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It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases). Among the 651 patients, [362 (55%) cases and 289 (45%) controls], a higher proportion of cases had impairment in ADLs (199 [68.9%] vs 101 [51.8%], OR 2.06, p < 0.0002) and reported symptoms impacting employment (159 [58.2%] vs 69 [35.6%] OR 2.53, p < 0.0001). There was no significant difference in the proportion with depression or anxiety between case and control groups overall. For cases, impairment of ADLs was associated with increased risk in female sex, age > 50 years and hypertension (OR 5.43, p < 0.003, 3.11, p = 0.02, 3.66, p = 0.04). Those receiving either statins or angiotensin converting enzyme (ACE) inhibitors had a lower risk of impairment in ADLs (OR 0.09, p = 0.0006, 0.17, p = 0.03). Patients with neurological or psychiatric complications of COVID-19 had worse functional outcomes than those with respiratory COVID-19 alone in terms of ADLs and employment. Female sex, age > 50 years, and hypertension were associated with worse outcomes, and statins or ACE inhibitors with better outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Reproducible and standardised neurological assessment scales are important in quantifying research outcomes. These scales are often performed by non-neurologists and/or non-clinicians and must be robust, quantifiable, reproducible and comparable to a neurologist's assessment. COVID-CNS is a multi-centre study which utilised the Neurological Impairment Scale (NIS) as a core assessment tool in studying neurological outcomes following COVID-19 infection. We investigated the strengths and weaknesses of the NIS when used by non-neurology clinicians and non-clinicians, and compared performance to a structured neurological examination performed by a neurology clinician. Through our findings, we provide practical advice on how non-clinicians can be readily trained in conducting reproducible and standardised neurological assessments in a multi-centre study, as well as illustrating potential pitfalls of these tools., Competing Interests: Declaration of competing interest T.S. is the Director of The Pandemic Institute which has received funding from Innova and CSL Seqirus and Aviva and DAM Health. T.S. was an advisor to the GSK Ebola Vaccine programme and the Siemens Diagnostic Programme. T.S. Chaired the Siemens Healthineers Clinical Advisory Board. T.S. Co-Chaired the WHO Neuro-COVID task force and sat on the UK Government Advisory Committee on Dangerous Pathogens, and the Medicines and Healthcare Products Regulatory Agency (MHRA) Expert Working Group on Covid-19 vaccines. T.S. Advised to the UK COVID-19 Therapeutics Advisory Panel (UK-TAP). T.S. was a Member of COVID-19 Vaccines Benefit Risk Expert Working Group for the Commission on Human Medicines (CHM) committee of the Medicines and Healthcare products Regulatory Agency (MHRA). T.S. has been a member of the Encephalitis Society since 1998 and President of the Encephalitis Society since 2019., (Copyright © 2024. Published by Elsevier Ltd.)

Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as second-line choices despite widespread consensus on their efficacy. We aimed to gather real-world data comparing the tolerability and reasons for discontinuation for these agents, by performing a national United Kingdom survey of side effects and reasons for discontinuation of immunosuppressants in myasthenia gravis. Of 235 patients, 166 had taken azathioprine, 102 mycophenolate, and 40 methotrexate. The most common side effects for each agent were liver dysfunction for azathioprine (23 %), diarrhoea for mycophenolate (14 %), and fatigue for methotrexate (18 %). Women were generally more likely to experience side effects of immunosuppressants. Azathioprine was significantly more likely to be discontinued than mycophenolate and methotrexate due to side effects. There was no significant difference in treatment cessation due to lack of efficacy. This study highlights the significant side-effect burden of treatment for myasthenia gravis. Mechanisms to reduce azathioprine toxicity should be utilised, however mycophenolate and methotrexate appear to be good treatment choices if teratogenicity is not a concern. Women are disadvantaged due to higher frequency of side effects and considerations around pregnancy and breastfeeding. Treatments with improved tolerability are needed., Competing Interests: Declaration of competing interest All authors completed an ICMJE disclosure form. Katherine Dodd is in receipt of research grants from the Manchester Myasthenia Gravis Research Fund (Northcare Charity), myaware and the Neuromuscular Study Group (NMSG), and received support from the NMSG to attend the NMSG Annual Scientific Meetings 2022 and 2023. Rohan Ahmed has no competing interests to declare. Philip Ambrose has received consulting fees from ArgenX and CSL Behring. James Holt has received consulting fees and payment for participation in an advisory board from Takenda, and support for attending a conference from CSL Behring. Saiju Jacob has received funding to his institution for a clinical research fellowship from myaware, consulting fees from ArgenX for clinical trials and myasthenia research, speaker fees from UCB pharmaceuticals, Janessen, Immunovant and Regeneron, and payment for participation in advisory boards for clinical trials from ArgenX, Alnylam, and Alexion. He is the Clinical Research Lead in neurological disorders for the National Institute of Health Research Clinical Research Network. M Isabel Leite has received funding from the NHS (Myasthenia and Related Disorders Service and National Specialised Commissioning Group for Neuromyelitis Optica, UK) and the University of Oxford, UK. She has been awarded research grants from the UK association for patients with myasthenia (myaware) and the University of Oxford. She has received speaker honoraria or travel grants from Biogen Idec, Novartis, UCB Pharma, and the Guthy-Jackson Charitable Foundation. She also serves on scientific or educational advisory boards for UCB Pharma, ArgenX and Viela/Horizon. James Miller has received payment for participation on advisory boards for ArgenX and UCB. Pyae Phyo San is undertaking a PhD with funding from myaware and received a travel grant for the Myasthenia Gravis Foundation of America 14th international conference. Jennifer Spillane has received speaker fees from ArgenX, support for attending conferences from UCB and ArgenX, taken part in advisory boards for UCB and ArgenX and has taken part in a Single Technology Appraisal for the National Institute for Clinical Excellence as a clinical expert. Stuart Viegas has received payment for speaking at the MG Masterclass Neurology Academy 2023. Jon Sussman has received payment from the National Institute for Clinical Excellence for expert testimony, and has an honorary role with the Association of British Neurologists., (Copyright © 2024. Published by Elsevier B.V.)

Background: Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection., Methods: Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment., Results: 807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres' catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups., Conclusions: Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Nitrous oxide (N 2 O) is the second most common recreational drug used by 16- to 24-year-olds in the UK. Neurological symptoms can occur in some people that use N 2 O recreationally, but most information comes from small case series., Methods: We describe 119 patients with N 2 O-myeloneuropathy seen at NHS teaching hospitals in three of the UK's largest cities: London, Birmingham and Manchester. This work summarises the clinical and investigative findings in the largest case series to date., Results: Paraesthesia was the presenting complaint in 85% of cases, with the lower limbs more commonly affected than the upper limbs. Gait ataxia was common, and bladder and bowel disturbance were frequent additional symptoms. The mid-cervical region of the spinal cord (C3-C5) was most often affected on MRI T2-weighted imaging. The number of N 2 O canisters consumed per week correlated with methylmalonic acid levels in the blood as a measure of functional B 12 deficiency (rho (ρ)=0.44, p=0.04)., Conclusions: Preventable neurological harm from N 2 O abuse is increasingly seen worldwide. Ease of access to canisters and larger cylinders of N 2 O has led to an apparent rise in cases of N 2 O-myeloneuropathy in several areas of the UK. Our results highlight the range of clinical manifestations in a large group of patients to improve awareness of risk, aid early recognition, and promote timely treatment., Competing Interests: Competing interests: DM leads a medical student-run unpaid campaign - ‘N2O: Know The Risks’ - which provides educational teaching sessions on the risks of nitrous oxide in East London., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To ensure readers are informed consumers of functional magnetic resonance imaging (fMRI) research in headache, to outline ongoing challenges in this area of research, and to describe potential considerations when asked to collaborate on fMRI research in headache, as well as to suggest future directions for improvement in the field., Background: Functional MRI has played a key role in understanding headache pathophysiology, and mapping networks involved with headache-related brain activity have the potential to identify intervention targets. Some investigators have also begun to explore its use for diagnosis., Methods/results: The manuscript is a narrative review of the current best practices in fMRI in headache research, including guidelines on transparency and reproducibility. It also contains an outline of the fundamentals of MRI theory, task-related study design, resting-state functional connectivity, relevant statistics and power analysis, image preprocessing, and other considerations essential to the field., Conclusion: Best practices to increase reproducibility include methods transparency, eliminating error, using a priori hypotheses and power calculations, using standardized instruments and diagnostic criteria, and developing large-scale, publicly available datasets., (© 2023 American Headache Society.)

Autoimmune diseases are characterized by a significant sex dimorphism, with women showing increased susceptibility to disease. This is, at least in part, due to sex-dependent differences in the immune system that are influenced by the complex interplay between sex hormones and sex chromosomes, with contribution from sociological factors, diet and gut microbiota. Sex differences are evident in the number and function of lymphocyte populations. Women mount a stronger pro-inflammatory response than males, with increased lymphocyte proliferation, activation and pro-inflammatory cytokine production, whereas men display expanded regulatory cell subsets. Ageing alters the immune landscape of men and women in differing ways, resulting in changes in autoimmune disease susceptibility. Here we review the current literature on sex differences in lymphocyte function, the factors that influence this, and the implications for autoimmune disease. We propose that improved understanding of sex bias in lymphocyte function can provide sex-specific tailoring of treatment strategies for better management of autoimmune diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dodd and Menon.)

Fused in sarcoma-related amyotrophic lateral sclerosis (FUS-ALS) accounts for 4% of all familial motor neurone disease, but has a much higher incidence in juvenile ALS. We present a case of a 17-year-old British man with rapidly progressive bulbar and respiratory failure. On examination he had weak periocular muscles, neck flexion weakness, and a wasted, fasciculating and weak tongue. There were no sensory, cerebellar, or extrapyramidal features but he had frequent myoclonic jerks of the limbs. Routine bloods were normal and an MRI of the neuroaxis as well as CT chest, abdomen and pelvis were unremarkable. NCS/EMG was consistent with anterior horn cell disorder and EEG showed multiple paroxysmal generalized spike-wave discharges. DNA sequencing demonstrated that he was heterozygous for the c.1483C>T pathogenic nonsense mutation in exon 14 of the FUS gene, consistent with ALS6. This is the first reported case of FUS-ALS presenting with prominent myoclonus.

Lumbar puncture (LP) is an important and frequently performed invasive procedure for the diagnosis and management of neurological conditions. There is little in the neurological literature on the topic of periprocedural management of antithrombotics in patients undergoing LP. Current practice is therefore largely extrapolated from guidelines produced by anaesthetic bodies on neuraxial anaesthesia, haematology groups advising on periprocedural management of antiplatelet agents and anticoagulants, and by neuroradiology on imaging-guided spinal procedures. This paper summarises the existing literature on the topic and offers recommendations to guide periprocedural antithrombotic management for LP, based on the consolidation of the best available evidence. ​., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite the established effectiveness of the brain-computer interface (BCI) therapy during stroke rehabilitation (Song et al., 2014a, 2015; Young et al., 2014a,b,c, 2015; Remsik et al., 2016), little is understood about the connections between motor network reorganization and functional motor improvements. The aim of this study was to investigate changes in the network reorganization of the motor cortex during BCI therapy. Graph theoretical approaches are used on resting-state functional magnetic resonance imaging (fMRI) data acquired from stroke patients to evaluate these changes. Correlations between changes in graph measurements and behavioral measurements were also examined. Right hemisphere chronic stroke patients (average time from stroke onset = 38.23 months, standard deviation (SD) = 46.27 months, n = 13, 6 males, 10 right-handed) with upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device. Eyes-closed resting-state fMRI (rs-fMRI) scans, along with T-1 weighted anatomical scans on 3.0T MRI scanners were collected from these patients at four test points. Immediate therapeutic effects were investigated by comparing pre and post-therapy results. Results displayed that th average clustering coefficient of the motor network increased significantly from pre to post-therapy. Furthermore, increased regional centrality of ipsilesional primary motor area ( p = 0.02) and decreases in regional centrality of contralesional thalamus ( p = 0.05), basal ganglia ( p = 0.05 in betweenness centrality analysis and p = 0.03 for degree centrality), and dentate nucleus ( p = 0.03) were observed (uncorrected). These findings suggest an overall trend toward significance in terms of involvement of these regions. Increased centrality of primary motor area may indicate increased efficiency within its interactive network as an effect of BCI therapy. Notably, changes in centrality of the bilateral cerebellum regions have strong correlations with both clinical variables [the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT)].

The primary goal of this work was to apply data-driven machine learning regression to assess if resting state functional connectivity (rs-FC) could estimate measures of behavioral domains in stroke subjects who completed brain-computer interface (BCI) intervention for motor rehabilitation. The study cohort consisted of 20 chronic-stage stroke subjects exhibiting persistent upper-extremity motor deficits who received the intervention using a closed-loop neurofeedback BCI device. Over the course of this intervention, resting state functional MRI scans were collected at four distinct time points: namely, pre-intervention, mid-intervention, post-intervention and 1-month after completion of intervention. Behavioral assessments were administered outside the scanner at each time-point to collect objective measures such as the Action Research Arm Test, Nine-Hole Peg Test, and Barthel Index as well as subjective measures including the Stroke Impact Scale. The present analysis focused on neuroplasticity and behavioral outcomes measured across pre-intervention, post-intervention and 1-month post-intervention to study immediate and carry-over effects. Rs-FC, changes in rs-FC within the motor network and the behavioral measures at preceding stages were used as input features and behavioral measures and associated changes at succeeding stages were used as outcomes for machine-learning-based support vector regression (SVR) models. Potential clinical confounding factors such as age, gender, lesion hemisphere, and stroke severity were included as additional features in each of the regression models. Sequential forward feature selection procedure narrowed the search for important correlates. Behavioral outcomes at preceding time-points outperformed rs-FC-based correlates. Rs-FC and changes associated with bilateral primary motor areas were found to be important correlates of across several behavioral outcomes and were stable upon inclusion of clinical variables as well. NIH Stroke Scale and motor impairment severity were the most influential clinical variables. Comparatively, linear SVR models aided in evaluation of contribution of individual correlates and seed regions while non-linear SVR models achieved higher performance in prediction of behavioral outcomes.

Interventional therapy using brain-computer interface (BCI) technology has shown promise in facilitating motor recovery in stroke survivors; however, the impact of this form of intervention on functional networks outside of the motor network specifically is not well-understood. Here, we investigated resting-state functional connectivity (rs-FC) in stroke participants undergoing BCI therapy across stages, namely pre- and post-intervention, to identify discriminative functional changes using a machine learning classifier with the goal of categorizing participants into one of the two therapy stages. Twenty chronic stroke participants with persistent upper-extremity motor impairment received neuromodulatory training using a closed-loop neurofeedback BCI device, and rs-functional MRI (rs-fMRI) scans were collected at four time points: pre-, mid-, post-, and 1 month post-therapy. To evaluate the peak effects of this intervention, rs-FC was analyzed from two specific stages, namely pre- and post-therapy. In total, 236 seeds spanning both motor and non-motor regions of the brain were computed at each stage. A univariate feature selection was applied to reduce the number of features followed by a principal component-based data transformation used by a linear binary support vector machine (SVM) classifier to classify each participant into a therapy stage. The SVM classifier achieved a cross-validation accuracy of 92.5% using a leave-one-out method. Outside of the motor network, seeds from the fronto-parietal task control, default mode, subcortical, and visual networks emerged as important contributors to the classification. Furthermore, a higher number of functional changes were observed to be strengthening from the pre- to post-therapy stage than the ones weakening, both of which involved motor and non-motor regions of the brain. These findings may provide new evidence to support the potential clinical utility of BCI therapy as a form of stroke rehabilitation that not only benefits motor recovery but also facilitates recovery in other brain networks. Moreover, delineation of stronger and weaker changes may inform more optimal designs of BCI interventional therapy so as to facilitate strengthened and suppress weakened changes in the recovery process.

Following a stroke, the resulting lesion creates contralateral motor impairment and an interhemispheric imbalance involving hyperexcitability of the contralesional hemisphere. Neuronal reorganization may occur on both the ipsilesional and contralesional hemispheres during recovery to regain motor functionality and therefore bilateral activation for the hemiparetic side is often observed. Although ipsilesional hemispheric reorganization is traditionally thought to be most important for successful recovery, definitive conclusions into the role and importance of the contralesional motor cortex remain under debate. Through examining recent research in functional neuroimaging investigating motor cortex changes post-stroke, as well as brain-computer interface (BCI) and transcranial magnetic stimulation (TMS) therapies, this review attempts to clarify the contributions of each hemisphere toward recovery. Several functional magnetic resonance imaging studies suggest that continuation of contralesional hemisphere hyperexcitability correlates with lesser recovery, however a subset of well-recovered patients demonstrate contralesional motor activity and show decreased functional capability when the contralesional hemisphere is inhibited. BCI therapy may beneficially activate either the contralesional or ipsilesional hemisphere, depending on the study design, for chronic stroke patients who are otherwise at a functional plateau. Repetitive TMS used to excite the ipsilesional motor cortex or inhibit the contralesional hemisphere has shown promise in enhancing stroke patients' recovery.

Background: Herpes simplex virus (HSV) encephalitis is the most common sporadic cause of encephalitis with significant morbidity and mortality that is drastically reduced by early antiviral treatment., Case Presentation: We report a 37 year old woman, 33 weeks pregnant, who presented with seizures due to proven HSV-1 encephalitis, and who had had a previous episode of probable viral encephalitis aged 14 years. She was successfully treated with aciclovir on both occasions and, in the latter, went on to deliver a healthy infant. This case is compared with 17 cases of HSV encephalitis in pregnancy in the literature identifying a predominance in the late 2nd and 3rd trimesters, perhaps in part due to immunological changes in pregnancy. The clinical presentation is also compared with non-pregnant patients with HSV encephalitis in the largest prospective UK and European studies. We also present practical advice on management from recent national guidelines., Conclusion: When pregnant women present with new seizures, headache, impaired consciousness or altered behaviour urgent investigation is required to identify common diagnoses, such as eclampsia, venous sinus thrombosis and metabolic disturbances. Nevertheless, viral encephalitis is a very treatable cause of this presentation with potentially serious complications if missed, and may be more common in latter stages of pregnancy. Encephalitis should not be discounted if the patient is afebrile, has a normal Glasgow coma score, or the cerebrospinal fluid white cell count is only slightly elevated, as these features are well recognised in viral encephalitis.