Liver function disturbances in Guillain-Barré syndrome: a prospective longitudinal study in 100 patients. Dutch Guillain-Barré Study Group.

In 100 consecutive patients with Guillain-Barré syndrome, we assessed liver function on admission and at fixed intervals after either intravenous immunoglobulin (IgIV) or plasma-exchange (PE) treatment. On admission, 38% showed a plasma alanine aminotransferase elevation, gamma glutamyl transferase elevation, or both or more than 1.5 times the upper limit of normal. Ten of these patients had serologic evidence of recent cytomegalovirus infection. The remaining 28 patients were negative for other known causes of liver damage, including infection with Epstein-Barr virus or hepatitis A, B, and C; alcohol abuse; hepatotoxic drugs; recent surgery; and concurrent liver disease. In a hospital control group of 100 consecutive patients with subarachnoid hemorrhage, only 5 had unexplained liver function disturbances on admission (p < 0.0001). In the IgIV-treated group, the percentage of patients with elevated liver function tests increased from 35% before to 69% shortly after treatment at 2 weeks postadmission (p < 0.005). In the PE-treated group, this percentage decreased somewhat from 41% to 36% (not significant). There was also a significant rise in median plasma activity of the various liver enzymes in the IgIV group. At 1 month, however, significant difference had disappeared. At 3 and 6 months, the percentage of patients with liver function disturbances reached a significantly lower level in both treatment groups compared with the time of admission. We concluded that many patients with Guillain-Barré syndrome had mild liver function disturbances without obvious cause. In addition, IgIV treatment was associated with mild transient liver function disturbances through an unknown mechanism.

Guillain-Barré syndrome without sensory loss (acute motor neuropathy). A subgroup with specific clinical, electrodiagnostic and laboratory features. Dutch Guillain-Barré Study Group.

We analysed data obtained from 27 out of a group of 147 patients with Guillain-Barré syndrome, who did not have sensory loss during a follow-up period of 6 months (motor Guillain-Barré syndrome). These patients had a distinctive clinical pattern compared with the other 120 Guillain-Barré syndrome patients. The clinical course was marked by a more rapid onset of weakness (3.9 versus 6.1 days, P = 0.002), an earlier nadir (6.3 versus 9.1 days, P < 0.001), an initially predominant distal weakness (67% versus 27%, P < 0.001), sparing of the cranial nerves (26% versus 68%, P < 0.001) and the disease was more often preceded by a gastro-intestinal illness (41% versus 13%, P = 0.001) often caused by a Campylobacter jejuni infection (67% versus 28% in the other Guillain-Barré syndrome patients, P < 0.001). High titres of anti-GM1 antibodies were also significantly more common in motor Guillain-Barré syndrome patients (42% versus 5%, P < 0.001). Electromyographic data of the motor Guillain-Barré syndrome patients at nadir revealed little or no evidence for demyelination. Abundant denervation activity was present in half of the patients. The response to immune globulin treatment was good but with plasma exchange significantly fewer motor Guillain-Barré syndrome patients reached the stage of independent locomotion after a follow-up period of 6 months especially if the acute motor neuropathy occurred after a C.jejuni infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-GM1 IgG antibodies and Campylobacter bacteria in Guillain-Barré syndrome: evidence of molecular mimicry.

In Guillain-Barré syndrome antibodies to GM1 and the presence of an antecedent Campylobacter jejuni infection are correlated with a more severe course of the disease. From a group of 137 consecutive GBS patients, 11 sera had elevated titers of anti-GM1 IgG antibodies during the acute stage of disease. Each serum sample was preincubated with three different Penner serotypes of whole C. jejuni (PEN O:4/59, PEN O:41) and Campylobacter coli (PEN O:22) bacteria. The PEN O:4/59 serotype, isolated from the stools of a Guillain-Barré syndrome patient, inhibited 63 to 93% of the anti-GM1 activity in 6 of 11 patients. The PEN O:41 inhibited 63 to 100% of the anti-GM1 antibody activity in 9 of 11 patients. The PEN O:22 inhibited anti-GM1 antibody activity in only 2 of 11 patients (80 and 86%). Two Guillain-Barré syndrome patients did not show antibody absorption by any of the Campylobacter serotypes tested, although this does not exclude the involvement of other serotypes. An Escherichia coli control strain did not significantly absorb anti-GM1 antibodies. The results of this study indicate that anti-GM1 IgG antibodies in Guillain-Barré syndrome sera recognize surface epitopes on whole Campylobacter bacteria and that this recognition is strain-specific. This provides evidence for molecular mimicry in the pathogenesis of Guillain-Barré syndrome.

Prognosis in the Guillain-Barré syndrome

We studied 147 patients participating in the multicenter Dutch study for comparasion of the effectiveness of high doses of human immunoglobulin with the effectiveness of plasmapheresis in the Guillain-Barré syndrome in order to determine the influence of the following on the prognosis of the syndrome: age, duration of the disease (ó7 days), artificial respiration, compound muscle action potential (CMAP) < 3mV (20 per cent) - identified as prognostic factors in previous studies - and functional grading, grading by the summation of the Medical Research Council (MRC) scale, anti-GM1 antibodies and positive serology for Campylobacter jejuni - investigated in the present study. The main prognostic criterion was defined as improvement of at least one grade on the scale by the end of the 4th week. The secondary prognostic criterion was defined as the time needed for improvement of one grade and time needed to acquire independent locomotion (F = 2). Functional evaluation was also done in a more subtle manner by measuring muscle strength in 6 individual muscle groups on both sides of the body using the MRC. The factors influencing prognosis are listed below. A change in grading for the better if 1F or more by the end of the fourth week: age, intravenous human immunoglobulin, anti-GM1 antibodies and positive serology for Campylobacter. Time needed for grading to improve for the better by 1F or more: age, CMAP, GM1, summation by the MRC scale. Time needed to reach improvement of 2F: age, GM1, summation by the MRC scale. We are still investigating how the factors determined can be used to predict the time course of each patient individually. At present, we can state that if a patient is less than 50 years old, if no anti-GM1 antibodies are detected and the summation on the MRC scale is above 40, there is a probality of 90 per cent or more that he will succeed in walking unaided before a period of 6 months (functional grade 2). If these 3 factors differ from what has been described above, the probability falls to 30 per cent

Prognosis in the Guillain-Barre syndrome / Prognosis in the Guillain-Barre syndrome

Estudamos 147 pacientes, participantes do estudo multicentrico holandes, para comparacao da efetividade de altas doses de imunoglobulina humana com a da plasmaferese na sindrome de Gillain-Barre, com o objetivo de verificar a influencia dos seguintes fatores no prognostico da sindrome: idade, duracao (menor igual 7 dias), respiracao artificial, potencial de acao muscular composto (PAMC) menor 3mV (20 por cento) - identificdos como fatores prognosticos em estudos previos - e graduacao funcional, graduacao pelo somatorio da escala do Medical Research Council 9mRC), anticorpos anti GMI e sorologia positiva para Campilobacter jejuni - explorados no presente estudo. Utilizamos, para gradacao da gravidade da sindrome, a seguinte escala de graduacao funcional (F): 0, normal; 1, sintomas e sinais menores, sendo o paciente completamente capaz de exercer tarefas manuais; 2, capaz de caminhar mais de 10 metros sem assistencia; 3, capaz de andar mais de 10 metros com assistencia; 4, restrito ao leitor ou a cadeira; e, ventilacao assistida requerida por, pelo menos, parte do dia; 6, morte. O criterio principal de prognostico foi definido como melhora ate o final da quarta semana em pelo menos um grau da escala. O criterio secundario de prognostico foi definido como os periodos de tempo: para haver melhora de um grau e para adquirir locomocao independente (F-2). A avaliacao funcional foi tambem efetivada, de uma maneira mais sutil, atraves da medida de forca muscular em seis grupos musculares individuais, em ambos os lados do corpo, usando a escala do MRC. A soma das 12 gradacoes, variando de 0 a 5, oferece uma pontuacao de 60, normal, a 0, tetraplegia. Os fatores que influenciam o prognostico estao relacionados a seguir Alteracao da graduacao para melhor, igual ou maior que IF, ate o final da quarta semana: idade, imunoglobulina humana endovenosa, anticorpos contra GMI e sorologia positiva para Campilobacter. Periodo de tempo para a graduacao se alterar para melhor, de IF ou mais idade, PAMC, GMI, somatorio pela escala do MRC. Periodo de tempo para se atingir 2F de melhora: idade, GMI, somatorio pela escala MRC. Estamos ainda analisando como os fatores determinados podem ser utilizados para predicao da evolucao de cada paciente, individualmente. Podemos, de momento, dizer que se um paciente tem menos de 50 anos de idade, se nao sao detectados anticorpos contra GMI e o somatorio na escala do MRC esta acima de 40, ha mais que 90 por cento de probabilidade de que o paciente consiga andar independentemente antes dos seis meses de idade (grau funcional 2). Se os tres fatores forem diferentes do que foi referido acima, a probabilidade cai para 30 por cento.

In vivo effects of sera from Guillain-Barré subgroups: an electrophysiological and histological study on rat nerves.

Serum from 20 patients with Guillain-Barré syndrome (GBS), 10 healthy controls and 10 patients with recent cytomegalovirus, Epstein-Barr virus, or Campylobacter jejuni/coli infections was injected into rat sciatic nerve. The 20 GBS patients consisted of 2 groups of 10 patients with different electrophysiological and clinical disease patterns. The main aim of the study was to investigate possible differences in humoral (auto)-immunity between these subgroups. We found no statistically significant differences in electrophysiological or histological parameters between nerves injected with sera from the 2 GBS groups. The sera of the GBS groups caused significantly more compound muscle action potential reduction at 3 to 5 days postinjection than the healthy control sera. No significant difference in nerve conduction was found between nerves injected with GBS serum and serum of patients with proven infections without GBS. Histological analysis of the same nerves that were studied electrophysiologically showed no significant differences in demyelination or other histological parameters between patients and controls at 5 days postinjection. Based on the findings in this study that sera of GBS groups with important differences in disease pattern and sera of patients with proven infection but without GBS show similar in vivo effects on rat nerves, we suggest it may be more likely that these effects are caused by aspecific serum factors associated with immune-system activation, especially by precedent infections, than by specific disease-related factors such as anti-myelin antibodies.