GBS and CIDP Spectrum and IVIg treatment

The spectrum of GBS, CIDP and its subforms is investigated in this thesis. We identified 32 relapsing GBS patients and compared their clinical characteristics with 476 non-recurrent GBS patients. Recurrences occurred more frequently in younger patients, those with milder symptoms and in the Miller Fisher syndrome. While neurological symptoms and signs were often similar, the nature of the preceding event often varied which may indicated that genetic and immunological host factors play an important role in recurrent GBS. We described four patients who had separate episodes of both GBS and CIDP. In 106 GBS patients who received one or more flu vaccinations, none reported a recurrence thereafter, therefore seasonal flu vaccinations seem relatively safe in patients who have had GBS. The second part of the thesis is focussed on the treatment of CIDP. In a randomised controlled trial we found no significant differences between two different immunoglobulins in CIDP. IVIg is an effective first-line treatment since 76% improves significantly to IVIg. Sixteen percent needs only one IVIg course but most patients need IVIg for a long period of time. Of the IVIg non-responders, about three quarters of patients still responds to plasma exchange, corticosteroids or both. CIDP patients with pronounced pain or a difference in weakness between arms and legs are less likely to be IVIg responsive. GBS patients all receive the same arbitrary dose of 2 g IVIg per kg of body weight. Not all patients however show a good recovery. Patients show considerable variability in the increase in serum IgG level two weeks after after this standard dose. Patients with a low increase in serum IgG level two weeks after IVIg have a more severe disease course, and are less likely to be able to walk unaided after six months. Even after adjustment for known prognostic factors a low increase in serum IgG level was independently associated with a worse outcome. This indicates that some GBS patients may benefit from a higher dosage or second course of IVIg. We also investigated serum IgG levels in clinical stable but IVIg dependent CIDP patients . All received an individually optimised dosage and interval, which did not correlate with body weight. Clinical stable CIDP patients seem to show a steady-state in serum IgG after serial IVIg infusions

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

Guillain-Barre syndrome after SARS-CoV-2 infection in an international prospective cohort study

In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barre syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12-22). Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not

Genetic biomarkers for intravenous immunoglobulin response in chronic inflammatory demyelinating polyradiculoneuropathy

Background and purpose: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a clinical and electrophysiological heterogeneous immune-mediated polyneuropathy. In

Second intravenous immunoglobulin dose in patients with Guillain-Barre syndrome with poor prognosis (SID-GBS):a double-blind, randomised, placebo-controlled trial

Background Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barre syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barre syndrome with a predicted poor outcome. Methods In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (>= 12 years) with Guillain-Barre syndrome admitted to one of 59 participating hospitals in the Netherlands. Patients were included on the first day of standard intravenous immunoglobulin treatment (2 g/kg over 5 days). Only patients with a poor prognosis (score of >= 6) according to the modified Erasmus Guillain-Barre syndrome Outcome Score were randomly assigned, via block randomisation stratified by centre, to SID (2 g/kg over 5 days) or to placebo, 7-9 days after inclusion. Patients, outcome adjudicators, monitors, and the steering committee were masked to treatment allocation. The primary outcome measure was the Guillain-Barre syndrome disability score 4 weeks after inclusion. All patients in whom allocated trial medication was started were included in the modified intention-to-treat analysis. Findings Between Feb 16, 2010, and June 5, 2018, 327 of 339 patients assessed for eligibility were included. 112 had a poor prognosis. Of those, 93 patients with a poor prognosis were included in the modified intention-to-treat analysis: 49 (53%) received SID and 44 (47%) received placebo. The adjusted common odds ratio for improvement on the Guillain-Barre syndrome disability score at 4 weeks was 1.4 (95% CI 0.6-3.3; p=0.45). Patients given SID had more serious adverse events (35% vs 16% in the first 30 days), including thromboembolic events, than those in the placebo group. Four patients died in the intervention group (13-24 weeks after randomisation). Interpretation Our study does not provide evidence that patients with Guillain-Barre syndrome with a poor prognosis benefit from a second intravenous immunoglobulin course; moreover, it entails a risk of serious adverse events. Therefore, a second intravenous immunoglobulin course should not be considered for treatment of Guillain-Barre syndrome because of a poor prognosis. The results indicate the need for treatment trials with other immune modulators in patients severely affected by Guillain-Barre syndrome. Funding Prinses Beatrix Spierfonds and Sanquin Plasma Products. Copyright (C) 2021 Elsevier Ltd. All rights reserved

A patient with an odontoid fracture and atrophy of the tongue: a case report and systematic review of the literature

BACKGROUND: Traumatic hypoglossal nerve palsy is a rare entity and has rarely been described in association with an odontoid fracture. CASE DESCRIPTION: We present a patient with a posttraumatic odontoid fracture who developed selective weakness of his arms and a unilateral hypoglossal nerve palsy. A systematic review of the literature is presented, and hypothetical causes for the injury are discussed. CONCLUSION: Bell's cruciate paralysis and central cord syndrome are probably expressions of the same mechanism rather than 2 separate entities based on a preferential damage of pyramidal crossing arm fibers. C2 fractures with concomitant lower cranial nerve injury are relatively rare and have a reasonably good outcome, especially when unilateral

Intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): mechanisms of action and clinical and genetic considerations

Introduction: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune peripheral nerve disorder that is characterized by subacute onset, progressive or relapsing weakness, and sensory deficits. Proven treatments include intravenous immunoglobulin (IVIg), corticosteroids, and plasma exchange. This review focuses on the mechanisms of action, pharmacodynamics, genetic variations, and disease characteristics that can affect the efficacy of IVIg. Areas covered: The proposed mechanisms of action of IVIg that can mediate its therapeutic effects are reviewed. These include anti-idiotypic interactions, inhibition of neonatal Fc receptors (FcRn), anti-complement activity, upregulation of inhibitory FcγRIIB receptors, and downregulation of macrophage activation or co-stimulatory and adhesion molecules. Clinical and genetic factors that can affect the therapeutic response include misdiagnosis, degree of axonal damage, pharmacokinetic variability, and genetic variations. Expert opinion: The mechanisms of action of IVIg in CIDP and their relative contribution to its efficacy are subject of ongoing investigation. Studies in other autoimmune neurological conditions, in addition, highlight the role of key immunopathological pathways and factors that are likely to be affected. Further investigation into the pathogenesis of CIDP and the mechanisms of action of IVIg may lead to the development of improved diagnostics, better utilization of IVIg, and more targeted and effective therapies