[Abdominal pain after a generalized tonic-clonic seizure]. / Buikpijn na een gegeneraliseerd tonisch-clonisch insult.

BACKGROUND: Skeletal injury following a generalized tonic-clonic insult is rare. It is often missed as patients are unable to adequately express their symptoms in the post-ictal state, the apparent lack of a trauma prior to the insult and the low a priori chance. However, in order to ensure adequate treatment, timely diagnosis of these injuries is of great importance. CASE DESCRIPTION: A 58-year old man had ongoing abdominal pain following a generalized tonic-clonic insult. Radiographic imaging showed these complaints to be the result of a bilateral acetabulum fracture, due to the forceful muscular contractions during the previous insult. Even though it is very rare and is only described 30 times worldwide, it is a potentially life-threatening injury. The patient was transferred to a specialized trauma center where he underwent open reduction and internal fixation. He recovered fully. CONCLUSION: It is important to be aware of possible musculoskeletal injury following a generalized tonic-clonic insult, as timely diagnosis is of great importance for adequate treatment and the patients' prognosis.

Guillain-Barré 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-Barré 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.

Second intravenous immunoglobulin dose in patients with Guillain-Barré 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-Barré 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-Barré syndrome with a predicted poor outcome. METHODS: In this randomised, double-blind, placebo-controlled trial (SID-GBS), we included patients (≥12 years) with Guillain-Barré 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-Barré 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-Barré 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. This study is registered with the Netherlands Trial Register, NTR 2224/NL2107. 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-Barré 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-Barré 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-Barré syndrome. FUNDING: Prinses Beatrix Spierfonds and Sanquin Plasma Products.

Interventions for fatigue in peripheral neuropathy.

BACKGROUND: Persistent feelings of fatigue (or subjective fatigue), which may be experienced in the absence of physiological factors, affect many people with peripheral neuropathy. A variety of interventions for subjective fatigue are available, but little is known about their efficacy or the likelihood of any adverse effects for people with peripheral neuropathy. OBJECTIVES: To assess the effects of drugs and physical, psychological or behavioural interventions for fatigue in adults or children with peripheral neuropathy. SEARCH METHODS: On 5 November 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, LILACS and AMED. We also searched reference lists of all studies identified for inclusion and relevant reviews, and contacted the authors of included studies and known experts in the field to identify additional published or unpublished data. We also searched trials registries for ongoing studies. SELECTION CRITERIA: We considered for inclusion randomised controlled trials (RCTs) and quasi-RCTs comparing any form of intervention for fatigue management in adults with peripheral neuropathy with placebo, no intervention or an alternative form of intervention for fatigue. Interventions considered included drugs, pacing and grading of physical activity, general or specific exercise, compensatory strategies such as orthotics, relaxation, counselling, cognitive and educational strategies. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias and extracted study data. We contacted study authors for additional information. We collected information on adverse events from the included trials. MAIN RESULTS: The review includes three trials, which were all at low risk of bias, involving 530 people with peripheral neuropathy. The effects of amantadine from one randomised, double-blind, placebo-controlled, cross-over trial comparing amantadine with placebo for the treatment of fatigue in 80 people with Guillain-Barré syndrome (GBS) were uncertain for the proportion of people achieving a favourable outcome six weeks post-intervention (odds ratio (OR) 0.56 (95% confidence interval (CI) 0.22 to 1.35, N = 74, P = 0.16). We assessed the quality of this evidence as low. Two parallel-group randomised double-blind, placebo-controlled trials comparing the effects of two doses of ascorbic acid with placebo for reducing fatigue in adults with Charcot-Marie-Tooth disease type 1A (CMT1A) showed that the effects of ascorbic acid at either dose are probably small (standardised mean difference (SMD) -0.12 (95% CI -0.32 to 0.08, n = 404, P = 0.25)) for change in fatigue after 12 to 24 months (moderate quality evidence). Neither ascorbic acid study measured fatigue at four to 12 weeks, which was our primary outcome measure. No serious adverse events were reported with amantadine. Serious adverse events were reported in the trials of ascorbic acid. However,risk of serious adverse events was similar with ascorbic acid and placebo. AUTHORS' CONCLUSIONS: One small imprecise study in people with GBS showed uncertain effects of amantadine on fatigue. In two studies in people with CMT1A there is moderate-quality evidence that ascorbic acid has little meaningful benefit on fatigue. Information about adverse effects was limited, although both treatments appear to be well tolerated and safe in these conditions.There was no evidence available from RCTs to evaluate the effect of other drugs or other interventions for fatigue in either GBS, CMT1A or other causes of peripheral neuropathy. The cost effectiveness of different interventions should also be considered in future randomised clinical trials.

Contribution of central and peripheral factors to residual fatigue in Guillain-Barré syndrome.

Many patients with Guillain-Barré syndrome (GBS) suffer from severe residual fatigue that has an uncertain basis. We determined the relative contribution of peripheral and central factors during a 2-min fatiguing sustained maximal voluntary contraction (MVC) in 10 neurologically well-recovered GBS patients and 12 age- and sex-matched healthy controls. Physiological fatigue was defined as the decline of voluntary force during an MVC of the biceps brachii. Relative amounts of peripheral fatigue and central activation failure were determined combining voluntary force and force responses to electrical stimulation. Surface electromyography was used to determine muscle-fiber conduction velocity. During the first minute of sustained MVC, peripheral fatigue developed more slowly in patients than in controls. Central fatigue only occurred in patients. The muscle-fiber conduction velocity was higher in patients. The initial MVC, decrease of MVC, initial force response, and initial central activation failure did not significantly differ between the groups. Although peripheral mechanisms cannot be excluded in the pathogenesis of residual fatigue after GBS, these results suggest that central changes are involved. This study thus provides further insight into the factors contributing to residual fatigue in GBS patients.

Nerve conduction studies in relation to residual fatigue in Guillain-Barré syndrome.

Many Guillain-Barré syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) patients recover well, but suffer from excessive fatigue, which may persist for years and reduce the quality of life considerably. In order to determine whether residual subclinical peripheral nerve dysfunction is a possible underlying mechanism of fatigue, we performed standardized nerve conduction (NC) studies in 16 fatigued patients, mean 6.5 years after diagnosis. Thirteen were relatively well recovered from GBS and 3 had stable CIDP. In contrast to CIDP, most NC values in GBS patients were remarkably restored and within normal values. No correlations were found between the electrophysiological findings and the fatigue scores,muscle strength, or functional scores. This study demonstrates that fatigue in GBS is not explained by residual nerve dysfunction, using conventional NC measurements.

Conduction velocity distribution in neurologically well-recovered but fatigued Guillain-Barré syndrome patients.

Many patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) suffer from excessive fatigue. To assess whether this fatigue might be related to changes in slow-conducting nerve fibers, we determined the conduction velocity distribution (CVD) in the median nerve. Thirteen fatigued but neurologically well-recovered GBS patients, 2 fatigued and stable CIDP patients, and 19 healthy controls participated in this study. Conventional maximal nerve conduction velocities (NCVs) did not show differences between GBS patients and healthy controls. However, in both GBS and CIDP patients the CVD was altered, showing significant narrowing of the velocity distribution with loss of the fastest- and slowest-conducting fibers. These changes were most pronounced in the subgroup of patients with the lowest fatigue scores. We therefore conclude that the observed CVD changes in patients are not likely to contribute to persisting complaints of fatigue after GBS.

Screening for anti-ganglioside antibodies in hypocretin-deficient human narcolepsy.

Narcolepsy is a sleep disorder caused by defective hypocretin (orexin) neurotransmission. It is thought to result from an autoimmune destruction of hypocretin producing neurons. Recently, low hypocretin levels were found in patients with Guillain-Barré syndrome, a post-infectious immune-mediated disorder in which a variety of circulating antibodies against neuronal gangliosides are found. We therefore considered gangliosides to be candidate antigens in narcolepsy as well, and screened for the presence of a panel of serum anti-ganglioside antibodies in a group of 28 well-characterized narcoleptic patients. We did not find a correlation between increased titers of anti-ganglioside antibodies and hypocretin-deficient narcolepsy. This study does not support the hypothesis that an autoimmune response is involved in narcolepsy. However, as an autoimmune attack may be selective and/or transient, future studies are needed to ultimately refute or confirm the autoimmune hypothesis.

Treatment of immune neuropathies.

PURPOSE OF THE REVIEW: Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating poly(radiculo)neuropathy (CIDP) and multifocal motor neuropathy (MMN) are potentially treatable disorders. The use of appropriate assessment scales to evaluate the effects of treatment is essential. Recent therapeutic trials and the question of whether patients with mild disease or other variants of these disorders need to be treated are discussed. RECENT FINDINGS: Recent clinical trials and Cochrane reviews give new information on the effect of various treatments in patients with GBS, CIDP and MMN. Intravenous immunoglobulin remains the only treatment proven to be effective in MMN. Combinations of treatment may be even more effective in GBS. Studies on prognostic factors related to improvement have been reported. Whether patients with Miller-Fisher syndrome or those with mild GBS should also be treated is still debated. New assessment scales at the disability and handicap level have now been evaluated for GBS and CIDP, and are ready for use. Results of studies in experimental models contribute to our understanding of the mechanism of action of intravenous immunoglobulin. SUMMARY: Recent new information on the use of intravenous immunoglobulin and steroids indicates that the former should remain the cornerstone of treatment for GBS and MMN, and probably also for CIDP. Whether steroids not only suppress disease activity in CIDP but also eradicate the disease remains to be established. Some GBS patients have secondary deterioration or finally turn out to have CIDP; additional information in this group of patients may lead to more appropriate disease management. Most patients with CIDP and those with MMN need long-term treatment. New treatment strategies should now focus also on the effect and the costs of treatment over long-term follow up.