Pain, autonomic dysfunction, and course of disease in Guillain-Barré Syndrome

The Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy. Until now, GBS remains a descripti ve diagnosis for which there are no specific diagnostic tests. The combinati on of rapidly progressive symmetrical weakness in arms and legs with or without sensory disturbances, hypo- or areflexia, in the absence of a cerebrospinal fluid (CSF) cellular reacti on, remains the hallmark for the clinical diagnosis of GBS. In GBS, there is a broad spectrum of clinical symptoms and severity in the acute phase. During the subsequent course of disease, the presence and severity of residual symptoms is highly variable. In most treatment studies only severely aff ected pati ents (those being unable to walk without assistance; GBS disability scale grade have been included. Because progressive paralysis is the most striking and alarming symptom of GBS, most att enti on generally is given to the rapid progression and severity of weakness in the acute phase. There are however some underexposed but important issues in GBS like residual fi ndings in parti cular in pati ents which limited weakness (mildly aff ected pati ents), a fl uctuati ng course aft er initi al improvement (treatment related fl uctuati ons (TRF)), the transiti on to chronic infl ammatory demyelinati ng polyneuropathy (CIDP) and the frequency and nature of pain and autonomic dysfuncti on that have been studied limited so far. These issues have formed the basis of the studies described in this thesis. The following cases illustrate the importance of these underexposed issues

IVIG Treatment and Prognosis in Guillain–Barré Syndrome

Introduction Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyneuropathy that often leads to severe weakness. Intravenous immunoglobulin (IVIG) is a proven effective treatment for GBS (class 1 evidence). However, about 25% of patients need artificial ventilation and 20% are still unable to walk unaided after 6 months. Important clinical factors associated with poor outcome are age, presence of preceding diarrhea and the severity of disability in the early course of disease. These clinical factors were combined in a clinical prognostic scoring scale, the Erasmus GBS Outcome Scale (EGOS). Materials and Methods GBS patients being unable to walk unaided are currently treated with a standard single IVIg dose (0.4 g/kg bodyweight for 5 days). A recent retrospective study in 174 GBS patients enrolled in one of our randomized controlled clinical trials showed that patients with a minor increase of serum IgG level after standard single IVIg dose recovered significantly slower. Additionally, fewer patients reached the ability to walk unaided at six months after correction for the known clinical prognostic factors (multivariate analysis; P<0.022). Discussion It is yet unknown why some GBS patients only have a minor increase after standard IVIg treatment. By using the EGOS it is possible to select GBS patients with a poor prognosis. These patients potentially may benefit from a second IVIg dose. Conclusion A standard dose of IVIG is not sufficiently effective in many GBS patients. Whether these patients might benefit from a second IVIg dose needs further investigation

Clinical features, pathogenesis, and treatment of Guillain-Barre syndrome

Guillairk-Barre syndrome (GBS) is an important cause of acute neuromuscular paralysis. Molecular mimicry and a cross-reactive immune response play a crucial part in its pathogenesis, at least in those cases with a preceding Campylobacter jejuni infection and with antibodies to gangliosides. The type of preceding infection and patient-related host factors seem to determine the form and severity of the disease. Intravenous immunoglobulin (IVIg) and plasma exchange are effective treatments in GBS; mainly for practical reasons, IVIg is the preferred treatment. Whether mildly affected patients or patients with Miller Fisher syndrome also benefit from IVIg is unclear. Despite medical treatment, GBS often remains a severe disease; 3-10% of patients die and 20% are still unable to walk after 6 months. in addition, many patients have pain and fatigue that can persist for months or years. Advances irk prognostic modelling have resulted in the development of a new and simple prognostic outcome scale that might also help to guide new treatment options, particularly in patients with GBS who have a poor prognosis