract, liquid emulsified vitamin A, beta carotene, No Flush Niacin, policosanol, pregnenolone, DHEA, Super Carnosine, L-theanine, Mineral Formula for Men, Mineral Formula for Women, magnesium, calcium, arginine, potassium, vitamin C, grape seed-skin extract, TMG, vitamin B6, Methylcobalamin (B12 sublingual tablets), vitamin B12 powder, folic acid + B12, melatonin, Kyolic Garlic, and Pure-Gar Caps can be ordered by calling (800) 544-4440 or by ordering online. You may also ask for a list of offshore suppliers of Hydergine, Piracetam, and Aminoguanidine. Coumadin is a prescription medication.

Disclaimer

This information (and any accompanying printed material) is not intended to replace the attention or advice of a physician or other health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a qualified health care professional.

The information published in the protocols is only as current as the day the book was sent to the printer. This protocol raises many issues that are subject to change as new data emerge. None of our suggested treatment regimens can guarantee a cure for these diseases.
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