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Guillain Barre' Syndrome
(Acute Idiopathic Polyneuritis)

Guillain-Barr?(Ghee-yaw Bah-ray) Syndrome, also called acute inflammatory demyelinating polyneuropathy and Landry's ascending paralysis, is a disorder of the peripheral nerves, those outside the brain and spinal cord. It is typically characterized by the rapid onset of muscle weakness and often, paralysis of the legs, arms and breathing muscles. The cause of Guillain-Barre' syndrome is not known; and why the disorder only occurs in certain patients is still not known. Research to date indicates that the nerves of the GBS patient are attacked by the body's own defense system against disease-antibodies and white blood cells. As a result of this autoimmune attack, the nerve insulation (myelin) and sometimes even the covered conducting part of the nerve (axon) is damaged.

 

The rapid onset of (ascending) weakness, frequently accompanied by abnormal sensations and pain that affect both sides of the body similarly, is a common presenting picture, and quite often, the patient's symptoms and physical exam are sufficient to indicate the diagnosis. The severity of Guillain-Barre' syndrome can vary greatly. In its milder form, it may cause a waddling or ducklike gait, and perhaps some tingling and upper limb weakness that may briefly, for days or weeks, impair a patients lifestyle. Some primary care physicians have described patients who complained of mild brief tingling and/or limb weakness accompanying or following a viral illness, such as a sore throat or diarrhea. Such a set of symptoms may represent a very mild form of GBS. In contrast to such mild forms, at the other extreme a GBS patient may become almost totally paralyzed and fraught with complications.

 

Although the exact percentages vary from study to study for long-term prognosis, up to 85 percent of GBS patients reach nearly complete recovery, although they may suffer chronic problems, such as muscular pain and weakness. Perhaps 5 to 15 percent of GBS patients will have severe long-term disabilities. Less than 5 percent die. GBS can develop in any person at any age, regardless of gender or ethnic background. It is important to emphasize that, as in many aspects of medicine the prognosis or expectation for degree of recovery for any particular patient cannot be predicted.

 

Not infrequently, after apparent recovery from Guillain-Barre' syndrome, patients may experience the recurrence of abnormal sensations, typically in the lower and/or upper limbs. They may consist of numbness, decreased sensations, tingling, burning, a sense of worms crawling under the skin, pain, muscle spasms or cramps in the form of severe Charlie Horses, and a variety of other disconcerting symptoms that the patient may even have difficulty describing.

 

A particularly frustrating consequence of this disorder is long-term recurrences of fatigue and/or exhaustion as well as abnormal sensations including pain and muscle aches. These problems can occur following the exertion of normal walking or working and can be alleviated by reduction of activity and rest. Many patients learn by trial and error how much activity they can tolerate.

 

Studies now suggest that the degree of damage or number of diminished axons, the conducting part of nerve cells or, if you will, the wire, rather than damage of its surrounding covering or insulation, the myelin sheath, may explain chronic or long-term damage and paralysis. Such studies are shedding light on some of the long-term effects of GBS. Several years after the recovery phase of the illness, some GBS patients experience symptoms identical to Post-Polio Sequela (Post-Polio Syndrome), a condition affecting many "recovered" Polio survivors.

 

Sometimes motor axon damage is not severe and the cells can recover much of their function. Other axons may sustain more complete and irreversible damage. Even if this is the case, however, function can often be restored by "sprouting". Motor axons have the ability to send out new branches that can innervate neighboring muscle fibers whose own axons have been destroyed. Nerve cells normally innervate between 200 and 500 individual muscle fibers. If a percentage of motor axons are destroyed, and sprouting takes place, the remaining axons may be innervating as much as four times the normal amount of muscle fiber. Some individuals may have gained a degree of recovery by building up the strength of their remaining musculature by exercise and intense use, similar to athletic training. These individuals, however, used this strength in their daily activity and thus the muscles have been performing continually at a level that is no longer tolerated.

 

Recurrent abnormal sensations may reflect the presence of residual nerve damage that had occurred during the initial stages of the syndrome's development. Frustration arises because the sensations are truly felt by the patient and can be quite severe or annoying but have no physical correlate outside the body and may be difficult to control. Furthermore, they can be difficult to demonstrate, measure, or otherwise document. One example is the sense of vibration while lying perfectly still in bed. Another example is the feeling of pain without an underlying injury. The pain may be severe enough so that routine analgesic medications don't give relief, and more potent analgesics such as narcotic pain relievers may be considered. The treating physician may be hard pressed to justify use of such drugs for a problem he can't prove exists. Such drugs, however, are relatively safe and there is no occurrence of addiction in these patients when given opioids to control chronic pain.

 

Persisting abnormal sensations, if sufficiently bothersome, may sometimes respond to a variety of treatment modalities. These can include simple and relatively safe approaches such as over-the-counter analgesics (for pain), including aspirin and acetaminophen. Some people find that the local applications of heat, especially moist heat, or cold may be beneficial. Should these initial measures give inadequate relief, alternative approaches, such as prescription medications, may be entertained, especially to treat persisting pain. For patients with persisting muscle group weakness, various methods (orthotic devices) can be used to circumvent the disability. For example, a dropped foot can be treated with a molded ankle foot orthosis (MAFO), a lightweight plastic device that fits behind the leg and under the foot.

 

Each case of Guillain-Barre' syndrome is different. It is important to realize that the complications and therefore treatments of Guillain-Barre' syndrome are not predictable. For the most part, treatments are highly individualized.


Residual Effects
Following
Guillain-Barre'

________________________________________________________________________

Gareth J. Parry
Consultant Neurologist Auckland Hospital, Professor of Neurology University of Minnesota


Guillain-Barre syndrome is a disorder whose excellent prognosis is invariably emphasized. Widely accepted figures suggest that 75%-85% of patients make a complete recovery, however, many of my patients have complained to me of minor but annoying persistent symptoms continuing for years after the initial paralytic event. Although I have made no systematic study of the proportion of patients with these residual complaints it is certainly more than the 15%-25% that the figures in the literature would suggest. The great majority of studies of GBS outcome are based on telephone interviews or retrospective chart reviews and seemingly minor complaints may have been missed or disregarded. Thus, patients are often asked if they have returned to their previous work or other previous activities but they may not have been asked whether they have more difficulty performing their former activities. A note of caution was sounded in one small study from Dr. J. McLeod and his colleagues in Australia who objectively evaluated a small group of 18 recovered GBS patients and found that half of them had residual neurological abnormalities. Even then the residual abnormalities were considered to be significant in only four patients. A recent important paper from Dr. I.S.J. Merkies and colleagues in Holland (Neurology 1999; 53:1648-1654) has established that residual effects from both GBS and CIDP are much more common than has been generally reported and that seemingly minor neurologic abnormalities may still result in annoying disabilities. The study used a validated index of fatigue severity to assess residual disability. It included 83 patients who had suffered from GBS an average of five years previously. About 80% of these patients experienced fatigue that was considered severe enough to interfere with their life despite the fact that the majority had normal strength or only minor weakness. They noted also that the fatigue did not seem to improve over time; the fatigue index score was the same in patients in whom many years had elapsed as it was in patients whose acute illness had occurred only 6-12 months previously. This paper provides sound scientific support for the validity of the observations of my patients who regularly complain of fatigue even when they have returned to all or most of their former activities and who are working full time at their former jobs. Although their strength may be normal when they are examined in the doctor's office they are clearly unable to sustain the same level of physical activity that they had performed prior to their GBS. A second under-appreciated symptom that may persist for many years is pain. Certainly, severe disabling pain is very rare. However, a number of my patients complain of persistent discomfort in their feet. The discomfort may take the form of annoying paresthesias (tingling) or there may be a vague aching discomfort. The symptoms have the same characteristics as typical neuropathic pain in that they tend to be worse in the evening or at night and are particularly annoying following days during which the patients have been up on their feet a lot. The discomfort is not particularly responsive to analgesics but usually does respond to drugs such as gabapentin or amitriptyline, drugs typically used in the treatment of neuropathic pain. However, these medications have to be taken on a daily basis to be effective and one problem with deciding whether to treat this residual symptom is that the discomfort is usually rather mild. Thus, patients may be daily irritated by their symptom but be reluctant to take a drug every day for a symptom that significantly bothers them only once or twice a month. I have seen no mention in the medical literature of this phenomenon. It is possible that I see a highly selected group of patients in my practice who had initially been more severely affected and that the prevalence of this annoying residual symptom is much higher in my patients than in the usual population of recovered GBS patients. I would be most interested to learn whether the group of patients reported by Merkies and colleagues also suffered from minor persistent discomfort.

 

The basis for both of these seemingly minor residual symptoms (fatigue and pain) is probably axonal degeneration. During the acute illness the predominant underlying pathology in most patients is segmental demyelination, a completely reversible phenomenon. However, some degree of axonal degeneration is almost invariable. As recovery occurs function is restored by a number of mechanisms. Axonal regeneration of motor axons probably plays very little role in restoration of function except in the more severe cases. Rather, surviving axons send out small branches called collateral sprouts that restore the nerve supply to those muscle fibers whose nerves have been damaged. This process of collateral sprouting is very effective at restoring strength to a muscle but the efficiency of the muscle suffers - the muscle must work harder to achieve its goals. Thus, fatigue may result even when there appears to be full restoration of strength. On the sensory side, even a small number of damaged sensory axons may be sufficient to generate spontaneous discharges that are registered as pain or discomfort.

 

It is entirely appropriate that the good outcome of GBS should be emphasized during the acute illness. During this time, the patient is losing control of many motor functions, sometimes including life preserving functions, and constant reassurance from the attending physicians plays a vital role in the recovery process. However, it is equally important to be aware that residual problems are experienced by "recovered" GBS patients. Acknowledgement that such residual problems exist will go a long way towards helping patients deal with the frustration of their incomplete recovery.

 

More research is needed to discover an effective treatment for the residual fatigue. In addition, since these persistent symptoms are probably related to the degree of axonal damage that occurs at the time of the initial attack, we also need to continue to strive for earlier and more effective treatment of the acute stage of the disease so that these residual problems are minimized.



Disability After
?Recovery? From GBS

____________________________________________

Kleopas A. Kleopa, M.D., Neuromuscular Fellow
Mark J. Brown, M.D., Professor
Department of Neurology, University of Pennsylvania
School of Medicine, Philadelphia, PA


Guillain-Barre syndrome (GBS) is the most common cause of acute neuromuscular paralysis in developed countries. Most patients recover and return to productive, independent lives. In a recent representative survey of 140 GBS patients, 70% made a complete neurological recovery within a year, 22% could walk but were unable to run, 8% were unable to walk unaided, and 2% remained bedridden or ventilator-dependent after a year. Thus, despite the good prognosis for recovery, GBS can cause long-term disability. Persisting disability is largely the result of weakness from the motor nerve injury that occurred during the acute illness. An estimated 25,000 to 50,000 persons in the United States alone are experiencing residual effects from the disease. Most research on GBS has focused on understanding the cause and finding better treatments. Much less attention has been paid to the long-term disability caused by GBS. In addition to the previously mentioned residual weakness, there may be pain, fatigue, psychosocial dysfunction, possible relapses of the illness, and late progression of weakness.

 

Pain

 

Moderate to severe pain is a well-recognized symptom during the course of acute GBS. For some patients neuropathic pain, consisting of abnormal painful sensations, may persist after recovery from the disease. In a recent prospective study of 55 GBS patients followed for up to 24 weeks, pain occurred during the course of the illness in almost 90% of cases. Whereas deep aching back and leg pain were the most common early on, abnormal painful sensations and myalgic-rheumatic type pain were observed during the recovery period. Musculoskeletal pain was common in association with physiotherapy. Painful abnormal sensations in the extremities tended to persist after 8 weeks, and were still present in some patients after 24 weeks. In two cases the pain was severe. Overall, pain can be effectively relieved with an escalating regimen of analgesic medications, starting with nonsteroidal anti-inflammatory drugs or acetaminophen, and if necessary including oral or parenteral opioids. Even severe pain can be controlled, sometimes with the addition of patient-controlled analgesia. In a large series of GBS patients treated for pain, these medications were generally effective, and no adverse effects on breathing function or narcotic addiction occurred.

 

Chronic fatigue

 

Fatigue following GBS is underrecognized by neurologists and rehabilitation physicians, because attention is directed toward the more objective weakness and sensory disturbances. In a recent study of 83 patients recovering from GBS, severe fatigue was reported as one of the three most disabling symptoms by over 80%. The incidence of fatigue did not correlate with age, or motor and sensory residual deficits, but fatigue was more common in women. Fatigue was unrelated to the time since the acute phase of the GBS, a median of 5.2 years in this group. Another study of 123 GBS patients, evaluated 3 to 6 years after the acute illness, concluded that psychosocial functioning, especially in areas such as sleep and rest, alertness, emotional behavior and social interaction, was seriously affected. This was true even when "complete" physical recovery was reached, or only minimal residual deficits were present. Deconditioning and less engagement in physical activities were discussed as possible explanations for persistent fatigue. A supervised training program and low-intensity aerobic exercise may reduce daily fatigue, with improvements in activities of daily living and functional capacity. Specific treatments for other factors associated with fatigue, such as sleep disturbances, pain, and daytime inactivity, are available.

 

Psychosocial dysfunction

 

Reports of long-term psychological sequela after GBS are rare, although this issue may be a major factor in psychosocial dysfunction of patients recovering from the disease. Many psychological factors could contribute to chronic fatigue and social dysfunction, including fear of disability, inability to cope with physical limitations, and depression following a major illness. The role of depression in psychosocial dysfunction after GBS is not fully understood. The sickness impact profile of GBS survivors was found to differ from the profile of other patients with depression. Nevertheless, further study of the long-term psychological impact of the disease is necessary, and depression should be considered on an individual basis when appropriate. Both supportive psychotherapy and/or pharmacologic treatment can be effective.

 

Post-traumatic stress disorder (PTSD) has been reported in a patient following severe GBS with paralysis and a prolonged intensive care stay. The GBS-induced PTSD shared the features of PTSD seen following other traumatic events. Even such profound psychological problems following GBS can be treated with supportive psychotherapy and appropriate medications. They may at least in part be prevented by adequate pain management and the use of a communication system, such as clear lucid letter-board in the event of near complete paralysis. Better understanding, prevention and treatment of these issues may have a positive impact on the quality of life for GBS survivors. Moreover, it is important for patients and their families to know that their psychosocial problems are also experienced by other patients after GBS.

 

Recurrence of GBS

 

Although GBS is thought to be a one-time disease, relapses and chronic recurrent forms can occur. Patients are often concerned about the risk of having additional episodes of GBS. In a study of 220 GBS patients, 15 were found to have a relapsing course, with one to 4 recurrent episodes. The interval between episodes ranged from 3 months to 25 years. Antecedent events such as a viral infection preceded most relapses, and patients presented each lime with the typical clinical and laboratory findings of acute GBS. All patients had long asymptomatic periods between the episodes. In a more recent study of 476 patients following GBS, 2.5% experienced a recurrence of the acute illness, with a mean period of 16 months between the episodes (range 2-47 months). One patient had three episodes. The authors found no relationship between the risk of having a recurrent episode and the severity of the first episode. Furthermore, the severity of the subsequent episode did not correlate with the intensity of the first episode. Reaching a correct diagnosis may be challenging in these cases. Even GBS experts may find it difficult to separate a "relapsing variant of GBS" from chronic inflammatory demyelinating polyneuropathy (CIDP), especially early in the course. Recurrent episodes of true GBS, although rare, may occur following similar preceding illnesses, and should be treated in the same way as the initial episode. They respond well to the same established treatment modalities.

 

Delayed progression

 

Weakness from GBS reaches its maximum during the first two or three weeks of the disease. This is the active or acute phase of the illness. After a plateau period of days or weeks, recovery begins, lasting between weeks and two years. During this time strength improves steadily. Strength and sensory function plateau after about two years. However, many decades after GBS, recovered muscles once weakened by the disease may again grow weak. This is a slow process that occurs over years, and may at first escape the patient's notice. It is likely that this delayed weakness is the effect of the normal gradual age-related nerve cell loss on muscles that have a reduced reserve nerve supply from earlier GBS. The same phenomenon has been observed after poliomyelitis ("post-polio syndrome") and other forms of acute nerve injury. The incidence of slowly progressive late weakness in GBS is unknown, but it is rare. When it does occur, the patient's physician must recognize that the new weakness of seemingly recovered muscles does not necessarily indicate a second attack of GBS.

 

For many patients recovering from GBS, residual motor or sensory deficits may be only one aspect of the long consequences of the disease. Other issues described here may have a considerable impact on their quality of life. Effective treatments are available for most of these problems.

 

References available on request.
Contact Dr. Kleopa at: kleopa@mail.med upenn.edu

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