Hyperthyroidism

Treatment for Hyperthyroidism

Hyperthyroidism develops when the body is exposed to excessive amounts of thyroid hormone. This disorder occurs in almost one percent of all Americans and affects women five to ten times more often than men. In its mildest form, hyperthyroidism may not cause recognizable symptoms. More often, however, the symptoms are discomforting, disabling, or even life-threatening.

WHAT ARE THE FEATURES OF HYPERTHYROIDISM?
When hyperthyroidism develops, a goiter (enlargement of the thyroid) is usually present and may be associated with some or many of the following features:
• Fast heart rate, often more than 100 beats per minute
• Becoming anxious, irritable, argumentative
• Trembling hands
• Weight loss, despite eating the same amount or even more than usual
• Intolerance of warm temperatures and increased likelihood to
perspire
• Loss of scalp hair
• Tendency of fingernails to separate from the nail bed
• Muscle weakness, especially of the upper arms and thighs
• Loose and frequent bowel movements
• Smooth skin
• Change in menstrual pattern
• Increased likelihood for miscarriage
• Prominent “stare” of the eyes
• Protrusion of the eyes, with or without double vision (in patients with Graves’ disease)
• Irregular heart rhythm, especially in patients older than 60 years of age
• Accelerated loss of calcium from bones, which increases the risk of osteoporosis and fractures

CAUSES
Graves’ disease
Graves’ disease (named after Irish physician Robert Graves) is an autoimmune disorder that frequently results in thyroid enlargement and hyperthyroidism. In some patients, swelling of the muscles and other tissues around the eyes may develop, causing eye prominence, discomfort or double vision. Like other autoimmune diseases, this condition tends to affect multiple family members. It is much more common in women than in men and tends to occur in younger patients.

Toxic multinodular goiter
Multiple nodules in the thyroid can produce excessive thyroid hormone, causing hyperthyroidism. Typically diagnosed in patients over the age of 50, this disorder is more likely to affect heart rhythm. In many cases, the person has had the goiter for many years before it becomes overactive.

Toxic nodule
A single nodule or lump in the thyroid can also produce more thyroid hormone than the body requires and lead to hyperthyroidism. This disorder is not familial.

Subacute thyroiditis
This condition may follow a viral infection and is characterized by painful thyroid gland enlargement and inflammation, which results in the release of large amounts of thyroid hormones into the blood.
Fortunately, this condition usually resolves spontaneously. The thyroid usually heals itself over several months, but often not before a temporary period of low thyroid hormone production (hypothyroidism) occurs.

Postpartum thyroiditis
Five to ten percent of women develop mild to moderate hyperthyroidism within several months of giving birth. Hyperthyroidism in this condition usually lasts for approximately one to two months.
It is often followed by several months of hypothyroidism, but most women will eventually recover normal thyroid function. In some cases, however, the thyroid gland does not heal, so the hypothyroidism becomes permanent and requires lifelong thyroid hormone replacement. This condition may occur again with subsequent pregnancies.

Silent thyroiditis
Transient (temporary) hyperthyroidism can be caused by silent thyroiditis, a condition which appears to be the same as postpartum thyroiditis but not related to pregnancy. It is not accompanied by a painful thyroid gland.

Excessive iodine ingestion
Various sources of high iodine concentrations, such as kelp tablets, some expectorants, amiodarone (Cordarone, Pacerone — a medication used to treat certain problems with heart rhythms) and x-ray dyes may occasionally cause hyperthyroidism in patients who are prone to it.

Overmedication with thyroid hormone
Patients who receive excessive thyroxine replacement treatment can develop hyperthyroidism. They should have their thyroid hormone dosage evaluated by a physician at least once each year and should NEVER give themselves “extra” doses.

DIAGNOSIS
Characteristic symptoms and physical signs of hyperthyroidism can be detected by a physician. In addition, tests can be used to confirm the diagnosis and to determine the cause.
TSH (thyroid – stimulating hormone or thyrotropin) test
A low TSH level in the blood is the most accurate indicator of hyperthyroidism. The body shuts off production of this pituitary hormone when the thyroid gland even slightly overproduces thyroid hormone.
If the TSH level is low, it is very important to also check thyroid hormone levels to confirm the diagnosis of hyperthyroidism.
Other tests
Estimates of free thyroxine and free triiodothyronine – the active thyroid hormones in the blood. When hyperthyroidism develops, free thyroxine and free triiodothyronine levels rise above previous values in that specific patient (although they may still fall within the normal range for the generalpopulation), and are often considerably elevated.
TSI (thyroid-stimulating immunoglobulin) – a substance often found in the blood when Graves’ disease is the cause of hyperthyroidism. This test is not routinely ordered since it does not usually affect treatment decisions or help in the diagnosis.
Radioactive iodine uptake (RAIU – a measurement of how much iodine the thyroid gland can collect) and thyroid scan (a thyroid scan shows how the iodine is distributed throughout the thyroid gland). This information can be useful in determining the cause of hyperthyroidism and ultimately its treatment.
Sometimes a general physician can diagnose and treat the cause of hyperthyroidism, but assistance is often needed from an endocrinologist, a physician who specializes in managing thyroid disease.

TREATMENT FOR HYPERTHYROIDISM
Before the development of current treatment options, the death rate from severe hyperthyroidism was as high as 50 percent. Now several effective treatments are available and, with proper management, death from hyperthyroidism is rare. Deciding which treatment is best depends on what caused the hyperthyroidism, its severity, and other conditions present. A physician who is experienced in the management of thyroid diseases can confidently diagnose the cause of hyperthyroidism and prescribe and manage the best treatment program for each patient.
Antithyroid drugs
In the United States, two drugs are available for treating hyperthyroidism: propylthiouracil (PTU) and methimazole (MMI). In general, AACE and the ATA recommend prescribing MMI over PTU. There are a few situations however where PTU should be used over MMI: during the first trimester of pregnancy to avoid an increased risk of a rare birth defect; if the patient is allergic to or intolerant of MMI; or when life-threatening thyrotoxicosis occurs. Some patients with hyperthyroidism caused by Graves’ disease experience a spontaneous or natural remission of hyperthyroidism after a 12- to 18-month course of treatment with these drugs, and may sometimes avoid permanent underactivity of the thyroid (hypothyroidism), which often occurs as a result of using the other methods of treating hyperthyroidism. Unfortunately, the remission is frequently only temporary, with the hyperthyroidism recurring after several months or years off medication and requiring additional treatment, so relatively few patients are treated solely with antithyroid medication in the United States.
Antithyroid drugs may cause an allergic reaction in about five percent of patients who use them. This usually occurs during the first six weeks of drug treatment. Such a reaction may include rash or hives; but after discontinuing use of the drug, the symptoms resolve within one to two weeks and there is no permanent damage. A more serious effect, but occurring in only about one in 250-500 patients during the first four to eight weeks of treatment, is a rapid decrease of white blood cells in the bloodstream. This could increase susceptibility to serious infection. Symptoms such as a sore throat, infection, or fever should be reported promptly to your physician, and a blood cell count should be done immediately. In nearly every case, when a person stops using the medication, the white blood cell count returns to normal.
Very rarely, antithyroid drugs may cause severe liver problems, which can be detected by blood tests or joint problems characterized by joint pain and/or swelling. Your physician should be contacted if there is yellowing of the skin (“jaundice”), fever, loss of appetite, or abdominal pain.
Radioactive iodine treatment
Iodine is an essential ingredient in the production of thyroid hormone. Each molecule of thyroid hormone contains either four (T4) or three (T3) molecules of iodine. Since most overactive thyroid glands are quite hungry for iodine, it was discovered in the 1940′s that the thyroid could be “tricked” into destroying itself by simply feeding it radioactive iodine. The radioactive iodine is given by mouth, usually in capsule form, and is quickly absorbed from the bowel. It then enters the thyroid cells from the bloodstream and gradually destroys them. Maximal benefit is usually noted within three to six months.
It is not possible to eliminate “just the right amount” of the diseased thyroid gland, since radioiodine eventually damages all thyroid cells. Therefore, most endocrinologists usually strive to completely destroy the diseased thyroid gland with a single dose of radioiodine. This results in the intentional development of an underactive thyroid state (hypothyroidism), which is easily, predictably and inexpensively corrected by lifelong daily use of oral thyroid hormone replacement therapy.
Although every effort is made to calculate the correct dose of radioiodine for each patient, not every treatment will successfully correct the hyperthyroidism, particularly if the goiter is quite large and a second dose of radioactive iodine is occasionally needed.
Thousands of patients have received radioiodine treatment, including former President of the United States George Bush and his wife, Barbara. The treatment appears to be a very safe, simple, and reliably effective one. Because of this, it is considered by most thyroid specialists in the United States to be the treatment of choice for hyperthyroidism cases caused by overproduction of thyroid hormone.
Radioactive iodine treatment should never be given to a pregnant woman! Small amounts of radioactive iodine will also be excreted in breast milk. Since radioiodine could permanently damage the infant’s thyroid, breast-feeding is not allowed. If radioiodine is inadvertently administered to a woman who is subsequently discovered to be pregnant, the advisability of terminating the pregnancy should be discussed with the patient’s obstetrician and endocrinologist. Therefore, prior to administering diagnostic or therapeutic radioiodine treatment, pregnancy testing is mandatory whenever pregnancy is possible.
Surgical removal of the thyroid
Although seldom used now as the preferred treatment for hyperthyroidism, operating to remove most of the thyroid gland may occasionally be recommended in certain situations, such as a pregnant woman with severe uncontrolled disease in whom radioiodine would not be safe for the baby. Surgery usually leads to permanent hypothyroidism and lifelong thyroid hormone replacement therapy.
Other treatments
A drug from the class of beta-adrenergic blocking agents (which decrease the effects of excess thyroid hormone) may be used temporarily to control hyperthyroid symptoms until other therapies take effect. In cases where hyperthyroidism is caused by thyroiditis or excessive ingestion of either iodine or thyroid hormone, this may be the only type of treatment required.
Appropriate management of hyperthyroidism requires careful evaluation and ongoing care by a physician experienced in the treatment of this complex condition.

he Ethics of Neural Prosthetics

A family of new medical devices designed to return sight to the blind, movement to the paralyzed, and hearing to the deaf are poised to enter the physician’s arsenal of weapons. Known collectively as neural prostheses, these implantable devices interact directly with the nervous system and allow for the amelioration of conditions that heretofore have been beyond the pale of medical ministrations.

Neural prostheses include retinal implants, auditory brainstem implants, functional electrical stimulation systems to activate paralyzed muscles, and brain-computer interface systems to enable locked-in patients to manipulate a computer via their thoughts. Cochlear implants, which have already returned hearing to thousands of deaf individuals, also fall into this category. Eventually, electrodes implanted in the brain – currently used for a brain-computer interface – could conceivably be used to enhance the memory, learning ability, concentration, and visual and auditory capabilities of able-bodied individuals as well.

Along with the potential to do great good, neural prostheses also present a minefield of ethical questions that must be dealt with as the technology approaches clinical utilization. Having learned from the missteps of some earlier medical researchers, it is now difficult, if not impossible, to find a neural prosthetic investigator who has not, to one extent or another, considered the ethical ramifications of his or her work. This fact became evident to me as I researched my recently released book about neural prostheses, Shattered Nerves: How Science Is Solving Modern Medicine’s Most Perplexing Problem.

Because many neural prosthetic devices are at or near the human testing stage, the ethical questions of most immediate concern revolve around determining when an implant is ready for human testing and how researchers can ensure that volunteers fully appreciate what they are getting into. As for when to test these implants in humans, physicians – who by nature and training are oriented toward taking quick action – are generally prone to come down on the side of  implanting sooner rather than later, whereas engineers tend to be a more cautious lot who favor waiting until every conceivable facet of animal testing is exhausted.

Indicative of the lack of census on this issue are the stances taken by Philip Troyk, a professor of bioengineering at the Illinois Institute of Technology in Chicago, who heads a visual cortex project, and Terry Hambrecht, a physician who is also an electrical engineer and the former head of the National Institutes of Health’s Neural Prosthesis Program. Hambrecht had experimentally implanted penetrating microelectrodes in the visual cortices of several humans following years of safety testing in monkeys. The work demonstrated that an individual who was totally blind could experience spots of light at precise locations in the visual field. Troyk, however, is not convinced that the brain will be able to create coherent images out of spots of light, and feels that before further human testing is conducted, his team needs to understand more about how the brain breaks the signals received from the million nerve fibers in the optic nerve into their constituent parts and then processes them to create vision.

“We feel we are obligated to try, to the best we scientifically can, to understand that we can manipulate the visual system at the fundamental level. Then we will have something to offer the human volunteer. . . . It’s a much more sophisticated argument than just saying, ‘Put it in, try it, and see what you get,’” said Troyk. Hambrecht takes exception. He feels that Troyk’s further experimentation in monkeys could “seriously delay the development of a visual prosthesis for blind humans. I feel that our NIH group’s human experimentation answered essentially all the significant questions that might have been asked in monkeys and raised pattern recognition, stimulation interaction, and cognitive adaptation questions that can only be answered with more sophisticated implants in blind humans,” he said.

When it comes to the related question of informed consent, however, there is universal acceptance of the need to ensure that potential test subjects are made fully aware of the risks involved and are not swayed by desperation. The numerous interviews I conducted with recipients of various neural prostheses indicate that investigators are doing a good job of informing volunteers of the pros and cons of their participation. All of the patients said they had been made fully aware of the fact that the devices they were receiving were experimental in nature and held little if any promise of benefiting them directly. While they obviously hoped to realize at least some improvement in their conditions, the patients had realistic views of the potential outcomes. In fact, I did not speak to one person who voiced regret over having volunteered to receive an implant, even though in some cases the benefit was small and in others there were setbacks. And surprisingly, none of them was greatly concerned about having an unproven foreign object implanted in their bodies.

While the physical risks of receiving experimental neural prosthetic implants are given careful scrutiny, academic discussions of informed consent tend to overlook the psychological impact of participation in test programs, which in the vast majority of cases is positive and substantial. Some test subjects draw considerable satisfaction from feeling that they are full-fledged members of the research teams developing their implants, a feeling that is reciprocated by the researchers themselves. The volunteers also derive satisfaction from knowing that they may be helping future generations of people with similar maladies. It seems to give their deprivations purpose. As Harold Churchey, an experimental retinal implant recipient blinded by retinitis pigmentosa, put it, “Even though I might be over the hill, if I can help some young person, I’m for it, so long as the good Lord gives me strength.”

As for the physical improvements realized by the volunteers, however small, it was uncanny that even though each of the patients I spoke with was interviewed individually, they virtually all used essentially the same language to describe their response, namely that “something is better than nothing.”

As Connie Schoeman who can now see small spots of light generated by the 16-electrode array that sits on her right retina told me, “With something like retinitis pigmentosa, where there has never been anything that could be done to help people, this is going to offer an opportunity, maybe not to get complete vision back, but something. And something, I tell you, sure beats nothing.” Ditto for Marilyn Davidson, who was the first person to be implanted with an auditory brainstem implant. The original device had to be removed due to complications, and though the hearing it afforded her was quite limited, she clamored for another system saying, “I had the ABI long enough to know it helped me, and anything is better than nothing.”

Then there is Jim Jatich, a quadriplegic who wears two hand manipulation implants, who asked, “How do you repay someone for giving you the use of your hands back?” And Jennifer French, paralyzed in a snowboarding accident yet able to walk down the aisle at her wedding with an experimental standing implant, who said, “There is nothing better than looking back at an empty wheelchair.”

The potential for neural prostheses to do good must be tempered with the understanding that the road to realization is pitted with potholes that remain to be negotiated. Yet the promise is stimulating indeed.



Read more: http://www.thehastingscenter.org/Bioethicsforum/Post.aspx?id=346&blogid=140#ixzz1IHbB2yh1

Arthritis-friendly home accommodations

Arthritis is a medical term used to describe a group of disorders that affect the joints and muscles in the human body. There are more than a hundred different forms of arthritis, each affecting one or more parts of the body. Rheumatoid arthritis and osteoarthritis are the most common types of this disease. Areas such as hands, elbows, feet, spine and knees fall prey to arthritis. What are the symptoms of arthritis? Inflammation, pain in joints, and inability to freely move the joints, are some of the most common symptoms of arthritis. Other (less common) symptoms include loss of appetite, weight loss, painful swelling and inflammation, fever and anemia.
Joint arthritis damages the cartilage, which is a fluid-like substance that holds a lubricant to facilitate movement. Being a form of chronic disease, arthritis stays with the patient for years. One must understand that arthritis is a complex degenerative disorder that can affect people at any stage of life. Anti-inflammatory drugs and other medications can provide temporary relief to patients. However, a healthy, disciplined lifestyle, which includes healthy food and regular exercise, can help arrest the development of arthritis.
Genetics, age and weight are some of the main causes of arthritis. For old people suffering with Rheumatoid arthritis or osteoarthritis, Arthritis-friendly home accommodations can provide the necessary facilities for treatment. These are not just old age-homes. These are special apartments for aged men and women suffering with acute arthritis. There are several Boston Apartments that have been specially designed for senior citizens suffering with arthritis.
Is there a natural cure for arthritis? The good news is that there are natural treatments and remedies that can control the growth of arthritis to a great extent. Low acid diet, for example, can provide immediate relief from joint pain. The Internet abounds in articles pertaining to arthritis, its symptoms, and various treatments.

For women with breast cancer

Breast cancer is a very important health problem in the United States and various other countries around the world. Breast cancer occupies second rank as the leading cause of cancer deaths among women in America. Until recently cancer of the breast topped the list of leading causes of cancer deaths in women, it still occupies an unenviable second position, second only to lung cancer. If skin cancer is excluded, cancer of the breast is the commonest cancer among women living in America. According to the WHO, more than 1.2 million women get the new diagnosis of breast cancer every year in the world. These numbers represent tremendous challenges posed by breast cancer within the United States of America and across the world.

Breast cancer claims the top position as the leading cause of deaths from cancer among women aged between 40 and 55 years. Breast cancer can occur in males too; with about 1450 new cases of male breast cancer diagnosed every year in the United States. It is comforting to note that the deaths from breast cancer among women of all ages have declined in US by 2.8 percent for every year from 1990 to 2000. The declining mortality rates may be attributed to the successful screening programs and progress in various therapy modalities of breast cancer.

Why is involvement of arteries and veins important in the treatment of pancreatic cancer?

The location of the pancreas deep within the abdomen places it close to numerous large blood vessels that are necessary for life (see “Where is the pancreas?” post).  As a result, cancers of the pancreas do not need to grow very large before invading these vessels and this poses a significant treatment problem. There are two main arteries in the area of the pancreas and these are called the celiac artery and the superior mesenteric artery. The celiac artery gives rise to the splenic artery and the hepatic artery and supplies blood to the liver, pancreas, spleen and stomach. The superior mesenteric artery gives rise to numerous branches that supply the small bowel, part of the colon and the pancreas. The venous system in this area is the portal vein and its tributaries. It drains blood from most of the gastrointestinal track back to the liver and ultimately to the heart through the hepatic veins. Pancreatic cancers that invade these major blood vessels are classified as Stage III which includes two subcategories – “border-line resectable” and “locally advanced, unresectable”.

Cancers that are found to completely surround one of the main arteries as determined by CT scan (“encasement”) are typically considered to not be operable (locally advanced, unresectable). An attempt at removal of such cancers has a very high probability of leaving a portion of the tumor behind (R2 resection) and thus the surgery will confer no survival benefit while potentially subjecting the person to debilitating side effects. Patients with locally advanced, unresectable pancreatic cancer will often undergo radiation and chemotherapy in hopes of shrinking the tumor away from the artery. Unfortunately, significant shrinkage of the tumor that converts it to removable occurs only 10% of the time. A tumor that grows next to one of the main arteries but does not surround it (“abutment”) is considered borderline resectable. In this case there is a good chance it can be removed without cutting though the tumor and, at worst, leaving only a few tumor cells behind (R1 resection). In most centers, including ours, patients with borderline resectable pancreatic cancer will receive radiation therapy prior to surgery in order to kill the cancer cells in the periphery of the tumor. This takes about 6 weeks and increases the likelihood of leaving no cancer behind at the margins (R0 resection). Unlike Stage III locally advanced pancreatic cancer, most patients with Stage III borderline resectable cancer will go on to have their tumor removed by surgery. The main exception to proceeding to surgery in borderline resectable patients is in the event the cancer grows further or develops distant metastases while receiving the chemotherapy and radiation therapy.

The assessment of whether or not a tumor is removable based on invasion of the main veins is very different than that of the arteries. Basically, any degree of involvement of the vein from abutment to encasement is considered to be borderline resectable as long as the tumor involves a portion of the vein that can be reconstructed once that section is removed. For example, if the tumor grows in the mid-portion of the vein (called the portal vein – superior mesenteric vein confluence), the tumor must be taken out with the vein attached and the two end of the vein can be reconnected to restore flow. If the same size tumor grows lower down on this vein (towards the feet), it will involve the portion of the vein that braches like numerous limbs of a tree. Removal of the vein in this area would leave the surgeon with one main “trunk” at the top and numerous “small braches” at the bottom. There would be no way to reconnect the ends. Thus for venous involvement, if it grows at a location in which the surgeon can technically remove the tumor and reconstruct the vein it is called Stage III borderline resectable. If removal and reconstruction is not possible it is called Stage III locally advanced. As described above for the arteries, patients with stage III cancers will most likely receive radiation therapy and most of those in the borderline resectable category will go on to surgery, while only 10% locally advanced will have significant tumor shrinkage.

There are numerous exceptions to this general algorithm based on feature that are unique to each individual patient. The complexity of the many treatment options underscores the need to be evaluated by an experienced team of specialists. We have found that this is best accomplished through a multidisciplinary clinic where patients are evaluated by all of the specialists in a single day. If you would like to learn more about this clinic please feel free to contact us at 410-933-PANC. We will be able to answer your questions and schedule a clinic appointment for you at your request.

Vagus Nerve Stimulation (VNS) and Treatment of Depression: To the Brainstem and Beyond

 Neuromodulation appears to be emerging gradually as a new therapeutic
field in psychiatric treatment. It encompasses neuropsychiatric medical
devices, such as vagus nerve stimulation (VNS), transcranial magnetic
stimulation (TMS), deep brain stimulation (DBS), and electroconvulsive
therapy (ECT). As a therapeutic approach to affective disorders,
neuromodulation shifts the focus from the monoamine synapse to neural
circuitry of the brain, which is dysregulated in depression. This neural
circuitry has been elaborated on over the course of 15 years of
neuroimaging research in mood disorders and is now believed to encompass
disturbances in a frontolimbic network. These include reduced
metabolism and blood flow in the prefrontal cortex and anterior
cingulate and pathologically increased activity in the subgenual
cingulate and amygdala.VNS is an implanted device that has established
efficacy in pharmaco-resistant epilepsy. It was approved by the FDA for
the treatment of severe, recurrent unipolar and bipolar depression in
July of 2005. VNS adopts a bottom-up approach to modulating the neural
circuitry of depression by stimulating vagal afferent fibers in the neck
, which carry impulses to the brain stem to target there the locus
ceruleus and dorsal raphe nucleus. Now that VNS has moved beyond the
experimental phase and into the clinic, psychiatrists are faced with
deciding who is an appropriate patient for this surgical implant and how
to integrate VNS into existing treatment in order to optimize both
efficacy and safety.This review of VNS will assess the efficacy and
safety data that led to the FDA approval. We will also review for the
busy clinician how VNS is likely to translate into clinical practice as
a treatment option for patients in need who are suffering from severe
depression.

MIGRAIN HEADACHE

Migraine can be defined as a paroxysmal affection, accompanied by severe headache, generally on one side of the head and associated with disorders of the digestion, the liver and the vision. It usually occurs when a person is under great mental tension or has suddenly got over that state.

Migraine is also known as "sick headache" because nausea and vomiting occasionally
accompany the excruciating pain which lasts for as long as three days.

Migraine usually gives warning before it strikes : black spots or a brilliant zig-zag line appears before the eyes or the patient has blurring of vision or has part of his vision blanked out. When the headache occurs, the patient may feel tingling, numbness, or weakness in an arm or leg.

Migraine sufferers have what is known as a "migrainous personality ". They are compulsive
workers and perfectionists, who feel that they have to do everything right away. When they complete a task, they are suddenly laid down from a state of temporary tension to a feeling of utmost relief. Then comes the migraine. It is a purely physiological process. The head and neck muscles, reacting to continuous stress, become overworked. The tightened muscles squeeze the arteries and reduce blood flow. When a person relaxes suddenly, the constricted muscles expand, stretching the walls of the blood-vessel. With every heart beat, the blood being pushed through this vessels expands them further and causes incredible pain.

When a headache strikes, one should stay on one’s feet in the daytime and do simple chores which do not require too much concentration or walk, move around and get some fresh air. The best remedy to prevent headaches is to build up physical resistance through proper nutrition, exercise and constructive thinking. As a first step, the patient should undertake a short fast.


During the fast, citrus fruit juices, diluted with water may be taken six times daily. By taking the load of digestion, the patient will at once save nervous energy which can be utilised for more important purposes. The blood and lymph will also be relieved of a great burden. After a short fast, the diet should be fixed in such a way as to put the least possible strain on the digestion.

Breakfast should consist of fruits, both fresh and dried. Lunch should consist largely of protein foods. Starchy foods such as whole wheat bread, cereals, rice or potatoes should be taken at dinner along with raw salads. Spices, tomatoes, sour buttermilk and oily foodstuffs SHOULD BE AVOIDED!!!. Drinking a glass of water ( warm water in winter and cool water in summer) mixed with a teaspoonful of honey the first thing in the morning, is also a good remedy.

Water Treatment
There are certain water applications which help relieve headaches. Copious drinking of water
can help , as do the cleansing enema with water temperature at 98.6 o F, the hot foot bath, a
cold throat pack, frequent applications of towels wrung out from very hot water to the back of the neck, a cold compress at 40 o to 60o F applied to the head and face or an alternate spinal
compress. Hot fomentations over the abdominal region just before retiring relieve headaches
due to stomach and liver upsets.

Yogic kriyas like jalneti and kunjal, pranayamas like anuloma-viloma, shitali and sitkari and
asanas such as uttanapadasana, sarvangasana, paschimottanasana, halasana and shavasana
are useful in the treatment of headaches.

CONCLUSIONS

DO some fasting (JUICE FAST)
Spices, tomatoes, sour buttermilk and oily foodstuffs SHOULD BE AVOIDED!!!

The New Aneurysm Clip System for Particularly Complex Aneurysm Surgery: Technical Note

Currently, there is an ongoing debate regarding the best treatment option for ruptured aneurysms. The International Subarachnoid Aneurysm Trial study suggests that an endovascular procedure is the best treatment. In some complex cases, or in patients with an additional large intracerebral hemorrhage, aneurysms require further microsurgical clipping.

OBJECTIVE:We introduce a new clip system to improve clipping procedures in especially complex aneurysms.

METHODS: The inverted opening mechanism of the clip in combination with the special clip applier provides the surgeon with a good overview in the operating field. The new design also enables a wider opening of the clip jaws in contrast to all other well-known titanium aneurysm clips. This should provide a better and safer application and decrease the danger of premature rupture.

RESULTS: From January 2006 to July 2008, 55 aneurysms were clipped in 45 patients. The most common aneurysm location was the anterior communicating artery (20 patients) followed by the M1 segment of the middle cerebral artery (16 patients). Four patients had 2, one had 3, and one had 5 aneurysms. Two clipping procedures were performed for an ateriovenous malformation-associated aneurysm. All aneurysms were clipped without any technical complication.

CONCLUSION: The use of the new clip system, especially in complex aneurysm surgery, has potential benefits because of the better surgical vision during clip application and the wider opening of the clip jaws. It is easy to handle and compatible with magnetic resonance imaging.

Imaging technique may trace development of Parkinson's disease

While finding a biomarker for Parkinson's disease that would let physicians screen for or track its progression remains an elusive goal, a team led by a University of Illinois at Chicago neuroscientist has shown that a non-invasive brain scanning technique offers promise. The tool may also help advance the development of new drugs or neuroprotective agents to treat or ward off Parkinson's. The findings, now online, will appear in a forthcoming issue of Neurology. David Vaillancourt, assistant professor of kinesiology at UIC, along with colleagues from UIC and Rush University, used a type of MRI scan called diffusion tensor imaging on 28 subjects, half with early symptoms of Parkinson's and the other half without. They scanned an area of the brain called the substantia nigra, a cluster of neurons that produce the neurotransmitter dopamine. Parkinson's patients have been found to have about half the number of dopaminergic neurons in certain areas of the substantia nigra as those without the disease. Determining loss of dopaminergic neurons using conventional methods such as metabolic PET scans is expensive, invasive, and requires injection of radioactive tracer chemicals. But the method studied by Vaillancourt and his group is non-invasive, relatively inexpensive, and does not use radioactive tracers. "We're suggesting it's possible to eventually diagnose Parkinson's disease non-invasively and objectively by examining the part of the brain thought to underlie the causes of the disease," said Vaillancourt. No tool currently available can do that, he said. The researchers say the technique may also help develop neuroprotective agents to treat Parkinson's. Vaillancourt said it's difficult to identify a neuroprotective agent using current measures because the results are skewed by any therapy used to treat symptoms. "When you have a symptomatic effect of the neuroprotective agent, you need a lot of patients from multiple centers to determine if the neuroprotective agent works," he said. "But if you have a disease marker not affected by a dopaminergic therapy, then you would be able to test neuroprotective agents among smaller groups." Vaillancourt thinks that would enable faster development of drugs to treat Parkinson's. He noted that while the technique his group studied works well as a trait biomarker, which allows for diagnosis, it has not yet been shown to measure the state of the disease's progression. Further research is planned.

Coronary Heart Disease Linked to Endogenous Testosterone

Higher levels of endogenous testosterone may associated with an increased risk of coronary heart disease (CHD) in men older than 65 years, according to a large U.S. multi-center study presented at the Endocrine Society’s 92nd annual meeting.
“The study finding contradicts smaller studies that have shown that testosterone levels are not associated with higher rates of cardiovascular disease,” said study investigator Kristen Sueoka, MD, a resident physician in the Department of Internal Medicine at the University of California, San Francisco. “Many in the general public are using testosterone supplements for various medical problems, including low sex drive and mood disorders, which are not life-threatening. These men may unknowingly be placing themselves at higher risk for cardiovascular disease.”

Dr. Sueoka and her colleagues examined endogenous sex hormone levels in older men as an independent risk factor for CHD events. They studied 697 community-dwelling men who were participating in the National Institutes of Health-funded study, Osteoporotic Fractures in Men (MrOS). None of these men were receiving testosterone therapy and all the men were recruited between 2000 and 2002 at six U.S. centers. The men had a mean age of 72 years. Investigators collected and stored fasting serum samples from the subjects at enrollment.
During an average follow-up of 3.9 years, 100 men (14%) had a coronary disease event. Men with total testosterone levels in the highest quartile (495 ng/dL or higher) had a 2.2 times increased risk of a CHD event compared with men in the lowest quartile (below 308 ng/dL). The researchers also found that the results were similar for bioavailable testosterone and free testosterone. Higher sex-hormone-binding globulin levels also were associated with an increased risk for CHD events, but estradiol and estrone levels were not.
“Our findings suggest there is some type of pathogenesis or interaction that is going on,” Dr. Sueoka said. “If a causal relationship is found between high testosterone and cardiovascular disease, then that would suggest that replacement therapy may put people at higher risk for cardiovascular disease.”
The investigators did not divide the men by normal or abnormal testosterone levels because the definition of abnormal levels depends on many factors, including increasing age. “Men with the highest testosterone could potentially be at risk for heart disease regardless of the definition of ‘normal’ levels,” Dr. Sueoka said.

RECENT ADVANCES IN PARKINSON'S DISEASE

Two days ago, National Public Radio's  All Things Considered broadcast a segment in its series This I believe with Mohammed Ali's contribution entitled "I Am Still The Greatest". The great boxing champion is suffering from Parkinson's disease. But that did not stop him to deliver his testimonial. Despite his condition, Muhammad Ali has risen to even greater championship after his boxing career ended, becoming a relentless ambassador for humanitarian causes and for more research in better treatments for this horribly destructive disease.

Parkinson's Disease is a degenerative disease of the central nervous system, resulting in severe tremor of limbs, motor arrest, and disruption of speech. Its cause is unknown, though a subset of people with the disease are known to carry an inherited genetic mutation that may predispose degeneration.

Nerve cells located in the basal ganglia, a group of forebrain structures situated nose-ward under the cerebral cortex, control our fine movements. They provide feedback to the nerve cells in the motor areas of the cerebral cortex that connect with nerve cells in the ventral horn of the spinal cord. The spinal nerve cells, known as motor neurons, innervate muscle fibers and control limb movement.

Basal ganglia functionality depends on a set of nerve cells located in a structure behind the basal ganglia, known as substantia nigra. In Parkinson's disease, the substantia nigra cells degenerate over decades and eventually die. The loss of their input to the basal ganglia perturbs motor control.

The nerve cells in the substantia nigra use the neurotransmitter dopamine to communicate with the nerve cells in the basal ganglia. Replacing the lost dopamine with the systemic administration of the drug levodopa ameliorates the symptoms. However, over time the brain develops increasing tolerance to the drug, and even high doses cannot control tremors anymore. Efforts pioneered by A. Björklund in Sweden at grafting into the brain undifferentiated cells induced to produce dopamine showed promising results in animal studies, but have not proved unequivocally successful in humans to date.

When medication eventually fails, surgically removing specific parts of the basal ganglia or inter-brain structures also involved in fine motor control may improve the condition (Çoban and others, 2009). In the last decade, however, deep brain stimulation has gained popularity. The method is less invasive and has produced superb outcome. It entails electrical stimulation of nerve cells in the basal ganglia or the inter-brain using thin implanted micro-electrode wires. The electrical impulses are thought to disrupt the persistent nerve cell activity causing the tremors. As a potential further improvement of this procedure, a research study published recently in the journal Science showed that the electrical stimulation of spinal cord nerve fibers with micro-electrodes, threaded between the vertebrae to touch the outer spinal cord where bundles of nerve fibers run that convey sensory information to the brain, may suffice to subdue tremors in Parkinsonian mice (Fuentes and others, 2009). The promising findings were reported on Mar. 19, 2009, in Julie Steenhuysen's post entitled "Spinal cord device helped mice with Parkinson's" on Reuters and Sandra Blakeslee's article entitled "Spinal Shocks Ease Parkinson’s in Mice" in The New York Times. If this procedure proved successful in people, brain surgery would be rendered unnecessary.

If Parkinson's disease runs in your family, you may be interested in gene chip tests for a predisposition available from 23andMe.

Addenda
Some patients with Parkinson's Disease benefitted from having fetal midbrain tissue rich in dopamine-producing nerve cells grafted into the dopamine-depleted basal ganglion known as striatum. However, dyskinesias, that is severe bouts of involuntary movements, hampered recovery despite major improvements in motor control. Using radioactively labeled markers and Positron Emission Tomography, Politis and others (2010) recently showed that the grafts produce extraordinary amounts of the neurotransmitter serotonin, suggesting that excessive serotonergic innervation of the striatum causes the dyskinesias. Hence, medication with long-lasting serotonin antagonists may subdue the undesired effect in grafted patients, and the use of grafts that lack great amounts of serotonergic nerve cells in future surgery may improve outcome in implantation therapy (07/03/10).
If you are considering stem cell therapy, you may find the information on the International Society for Stem Cell Research site helpful (07/26/10).

75 Reasons to Drink Mangosteen Juice Every Day

Establishing a mangosteen dosing regimen can create robust health and vitality, preventing many illnesses from striking in the first place.

WHOLE BODY HEALTH

Strengthen the immune system. The flavonoids & flavones boost other antioxidants, including vitamins C & E, to a more protective level.
Combats inflammation. Helps prevent tissue swelling which can lead to many debilitating diseases & conditions.
Improves cell communication. The xanthones in mangosteen improve the body’s cell to cell communication to fight disease from attacking & spreading. It also speeds up healing & repair.
Thwarts DNA damage. Xanthones have been shown to thwart DNA damage, lowering risks from carcinogens & mutagens.
Aids the lymphatic system. Helps the lymphatic system eliminate cell waste.
Keeps thyroid functioning optimally. Mangosteen’s energy boosting ability helps overcome low thyroid conditions.
Reduces insulin resistance. Xanthones can help normalize blood sugar levels.
Helps lower body fat. Balances cortisol which can stimulate fat deposits in various parts of the body.
Heals nerve damage. The anti-neuralgic & anti-inflammatory properties help repair cellular damage that causes neurological pain & discomfort, including diabetic neuropathy.
Balances the endocrine system. Favorably affects the balance of hormones & other neurochemicals produced by the endocrine system.
Aids body synergy. Mangosteen’s disease microbial-fighting abilities & immune system-strengthening qualities empower the entire body.
Reduces hemorroids. Alleviates the pain & swelling caused by inflammation.
Helps alleviate hypoglycemia. Counters fatigue brought on by low blood-sugar levels.
Relieves psoriasis. Xanthones can help detoxify the liver, which can cause psoriasis.
Helps heal lesions. Promotes rapid healing of topical wounds.
Reduces pain of carpal tunnel syndrome. Stops hand and wrist pain by reducing inflammation.
Relieves neurodermatitis. Mangosteen’s anti-inflammatory properties counteract this scaly & itching skin disorder.
HEART HEALTH

Helps prevent heart disease. Xanthones neutralize free radical damage which may play a role in the inflammatory process.
Strengthens blood vessels. Improves the flow of nutrients to the body’s cells.
Lowers LDL cholesterol. Since mangosteen inhibits free radical damage, it may help reduce LDL oxidation in the blood.
Reduces high blood pressure. Mangosteen’s ability to strengthen heart muscles & help you lose weight may lead to lower blood pressure.
Helps prevents arteriosclorosis. Mangosteen’s anti-inflammatory effect may reduce plaque buildup in artery walls.
DIGESTIVE HEALTH

Helps overcome acid reflux disease (GERD). Mangosteen’s antioxidants may help protect & repair the lower esophagus damaged by gastro-esophageal reflux disease (GERD). Its acid-suppression effects may reduce stomach content acidity.
Helps heal ulcers. Xanthones kill bad bacteria, fungi & parasites, including H-pylori, the ulcer-causing bacteria.
Relief for irritable bowel syndrome (IBS). Blocks IBS-causing serotonin in the digestive system.
Helps stop diarrhea. The anti-inflammatory & anti-bacterial properties of the rind or pericarp can stop diarrhea.
Can relieve Crohn’s disease. The anti-inflammatory properties can prevent the malabsorption of vital nutrients by preventing damage to the wall of the small intestine.
May prevent diverticulitis. Can prevent infections in the pockets that form in the lining of the colon.
YOUTHFUL LIVING

Boosts energy; improves resilience & increase stamina. Mangosteen’s nutrients provide needed energy.
Slows the aging process. Mangosteen’s regenerative nutrients & strong antioxidants keep cells operating optimally.
Helps prevent dementia & Alzheimer’s. Mangosteen’s flavonoids can stop simple memory loss.
Helps prevent kidney stones. The alkaline quality of mangosteen helps neutralize stone-forming acids in the body.
Helps prevent Parkinson’s disease. Mangosteen’s antioxidant qualities prevent oxidation, a factor in Parkinson’s.
Reduces pain from arthritis . The anti-inflammatory effect can reduce pain.
Repairs damage from NSAID use. Mangosteen has been shown to block the H1 & H2 receptors (histamine molecules linked to allergies & the production of stomach acid) naturally. Its anti-inflammatory properties may reduce stomach acid & protect the stomach lining from acid damage.
Aids in eye function. The antioxidant abilities protect cells from the oxidative damage that leads to aging and disease.
FAMILY HEALTH

Lowers fever. By fighting inflammation, offering immune system support & hydration, mangosteen can help fight fever.
Fights food poisoning. Xanthones can destroy Salmonella typhi.
Soothes sore throats. Anti-inflammatory effect can offer relief.
Helps heal mouth & canker sores. The natural antibiotic, antiviral & antifungal ability combats the pathogens that cause these sores.
Fights bad breath. Antibacterial properties help fight bad breath caused by bacteria.
Helps lessen migraines. Mangosteen can potentially correct abnormal serotonin functions in blood vessels that lead to migraines.
Relieves toothache pain. Anti-inflammatory effect can help relieve this pain.
Acts as a natural sleep aid. Helps balance hormones, which aids in balancing the sleep cycle.
Improves ability to deal with stress. Helps balance hormones like cortisol, which is overproduced during stress.
Improves mood & reduces depression. Acts as a “mood elevator” by correcting brain chemical imbalances.
Aids muscles and joint health. Pain can be reduced by the anti-inflammatory properties of mangosteen.
Helps clear acne & skin blemishes. The detoxifying & anti-inflammatory properties of mangosteen can prevent & clear up skin problems.
Treats bug bites, burns & poisonous plant contact. When made into a paste, the anti-bacterial & anti-inflammatory properties can relieve pain & swelling.
Relieves sprained & strained muscles & ligaments. Mangosteen can be massaged onto skin for topical relief.
Relieves stomachaches. Anti-bacterial and anti-inflammatory properties relieve stomachaches caused by bacterial infections.
Relieves bronchitis, emphysema & pneumonia. Mangosteen’s anti-viral, anti-bacterial & anti-fungal effect can reduce the frequency of lung infections & other pulmonary diseases.
Works as a decongestant. Mangosteen’s anti-inflammatory properties help as a decongestant.
MEN’S HEALTH

Helps prevent male infertility. Mangosteen’s anti-inflammatory & anti-oxidant strengths can counter infertility due to stress, pollution & free radical-related factors.
Helps prevent prostate enlargement. The anitioxidant punch of mangosteen’s xanthones may be a powerful weapon in the fight against an enlarged prostate.
WOMEN’S HEALTH

Relieves urinary difficulties . The rind from mangosteen can relieve cystitis (inflammation of the bladder), caused by a bacterial infection.
Offers a gentle laxative effect . Unlike harsh laxatives that irritate the bowel, it heals and unblocks areas of bowel restriction.
Minimizes PMS . Reduces symptoms of moodiness & inflammation.
Relieves menopause symptoms . Removes stress from the body & helps maintain adequate levels of estrogen, thus slowing the effects of menopause.
Reduces menstrual swelling . The anti-inflammatory properties of mangosteen may counteract this bothersome side effect of PMS.
Reduces pain from fibromyalgia . Mangosteen exhibits a neurological pain-reducing effect.
Reduces pain from osteoporosis. Mangosteen’s neurological pain-reducing effect can offer relief from osteoporosis.
CHILDREN’S HEALTH

Helps relieve asthma. Mangosteen’s anti-viral, anti-bacterial & anti-fungal effect can reduce the frequency of lung infections & other pulmonary diseases.
May prevent ADHD & food allergies. Studies have found a strong connection between hyperactive behavior & food allergies. Mangosteen stops antigen/antibody reactions & reduces the body’s allergic reactions. It may also help reduce lead in children’s bodies which is linked to ADHD.
Builds stronger teeth and bones. Mangosteen aids in the efficient conversion of sunlight to vitamin D.
FIGHT DISEASE

Prevents gum disease. The anti-bacterial effect helps prevent gum disease.
Combat tuberculosis. Xanthones can overpower the bacteria responsible for causing TB.
Reduces lactose intolerance side effects. Mangosteen’s anti-inflammatory ability can reduce side effects, such as bloating & abdominal cramps.
Helps prevent dysentery. Effective fights Shigella, the bacterium that causes baciliary dysentery & the amoeba that causes amoebic dysentery..
Helps prevent multiple sclerosis (MS). Balances levels of tryptophan, serotonin and melatonin & prevents oxidative damage.
May thwart cancer. Xanthones have demonstrated anti-tumor properties in leukemia, liver, stomach & lung cancer, breast cancer & colon neoplasms.
Relieves Ankylosing Spondylitis (AS). Anti-inflammatory properties can relieve the cause of holes in the mucosal membrane, strengthening the body’s defenses.
Helps prevent cystic fibrosis (CF) infections. Mangosteen’s antioxidant & anti-microbial abilities may prevent excesss mucus found in CF.
Prevent lupus-related symptoms. Anti-inflammatory & autoimmune strengthening qualities can help lupus symptoms.
Counteracts Myasthenia Gravis. Counteracts the symptoms of this autoimmune disease by strengthening the immune system.

First Psychiatrist Visit: Mood Disorder & Depression

I took the first step today towards regaining my self confidence and mental well being.  I had my first appointment with a psychiatrist!  I have been in a state of depression since age 17, and I am 28 years old now.  In the 11 years that I have been experiencing mental meltdowns, I have never had any of my doctors suggest I see a psychiatrist!

You would think that I would come to the conclusion on my own and take it upon myself to see a psychiatrist, however, when you have numerous health conditions which can cause depression, you tend to trust the one treating you for those conditions.  Lupus and fibromyalgia can both cause depression, so I always left my treatment options for depression up to my rheumatologist.  I have so many different specialists that I figured one of them had to know about treating depression.

My depression has always come and gone on a regular basis.  I have been able to control my depression to the extent that those around me would not know what I was feeling inside of me.  I have been prescribed Lexapro, Citalopram and Prozac in the past to aid in the treatment of my depression.  The Lexapro helped for a bit, but the dosage needed to be increased within the first year of taking it.  After about 5 years of being on Lexapro, I had asked to be switched to something less expensive and was switched to the Citalopram, which is generic for Celexa.  The Citalopram is supposed to be a medication very similar to Lexapro, so I felt comfortable jumping right into this medication.

The Citalopram seemed to make no more of a difference than the Lexapro had made.  Yes, the medication helped and was less expensive than the Lexapro, but it did not seem as if it helped as well as it should have.  With all of the other health issues I have, depression was one issue that I would yet again put on the back burner and just pray that the medication would work better or that I would miraculously heal from the horrible mental instability I felt brewing from within each and every day.

Lets fast forward, seeing as though I am a very long winded person and could tell you my life story before even realizing I’ve done so! ………….

Finally, I switched to a new rheumatologist in September 2009.  I felt that the treatment I was receiving from my rheumatologist at the time for my lupus and fibromyalgia was less than adequate, but that is a whole other story all together.  The new rheumatologist has been extremely thorough with my care and concerns.  He tried me on Prozac for my depression, which had actually caused me additional depression and anxiety.  The next medication he tried me on was Cymbalta to combat both fibromyalgia and depression.  The Cymbalta has helped slightly for the fibromyalgia, however has not touched upon the depression.  To top it all off, I am on such a high dosage of Prednisone (80 mg) that can also cause depression.  I am being hit with a double whammy at the moment.  Due to my many medical conditions, my rheumatologist tells me that he would like me to see a psychiatrist for additional help with my depression.

I went to the psychiatrist today for the first time.  When I arrived at the office, I filled out the usual paperwork with my contact information and insurance information.  I was also given a questionnaire to fill out with questions such as:  history of physical, mental and sexual abuse; drug use; childhood.  I filled out the paperwork and was called back to see the psychiatrist, Dr. G,  shortly after.  While in the psychiatrist office, Dr. G went over the same information that I had filled out and had also gone over my medications, medical history, and had asked me to describe what depression felt like to me.  My answer:  I cry and sometimes I am not sure why.  Other times I cry over things that most people would not find upsetting.

While sitting on the couch in Dr. G’s office, I suddenly felt like I was going to cry, and then I got angry.  I cannot explain why I suddenly felt a rage and just wanted to scream at Dr. G.  He did not do anything but ask me how I felt and asked me to describe my feelings.  I started letting him know that if things are not exactly the way I want them, at times I just get so upset and angry and my mouth gets the best of me.  I will practically bite heads off.  I don’t know why I can be fine one minute, and then in an instant turn into a monster.  He asked me if I had ever hurt anyone, and I said no.  He asked me more questions about my rage, and I answered them.  In the end he came to the conclusion that yes, the Prednisone has increased this rage, however that because of having Lupus and Fibromyalgia he believes that I have a mood disorder on top of depression.

Dr. G asked me if I had ever taken any other medications besides the Lexapro, Citalopram, Prozac and Cymbalta.  I said no.  He double checked with me by naming off about 10 different medications used to treat depression and mood disorders, and all answers were no.  So, he gave me options and let me know what he thought would be best for me.  We decided upon starting Abilify 2.5 mg (pending results on my white blood count, as this is not recommended if one has a low white blood count) and increasing my Cymbalta (pending my creatine level and other kidney function levels he wants to check first).  Dr. G also stated that he wants to do a Homocysteine (specific B12) test, thyroid test, and several other tests, along with requesting my medical records so that he may delve deeper into my mood disorder.

All in all, the visit to the psychiatrist was well worth it.  I return to see Dr. G in 1 month and he will let me know in the meantime when I have the go ahead to start Abilify and to increase my dosage of Cymbalta.  Of course, when I left his office, I felt sad and I could only assume it is because of having to sit and tell someone all of my downfalls.

Central Nervous System Vasculitis

Necrotizing vasculitis may affect the central and peripheral nervous system. The vasculitides may become life threatening due to ischemic ulceration of the gut, kidney failure, and myocarditis; but it may also primarily involve the nervous system.

Although mild cases have been reported, a fulminant course is much more common. Therefore, its early recognition is paramount to secure a good outcome. Unfortunately, its perplexing initial presentation in many patients makes it very challenging to diagnose. This is also partly because this disorder may affect the central nervous system alone. Not uncommonly a major localizing deficit has occurred at the time of diagnosis. Angiitis of the central nervous system can be part of the systemic disorder which has to be uncovered before treatment is initiated. Three primary CNS vasculitides have been identified, many others are secondary to systemic vasculitis, connective tissue disease, malignancy, infections, and drugs. This section summarizes the most important clinical findings, the differential diagnosis, neuroimaging, and pathological characteristics. It also provides a recommendation for treatment.

Pathology and Classification
Vasculitis (or angiitis) on histologic analysis is characterized by inflammation involving layers of polymorphonuclear cells, mononuclear cells, and giant cells destroying the vessel wall resulting in fibrinoid necrosis, aneurysm formation, and possibly hemorrhage.

The pathological mechanisms that lead to vasculitis have not been elucidated. There is some evidence of cell-mediated immunity and when infiltrates are examined closely, they consist particularly of CD4 lymphocytes. Circulating immunocomplexes or a marked decrease in complement is not a typical feature in isolated CNS angiitis. When pathology is available either at autopsy or from a brain biopsy specimen, angiitis typically involves smaller blood vessels. The criteria for vasculitis have been outlined by Kolodny. These criteria include the following: a) intimal swelling and hyperplasia in arteries, b) adventitial lymphocytes infiltration in veins, c) subintimal and intimal fibrinoid change with adventitial accumulation of histiocytes, d) necrosis and fibrinoid change in media, e) fragmentation of internal elastic lamina, f) panmural infiltration of lymphocytes and histiocytes, g) and the presence of granulomas replacing all or part of the vessel wall.

These lesions involve a cluster of lymphocytes, large monocular cells, fibroblasts, multinucleated giant cells, and plasma cells. Inflammation of the small arteries and veins preferably involve the vessels of the leptomeninges and the branches that penetrate the cortex. (This characteristic is useful when performing a brain biopsy). Most notable is a panangiitis in a longitudinal and circumferential direction. In some patients, the abnormality involves the spinal cord arteries and arterioles, but this is an extremely uncommon cause of a myelopathy. Pathology involving the eye vasculature is uncommon and more widespread not only leading to retinal vasculitis but also uveitis or epiduritis.

The necrosis of the vessel wall results in occlusion and ischemia. A vessel wall rupture commonly leads to subarachnoid hemorrhage often involving the sulci and not the basal cisterns as in rupture from aneurysms located at the circle of Willis. Generally a brain biopsy is done at the time of diagnosis and should ideally involve the area that is abnormal on MRI scan. Although several series claim a sensitivity of 70%, a random brain biopsy has a much lower yield. If a brain biopsy is done, the specimen should include dura, leptomeninges, cortex, and white matter and fixated in 10% buffered formalin for light microscopy. Additional specimen can be frozen or stored with dry ice to be further examined by electron microscopy. Isolated angiitis of the central nervous system has been also termed granulomatous angiitis, but this connotation has been deleted because granulomatous changes are absent in 50% of the cases. When an underlying disorder is absent, central nervous system vasculitis is quite rare with only 300 cases or so reported. Related disorders are Eales disease, seen in India and the Middle East, with predominant retinal artery and vein involvement. Retinal hemorrhages and peripheral scotomas are common, but ischemic strokes have been reported.

Another disorder confined to the central nervous system is radiation angiitis due to carcinoma of the larynx, optic glioma, or pituitary tumor. A marked delay (often decades) is typical, but the effects can be devastating and the arteritis is not responsive to immunosuppression.

Clinical Diagnosis
Isolated CNS angiitis is typically seen in younger (30-50 years) individuals with some predilection for females. It may present as an encephalopathy or dementia, multiple cranial neuropathies or recurrent transient ischemic attacks. Many reviews have noted the predominance of headache at presentation. Biller and Adam’s review claim that diffuse encephalopathy signs are present in up to 80% of the patients, but other reviews have predominantly highlighted the presence of behavioral changes. Obviously, a psychiatric presentation can make the diagnosis extremely challenging. This presentation may involve emotional lability but also at times histrionic behavior, confusional states mimicking dementia, suicidal depression, and acute psychotic exacerbations with visual hallucinations particularly when the occipital lobes have become infarcted. Localizing neurologic findings such as aphasia, apraxia, or hemiparesis often emerge. These neurologic signs and symptoms may be associated not only with infarction but also associated with lobar hemorrhages.

Because vasculitis of the central nervous system more likely can be seen in a setting of other disorders, a comprehensive medical examination is needed. For example, CNS angiitis can be seen in Behcet’s disease in which oral and genital ulcers and many other skin manifestations such as erythema nodosa and multiple pustules are present. Pustules may form 24 hours after a sterile needle prick (Pathergy) and may clinch the diagnosis. However when fever, weight loss and malaise, nondeforming arthritis, abdominal pain, as well as proteinuria and progressive renal failure occurs, polyarteritis nodosa or a more systemic necrotizing vasculitis should be considered. CNS vasculitis has been linked to drug abuse (e.g. amphetamine). However, histopathology available in the reported cases is scanty leading some investigators to conclude that the relationship between amphetamine and vasculitis is tentative at best. The proof of vasculitis due to cocaine is also weak. Many reported cases do show a vasculopathy, but inflammation is rarely impressive. We have noted a very severe occlusive vasculopathy (with a moyamoya pattern) but no evidence of vasculitis on biopsy. Other signs are absent peripheral pulses and difficulty recording blood pressure (Takayasu’s arteritis), uveitis (sarcoidosis), and recent asthma (Churg-Strauss).

The classification of the vasculitides is shown in Table 1.

Table 1 – Classification of angiitis

Isolated CNS vasculitis

Isolated angiitis (granulomatous)
Eales Disease
Radiation vasculitis
CNS vasculitis due to secondary causes

Polyarteritis nodosa
Giant cell arteritis
Takayasu’s arteritis
Wegener’s granulomatosis
Churg-Strauss
Behcet’s disease
Sarcoidosis
SLE, RA
Sjörgen’s disease
Malignancies (lymphoma)
Infections (herpes zoster, syphilis)
Cocaine, amphetamine
Moore’s clinical criteria for the diagnosis of CNS vasculitis are shown here in table 2 for reference. However it remains difficult to define a perfect set of criteria in this rare disorder (more experts than patients) and diagnostic tests, particularly interpretation of brain biopsy may not resolve uncertainties.

Table 2 – Moore’s clinical criteria for diagnosis of isolated angiitis of the CNS

Recent severe onset of headaches, confusion, or multifocal neurologic deficits that are recurrent of progressive
Typical angiographic findings
Exclusion of systemic disease or infection
Leptomeningeal or parenchymal biopsy findings confirming vascular inflammation with exclusion of infection, neoplasia, and non-inflammatory vascular disease
Diagnostic tests
Central nervous system vasculitis is first suggested after routine neuroimaging. The CT scan may show cerebral infarcts in multiple territories but typically involving cortical structures. Although at times, a CT scan may be helpful in diagnosing Wegener’s granulomatosis in which bone thickening focal erosive changes of the natal septum and typical soft tissue mass in the sinuses are seen. The MRI scan more likely will document abnormalities in multiple and cortical structures but may also may be limited to scattered lesions in the white matter as well. Meningeal enhancement due to involvement of the meningeal vessels has been noted. Conversely, one may make an argument that a completely normal MRI scan including diffusion-weighted images would make the diagnosis of fulminant angiitis of the central nervous system highly unlikely. Obviously multiple cerebral infarcts on MRI are nonspecific findings and many disorders (although equally uncommon) may produce similar findings. They are listed in Table 3 and should be excluded before invasive tests (e.g. brain biopsy) are performed.

Table 3 – Differential diagnosis of multiple cerebral infarctions

Generalized atherosclerosis
Endocarditis
Cardiac tumor (myxoma)
Antiphospholipid antibody syndrome
Cholesterol embolization syndrome
Thrombotic thrombocytopenia purpura
Coagulopathy (inherited)
Paraproteinemia
MR angiogram should be considered inferior to a conventional cerebral angiogram and current sequencing techniques may not visualized involvement of smaller arteries. Cerebral angiogram remains an important diagnostic test; but again, the findings are nonspecific and may be mimicked by many other disorders (Table 4).

Table 4 – Disorders with angiographic findings that can simulate vasculitis

Neoplastic angioendotheliosis
Cerebral vasospasm following aneurysmal or traumatic subarachnoid hemorrhage
Advanced atherosclerosis
Multiple arterial dissections
Acute migraine (thunderclap) attack
Fibromuscular dyplasia
Radiation angiopathy
Moyamoya disease
However, many of the angiographic findings can be very suggestive of vasculitis particularly when there is alternating constrictions and obliterations ("cutoffs"), irregularities, and dilations in a beading pattern. These abnormalities are typically in the smaller blood vessels and careful viewing of the smaller branches is necessary to find these abnormalities.

The utility of cerebrospinal fluid in the diagnosis of central nervous system angiitis is very questionable. Cerebrospinal fluid examination may show entirely normal protein and cell count including at the time of flare-up. However, mildly increased protein can be seen, and some patients have only a mild pleocytosis with less than 20 lymphocytes per cubic mm. CSF is needed to exclude infectious causes of cerebral arteritis and might be found in cultures and serology. Fungi, tuberculosis, and syphilis may all cause a cerebral arteritis that has to be excluded by CSF and other diagnostic tests and is treated differently.

Blood and serology tests are necessary to exclude a connective tissue disorder. This should include antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibodies, sedimentation rate and serology against an immunodeficiency virus, herpes zoster virus, cytomegalovirus, syphilis, and toxoplasma. A drug screen is essential to exclude the recent use of cocaine or amphetamines. Ideally, the diagnosis is confirmed by a brain biopsy. Diagnostic evaluation are shown in Table 5.

Table 5 – Diagnostic tests in CNS vasculitis

· CBC with platelets

· Chemistry

· ESR

· C3/C4, CH-50

· ANCA

· ANA, ds DNA

· Rheumatoid factor

· VDRL

· Hepatitis serology

· Viral serology (HZV, HIV)

· Urine analysis for glomerular red cells

· Cerebrospinal fluid

· Neurophthalmologic evaluation

· MRI with gadolinium

· Cerebral angiogram

· Brain and meningeal biopsy

False negative brain biopsies remain a major problem in its diagnosis; and in some cases, the diagnosis remains probable on the basis of multiple infarction, cerebral angiographic findings, involvement of other arterial territories, and exclusion of an infectious trigger. Generally, temporal artery biopsy is negative in isolated CNS vasculitis.

The diagnostic evaluation of CNS vasculitis should take into account the presence of systemic signs. If present it may be more practical and safe to obtain a less invasive biopsy such as skin, muscle and kidney. It is useful to perform an MRA in a patient with multiple hyperintensity in cortical areas indicating vasculitis. The MRA may show in some instances fibromuscular dysplasia, atheromatous disease and intracranial stenosis or dissections. MRA should be followed by a cerebral angiogram and a meningeal or brain biopsy. In fulminant cases aggressive immuno-suppressive agents should be started before invasive diagnostic tests.

Management
Many experts prefer a combination of corticosteroids and cyclophosphamide. There is good evidence that aggressive therapy with corticosteroids using 1–2 mg/kg per day in two divided doses and cyclophosphamide, 2 mg/kg per day orally may reverse isolated CNS vasculitis. Typically, corticosteroids are given for at least one month at a high dose and then start gradually tapering with alternate-day and morning dose. The side effects of corticosteroids are significant and involve cushingoid stigmata, delirium, paroxysmal myopathy, hypertension and rarely epidural lipomatosis with cord compression, hyperosmolar nonketotic hyperglycemia, and herpes zoster infections. Osteoporosis is uncommon with a comparatively short treatment, but supplemental calcium should be considered. Cyclophosphamide is probably needed in patients who have a fulminant form and there is some initial evidence that the corticosteroids alone may not reverse vasculitis. Cyclophosphamide is an alkylating agent and is used in an oral dose but has major toxicity including myelosuppression, increased risk of later malignancy particularly leukemia and lymphomas, and a risk of infertility. Egg and sperm harvesting should offered to young patients. The white blood cell count should be carefully monitored (>3000/mm3). Urinalysis may indicate the development of hemorrhagic cystitis. Cyclophosphamide can be tapered after one year. A follow-up cerebral angiogram may not be useful because scar tissue may result in persistent abnormal findings. MRI follow-up documenting absence of further infarction is probably a better monitoring tool. Recurrence is very uncommon.

VASCULITIS OF THE PERPHERAL NERVOUS SYSTEM

The peripheral nervous system may become involved in a variety of acute vasculitis syndromes but may occur isolated. It is present in up to 70 percent in vasculitic syndromes. It may be the first manifestation but features of a more generalized vasculitis become more obvious soon after presentation. Most commonly it is observed in polyarteritis nodosa, Churg-Strauss syndrome, and Wegener’s granulomatosis.

Clinical Diagnosis
Commonly peripheral nerves are an innocent bystander and the ravaging organ involvement is apparent. Acute mode of onset is not very common (although expected when infarction is the presumed causation) and progression over weeks is typical.

In many connective tissue disorders it may take months to develop a functional disturbance. Transitory shooting pain and paresthesias, foot and wrist drop, and diminished sensation over large skin patches is typical. A "sock-glove" distal sensory-motor polyneuropathy is most common; however, cranial nerves may become involved as well (III, V,VI). Pain and a rapid crippling state are typical if untreated. An ascending paralysis resulting in a quadriparesis may occur, but the marked asymmetry makes a confusion with Guillain-Barré syndrome less likely. Cramping and burning sensation with inability to walk and constant sensation of "rock in a shoe" or "tight band in calves" are common complaints. Examination often shows some skin involvement (purpura, erythema multiforme). Radial, ulnar, and femoral nerves are commonly involved.

Diagnostic tests
Nerve conduction studies will confirm nerve involvement. General observations in axonal damage are poor recruitement of motor units with voluntary effort, reduced amplitude of the motor response and mild slowing of the nerve conduction velocity. Over time reinnervation will produce long duration-high amplitude- motor unit potentials.

The diagnosis hinges on confirmation by sural nerve biopsy but biopsy may also include muscle (30% positive result), rectum (15% positive result), and liver (7% positive result).

The diagnosis of vasculitis is highly probable with transmural inflammatory cell infiltration but other features are very suggestive such as vascular thickening and sclerosis in combination with Wallerian degeneration, obliteration of vessel lumen, periadventitial hemosiderin and epineural capillary proliferation. A recent study found that biopsy of the superficial peroneal and peroneus brevis muscle resulted in a higher yield. Additional iron stains and immune staining for immunoglobulin could further increase the sensitivity.

Treatment
Both cyclophosphamide (1–2 mg/kg orally) and prednisone (1 mg/kg/day) for 2 months followed by a tapering schedule can reduce damage and lead to improvement. Plasma exchange or azathioprine may be useful. Neuropathic pain can be treated with gabapentin, 900 to 3600 mg/day or low dose of prednisone, 10 mg/day after initial high-dose therapy of nortriptyline or amitriptyline. A recent report of a necrotizing vasculitis associated with cold agglutinins suggest improvement with plasma exchange.

Central Nervous System Vasculitis

Necrotizing vasculitis may affect the central and peripheral nervous system. The vasculitides may become life threatening due to ischemic ulceration of the gut, kidney failure, and myocarditis; but it may also primarily involve the nervous system.

Although mild cases have been reported, a fulminant course is much more common. Therefore, its early recognition is paramount to secure a good outcome. Unfortunately, its perplexing initial presentation in many patients makes it very challenging to diagnose. This is also partly because this disorder may affect the central nervous system alone. Not uncommonly a major localizing deficit has occurred at the time of diagnosis. Angiitis of the central nervous system can be part of the systemic disorder which has to be uncovered before treatment is initiated. Three primary CNS vasculitides have been identified, many others are secondary to systemic vasculitis, connective tissue disease, malignancy, infections, and drugs. This section summarizes the most important clinical findings, the differential diagnosis, neuroimaging, and pathological characteristics. It also provides a recommendation for treatment.

Pathology and Classification
Vasculitis (or angiitis) on histologic analysis is characterized by inflammation involving layers of polymorphonuclear cells, mononuclear cells, and giant cells destroying the vessel wall resulting in fibrinoid necrosis, aneurysm formation, and possibly hemorrhage.

The pathological mechanisms that lead to vasculitis have not been elucidated. There is some evidence of cell-mediated immunity and when infiltrates are examined closely, they consist particularly of CD4 lymphocytes. Circulating immunocomplexes or a marked decrease in complement is not a typical feature in isolated CNS angiitis. When pathology is available either at autopsy or from a brain biopsy specimen, angiitis typically involves smaller blood vessels. The criteria for vasculitis have been outlined by Kolodny. These criteria include the following: a) intimal swelling and hyperplasia in arteries, b) adventitial lymphocytes infiltration in veins, c) subintimal and intimal fibrinoid change with adventitial accumulation of histiocytes, d) necrosis and fibrinoid change in media, e) fragmentation of internal elastic lamina, f) panmural infiltration of lymphocytes and histiocytes, g) and the presence of granulomas replacing all or part of the vessel wall.

These lesions involve a cluster of lymphocytes, large monocular cells, fibroblasts, multinucleated giant cells, and plasma cells. Inflammation of the small arteries and veins preferably involve the vessels of the leptomeninges and the branches that penetrate the cortex. (This characteristic is useful when performing a brain biopsy). Most notable is a panangiitis in a longitudinal and circumferential direction. In some patients, the abnormality involves the spinal cord arteries and arterioles, but this is an extremely uncommon cause of a myelopathy. Pathology involving the eye vasculature is uncommon and more widespread not only leading to retinal vasculitis but also uveitis or epiduritis.

The necrosis of the vessel wall results in occlusion and ischemia. A vessel wall rupture commonly leads to subarachnoid hemorrhage often involving the sulci and not the basal cisterns as in rupture from aneurysms located at the circle of Willis. Generally a brain biopsy is done at the time of diagnosis and should ideally involve the area that is abnormal on MRI scan. Although several series claim a sensitivity of 70%, a random brain biopsy has a much lower yield. If a brain biopsy is done, the specimen should include dura, leptomeninges, cortex, and white matter and fixated in 10% buffered formalin for light microscopy. Additional specimen can be frozen or stored with dry ice to be further examined by electron microscopy. Isolated angiitis of the central nervous system has been also termed granulomatous angiitis, but this connotation has been deleted because granulomatous changes are absent in 50% of the cases. When an underlying disorder is absent, central nervous system vasculitis is quite rare with only 300 cases or so reported. Related disorders are Eales disease, seen in India and the Middle East, with predominant retinal artery and vein involvement. Retinal hemorrhages and peripheral scotomas are common, but ischemic strokes have been reported.

Another disorder confined to the central nervous system is radiation angiitis due to carcinoma of the larynx, optic glioma, or pituitary tumor. A marked delay (often decades) is typical, but the effects can be devastating and the arteritis is not responsive to immunosuppression.

Clinical Diagnosis
Isolated CNS angiitis is typically seen in younger (30-50 years) individuals with some predilection for females. It may present as an encephalopathy or dementia, multiple cranial neuropathies or recurrent transient ischemic attacks. Many reviews have noted the predominance of headache at presentation. Biller and Adam’s review claim that diffuse encephalopathy signs are present in up to 80% of the patients, but other reviews have predominantly highlighted the presence of behavioral changes. Obviously, a psychiatric presentation can make the diagnosis extremely challenging. This presentation may involve emotional lability but also at times histrionic behavior, confusional states mimicking dementia, suicidal depression, and acute psychotic exacerbations with visual hallucinations particularly when the occipital lobes have become infarcted. Localizing neurologic findings such as aphasia, apraxia, or hemiparesis often emerge. These neurologic signs and symptoms may be associated not only with infarction but also associated with lobar hemorrhages.

Because vasculitis of the central nervous system more likely can be seen in a setting of other disorders, a comprehensive medical examination is needed. For example, CNS angiitis can be seen in Behcet’s disease in which oral and genital ulcers and many other skin manifestations such as erythema nodosa and multiple pustules are present. Pustules may form 24 hours after a sterile needle prick (Pathergy) and may clinch the diagnosis. However when fever, weight loss and malaise, nondeforming arthritis, abdominal pain, as well as proteinuria and progressive renal failure occurs, polyarteritis nodosa or a more systemic necrotizing vasculitis should be considered. CNS vasculitis has been linked to drug abuse (e.g. amphetamine). However, histopathology available in the reported cases is scanty leading some investigators to conclude that the relationship between amphetamine and vasculitis is tentative at best. The proof of vasculitis due to cocaine is also weak. Many reported cases do show a vasculopathy, but inflammation is rarely impressive. We have noted a very severe occlusive vasculopathy (with a moyamoya pattern) but no evidence of vasculitis on biopsy. Other signs are absent peripheral pulses and difficulty recording blood pressure (Takayasu’s arteritis), uveitis (sarcoidosis), and recent asthma (Churg-Strauss).

The classification of the vasculitides is shown in Table 1.

Table 1 – Classification of angiitis

Isolated CNS vasculitis

Isolated angiitis (granulomatous)
Eales Disease
Radiation vasculitis
CNS vasculitis due to secondary causes

Polyarteritis nodosa
Giant cell arteritis
Takayasu’s arteritis
Wegener’s granulomatosis
Churg-Strauss
Behcet’s disease
Sarcoidosis
SLE, RA
Sjörgen’s disease
Malignancies (lymphoma)
Infections (herpes zoster, syphilis)
Cocaine, amphetamine
Moore’s clinical criteria for the diagnosis of CNS vasculitis are shown here in table 2 for reference. However it remains difficult to define a perfect set of criteria in this rare disorder (more experts than patients) and diagnostic tests, particularly interpretation of brain biopsy may not resolve uncertainties.

Table 2 – Moore’s clinical criteria for diagnosis of isolated angiitis of the CNS

Recent severe onset of headaches, confusion, or multifocal neurologic deficits that are recurrent of progressive
Typical angiographic findings
Exclusion of systemic disease or infection
Leptomeningeal or parenchymal biopsy findings confirming vascular inflammation with exclusion of infection, neoplasia, and non-inflammatory vascular disease
Diagnostic tests
Central nervous system vasculitis is first suggested after routine neuroimaging. The CT scan may show cerebral infarcts in multiple territories but typically involving cortical structures. Although at times, a CT scan may be helpful in diagnosing Wegener’s granulomatosis in which bone thickening focal erosive changes of the natal septum and typical soft tissue mass in the sinuses are seen. The MRI scan more likely will document abnormalities in multiple and cortical structures but may also may be limited to scattered lesions in the white matter as well. Meningeal enhancement due to involvement of the meningeal vessels has been noted. Conversely, one may make an argument that a completely normal MRI scan including diffusion-weighted images would make the diagnosis of fulminant angiitis of the central nervous system highly unlikely. Obviously multiple cerebral infarcts on MRI are nonspecific findings and many disorders (although equally uncommon) may produce similar findings. They are listed in Table 3 and should be excluded before invasive tests (e.g. brain biopsy) are performed.

Table 3 – Differential diagnosis of multiple cerebral infarctions

Generalized atherosclerosis
Endocarditis
Cardiac tumor (myxoma)
Antiphospholipid antibody syndrome
Cholesterol embolization syndrome
Thrombotic thrombocytopenia purpura
Coagulopathy (inherited)
Paraproteinemia
MR angiogram should be considered inferior to a conventional cerebral angiogram and current sequencing techniques may not visualized involvement of smaller arteries. Cerebral angiogram remains an important diagnostic test; but again, the findings are nonspecific and may be mimicked by many other disorders (Table 4).

Table 4 – Disorders with angiographic findings that can simulate vasculitis

Neoplastic angioendotheliosis
Cerebral vasospasm following aneurysmal or traumatic subarachnoid hemorrhage
Advanced atherosclerosis
Multiple arterial dissections
Acute migraine (thunderclap) attack
Fibromuscular dyplasia
Radiation angiopathy
Moyamoya disease
However, many of the angiographic findings can be very suggestive of vasculitis particularly when there is alternating constrictions and obliterations ("cutoffs"), irregularities, and dilations in a beading pattern. These abnormalities are typically in the smaller blood vessels and careful viewing of the smaller branches is necessary to find these abnormalities.

The utility of cerebrospinal fluid in the diagnosis of central nervous system angiitis is very questionable. Cerebrospinal fluid examination may show entirely normal protein and cell count including at the time of flare-up. However, mildly increased protein can be seen, and some patients have only a mild pleocytosis with less than 20 lymphocytes per cubic mm. CSF is needed to exclude infectious causes of cerebral arteritis and might be found in cultures and serology. Fungi, tuberculosis, and syphilis may all cause a cerebral arteritis that has to be excluded by CSF and other diagnostic tests and is treated differently.

Blood and serology tests are necessary to exclude a connective tissue disorder. This should include antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibodies, sedimentation rate and serology against an immunodeficiency virus, herpes zoster virus, cytomegalovirus, syphilis, and toxoplasma. A drug screen is essential to exclude the recent use of cocaine or amphetamines. Ideally, the diagnosis is confirmed by a brain biopsy. Diagnostic evaluation are shown in Table 5.

Table 5 – Diagnostic tests in CNS vasculitis

· CBC with platelets

· Chemistry

· ESR

· C3/C4, CH-50

· ANCA

· ANA, ds DNA

· Rheumatoid factor

· VDRL

· Hepatitis serology

· Viral serology (HZV, HIV)

· Urine analysis for glomerular red cells

· Cerebrospinal fluid

· Neurophthalmologic evaluation

· MRI with gadolinium

· Cerebral angiogram

· Brain and meningeal biopsy

False negative brain biopsies remain a major problem in its diagnosis; and in some cases, the diagnosis remains probable on the basis of multiple infarction, cerebral angiographic findings, involvement of other arterial territories, and exclusion of an infectious trigger. Generally, temporal artery biopsy is negative in isolated CNS vasculitis.

The diagnostic evaluation of CNS vasculitis should take into account the presence of systemic signs. If present it may be more practical and safe to obtain a less invasive biopsy such as skin, muscle and kidney. It is useful to perform an MRA in a patient with multiple hyperintensity in cortical areas indicating vasculitis. The MRA may show in some instances fibromuscular dysplasia, atheromatous disease and intracranial stenosis or dissections. MRA should be followed by a cerebral angiogram and a meningeal or brain biopsy. In fulminant cases aggressive immuno-suppressive agents should be started before invasive diagnostic tests.

Management
Many experts prefer a combination of corticosteroids and cyclophosphamide. There is good evidence that aggressive therapy with corticosteroids using 1–2 mg/kg per day in two divided doses and cyclophosphamide, 2 mg/kg per day orally may reverse isolated CNS vasculitis. Typically, corticosteroids are given for at least one month at a high dose and then start gradually tapering with alternate-day and morning dose. The side effects of corticosteroids are significant and involve cushingoid stigmata, delirium, paroxysmal myopathy, hypertension and rarely epidural lipomatosis with cord compression, hyperosmolar nonketotic hyperglycemia, and herpes zoster infections. Osteoporosis is uncommon with a comparatively short treatment, but supplemental calcium should be considered. Cyclophosphamide is probably needed in patients who have a fulminant form and there is some initial evidence that the corticosteroids alone may not reverse vasculitis. Cyclophosphamide is an alkylating agent and is used in an oral dose but has major toxicity including myelosuppression, increased risk of later malignancy particularly leukemia and lymphomas, and a risk of infertility. Egg and sperm harvesting should offered to young patients. The white blood cell count should be carefully monitored (>3000/mm3). Urinalysis may indicate the development of hemorrhagic cystitis. Cyclophosphamide can be tapered after one year. A follow-up cerebral angiogram may not be useful because scar tissue may result in persistent abnormal findings. MRI follow-up documenting absence of further infarction is probably a better monitoring tool. Recurrence is very uncommon.

VASCULITIS OF THE PERPHERAL NERVOUS SYSTEM

The peripheral nervous system may become involved in a variety of acute vasculitis syndromes but may occur isolated. It is present in up to 70 percent in vasculitic syndromes. It may be the first manifestation but features of a more generalized vasculitis become more obvious soon after presentation. Most commonly it is observed in polyarteritis nodosa, Churg-Strauss syndrome, and Wegener’s granulomatosis.

Clinical Diagnosis
Commonly peripheral nerves are an innocent bystander and the ravaging organ involvement is apparent. Acute mode of onset is not very common (although expected when infarction is the presumed causation) and progression over weeks is typical.

In many connective tissue disorders it may take months to develop a functional disturbance. Transitory shooting pain and paresthesias, foot and wrist drop, and diminished sensation over large skin patches is typical. A "sock-glove" distal sensory-motor polyneuropathy is most common; however, cranial nerves may become involved as well (III, V,VI). Pain and a rapid crippling state are typical if untreated. An ascending paralysis resulting in a quadriparesis may occur, but the marked asymmetry makes a confusion with Guillain-Barré syndrome less likely. Cramping and burning sensation with inability to walk and constant sensation of "rock in a shoe" or "tight band in calves" are common complaints. Examination often shows some skin involvement (purpura, erythema multiforme). Radial, ulnar, and femoral nerves are commonly involved.

Diagnostic tests
Nerve conduction studies will confirm nerve involvement. General observations in axonal damage are poor recruitement of motor units with voluntary effort, reduced amplitude of the motor response and mild slowing of the nerve conduction velocity. Over time reinnervation will produce long duration-high amplitude- motor unit potentials.

The diagnosis hinges on confirmation by sural nerve biopsy but biopsy may also include muscle (30% positive result), rectum (15% positive result), and liver (7% positive result).

The diagnosis of vasculitis is highly probable with transmural inflammatory cell infiltration but other features are very suggestive such as vascular thickening and sclerosis in combination with Wallerian degeneration, obliteration of vessel lumen, periadventitial hemosiderin and epineural capillary proliferation. A recent study found that biopsy of the superficial peroneal and peroneus brevis muscle resulted in a higher yield. Additional iron stains and immune staining for immunoglobulin could further increase the sensitivity.

Treatment
Both cyclophosphamide (1–2 mg/kg orally) and prednisone (1 mg/kg/day) for 2 months followed by a tapering schedule can reduce damage and lead to improvement. Plasma exchange or azathioprine may be useful. Neuropathic pain can be treated with gabapentin, 900 to 3600 mg/day or low dose of prednisone, 10 mg/day after initial high-dose therapy of nortriptyline or amitriptyline. A recent report of a necrotizing vasculitis associated with cold agglutinins suggest improvement with plasma exchange.