Guillain-Barré syndrome is an acute inflammatory demyelinating polyneuropathy characterized by progressive muscle weakness and loss of reflexes. It is usually preceded by a gastrointestinal or respiratory infection and can cause paralysis. Treatment involves plasmapheresis or intravenous immunoglobulin to reduce antibodies, with most patients recovering fully or having minor deficits, but 5-10% having permanent disability and 3-8% dying despite intensive care.

1. Guillain-Barré syndrome Suhail Allaqaband Sinai Samaritan Medical Center Milwaukee, WI

2. Guillain-Barré syndrome is an acute inflammatory demyelinating polyneuropathy characterized by progressive muscle weakness and areflexia It has an annual incidence of 0.6 to 2.4 cases per 100,000 population and occurs at all ages and in both sexes With the marked decline in the incidence of polio, Guillain-Barré syndrome is now the most common cause of acute flaccid paralysis in healthy people

3. PATHOGENESIS Peripheral nerve demyelination in Guillain-Barré syndrome is believed to be immunologically mediated Humoral factors and cell-mediated immune phenomena have been implicated in the damage of myelin and/or the myelin-producing Schwann cells

4. Guillain-Barré syndrome has been reported to follow vaccinations epidural anesthesia thrombolytic agents It has been associated with some systemic processes, such as Hodgkin's disease SLE Sarcoidosis, and infection with Campylobacter, Lyme disease, EBV, CMV, HSV, mycoplasma, and recently acquired HIV infection

5. Campylobacter infection Campylobacter infection is the most commonly identified precipitant of Guillain-Barré syndrome A case-control study involving 103 patients with the disease found that 26% of affected individuals had evidence of recent C. jejuni infection compared with 2% of household and 1% of age-matched controls Seventy percent of those infected with C. jejuni reported a diarrheal illness within 12 weeks before the onset of the neurologic illness Campylobacter jejuni infection and Guillain-Barre syndrome N Engl J Med 1995 Nov 23;333(21):1374-9

6. The main lesions are acute inflammatory demyelinating neuropathy and, particularly in patients with Campylobacter-associated disease, acute axonal degeneration These changes may be caused by cross-reacting antibodies to GM1 ganglioside (present in high concentrations in peripheral nerve myelin) formed in response to similar epitopes expressed by the infecting Campylobacter strain However, mechanisms other than molecular mimicry may be associated with the production of antibodies to GM1 ganglioside

7. The Guillain-Barré syndrome variant known as Miller Fisher syndrome, in which the cranial nerves are affected, is also associated with Campylobacter infection In these patients cross-reacting antibodies to GQ1b ganglioside, which is present in cranial nerve myelin, have been found

8. CLINICAL FEATURES Two-thirds of patients develop the neurologic symptoms 2-4 weeks after what appears to be a benign respiratory or gastrointestinal infection The initial symptoms are fine paresthesias in the toes and fingertips, followed by lower extremity weakness that may ascend over hours to days to involve the arms, cranial nerves, and in severe cases the muscles of respiration

9. CLINICAL FEATURES Early in the course, patients frequently complain of aching or sciatica-like lower back or leg pain At some point during their illness, up to 25 percent of patients require mechanical ventilation More than 90% of patients reach the nadir of their function within two to four weeks, with return of function occurring slowly over weeks to months

10. Physical Examination Symmetric limb weakness with diminished or absent reflexes Minimal loss of sensation despite paresthesias Signs of autonomic dysfunction are present in 50 percent of patients, including Cardiac dysrhythmias (asystole, bradycardia, sinus tachycardia, and atrial/ventricular tachyarrhythmias) Orthostatic hypotension Transient or persistent hypertension Paralytic ileus Bladder dysfunction Abnormal sweating

11. DIAGNOSTIC STUDIES Electrophysiologic studies are the most specific and sensitive tests for diagnosis of the disease They demonstrate a variety of abnormalities indicating evolving multifocal demyelination Slowed nerve conduction velocities Partial motor conduction block Abnormal temporal dispersion Prolonged distal latencies A normal study after several days of symptoms, makes the diagnosis of Guillain-Barré syndrome unlikely

12. DIAGNOSTIC STUDIES After the first week of symptoms, analysis of the cerebrospinal fluid (CSF) typically reveals normal pressures few cells (typically mononuclear) an elevated protein conc. (greater than 50 mg/dL) Early in the course (less than one week), protein levels may not yet be elevated, but only rarely do they remain persistently normal If CSF pleocytosis is noted, other diseases associated with Guillain-Barré syndrome eg, HIV infection, Lyme disease, malignancy, and sarcoidosis should be considered

13. TREATMENT The main modalities of therapy for Guillain-Barré syndrome include Plasmapheresis and Administration of intravenous immune globulin

14. Plasmapheresis Plasma exchange is recommended for patients who Are unable to walk unaided Demonstrate worsening vital capacities Require mechanical ventilation Have significant bulbar weakness As a result of the cost, risk, and discomfort to the patient, plasma exchange is generally not used for ambulatory patients with mild disease or for patients whose symptoms are no longer progressing after three weeks

15. Efficiency of plasma exchange in Guillain-Barre syndrome. French Cooperative Group on Plasma Exchange in Guillain-Barre syndrome Ann Neurol 1987 Dec;22(6):753-61 The goals of this multicenter controlled trial were: Study the short-term effect of plasma exchange in the Guillain-Barre syndrome when applied alone within 17 days of onset of the disease Compare two replacement fluids, diluted albumin and fresh frozen plasma (FFP) with regard to efficacy and morbidity

16. 218 patients were included, 111 in the control group, 109 in the plasma exchange group, 57 of whom were assigned to receive albumin and 52 to receive FFP Treatment consisted of four plasma exchanges repeated on alternate days Significant short-term benefits appeared in the group that received plasma exchange Reduction in the proportion of patients who required assisted ventilation Decrease in time before beginning weaning from ventilator Time to onset of motor recovery, and time to walk with and without assistance

17. TREATMENT The main modalities of therapy for Guillain-Barré syndrome include Plasmapheresis and Administration of IVIG

18. A randomized trial comparing IVIG and plasma exchange in Guillain-Barre syndrome. Dutch Guillain-Barre Study Group N Engl J Med 1992 Apr 23;326(17):1123-9 Multicenter trial to determine whether IVIG is as effective as the more complicated treatment with plasma exchange To enter the study, patients had to have had Guillain-Barre syndrome for less than two weeks and had to be unable to walk independently

19. 150 patients with Guillain-Barré syndrome were randomized to five doses of IVIG (0.4 g/kg per day) or five plasma exchanges Strength improved by one grade or more in 34% of those treated with plasma exchange, as compared with 53% of those treated with IVIG The median time to improvement by one grade was 41 days with plasma exchange and 27 days with immune globulin therapy The immune globulin group had significantly fewer complications and less need for artificial ventilation

20. Randomised trial of plasma exchange, IVIG and combined treatments in Guillain-Barre syndrome Lancet 1997 Jan 25;349(9047):225 International, multicentre, randomised trial of 383 adult patients with Guillain-Barre syndrome The inclusion criteria were severe disease (aid needed for walking) and onset of neuropathic symptoms within the previous 14 days

21. Patients were randomly assigned PE, IVIG, or PE course immediately followed by the IVIG course Assessment at 4 weeks by an observer unaware of the treatments received, revealed No significant differences on a 17 point disability scale or in duration of mechanical ventilation among patients treated with plasma exchange or IVIG The combination of the two therapies did not confer any significant advantage

22. Additional considerations Corticosteroids, once the mainstay of therapy for Guillain-Barré syndrome, have not been shown to be beneficial and have no role in the management of GBS Interferon-ß has been reported to be beneficial in individual cases, but its safety and efficacy have not been established in clinical trials Close monitoring of blood pressure, fluid status, and cardiac rhythm is essential to the management of these patients

23. OUTCOME The majority of patients with GBS either recover completely or are left with only minor deficits eg, distal numbness or foot-drop However, 5 to 10 percent of patients will suffer permanent disabling weakness, imbalance, or sensory loss 3 to 8 percent of patients die despite intensive care

24. OUTCOME Causes of death include ARDS, sepsis, pulmonary emboli, and unexplained cardiac arrest. Factors associated with a poorer outcome include Older age Severe, rapidly progressive disease Prolonged mechanical ventilation (>1 month) Persistent, severely abnormal findings on electromyography