Comparison of IVIg and TPE efficacy in the treatment of neurological disorders: a systematic literature review.

Background: Intravenous immunoglobulin (IVIg) and therapeutic plasma exchange (TPE) are among the main immunotherapies for neurological disorders. Their benefit is greatest in immune-mediated conditions, but their distinct efficacy cannot be simply explained. Objectives: This review aimed to systematically identify studies comparing the efficacy of TPE and IVIg treatments for selected autoimmune neurological disorders and identify optimal therapies for each condition. Data Sources and Methods: PubMed, MEDLINE and Embase databases were searched for original publications from 1990 to 2021. Additional publications were identified via expert recommendations. Conference abstracts older than 2017, review articles and articles without information on TPE and IVIg comparison in title and abstract were excluded. Risks of bias were descriptively addressed, without a meta-analysis. Results: Forty-four studies were included on Guillain-Barré syndrome (20 studies - 12 adult, 5 paediatric, 3 all ages), myasthenia gravis (11 studies -8 adult, 3 paediatric), chronic immune-mediated polyradiculoneuropathy (3 studies -1 adult, 2 paediatric), encephalitis (1 study in adults), neuromyelitis optica spectrum disorders (5 studies -2 adult, 3 all ages) and other conditions (4 studies - all ages). TPE and IVIg were mostly similarly efficacious, measured by clinical outcomes and disease severity scores. Some studies recommended IVIg as easy to administer. TPE procedures, however, have been simplified and the safety has been improved. TPE is currently recommended for management of neuromyelitis optica spectrum disorder relapses and some myasthenia gravis subtypes, in which rapid removal of autoantibodies is crucial. Conclusion: Despite some limitations (e.g. the low evidence levels), this review provides an extensive 30-year-long overview of treatments for various conditions. Both IVIg and TPE are usually comparably efficacious options for autoimmune neurological disorders, with few exceptions. Treatment choices should be patient-tailored and based on available clinical resources. Better designed studies are needed to provide higher-level quality of evidence regarding clinical efficacy of TPE and IVIg treatments.

Clinical trials in amyotrophic lateral sclerosis: a systematic review and perspective.

Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of Phase II, Phase II/III and Phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15 000 people with amyotrophic lateral sclerosis. About 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis.

Desminopathy presenting as late onset bilateral facial weakness, with diagnosis supported by lower limb MRI.

A 63 year old male presented with a 20 year history of facial weakness and several years of nasal regurgitation and dysphonia. Examination revealed bilateral facial weakness with nasal speech. Serum creatine kinase was 918 U/L. Neurophysiological studies suggested a myopathy and biopsy of the left vastus lateralis showed serpentine basophilic inclusions in the sarcoplasm and strong oxidative enzyme activity suggesting mitochondria accumulation. The muscle MRI showed selective fatty replacement within semitendinosus, gastrocnemius and soleus indicative of a desminopathy. A heterozygous missense variant c.17C>G (p.Ser6Trp) was identified within DES, predicted to be pathogenic in silico and previously described in a family with distal limb weakness. There are no previous case reports of desminopathy presenting with facial weakness, to our knowledge. Diagnosis was suggested following myoimaging of clinically unaffected muscles. Our study highlights the importance of muscle MRI in the diagnostic evaluation of muscle disease and further expands the known phenotypic heterogeneity of desminopathies.

Epidemiological and cohort study finds no association between COVID-19 and Guillain-Barré syndrome.

Reports of Guillain-Barré syndrome (GBS) have emerged during the Coronavirus disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. The epidemiology of GBS cases reported to the UK National Immunoglobulin Database was studied from 2016 to 2019 and compared to cases reported during the COVID-19 pandemic. Data were stratified by hospital trust and region, with numbers of reported cases per month. UK population data for COVID-19 infection were collated from UK public health bodies. In parallel, but separately, members of the British Peripheral Nerve Society prospectively reported incident cases of GBS during the pandemic at their hospitals to a central register. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases in this cohort were compared. The incidence of GBS treated in UK hospitals from 2016 to 2019 was 1.65-1.88 per 100 000 individuals per year. GBS incidence fell between March and May 2020 compared to the same months of 2016-19. GBS and COVID-19 incidences during the pandemic also varied between regions and did not correlate with one another (r = 0.06, 95% confidence interval: -0.56 to 0.63, P = 0.86). In the independent cohort study, 47 GBS cases were reported (COVID-19 status: 13 definite, 12 probable, 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome between these groups. Intubation was more frequent in the COVID-19 affected cohort (7/13, 54% versus 5/22, 23% in COVID-19-negative) attributed to COVID-19 pulmonary involvement. Although it is not possible to entirely rule out the possibility of a link, this study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic, which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses.

Lyme disease: diagnosis and management.

Lyme disease (borreliosis) is a tick-borne bacterial infection caused by the spirochaete Borrelia burgdoferi, transmitted by hard-backed Ixodes ticks. Actual numbers of cases are increasing and it appears that the distribution across the UK is widening; however, it occurs most frequently in area of woodland, with temperate climate. It typically presents in mid to late summer. Lyme disease is a multisystem disease. The nervous system is the second most commonly affected system after the skin. Other systemic manifestations, such as carditis, keratitis, uveitis and inflammatory arthritis, rarely occur in European Lyme disease. In 2018, the National Institute for Health and Care Excellence has updated its guidelines on the diagnosis and management of Lyme disease. Here, we highlight important aspects of this guidance and provide a more detailed review of the clinical spectrum of neuroborreliosis, illustrated by cases we have seen.

Corticosteroid-responsive focal granulomatous herpes simplex type-1 encephalitis in adults.

We describe corticosteroid-responsive focal granulomatous encephalitis as a manifestation of herpes simplex virus (HSV) type 1 disease in the brain: something easily missed and easily treated. Two adult cases presented with cognitive symptoms progressing over weeks, despite aciclovir treatment. Brain imaging showed temporal lobe abnormalities, with gadolinium enhancement but no abnormal diffusion restriction. HSV-1 PCR analysis was negative in cerebrospinal fluid (CSF) but positive in brain biopsies, which showed vasocentric granulomatous inflammation. Paired blood and CSF samples showed intrathecal synthesis of HSV-1 type-specific IgG. The patients improved clinically only after immunosuppression. Despite profound cognitive impairment at their clinical nadir, both patients recovered fully. We suggest that, at least in a subset of patients with HSV-1 encephalitis, adjunctive corticosteroid treatment is critical to improve the outcome of the disease.