Detection and prevalence of alpha-latrotoxin-like effects of serum from patients with Guillain-Barré syndrome

Anti-GQ1b antibodies are associated with the Miller Fisher syndrome (MFS), a variant of the Guillain-Barré syndrome (GBS). In the ex vivo mouse diaphragm, anti-GQ1b-positive MFS serum induces muscle fiber twitching, a temporary dramatic increase of spontaneous quantal acetylcholine release, and transmission blockade at neuromuscular junctions (NMJs). These effects resemble those of alpha-latrotoxin (alpha-LTx) and are induced by antibody-mediated activation of complement. We developed an assay for detection of the alpha-LTx-like effect, using muscle fiber twitching as indicator. We tested 89 serum samples from GBS, MFS, and control subjects, and studied correlations with clinical signs, anti-ganglioside antibodies, micro-electrode physiology, and complement deposition at NMJs. Twitching was observed with 76% of the MFS and 10% of the GBS samples. It was associated with ophthalmoplegia and anti-GQ1b antibodies in patients, and with increased spontaneous acetylcholine release and C3c-deposition at mouse NMJs. This study strongly suggests that antibodies to GQ1b (with cross-reactivity to related gangliosides) are responsible for the alpha-LTx-like activity. The twitching assay is an efficient test for detection of this effect, and allows for screening of large numbers of samples and modifying drugs.     

Supportive care for patients with Guillain-Barré syndrome

A multidisciplinary consensus group searched MEDLINE from 1966 to May 2003, extracted relevant references, and prepared recommendations on supportive care for Guillain-Barré syndrome. In the absence of randomized controlled trials, we agreed on recommendations by consensus based on observational studies and expert opinion. In the acute phase in bed-bound adult patients, the group recommended the use of heparin and graduated pressure stockings to prevent deep vein thrombosis, monitoring for blood pressure, pulse, autonomic disturbances, and respiratory failure, and the timely institution of artificial ventilation and tracheostomy. Pain management is difficult, but carbamazepine or gabapentin may help. The cautious use of narcotic analgesics may be needed. Disabled patients should be treated by a multidisciplinary rehabilitation team and should receive an assistive exercise program. Persistent fatigue following Guillain-Barré syndrome is common and may be helped by an exercise program. Because of a very small and possibly only theoretical increase in the risk of recurrence following immunization, the need for immunization should be reviewed on an individual basis. More research is needed to identify optimal methods for all aspects of supportive care.     

IgG from patients with Guillain-Barré syndrome interact with nicotinic acetylcholine receptor channels

In Guillain-Barré syndrome (GBS), immunoglobulin G (IgG) antibodies block neuromuscular transmission pre- and postsynaptically and thus are of potential pathogenic relevance. We investigated whether IgG from GBS patients has a direct interaction with nicotinic acetylcholine receptor (nAChR) channels. Purified IgG fractions from six GBS patients that blocked neuromuscular transmission in a previous study were analyzed by the patch-clamp technique in combination with an ultrafast system for solution exchange. Sera from three patients with other inflammatory neurological disorders were used as controls. Mouse myotubes expressing native embryonic-type nAChR channels and human embryonic kidney (HEK) 293 cells transiently transfected with recombinant adult-type nAChR channels were used. Repeated 20-ms pulses of acetylcholine (ACh) were applied to outside-out patches in the presence of GBS-IgG. IgG of the patients had a significant reversible blocking action on embryonic- and adult-type nAChR channels with some variability in the magnitude of the block. Activation and desensitization kinetics were not affected when GBS-IgG was applied. None of the control sera blocked the AChR channels. The observed postsynaptic block effect fulfills the criteria of a channel-blocking IgG antibody similar to those seen in autoimmune myasthenia and may contribute to muscle weakness during the acute phase of GBS.     

Abnormal serum factors in Guillain-Barré syndrome

The Guillain-Barré Syndrome (GBS) is generally considered to be a cell-mediated immunopathologic disease of the peripheral nervous system (PNS), although the evidence for this is indirect. Both in vitro and in vivo studies of sera from experimental animals with autoimmune demyelinating neuropathies suggest that serum factors, including antibodies to PNS myelin and/or Schwann cells, may be important in the pathogenesis of some of these disorders. More recently, similar in vitro and in vivo techniques, including the production of demyelination following intraneural injection in the rat have been employed to study sera from patients with GBS. The results of these studies demonstrate the presence of factor(s), as yet not fully characterized, that may be important in mediating demyelination. Moreover, in some patients with chronic or relapsing demyelinative inflammatory neuropathies and monoclonal gammopathy, there is evidence of antimyelin antibodies to PNS myelin. Further studies of serum from patients with acute GBS and these other neuropathies may clarify the role of serum factors in acquired inflammatory diseases of the PNS.     

Primary cytomegalovirus infection in patients with Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is frequently associated with the presence of CMV-specific IgM-antibodies or CMV-DNA in serum. Detection of IgM-antibodies or viremia may indicate primary infection, but also reactivation or reinfection. We identified 46 GBS patients with detectable CMV-specific IgM- or IgG-antibodies, or both. Sera from these patients were tested for the presence of CMV-specific, low-avidity IgG-antibodies, which indicate primary infection that occurred <6 months before sample collection, and for the presence of CMV-DNA by polymerase chain reaction (PCR). Primary infection was identified by the presence of low-avidity IgG-antibodies in 9/46 (20%) or by detection of IgM-antibodies in the absence of IgG-antibodies in 1/46 (2%) patients. CMV-DNA was detectable in 17/46 (37%) sera. In contrast, CMV-DNA was detected in only 2% of sera from 46 age-matched patients with neuroborreliosis. The likelihood of viremia decreased in GBS patients significantly with increasing antibody-avidity (P=0.041). Detection of IgM-antibodies correlated with that of CMV-DNA in patients with low-avidity IgG-antibodies (P=0.048) but not in those with high-avidity IgG-antibodies (P=0.543). In 45 age-matched healthy controls, low-avidity IgG-antibodies and CMV-DNA were detected in only 2% and 0% of sera, respectively. Our findings further strengthen evidence for an association between CMV infection and GBS. Primary CMV infection was identified in almost one-fourth of patients with detectable CMV-specific antibodies. Nevertheless, endogenous reactivation and reinfection have to be considered also as relevant events associated with GBS.     

Horner''s syndrome associated with Guillain-Barré syndrome

Autonomic dysfunctions are classically described during the acute phase of Guillain-Barré syndrome (GBS). This involvement concerns visceral afferent, parasympathetic and/or sympathetic efferent fibers and is closely related to sudden deaths in the acute phase of the disease. We report a case of a patient suffering from a GBS associated with a transient Horner syndrome without extraocular muscle involvement. Pharmacological tests of the pupils pointed to an orthosympathetic pre-ganglionic disturbance. Neither clinical nor electrophysiological parameter suggested a broader involvement of the autonomic nervous system.     

Factors predicting extubation success in patients with Guillain-Barré syndrome

Introduction  

Accurate prediction of successful extubation in patients with Guillain-Barré syndrome (GBS) is an important clinical problem. We hypothesized that reversal of clinical indices used to intubate a patient (i.e., declining vital capacity [VC]) predict extubation.     

Interleukin-10 promoter polymorphisms in patients with Guillain-Barré syndrome

Interleukin-10 (IL-10) may have both pro- and anti-inflammatory effects in Guillain-Barré syndrome (GBS). The distribution of polymorphisms in the IL-10 gene (-1082 (G/A), -819 (T/C) and -592 (A/C)) was analysed to determine whether they could influence disease susceptibility or clinical course in GBS. The -592 CC and -819 CC genotypes associated with increased IL-10 response were more frequent in the GBS patients than in the controls (P=0.027), but the polymorphisms did not influence the clinical course of the disease.     

Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is currently divided into the two major subtypes: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). This review highlights relevant recent publications, particularly on the pathophysiology of AMAN. Molecular mimicry of the bacterial lipo-oligosaccharide by the human gangliosides is now considered an important cause of AMAN. Gangliosides GM1, GM1b, GD1a, and GalNAc-GD1a expressed on the motor axolemma are likely to be the epitopes for antibodies in AMAN. At the nodes or paranodes, deposition of antiganglioside antibodies initially cause reversible conduction block followed by axonal degeneration. Electrodiagnostic findings support this process. Disruption of glycolipids, which are important to maintain ion channel clustering at the nodes and paranode, may impair nerve conduction. Genetic polymorphisms of Campylobacter jejuni determine the expression of the gangliosides on the bacterial wall. In contrast, target molecules in AIDP have not yet been identified. Meta-analyses show efficacy of plasmapheresis and immunoglobulin therapy, but not corticosteroids, in hastening recovery.     

Psychotic symptoms and emotional distress in patients with Guillain-Barré syndrome

Psychological disturbances in 49 most severely compromised Guillain-Barré syndrome patients were prospectively studied by a semistructured interview and assessed by repeat psychiatric examination during the patients' stay in the neuro-intensive care unit (ICU). Additional information was obtained from attending physicians, nurses and relatives. Anxiety (82%), acute stress disorder, depressive episodes (67%) and brief reactive psychosis (25%) were observed, with oneiroid psychosis (14%) among the latter. Psychotic episodes were strongly associated (p < 0.001) with severe tetraparesis, artificial ventilation and multiple cranial nerve dysfunction. CSF protein concentration was also correlated with the occurrence of psychotic symptoms. Patients themselves experienced loss of communication to be the most difficult condition to cope with. Fifty-five percent explicitly felt reassured by the environment of the ICU and 90% described contact with relatives to be most helpful. Our data suggest that motor deprivation and loss of communication are the conditions most closely connected with the occurrence of psychotic symptoms. Therapeutically, continuous psychosocial support and psychopharmacological measures may both be valuable tools to ameliorate distress.     

Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute-onset, monophasic, immune-mediated polyneuropathy that often follows an antecedent infection. The diagnosis relies heavily on the clinical impression obtained from the history and examination, although cerebrospinal fluid analysis and electrodiagnostic testing usually provide evidence supportive of the diagnosis. The clinician must also be familiar with mimics and variants to promptly and efficiently reach an accurate diagnosis. Intravenous immunoglobulin and plasma exchange are efficacious treatments. Supportive care during and following hospitalization is also crucial.     

Long-term outcome in patients with Guillain-Barré syndrome requiring mechanical ventilation

OBJECTIVE: To analyze long-term recovery and predictors of outcome in patients with Guillain-Barré syndrome (GBS) requiring mechanical ventilation. METHODS: The clinical and electrophysiologic data of 114 patients with GBS admitted to the intensive care unit between 1976 and 1996 (60 mechanically ventilated, 54 nonventilated) were reviewed. Functional disability and predictors of outcome were determined at 1 year and at maximal recovery using the Hughes scale. Good outcome was defined as ability to ambulate without assistance; poor outcome was defined as inability to ambulate independently. RESULTS: Mechanical ventilation was required in 81% of patients with a poor outcome. Mortality was 20% in patients ventilated for GBS. However, ventilated patients who survived did well, with 79% eventually regaining independent ambulation. Nineteen percent of patients improved at least one functional grade beyond 1 year. Univariate predictors of poor maximal recovery in ventilated GBS patients were increased age (p < 0.001)), upper limb paralysis (p = 0.004), duration of ventilation (p = 0.006), and delay of more than 2 days to transfer to a tertiary center (p < 0.001). However, only age (OR 1.99, p = 0.004) and delayed transfer (OR 19.8, p = 0.002) were independently predictive of poor outcome on multivariate analysis. CONCLUSION: Mechanically ventilated patients constitute the majority of GBS patients with a poor outcome, and mortality remains substantial in this subgroup (20%). Although recovery from severe GBS may be prolonged, most survivors regain independent ambulation.     

Effects on axonal conduction of anti-ganglioside sera and sera from patients with Guillain-Barré syndrome

The efficacy of plasma exchange as a therapy for Guillain-Barré syndrome (GBS) suggests that humoral factors might contribute to the axonal conduction block responsible for the major symptoms of the disease. To explore this possibility, we have applied sera to rat spinal roots in vitro while monitoring axonal conduction. Neither fresh sera from 12 patients with GBS or Miller-Fisher syndrome (MFS), nor serum from rabbits immunised with Campylobacter jejuni from patients with GBS, MFS or gastroenteritis were effective in causing acute conduction block, despite the presence of antibodies to gangliosides GD3, GM1, GQ1b and GT1a. Potential explanations are advanced.     

Lymphocyte subset proportions in Guillain-Barré syndrome patients treated with plasmapheresis

We examined the changes in the proportions of certain T cell subsets in 18 Guillain-Barré syndrome patients treated with plasmapheresis (PP). PP was performed within 8 days after the onset using a continuous-flow blood cell separator or immunoadsorption. The proportions of CD3+, CD4+ and CD4+CD45RA+ cells at the onset were decreased and that of CD19+ was increased compared with those of 25 normal controls. However, the proportions of CD4+CD45R-, CD4+HLADR+, CD4+CD25+ cells and the CD8+ subpopulations were similar in patients and controls. After PP, the altered subsets tended to normalize, particularly in the group that improved after PP.     

Experimental axonopathy induced by immunization with Campylobacter jejuni lipopolysaccharide from a patient with Guillain-Barré syndrome

New Zealand white rabbits were immunized with a lipopolysaccharide (LPS) extracted from a Campylobacter jejuni HS:19 strain isolated from a GBS patient expressing GM1 and GD1a-like epitopes, Freund's adjuvant (group I) and Freund's adjuvant plus keyhole lympet hemocyanin (KLH) (group II). Both groups showed high titers of anti-LPS and anti-GM1 and lower titers of anti-GD1b and anti-GD1a antibodies. Weakness and axonal degeneration in sciatic nerves was detected in 1/11 of group I and 6/7 of group II. This model replicates, at least in part, the pathogenetic process hypothesized in the human axonal GBS with antiganglioside antibodies post C. jejuni infection and indicates that KLH plays an additional role in neuropathy induction.     

Distinguishing acute-onset CIDP from Guillain-Barré syndrome with treatment related fluctuations

Guillain-Barré syndrome (GBS) patients may worsen after initial treatment (treatment-related fluctuation [TRF]). It is difficult to distinguish GBS-TRF from chronic inflammatory demyelinating polyneuropathy with acute onset (A-CIDP). The authors compared 13 patients with A-CIDP with 11 patients with GBS-TRF and concluded that A-CIDP should be suspected when a patient with GBS deteriorates after 9 weeks from onset or when deterioration occurs three times or more. Maintenance treatment should then be considered.