Case 28

Published on 18/02/2015 by admin

Filed under Allergy and Immunology

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 1329 times

CASE 28

Fred, a 40-year-old man, is well known to the local shelters, including the one you supervise, because he has lived on the streets for several years. He is a known alcoholic and has had tuberculosis in the past, for which he was successfully treated under careful supervision. You have noticed that he has been moving more slowly over the past few days and inquire whether he is feeling like himself. He admits to some general fatigue, particularly in the legs, which just “don’t seem to want to carry him around anymore like they used to.” The following morning, the fellow who sleeps in the cot next to Fred indicates to you that Fred cannot seem to get out of bed. You confirm this problem, and you call the emergency medical service (EMS) to transport him to the hospital. To your surprise, when you get to the hospital to visit him, the receptionist tells you that he is seriously ill, is in the intensive care unit, and has been intubated because he was no longer able to breathe for himself.

You arrive at the intensive care unit to find Fred in the condition reported. The attending physician describes Fred’s condition as one of ascending paralysis, typical of Guillain-Barré syndrome. He asks if Fred has recently suffered from a diarrheal illness (which he did, you recall, about 4 weeks ago), as well as about Fred’s alcohol history and other medical disorders. A stool culture was ordered to test for enteric bacteria.

The physician ordered a blood test for creatinine kinase (an enzyme released from destroyed muscle), a stool sample, and assays to detect antibodies that target the gangliosides GM1 and GQ1b. These are distributed throughout peripheral nervous system myelin.

QUESTIONS FOR GROUP DISCUSSION

1. This patient is an alcoholic. Despite this, alcoholic myopathy is low on your list of considerations. Explain. How would you rule out myopathy as a cause of Fred’s problem?
2. What factors, other than alcoholic myopathy, have been shown to cause altered neurotransmission with resulting paralysis?
3. Why would botulism toxin not be a consideration as the cause of Fred’s clinical presentation?
4. Fred’s condition is one of ascending paralysis, typical of Guillain-Barré syndrome. In this syndrome the myelin sheath of nerves is destroyed such that the nerve conduction is altered. Explain how this would lead to loss of muscle mass with time.
5. Antecedent infection with Campylobacter jejuni or cytomegalovirus may lead to Guillain-Barré syndrome and production of autoantibodies to gangliosides present in myelin, GM1 and GM2, respectively. Explain how an infection can lead to the production of autoantibodies.
6. What is the most common source of C. jejuni infection? What are the symptoms?
7. Describe possible mechanisms for destruction of myelin sheath after production of anti-GM1 or anti-GM2 autoantibodies.
8. Explain why Fred’s cerebrospinal fluid (CSF) analysis would show an elevated level of protein.
9. Explain why muscle paralysis is life threatening.
10. Describe the two recommended therapies for Guillain-Barré syndrome.

RECOMMENDED APPROACH

Implications/Analysis of Family History

We are not provided with any family history; however, congenital disorders are clearly unlikely again given the historical context in which this disease is presenting. We are told that the symptoms are typical of Guillain-Barré syndrome, which is an autoimmune disorder that is directed at myelin sheaths, resulting in progressive demyelination and altered nerve conduction, which leads to altered neuromuscular contraction. Familial cases of Guillain-Barré syndrome are almost nonexistent, as are data to support a linkage with any particular HLA haplotype.

Implications/Analysis of Clinical History

Alcoholism and Drug Reactions

Alcoholism itself causes muscle wasting, particularly of the proximal muscle girdles (hip/shoulder muscles). However, the tempo of this disorder is too severe for an alcoholic myopathy. Some drug-induced inflammatory disorders (causing myositis) would potentially present in this fashion, but again the tempo is severe.

Metal or Toxin Poisoning

Lead poisoning (with altered neuromuscular transmission) is possible, as are toxins, but neither you nor the attending physician has been given any history suggestive of toxin ingestion. Botulism toxin, which presents in a similar manner, causes descending, not ascending, paralysis. A variant of Guillain-Barré syndrome (Fischer variant) also causes descending paralysis and is difficult to distinguish from botulism toxin.

Campylobacter jejuni Infection

Of significance is the fact that Fred has had gastroenteritis during the past month. Some infectious agents, particularly C. jejuni, are known to precede development of Guillain-Barré syndrome. Stool samples of patients infected with C. jejuni may contain viable bacteria for 2 to 4 weeks after cessation of diarrhea. Studies have shown that the lipo-oligosaccharide fraction of C. jejuni’s outer capsular structure is similar to gangliosides. Furthermore, anti-ganglioside antibodies from patients with Guillain-Barré syndrome do cross react with the C. jejuni lipo-oligosaccharide fraction.

C. jejuni is the most common bacterial cause of diarrhea in the United States, with 1% of the population infected annually. Contaminated poultry is the cause in more than 60% of cases. Symptoms (fever, diarrhea, abdominal pain) usually resolve in 1 week, with few (<0.02%) cases having more severe sequelae.

Other Infectious Agents

Other infectious agents that are associated with Guillain-Barré syndrome include Epstein-Barr virus, Mycoplasma pneumoniae, and cytomegalovirus, but severe axonal degeneration in Guillain-Barré syndrome is associated with C. jejuni infections more often than with other infectious agents. About 66% of patients with Guillain-Barré syndrome report antecedent illness with one of these infectious agents. Recent immunization may also precede Guillain-Barré syndrome (e.g., swine influenza vaccine).

Implications/Analysis of Laboratory Investigation

Stool cultures confirmed C. jejuni infection. Assays to detect autoantibodies indicated that anti-GM1 antibodies were present; however, autoantibodies to GQ1b were not detected. High titers of anti-ganglioside autoantibodies (GM1) may occur in patients when Guillain-Barré syndrome is preceded by C. jejuni infection. Autoantibodies to ganglioside GQ1b are associated with the Fischer variant of Guillain-Barré syndrome. Autoantibodies to ganglioside GM2 may be present when cytomegalovirus is the antecedent infectious agent.

To rule out myopathy as a cause of Fred’s problem, a blood sample was tested for creatinine kinase enzyme, which is released from destroyed muscle. Fred’s creatinine kinase enzyme level was normal (see Appendix for reference value).

CSF analysis was requested to test for the presence of protein and white blood cells, a nonspecific test for inflammatory processes of the central nervous system. Nerve conduction studies were also requested to determine whether myelin was being destroyed.

Additional Laboratory Tests

CSF analysis indicated an elevated CSF protein level, again suggestive of inflammation, without an increase in leukocytes (pleocytosis). Nerve conduction studies were confirmatory, showing a slowing of conduction velocities, indicating loss of myelin. This is not surprising given that anti-myelin had been detected in Fred’s serum.

DIAGNOSIS

Fred was diagnosed with Guillain-Barré syndrome.

THERAPY

The key problem (at least initially) is overcoming the wasting that is causing difficulty with respiratory muscles. Plasma exchange therapy (plasmapheresis) and high doses of intravenous immunoglobulin (IVIG) have been tried with some success. The choice of therapy seems to vary from area to area.

Plasmapheresis

Plasmapheresis is a technique in which autoantibodies (and other proteins) are mechanically removed from the patient. Basically, in this approach, the plasma is separated from the blood cells in a cell separator. The cells are returned to the patient, and intravenous fluid (or antibody-free donated plasma) is used to replace the plasma (the plasma containing antibodies is discarded). Treatment of this problem using this therapy, thus depends on plasmapheresis until such time as production of anti-myelin antibodies decays to levels inadequate to cause symptoms.

Intravenous Immunoglobulin

IVIG is pooled human plasma that consists primarily of IgG antibodies of different specificities, collected from thousands of healthy individuals. The mechanism by which this therapy works is unclear, but it has been proposed that the high concentration of IgG antibodies downregulates B cells by binding to inhibitory Fcγ receptors on these cells.

ETIOLOGY: GUILLAIN-BARRÉ DISEASE

Guillain-Barré disease is an autoimmune disorder in which the myelin sheath of peripheral nerves is attacked by the immune system. It is now believed these attacks represent a classic example of antigen mimicry, where antigens at the surface of infectious agents (e.g., C. jejuni) result in production of antibodies that react with, and form, immune complexes that activate complement and destroy the myelin sheath of nerves, preventing nerve conduction. Muscle biopsy shows that, at least initially, the muscle tissue is absolutely normal, although nerves show demyelination. With time, loss of muscle mass occurs from wasting (absence of nerve impulses).

Most individuals recover completely from this disorder (in 3 to 6 months), although a small unfortunate population (<5%) is left with some residual infirmity. In the most severe cases this can even necessitate a life-long tracheostomy with ongoing ventilatory assistance.

Related posts:

Default ThumbnailCase 7 Case 35 Case 6 Case 9 Default ThumbnailCase 21 Case 23