bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term assessment of efgartigimod in patients with generalised myasthenia gravis: ADAPT+ study interim results
Authors: Jacob Saiju , Howard James , Bril Vera , Peric Stojan , Bleecker Jan De , T’joen Carolin , Travers Jackalyne , Utsugisawa Kimiaki , Verschuuren Jan , Mantegazza Renato 
Published: August 2022

IntroductionIn ADAPT, efgartigimod, a human IgG1 antibody Fc-fragment blocking neonatal Fc receptor, resulted in clinically meaningful improvement (CMI) in myasthenia gravis (MG)-specific measures. Patients completing ADAPT were eligible to enrol in ADAPT+ (open-label, 3-year extension study).MethodsEfgartigimod, 10 mg/kg intravenous infusion administered once-weekly for 4 weeks; subsequent cycles initiated based on predefined criteria. Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative MG (QMG) scales were completed every cycle.ResultsFrom ADAPT 91% patients (151/167) entered ADAPT+. As of February 2021, 106 AChR-Ab+ and 33 AChR-Ab– had received ≥1 dose of efgartigimod (including 66 ADAPT placebo patients). Mean(SD) study duration: 363(114) days. The most common adverse events (AEs) in the efgartigimod-efgartigimod and placebo-efgartigimod arms: headache (15.1%/30.3%), nasopharyngitis (8.2%/13.6%), diarrhoea (6.8%/10.6%). Five deaths occurred, none considered efgartigimod-related by investigators. AEs were predominantly mild or moderate. CMI was observed in AChR-Ab+ patients during each cycle (up to 10 cycles), comparable to improvements at week 3, cycle 1 (mean[SE]: MG-ADL, –5.1[0.34]; QMG, –4.7[0.41]). Clinical improvements mirrored maximal reductions in total IgG and AChR-Abs across all cycles. Similar results observed in AChR-Ab– patients.ConclusionsThis suggests long-term efgartigimod was well-tolerated and efficacious, regardless of antibody status. No new safety signals were identified.
164 The role of MEG in assessment and diagnosis in mTBI
Authors: Allen Christopher , Rier Lukas , Gascoyne Lauren , Dineen Robert , DasNair Roshan , Brookes Matthew , Evangelou Nikos 
Published: August 2022

IntroductionThis MRC Confidence in Concept funded study (Clinical Trials reference:NCT03867513) combined magnetoencephalography (MEG) with ultrahigh field 7T MRI, to look for functional and struc- tural abnormalities in mild traumatic brain injury (mTBI).ObjectivesCan those with mTBI be differentiated from non-head injured orthopaedic trauma controls by measuring brain wave activity.MethodsWe scanned 40 participants within two weeks of an emergency department visit and they underwent resting state and task specific MEG followed by 7T MRI including structural, susceptibility, and diffusion sequences. Questionnaire assessment was completed at baseline, three, and six months.ResultsWhilst most individuals with mTBI recover a significant proportion have persistent difficulties. Using a Hidden Markov Model in the mTBI cohort, we were able to demonstrate reduced beta band connec- tivity results from a loss in the temporal coincidence of bursts of activity in spatially distinct regions. This replicates our findings in a distinct sub-acute mTBI cohort. Susceptibility weight imaging revealed only two mTBI participants with microhaemorrhages, their clinical care, markers of injury severity, and recovery did not differentiate them from others in the mTBI cohort.ConclusionsOur results suggests that mTBI may impair the dynamic coordination of neural network activity and this requires further exploration.
165 The advanced BRAIN health clinic and study of long-term neurological outcomes in retired elite athletes
Authors: Graham Neil SN , Zimmerman Karl , Parker Thomas D , Friedland Daniel , Sylvester Richard , Sharp David J 
Published: August 2022

The long-term effects of elite contact sports participation on brain health are poorly understood. This clinic aims to provide expert clinical review of retired players with neurocognitive and neuropsychiatric symptoms and, in an integrated research programme, better understand their neurological outcomes.Former professional rugby players aged 30-55 are eligible, expanding to include footballers and control participants shortly. Assessment includes questionnaires documenting head injury exposure (Ohio State Method), substance use, affective, sleep, post-traumatic and post-concussive symptoms, quality of life and behavioural difficulties, including caregiver collateral. 3T MRI is acquired incorporating volumetric T1w, FLAIR, DTI, SWI and resting state-fMRI. Blood markers of neuronal damage and neurodegeneration are taken including neurofilament light and ptau181. Plasma/serum are stored for further research analyses. Neuropsychological performance is assessed including working memory, processing speed, executive functioning and performance validity testing. Participants undergo neurological review, receiving indi- vidual level multidisciplinary assessment and support. Assessment is repeated longitudinally after two and four years.We will test the relationship of head injury exposure, genotype, biomarkers of injury and neurodegenera- tion, cognitive, neuropsychiatric and functional status. Sub-studies incorporating 7T MRI and tau PET are planned to further clarify disease mechanisms. The work is funded by but performed independently of the Rugby Football Union.
166 Exploring interactions between traumatic brain injury and cognitive co-morbidity: descriptive case analysis from real-world monitoring
Authors: Parkinson Megan , Curtis Francesca , Dani Mel , Fertleman Michael , Kolanko Magda , Soreq Eyal , Barnaghi Payam , Sharp David , Li Lucia ,   the UK DRI Care Research & Technology Centre
Published: August 2022

IntroductionTraumatic Brain Injury (TBI) is common, and increasing in older adults, in whom functional outcomes can be particularly poor. We studied post-TBI recovery using Minder, a remote home monitor- ing system that records sleep and activity data.MethodsWe installed Minder in recently discharged patients >60years with moderate-severe TBI. We present comparative descriptive analyses of early post-discharge recovery for two male patients, cross referencing observed data against verified activities and events. Both have similar socioeconomic back- grounds, non-neurological comorbidity burden and household set-up. One had prior cognitive impair- ment (PAT1), whilst the other did not (PAT2).ResultsWe present 10 weeks of sleep and activity data. The data from PAT1 revealed extremely regular sleep-wake schedule, which remained stable. There was minimal time out of bed overnight, with corresponding bathroom activity, consistent with self-reported overnight toilet trips. Conversely, PAT2’s data revealed highly irregular and fragmented sleep patterns, despite PAT2 reporting good sleep. There were significant periods out of bed overnight with activity detected in rooms throughout the house, con- sistent with carer reports of night-time wandering. A period of increased overnight activity coincided with a sequence of falls, necessitating increases in care.DiscussionOur data suggests important interactions between cognitive comorbidity and injury on function after TBI. Our novel approach provides valuable ‘real world’ insights into TBI recovery, particularly in those with poor insight, and could also help guide clinical care.
174 Croydon neurology audit of the site of death of patients with motor neurone disease
Authors: Kanagaratnam Meneka , Boodhoo Ajay , Jeffries-Shaw Caroline , Nitkunan Arani 
Published: August 2022

Getting It Right First Time (GIRFT) Neurology recommended in September 2021 to audit the site of death of patients with motor neurone disease (MND) as an indicator for whole-life management.This retrospective audit collected data on patients with MND admitted to Croydon University Hospital during a 2-year period from April 2018. Site of death is currently not recorded so data were obtained from the multi-disciplinary team. As per NICE guidelines, data were extracted on documentation of discussions regarding resuscitation status.Of the 20 patients admitted, 12 died. Compared to national statistics, more patients died at home (42% locally vs 27% nationally), with fewer dying in hospital (17% vs 39% nationally) and similar proportions dying in a hospice (~15%). In 8 of the 17 non-elective admissions, patients had their resuscitation status clearly documented before or during the admission.Patients with MND at Croydon are being managed appropriately compared to national data. Systems like Coordinate My Care enable communication between primary and secondary care settings and should be used consistently. Site of death is to be documented in Model Hospital enabling easier audit of this in the future.
181 The diagnostic crisis in mTBI – proposal of a novel neurovascular approach
Authors: Das Abhijit , Dutta Anirban , Wylie Glenn , Sekhar Alakendu 
Published: August 2022

Mild traumatic brain injury (TBI) is common and associated with a spectrum of symptoms, which usually resolve within 3 months. But 5%–15% of patients are left with chronic disabling symptoms which challenge the current construct of mTBI. Increasingly mTBI has been a common subject of legal cases where neu- rologists have been ensnared.The main reason for such legal challenges is the lack of clarity in mTBI definition and prognosis. The current mTBI construct is heavily dependent on the Mayo classification of Brain Injury Assessment, where Post-traumatic amnesia (PTA) is often taken as the principal index of severity, without attention to other relevant phenomena. Unfortunately, PTA is an unreliable indicator for the whole spectrum of brain injury and there is an urgent need for a better diagnostic construct, specifically utilizing the recent advances in TBI-pathophysiology (neurovascular cascade and cone of vulnerability).We propose 1) evaluation for all brain injuries using multimodal imaging (MRI/fNIRS) protocol to capture the dynamic neurovascular changes seen in the entire spectrum of TBI severity. 2)Explore the relation between neuroimaging changes to the clinical symptoms occurring in various TBI stages by correlat- ing the comprehensive imaging data to the structured clinical assessments. 3) We will develop a novel clinical scoring system of injury severity across the spectrum of TBI by integrating the clinical outcome data with radiological (microvascular & macroscopic) and molecular biomarkers (Salivary RNA) for use in routine clinical practice.
COVID-19 vaccination and Guillain-Barré syndrome: analyses using the National Immunoglobulin Database
Authors: Keh Ryan YS , Scanlon Sophie , Donegan Katherine , Cavanagh Sally , Foster Mark , Skelland David , Palmer James , Machado Pedro M , Carr Aisling S , Lunn Michael P 
Published: August 2022

Anti-viral vaccination has rarely been associated with Guillain-Barré syndrome(GBS). We performed a population-based study of NHS England data and a UK multicentre surveillance study to investigate the relationship between COVID-19 vaccination and GBS.We linked GBS cases from England’s National Immunoglobulin Database(NID) with COVID-19 vaccina- tion data from December 2020–July 2021. GBS temporally associated within a 6-week risk window of any COVID-19 vaccine was identified.We prospectively collected incident UK GBS cases January–November 2021 regardless of vaccine exposure.The NID recorded 996 English GBS cases January–October 2021. A spike of cases above the 2016-2020 average occurred March–April 2021. 198 cases occurred within 6 weeks of first-dose COVID-19 vaccina- tion (0.618cases/100,000vaccinations: 176 ChAdOx1 nCoV-19, 21 tozinameran, 1 mRNA-1273). First-dose ChAdOx1 nCoV-19 accounted for the excess of 98-140 GBS cases with a peak 24 days post-vaccination. First-dose tozinameran and second-dose any vaccination showed no excess GBS risk. The UK multicen- tre surveillance dataset (121 patients) identified no phenotypic or demographic differences between vaccine-linked and unlinked cases.First-dose ChAdOx1 nCoV-19 vaccination is associated with excess GBS risk 0.576 (95%CI 0.481-0.691) cases/100,000 doses. No specific features are associated with vaccination-related GBS cases. The mechanism of immunogenicity of ChAdOx1 nCoV-19- warrants further study.
190 Nusinersen treatment in adults with spinal-muscular-atrophy with complex-spinal anatomy at St. George’s Hospital, London
Authors: Ambawatte Sathyajith Buddhika , Chhabda Sahil , Johnson Declan , Weidner Derek , Chatfield Sherryl , Appleton Pamela , Matthews Emma , Nirmalananthan Niranjanan , Galtrey Clare 
Published: August 2022

We describe nusinersen, the only licensed treatment for adults with SMA in the UK, administra- tion with Single-Plane-Fluoroscopic-Guided(SPFG), Bi-Plane-Fluoroscopic-Guided(BPFG), or Computerised-Tomography-guided(CTG).We treated three patients with type-2-SMA (two with Severe-Scoliosis[SS], one with Posterior-Spinal- Fusion[PSF]) and four with type-3-SMA (two ambulant, one with Normal-Spine[NS] and one Mild-Lumbar- Spinal-Deformities[MLSD] and two non-ambulant; one each with PSF and MLSD) aged 17 to 57-years. All had homozygous exon-7 and 8 deletions. One had two copies, four had three copies, and the remainder had four copies of SMN-2-gene.At baseline, forced-vital-capacity was between 38% to 153%. Ambulant patients were assessed with HFMSE(score 37-60), RHS(scores 31-67) and, 6MTM(range 43-492m), and non-ambulant patients were assessed with CHOP-ATTEND(score 17-38), RUL(2-33), 9-hole-peg-test and dynamometer as appropriate.In type-2, patients with SS had a total of 6(20.7%) BPFG-injections. Only one had severe hypokalemia requiring ITU and treatment cessation. In one with PSF, BPFG-injection was unsuccessful.In type-3, SPFG-injections were successful in all 19 attempts with MLSD or NS. One each was complicated by transient low-pressure symptoms and radicular pain. Three CTG-injections on a patient with PSF were uncomplicated. All with successful LPs(96.5%) did not drop out.We found that nusinersen could be administered regardless of the spinal anatomy with interventional radiology.
196 Clinical and molecular characterisation of a Scottish Charcot-Marie-Tooth disease cohort
Authors: Watson-Fargie Taylor , Boyd Marcus , Mahjoub Aisha , Brennan Kathryn 
Published: August 2022

Charcot-Marie-Tooth (CMT) disease is the commonest inhereted neuropathy with previous studies charac- terising cohorts in Europe and USA. This Scottish single-centre retrospective cross-sectional study aimed to report frequency of CMT subtypes and characterise clinical, genetic, and electrophysiological features.Electronic medical record data were collected from patients attending a specialist clinic. Data included patient demographics, neurological examination, family history, pain, and reports from allied health pro- fessionals, genetics, and neurophysiology. Data were analysed using descriptive statistics.150 molecularly characterised and 39 uncharacterised patients were included comprising 78 patients with CMT1A (78), 5 with CMT1B, 5 with CMT1E, 25 with CMT1X, 17 with CMT2, 3 with CMT4 and 14 with Hereditary Neuropathy with Liability to Pressure Palsies (HNPP). There were similarities in generic neuropathy features, however, differences were observed. In this cohort, CMT1A patients had a lower prevalence of distal muscle wasting; CMT1B patients had an earlier mean presentation age and greater scoliosis prevalence; CMT1E patients had a later mean presentation age; CMT1X patients had greater tremor prevalence; HNPP patients showed lower morbidity.This study provides the first Scottish data on CMT subtypes and their associated characteristics. It is anticipated this provides a representative baseline that will support investigation, management, and research of CMT.
T-cell response following COVID booster vaccination in seronegative people with multiple sclerosis
Authors: Tallantyre Emma , Vickaryous Nicola , Richards Aidan , Rios Francesca , George Katila , Scurr Martin , Godkin Andrew , Loveless Samantha , Dobson Ruth ,   et al,   on behalf of UK COVID-MS study group
Published: August 2022

BackgroundAttenuated vaccine response is a concern in people receiving immunosuppression. It is unclear whether booster vaccinations improve immunity in this context.MethodsT-cell and antibody responses to Sars-COV-2 RBD (spike protein) were measured following third COVID-19 vaccine (v3) in people with MS who were IgG seronegative after vaccines 1&2.Results41 people with MS (30:11 female:male; mean age 45.6 years) were included; 28 receiving ocreli- zumab and 6 fingolimod, the remainder were on other immunosuppressants. Samples were taken 4-8 weeks following v3. Anti-RBD seroconversion after v3 occurred in 10/28 (36%) on ocrelizumab and 5/6 (83%) on fingolimod. T-cell responses were detected in 24/28 (86%) treated with ocrelizumab and 0/6 (0%) treated with fingolimod. All those with T-cell responses had seroconverted. There was an association between evidence of previous infection and seroconversion (p=0.0025), but not T-cell response to vaccination following v3 (Fisher’s exact p=0.2). Four patients (all on ocrelizumab) had experienced confirmed COVID since March 2020; 2 were admitted to hospital.ConclusionsSeroconversion occurs in a proportion of seronegative people following COVID-19 vaccine dose 3. T-cell response is frequently seen despite the lack of humoral immunity. The clinical correlates of antibody and T cell responses to COVID-19 remain to be established.
Single-cell profiling of MS CSF B cells highlights roles for TNFα and mTORC1 signalling
Authors: Jacobs Benjamin , Ban Maria , Baker Amie , Al-Najjar Raghda , Else Jonathan , Sawcer Stephen 
Published: August 2022

The presence of oligoclonal immunoglobulin bands in the cerebrospinal fluid (CSF) has long been rec- ognised as a characteristic manifestation of the immune dysregulation underlying multiple sclerosis (MS). However, it remains unclear how or why these bands develop, and little is known about the nature of the aberrantly expanded B cell clones that produce these immunoglobulins. To explore these questions we have performed single-cell RNA sequencing in CSF (108,219 cells) and PBMCs (232,587 cells) obtained from 104 individuals; 66 with multiple sclerosis, 25 with Non-Inflammatory Neurological Conditions (NINCs) and 13 with other Inflammatory Neurological Conditions (INCs).We found that MS CSF harbours an 8-fold higher proportion of plasma cells than control CSF. Plasma cells in the MS CSF up-regulate diverse pathways implicated in pro-inflammatory signalling and antibody synthesis, including TNFα and mTORC1 signalling, compared with their peripheral counterparts.We identified a large number of clonally-expanded cells in the MS CSF which are largely IgG+ plasma cells with evidence of intrathecal antigen experience. These clonally-expanded cells display clonal connections to the periphery.Our findings elucidate the phenotype of a critical cell population in MS biology – clonally-expanded CSF plasma cells. These insights have potential diagnostic and therapeutic implications, and may lead to more general insights into B cell autoimmunity.
Case presentation competition|5 Back to basics
Authors: Sim Nicholas Keyi , Foo Eng Chuan , Lwin Khine , Tun Shwe Zin , Dafalla Badr 
Published: August 2022

Serotonin syndrome associated with clozapine withdrawal and concurrent selective serotonin reuptake inhibitor (SSRI) use has previously been reported.A 56-year-old female with schizophrenia was admitted for pyrexia, rigidity, and altered mental state after her second dose of clozapine restart. She had discontinued her long-term clozapine 2 weeks prior. She developed ventilatory failure, reduced consciousness, eye deviation, and worsening rigidity, requiring ICU support. Examination showed a right upper motor neurone syndrome with absent ankle reflexes.She had raised inflammatory markers and creatine kinase. Serum neuropathy, encephalitis screen, and COVID PCR were negative. Respiratory investigations were unfruitful. MRI head and spine did not show brain or cord signal change to correlate to signs. Lumbar puncture showed a quiet CSF, negative culture, viral PCR, and encephalitis antibodies. EEG showed bihemispheric background slowing.Despite clinical improvement, repeat examination showed persistent signs. She was diagnosed with serotonin syndrome after developing a bilateral tremor. Treatment with cyproheptadine correlated with an improvement in her signs, cognitive state, and EEG.Serotonin syndrome can present with reversible neuromuscular signs. With clozapine withdrawal, it can require a prolonged time course of recovery in contrast with classical serotonin syndrome. Cyprohepta- dine can cause agranulocytosis and this delays clozapine restart.
001 An unusual cause of lymphocytic meningitis
Authors: Alexandratou Anna , Ashjaei Shayan , Coutinho Ester , Stanton Biba 
Published: August 2022

A 36-year-old Spanish man, with a background of ketamine use, presented with a 10-day history of severe headache, photophobia, nausea, unsteadiness and slurring of speech. His CT head was normal. CSF white cell count was 151 (lymphocytes), protein 0.7, glucose 2.3 (serum 3.6). He was treated with IV acyclovir for two weeks with no clinical improvement.On examination he remained distressed by headache and photophobic with severe dysarthria, bidirec- tional nystagmus and ataxia.Blood tests were normal or negative including HIV, serology for syphilis, mycoplasma, lyme and brucella, ANA, ENA, dsDNA, ANCA, ACE, LGI1 and NMDA antibodies, anti-Hu, Ri and Yo. IGRA was positive. MRI brain scan was normal. Serial lumbar punctures showed a variable CSF white cell count, with a negative extended virology panel, TB PCR, bacterial cultures, cytology and immunophenotyping.There was no improvement with pulsed steroids or antimicrobial cover for listeria. After 5 plasma exchanges there was some improvement in his CSF white cell count and headache, but he remained very ataxic.An extended paraneoplastic panel revealed positive anti-Tr antibodies. This is a well recognised cause of paraneoplastic cerebellar degeneration, normally associated with Hodgkin’s lymphoma. There have been no previous reported cases of anti-Tr antibodies associated with meningitic symptoms.
An audit of pregnancy and outcomes in the congenital myasthenic syndromes
Authors: Rooney Tatiana , O’Connell Karen , Alabaf Setareh , Ramdas Sithara , Beeson David , Palace Jacqueline 
Published: August 2022

BackgroundThe congenital myasthenic syndromes(CMS) are a heterogenous group of genetic disorders leading to disordered neuromuscular junction transmission. Due to their rarity, data on pregnancy outcomes is limited.MethodsAll CMS women with documented pregnancy were invited to complete a pregnancy and outcomes audit questionnaire.ResultsAmongst 16 women with CMS there were 27 pregnancies recorded: 26 single and 1 twin pregnancy. CMS related symptom worsening was reported in 63%, (AChR deficiency in 2/6, slow channel syndrome in 2/3, DOK7 in 8/9, RAPSYN in 3/6 and glycosylation {DPAGT1 and GFPT1} in 2/3), improvement was only reported in 2 (both RAPSYN). Recovery to baseline function was seen in all but one patient.Miscarriage and caesarean section occurred in 31% and 33% of women. Over half of patients continued their medication during pregnancy which included: pyridostigmine (10), 3,4-DAP (9), ephedrine (3), salbutamol (3) and quinine (1). No foetal malformations were recorded.DiscussionWe report pregnancy outcomes in a relatively large CMS cohort. Whilst clinical worsening is common, it was usually reversible, and rates of miscarriage and caesarean section appeared similar to the background population.1Foetal outcomes appeared good and no safety signal was generated in relation to medication use during pregnancy.Reference1. Child and Maternal Health. 3/11/2020]; Available from: https://fingertips.phe.org.uk/profile/ child-health-profiles/data#page/1/gid/1938133222