Nervous tissue.

Guillain barre syndrome.

Guillain-Barre syndrome is a serious disorder that occurs when the body's defense (immune) system mistakenly attacks part of the nervous system. This leads to nerve inflammation that causes muscle weakness.

Guillain Barré syndrome is one of the best examples of a post infectious immune disease and offers insights into the mechanism of tissue damage in other more common autoimmune diseases. Controlled epidemiological studies have linked it to infection with Campylobacter jejuni in addition to other viruses including cytomegalovirus and Epstein Barr virus. The syndrome includes several pathological subtypes, of which the most common is a multifocal demyelinating disorder of the peripheral nerves in close association with macrophages. Evidence from histological examination of peripheral nerve biopsy and postmortem samples suggests that both cell mediated and humoral mechanisms are involved in the pathogenesis. Immunological studies suggest that at least one third of patients have antibodies against nerve gangliosides, which in some cases also react with constituents of the liposaccharide of C jejuni. In the Miller Fisher variant of the disease, these antiganglioside antibodies have been shown to produce neuromuscular block, and may in part explain the clinical signs of that disorder. Treatment with both intravenous immunoglobulin and plasma exchange reduces the time taken for recovery to occur, although mortality remains around 8%, with about 20% of patients remaining disabled.

Antecedent events

Although Guillain, Barré, and Strohl did not comment on the association of this illness with infection, extensive clinical observations supported by epidemiological studies suggest that about 75% of patients have a history of preceding symptoms of infection. Serological studies reveal evidence of antecedent infection in about 30% to 50% of cases. These data are supported by accounts of outbreaks of Guillain Barré syndrome and an association between clinical cases of food poisoning and Guillain Barré syndrome within communities. Case controlled studies confirm a significant association with C jejuni, cytomegalovirus, and probably Epstein-Barr virus. Of these, the association with C jejuni remains the most highly studied. Numerous anecdotal reports of associations with other infections exist in the literature. Some immunisations also appear to be recognised triggers of the disease, including swine flu and rabies. Serological evidence of C jejuni infection occurs in about 30% of patients with Guillain Barré syndrome and appears to be associated with slightly more severe disease and with acute motor axonal neuropathy (AMAN) variants. Many examples of persistent excretion of this organism in the stools of clinical cases of Guillain Barré syndrome are described, strengthening the association.

Pathology

The studies of Asbury and colleagues suggested that the earliest hall mark of Guillain Barré syndrome was the presence of perifascicular lymphocytic cuffs of small vessels in the endoneurium and perineurium. This appears to be associated with demyelination, which is typically macrophage associated. In this regard, the pathology has many similarities with the animal model, experimental allergic neuritis (EAN). More recent pathological studies have shown that several pathological subtypes of Guillain Barré syndrome exist, although the demyelinating form of the disease is the most common, and probably represents at least 75% of cases. Some cases of Guillain Barré syndrome are associated with a primarily axonal process, in which macrophages may be found in close proximity to the axon, with sparing of myelin. This histological finding has been interpreted as indicating an immunological attack on antigens of axonal origin, rather than a myelin antigen in demyelinating forms of the disease.

Still other cases of the disease appear to involve both sensory and motor axons and such cases are termed acute motor and sensory axonal neuropathy (AMSAN). This variant of the disease appears to be the most uncommon and perhaps accounts for only 5% of the clinical syndrome.

Treatment

The mainstay of treatment of Guillain Barré syndrome remains good intensive care, with respiratory support where required and early recognition of respiratory failure. The routine use of prophylaxis for deep venous thrombosis is generally accepted, although it has never been subjected to controlled trial. Positive pressure ventilation with frequent turning to avoid atelectasis and frequent physiotherapy are also useful. Passive limb movement helps to prevent contractures that hinder rehabilitation.

Several specific attempts at treatment have been tried. Unlike the more chronic disorder, chronic inflammatory demyelinating polyneuropathy, Guillain Barré syndrome has not been shown to respond to treatment with oral or intravenous steroids. Several controlled clinical trials have shown that both plasma exchange and intravenous immunoglobulin shorten the time to recovery when used in the early stages of the neuropathy. In the largest study of plasma exchange carried out in North America, this procedure improved the time to achieve walking unaided by 32 days. Whereas plasma exchange clearly removes a blood borne substance mediating the neuropathy, possibly an antibody, the mechanism of action of intravenous immunoglobulin administration is more complicated. This probably includes blockage of Fc receptors, increased catabolism of autoimmune immunoglobulin, and possible roles in providing anti-idiotypic antibodies and in promoting remyelination.

Multiple sclerosis

Multiple sclerosis (MS) is a potentially debilitating disease in which your body's immune system eats away at the protective sheath that covers your nerves. This interferes with the communication between your brain and the rest of your body. Ultimately, this may result in deterioration of the nerves themselves, a process that's not reversible.

Symptoms vary widely, depending on the amount of damage and which nerves are affected. People with severe cases of multiple sclerosis may lose the ability to walk or speak. Multiple sclerosis can be difficult to diagnose early in the course of the disease because symptoms often come and go — sometimes disappearing for months.

There's no cure for multiple sclerosis. However treatments can help treat attacks, modify the course of the disease and treat symptoms.

Symptoms

Signs and symptoms of multiple sclerosis vary widely, depending on the location of affected nerve fibers. Multiple sclerosis signs and symptoms may include:

• Numbness or weakness in one or more limbs, which typically occurs on one side of your body at a time or the bottom half of your body
• Partial or complete loss of vision, usually in one eye at a time, often with pain during eye movement (optic neuritis)
• Double vision or blurring of vision
• Tingling or pain in parts of your body
• Electric-shock sensations that occur with certain head movements
• Tremor, lack of coordination or unsteady gait
• Fatigue
• Dizziness

Most people with multiple sclerosis, particularly in the beginning stages of the disease, experience relapses of symptoms, which are followed by periods of complete or partial remission. Signs and symptoms of multiple sclerosis often are triggered or worsened by an increase in body temperature.

Causes

The cause of multiple sclerosis is unknown. It's believed to be an autoimmune disease, in which the body's immune system attacks its own tissues. In multiple sclerosis, this process destroys myelin — the fatty substance that coats and protects nerve fibers in the brain and spinal cord.

Myelin can be compared to the insulation on electrical wires. When myelin is damaged, the messages that travel along that nerve may be slowed or blocked.

Doctors and researchers don't understand why multiple sclerosis develops in some people and not others. A combination of factors, ranging from genetics to childhood infections, may play a role.

Risk factors

These factors may increase your risk of developing multiple sclerosis:

• Being between the ages of 20 and 40. Multiple sclerosis can occur at any age, but most commonly affects people between these ages.
• Being female. Women are about twice as likely as men are to develop multiple sclerosis.
• Having a family history. If one of your parents or siblings has had multiple sclerosis, you have a 1 to 3 percent chance of developing the disease — as compared with the risk in the general population, which is just a tenth of 1 percent. But the experiences of identical twins show that heredity can't be the only factor involved. If multiple sclerosis was determined solely by genetics, identical twins would have identical risks. However, an identical twin has only a 30 percent chance of developing multiple sclerosis if his or her twin already has the disease.
• Having certain infections. A variety of viruses have been linked to multiple sclerosis. Currently the greatest interest is in the association of multiple sclerosis with Epstein-Barr virus, the virus that causes infectious mononucleosis. How Epstein-Barr virus might result in a higher rate of MS remains to be clarified.
• Being white. White people, particularly those whose families originated in northern Europe, are at highest risk of developing multiple sclerosis. People of Asian, African or Native American descent have the lowest risk.
• Living in countries with temperate climes. Multiple sclerosis is far more common in Europe, southern Canada, northern United States, New Zealand and southeastern Australia. The risk seems to increase with latitude.
  A child who moves from a high-risk area to a low-risk area, or vice versa, tends to have the risk level associated with his or her new home area. But if the move occurs after puberty, the young adult usually retains the risk level associated with his or her first home.
• Having certain other autoimmune diseases. You're very slightly more likely to develop multiple sclerosis if you have thyroid disease, type 1 diabetes or inflammatory bowel disease.

Complications

In some cases, people with multiple sclerosis may also develop:

• Muscle stiffness or spasms
• Paralysis, most typically in the legs
• Problems with bladder, bowel or sexual function
• Mental changes, such as forgetfulness or difficulties concentrating
• Depression
• Epilepsy

Treatments and drugs

There is no cure for multiple sclerosis. Treatment typically focuses on strategies to treat attacks, to modify the course of the disease and to treat symptoms. Some people have such mild symptoms that no treatment is necessary.

Strategies to treat attacks

• Corticosteroids. The most common treatment for multiple sclerosis, corticosteroids reduce the inflammation that spikes during a relapse. Examples include oral prednisone and intravenous methylprednisolone. Side effects may include increased blood pressure, mood swings and weight gain. Long-term use can lead to cataracts, high blood sugar and increased risk of infections.
• Plasma exchange (plasmapheresis). This procedure looks a little like dialysis as it mechanically separates your blood cells from your plasma, the liquid part of your blood. Plasma exchange is sometimes used to help combat severe symptoms of multiple sclerosis relapses in people who aren't responding to intravenous steroids.

Strategies to modify the course of the disease

• Beta interferons. These types of drugs — such as Avonex, Betaseron, Extavia and Rebif — appear to slow the rate at which multiple sclerosis symptoms worsen over time. Interferons can cause side effects, including liver damage, so you'll need blood tests to monitor your liver enzymes.
• Glatiramer (Copaxone). Doctors believe that glatiramer works by blocking your immune system's attack on myelin. You must inject this drug subcutaneously once daily. Side effects may include flushing and shortness of breath after injection.
• Fingolimod (Gilenya). An oral medication given once daily, this works by trapping immune cells in lymph nodes. It reduces attacks of MS and short-term disability. To take this drug, you'll need to have your heart rate monitored for six hours after the first dose because the first dose can slow your heartbeat (bradycardia). You'll also need to be immune to the chickenpox virus (varicella-zoster virus). Other side effects include high blood pressure and visual blurring.
• Natalizumab (Tysabri). This drug is designed to work by interfering with the movement of potentially damaging immune cells from your bloodstream to your brain and spinal cord. Tysabri is generally reserved for people who see no results from or can't tolerate other types of treatments. This is because Tysabri increases the risk of progressive multifocal leukoencephalopathy — a brain infection that is usually fatal.
• Mitoxantrone (Novantrone). This immunosuppressant drug can be harmful to the heart, and it's associated with development of blood cancers like leukemia, so it's usually used only to treat severe, advanced multiple sclerosis.

Stroke

A stroke occurs when the blood supply to part of your brain is interrupted or severely reduced, depriving brain tissue of oxygen and food. Within minutes, brain cells begin to die.

A stroke is a medical emergency. Prompt treatment is crucial. Early action can minimize brain damage and potential complications.

The good news is that strokes can be treated and prevented, and many fewer Americans die of stroke now than even 15 years ago. Better control of major stroke risk factors — high blood pressure, smoking and high cholesterol — may be responsible for the decline

Symptoms

Watch for these signs and symptoms if you think you or someone else may be having a stroke. Note when your signs and symptoms begin, because the length of time they have been present may guide your treatment decisions.

• Trouble with walking. You may stumble or experience sudden dizziness, loss of balance or loss of coordination.
• Trouble with speaking and understanding. You may experience confusion. You may slur your words or have difficulty understanding speech.
• Paralysis or numbness of the face, arm or leg. You may develop sudden numbness, weakness or paralysis in your face, arm or leg, especially on one side of your body. Try to raise both your arms over your head at the same time. If one arm begins to fall, you may be having a stroke. Similarly, one side of your mouth may droop when you try to smile.
• Trouble with seeing in one or both eyes. You may suddenly have blurred or blackened vision in one or both eyes, or you may see double.
• Headache. A sudden, severe headache, which may be accompanied by vomiting, dizziness or altered consciousness, may indicate you're having a stroke.

Causes

A stroke occurs when the blood supply to your brain is interrupted or reduced. This deprives your brain of oxygen and nutrients, which can cause your brain cells to die. A stroke may be caused by a blocked artery (ischemic stroke) or a leaking or burst blood vessel (hemorrhagic stroke). Some people may experience a temporary disruption of blood flow through their brain (transient ischemic attack).

Ischemic stroke

About 85 percent of strokes are ischemic strokes. Ischemic strokes occur when the arteries to your brain become narrowed or blocked, causing severely reduced blood flow (ischemia). The most common ischemic strokes include:

• Thrombotic stroke. A thrombotic stroke occurs when a blood clot (thrombus) forms in one of the arteries that supply blood to your brain. A clot often may be caused by fatty deposits (plaque) that build up in arteries and cause reduced blood flow (atherosclerosis) or other artery conditions.
• Embolic stroke. An embolic stroke occurs when a blood clot or other debris forms away from your brain — commonly in your heart — and is swept through your bloodstream to lodge in narrower brain arteries. This type of blood clot is called an embolus.

Hemorrhagic stroke

Hemorrhagic stroke occurs when a blood vessel in your brain leaks or ruptures. Brain hemorrhages can result from many conditions that affect your blood vessels, including uncontrolled high blood pressure (hypertension) and weak spots in your blood vessel walls (aneurysms). A less common cause of hemorrhage is the rupture of an arteriovenous malformation (AVM) — an abnormal tangle of thin-walled blood vessels, present at birth. The types of hemorrhagic stroke include:

• Intracerebral hemorrhage. In an intracerebral hemorrhage, a blood vessel in the brain bursts and spills into the surrounding brain tissue, damaging brain cells. Brain cells beyond the leak are deprived of blood and damaged. High blood pressure, trauma, vascular malformations, use of blood-thinning medications and other conditions may cause intracerebral hemorrhage.
• Subarachnoid hemorrhage. In a subarachnoid hemorrhage, an artery on or near the surface of your brain bursts and spills into the space between the surface of your brain and your skull. This bleeding is often signaled by a sudden, severe headache. A subarachnoid hemorrhage is commonly caused by the rupture of an aneurysm, a small sack-shaped or berry-shaped outpouching on an artery in the brain. After the hemorrhage, the blood vessels in your brain may widen and narrow erratically (vasospasm), causing brain cell damage by further limiting blood flow to parts of your brain.

Transient ischemic attack (TIA)

A transient ischemic attack (TIA) — also called a ministroke — is a brief episode of symptoms similar to those you'd have in a stroke. A transient ischemic attack is caused by a temporary decrease in blood supply to part of your brain. TIAs often last less than five minutes.

Like an ischemic stroke, a TIA occurs when a clot or debris blocks blood flow to part of your brain. A TIA doesn't leave lasting symptoms because the blockage is temporary.

Seek emergency care even if your symptoms seem to clear up. If you've had a TIA, it means there's likely a partially blocked or narrowed artery leading to your brain, putting you at a greater risk of a full-blown stroke that could cause permanent damage later. It's not possible to tell if you're having a stroke or a TIA based only on your symptoms. Up to half of people whose symptoms appear to go away actually have had a stroke causing brain damage.

Treatments and drugs

Emergency treatment for stroke depends on whether you're having an ischemic stroke blocking an artery — the most common kind — or a hemorrhagic stroke involving bleeding into the brain.

Ischemic stroke

To treat an ischemic stroke, doctors must quickly restore blood flow to your brain.

Emergency treatment with medications. Therapy with clot-busting drugs (thrombolytics) must start within 4.5 hours if they are given into the vein — and the sooner, the better. Quick treatment not only improves your chances of survival but also may reduce the complications from your stroke. You may be given:

• Aspirin. Aspirin, an anti-thrombotic drug, is an immediate treatment after an ischemic stroke to reduce the likelihood of having another stroke. Aspirin prevents blood clots from forming. In the emergency room, you may be given a dose of aspirin. The dose may vary, but if you already take a daily aspirin for its blood-thinning effect, you may want to make a note of that on an emergency medical card so doctors will know if you've already taken some aspirin.
  Other blood-thinning drugs, such as heparin, also may be given, but this drug isn't proven to be beneficial in the emergency setting so it's used infrequently. Clopidogrel (Plavix), warfarin (Coumadin), or aspirin in combination with extended release dipyridamole (Aggrenox) may also be used, but these aren't usually used in the emergency room setting.
• Intravenous injection of tissue plasminogen activator (TPA).Some people who are having an ischemic stroke can benefit from an injection of a recombinant tissue plasminogen activator (TPA), also called alteplase, usually given through a vein in the arm. This potent clot-busting drug needs to be given within 4.5 hours after stroke symptoms begin if it's given into the vein. This drug restores blood flow by dissolving the blood clot causing your stroke, and it may help people who have had strokes recover more fully. Your doctor will consider certain risks, such as potential bleeding in the brain, to determine if TPA is the most appropriate treatment for you.

Emergency procedures. Doctors sometimes treat ischemic strokes with procedures that must be performed as soon as possible.

• Medications delivered directly to the brain. Doctors may insert a long, thin tube (catheter) through an artery in your groin and thread it to your brain, and then release TPA directly into the area where the stroke is occurring. The time window for this treatment is somewhat longer than for intravenous TPA but still limited.
• Mechanical clot removal. Doctors may use a catheter to maneuver a tiny device into your brain to physically grab and remove the clot.