bluuebunny/crossref_metadata_2025_split huggingface dataset:
CSF-resident CD4+ T-cells display a distinct gene expression profile relevant to multiple sclerosis
Authors: Hrastelj James , Andrews Robert , Loveless Samantha , Morgan Joanne , Bishop Mark , Bray Nicholas , Williams Nigel , Robertson Neil 
Published: May 2022

BackgroundThis study reports the largest transcriptomic analysis of purified CSF cell subpopulations to date. This has relevance for understanding CNS immune surveillance and multiple sclerosis pathogenesis and treatment discovery.MethodsCD4+ T-cells were purified from CSF and blood using fluorescence-activated cell sorting, from 21 patients with treatment-naïve multiple sclerosis and 20 individuals with non-inflammatory disorders. Their transcriptomes were profiled through RNA sequencing. A paired comparison was performed between CSF and blood within individuals. A further case-control comparison was performed in an extended cohort of CSF samples.ResultsPaired comparisons between CD4+ T-cells from CSF and blood identified 5,156 differentially expressed genes in controls and 4,263 differentially expressed in multiple sclerosis patients at false discovery rate (FDR) < 5%. Differential expression analysis of CSF CD4+ T-cells highlighted genes involved in; migration, activation, cholesterol biosynthesis and signalling, including those relevant to multiple sclerosis patho- genesis and treatment. In an extended cohort of multiple sclerosis cases (N=41), analysis of CSF CD4+ T-cells compared with non-inflammatory disorder controls (N = 38) identified 140 differentially expressed genes at FDR < 5%.ConclusionWe report numerous gene expression differences between CSF and blood CD4+ T-cells. Identi- fied genes have relevance to multiple sclerosis pathogenesis and could contain novel treatment targets.james.hrastelj@gmail.com
Charcot-Marie-Tooth disease secondary to biallelic mutations in SORD
Authors: Record Christopher J , Pipis Menelaos , Rossor Alexander M , Laura Matilde , Skorupinska Mariola , Cortese Andrea , Reilly Mary M 
Published: May 2022

IntroductionSORD is a newly described autosomal recessive gene that is emerging as the commonest cause of autosomal recessive CMT (Charcot-Marie-Tooth disease) and hereditary motor neuropathy (HMN).MethodsWe present nine cases of SORD-related neuropathy.ResultsNine unrelated patients were found to have biallelic mutations in SORD. Eight were male (89%) and median age of assessment was 34 years (range 18–55 years). Median age of symptom onset was 15 years (range 12–18 years) and all patients initially presented with difficulty walking and/or problems involving distal lower limbs. Only one patient (11%) had sensory symptoms. 5/9 (56%) had distal upper limb weakness and all had distal lower limb weakness. Sensory examination was abnormal to at least one modality in 7/9 cases (78%). The median CMT Examination and CMT Neuropathy Scores were 6 (range 2–12) and 7.5 (range 3–14) respectively. Neurophysiology showed conduction velocities in the axonal or intermediate ranges in all cases. Clinical diagnosis was distal HMN in 5/9 (56%), CMT2 in 2/9 (22%) and CMT intermediate in 2/9 (22%).ConclusionsThe SORD phenotype is typically a slowly progressive, length-dependent motor neuropathy of onset during the second decade. Sensory symptoms are rare and sensory signs minimal.chris.record@ucl.ac.uk
Neurologic and radiographic findings associated with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS)
Authors: Abdel-Mannan Omar , Penner Justin , Hassell Jane , Loebel Ulrike , Maillard Sue , Johnson Mae , Pressler Ronit , Bamford Alasdair , Moshal Karyn , Hacohen Yael 
Published: May 2022

ObjectiveOur aim was to report neurological manifestations of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS).MethodsPatients (<18yrs) presenting to Great Ormond Street Hospital between March 1, 2020, and June 21, 2020 fulfilling RCPCH PIMS-TS criteria, were included. Clinical and paraclinical features were retrieved retrospectively from electronic patient records.ResultsNew-onset neurological symptoms/signs were reported in 23/45 (51.1%); headaches (n=16), encephalopathy (n=7), dysarthria/dysphonia (n=6), hallucinations (n=4), ataxia (n=4), peripheral nerve involvement (n=3), and seizures (n=1). Five (21.7%) patients had CSF analysis; 1 patient had 118 leuko- cytes in CSF. Splenium signal changes were seen in 4/14 patients who had brain MRI. A mild excess of slow activity was found in 10/10 who had an EEG and mild myopathic and neuropathic changes were seen 4/5 who underwent nerve conduction studies and electromyography. Children with neurological involvement had higher peak inflammatory markers and were more likely to be ventilated and require inotropic support in PICU (p<0.05).ConclusionsChildren with PIMS-TS presented with new neurological symptoms involving both the central and peripheral nervous systems, in the absence of respiratory symptoms. Neurological symptoms were seen more frequently in more severe presentations.o.abdel-mannan@ucl.ac.uk
Genomic features specific to the human lineage are associated with neurological diseases and intelligence
Authors: Chen Zhongbo , Zhang David , Reynolds Regina , Gustavsson Emil , Ruiz Sonia Garcia , Hardy John , Houlden Henry , Taliun Sarah Gagliano , Botia Juan , Ryten Mina 
Published: May 2022

While encephalisation has provided advantages to human evolution, it may have also predisposed us to neurological diseases as common neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease do not occur naturally in aged non-human primates. Thus, human lineage-specific genomic features may provide insights into brain-related diseases. We leveraged high-depth whole genome sequencing data to generate a novel annotation that identifies genomic regions specific to humans and not conserved within non-human primates (termed constrained, non-conserved regions; CNCRs). We proposed that these regions have been subject to human-specific purifying selection and are enriched for brain-specific elements, relevant to human-specific disease. We found that CNCRs are depleted from protein-coding genes but enriched within the non-coding genome. Per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs including intelligence, Parkinson’s disease and schizophrenia. We found that genes implicated in neurological diseases have high CNCR density, in par- ticular: APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we showed this human-specific intron-3-retaining transcript to be more abundant in Alzheimer’s disease with more severe tau and amyloid pathological burden. Thus, we demonstrate the importance of human-lineage-specific genomic sequences in neurological disease and make this information available in a public platform online.zhongbochen@ucl.ac.uk18
Bariatric surgery versus community weight management intervention for idiopathic intracranial hypertension: a randomised controlled trial
Authors: Mollan Susan , Mitchell James , Ottridge Ryan , Aguiar Magda , Yiangou Andreas , torovic Zerin Alimajs- , Cartwright David , Grech Olivia ,   IIH WT Investigator group, Sinclair Alex J 
Published: May 2022

ObjectiveThe IIH weight trial (IIH: WT) aimed to compare the efficacy of bariatric surgery with a community weight management intervention (CWI) in active IIH.MethodsThis was a five-year randomized control trial which enrolled participants between March 1, 2014 and May 25, 2017 at five NHS hospitals in the United Kingdom. Participants with active IIH and body mass index (BMI) ≥35kg/m2 were screened. The primary outcome was change in intracranial pressure (ICP) measured by lumbar puncture (LP) opening pressure (OP) at 12 months.ResultsSixty-six women were randomised (mean age, 32 years). ICP was significantly lower in the bariatric surgery arm at 12 months (adjusted mean difference -6.00cm cerebrospinal fluid [CSF] 95% confidence interval [CI] -9.5 to -2.4]; p= 0.001) and at 24 months (adjusted mean difference -8.2cmCSF [95% CI, -12.2 to -4.2]; p< 0.001) compared with the CWI arm. Weight was significantly lower in the bariatric surgery arm at 12 months (adjusted mean difference -21.4Kg 95% CI, -32.1 to -10.7]; p< 0.001) and at 24 months (adjusted mean difference -26.6kg [95% CI, -37.5 to -15.7]; p< 0.001) compared with the CWI arm. Quality of life (SF36, physical component score) improved significantly at 12 and 24 months (adjusted mean dif- ference p=.043; p=.006, respectively).Conclusions and RelevanceIn this study of women with active IIH and a BMI ≥35kg/m2, bariatric surgery was superior to a CWI in lowering ICP.soozmollan@doctors.org.uk
Clinician burnout: results of an ABN survey of British neurologists
Authors: Kipps Christopher , Kinton Lucy , McCarron Mark , Nitkunan Arani , Petheram Kate , Ross-Russell Amy , Tripp Anand , Warner Graham , Zarkali Angeliki 
Published: May 2022

Rising demand and increasing workload in the face of constrained resources are factors known to con- tribute to clinician burnout. Emotional exhaustion, depersonalisation and career dissatisfaction are some of the consequences. In the USA, neurologists are amongst the clinicians with the highest rates of burnout, but is this also a problem for British neurologists?Through the last quarter of 2019, the entire working membership of the ABN (neurologists and trainees) was surveyed using the well-validated Maslach Burnout Inventory. Other demographic and working practice data were also obtained. Of 1252 members, a total of 563 responses were obtained (45%).Over half the membership felt that neurologist burnout was an issue that the ABN should be involved with. Most respondents felt their work was meaningful and would choose neurology again as a specialty. Although job satisfaction overall was good, the majority felt that their schedule left insufficient family time. There were particular concerns regarding autonomy, the amount of administrative work and the lack of administrative support. A significant proportion of neurologists indicated that they had symptoms contributing to a sense of burnout once a week or more.Full results of the Maslach Burnout Inventory will be presented.ckipps@nhs.net
Nuclear countdown
Authors: Rice-Wilson Daniel , Jareonsettasin Prem , Madi Heba , Sesath Randiva , Shah Apeksha 
Published: May 2022

Case: A 50-year-old woman presented with a 10-year history of progressive symptoms, beginning with right facial numbness. She developed dysgeusia, and dysphagia before the onset of dysarthria. She had progressive gait instability with frequent backwards falls. A gastrostomy was inserted for persistent weight loss. She required hospital admission for aspiration pneumonia and type 2 respiratory failure. On examina- tion she had a head drop and staring expression with reduced blink frequency and hypophonia. There was bilateral facial weakness with temporalis and tongue wasting. She had a supranuclear gaze palsy and her saccadic eye movements were almost absent in all directions. Limbs were hypotonic with distal weakness and reduced reflexes.InvestigationsNCS/EMG showed chronic widespread partial denervation in the facial, trigeminal (motor) and hypoglossal-innervated muscles. Blink reflexes were absent bilaterally. There were chronic denerva- tion changes in the cervical and lumbar spinal segments. MRI brain showed global atrophy particularly implicating the temporal lobes and brainstem.DiagnosisA diagnosis of Facial-Onset Sensory and Motor Neuronopathy (FOSMN) was made. Given the additional clinical features of supranuclear gaze palsy we believe this is the first case of FOSMN-PSP overlap syndrome.ConclusionWe report a unique FOSMN case with some overlap features of PSP, not previously described. daniel.rice-wilson@nhs.net23
002  A review of the performance of referring centres in diagnosing sCJD on MRI
Authors: Sequeira Danielle , Jesuthasan Aaron , Hyare Harpreet , Odd Hans , Rudge Peter , Mok Tze How , Nihat Akin , Collinge John , Mead Simon 
Published: May 2022

IntroductionMRI sensitivity of up to 96% for pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) has previously been reported. However, in 2012, Carswell et al. found that the initial neuroradio- logical report often failed to identify CJD-associated MRI changes (47% sensitivity). These patients were at a more advanced stage of disease when referred to specialist services. Here we assessed whether there has been a change over time.MethodsWe reviewed MRI scans of 106 patients (sCJD=102, IPD=4) referred to the NPC between 2015- 2019, and compared our findings with the formal reports from referring centres. We recorded the MRC Scale scores at initial patient assessment.ResultsWe found characteristic MRI abnormalities in 101 out of 102 sCJD cases. A differential diagnosis of CJD was documented on the neuroradiological reports of 70 of these cases, giving a significantly improved sensitivity of 69% compared to 2012. There was no association between the location of signal change and reporting accuracy. Patients had less advanced disease compared to 2012.ConclusionsMRI reporting of sCJD by referring centres has improved, but further improvement seems possible. We re-emphasize the importance of analysing scans thoroughly for characteristic MRI patterns of sCJD to enable earlier identification of these patients.daniellesequeira@nhs.net|ABN Bursary26
003  Neuroanatomical signatures of genetic risk for Alzheimer’s disease in healthy adults
Authors: Watson Cameron , Waters Sheena , Jacobs Benjamin , Foote Isabelle , Dey Sumit , Noyce Alastair , Marshall Charles ,   equal contribution
Published: May 2022

BackgroundEarly detection of Alzheimer’s disease (AD) is critical for the development of interventions that delay or prevent neurodegeneration. Previous studies suggest that genetic liability to AD may be associated with structural brain changes that start 20–30 years before symptoms manifest.MethodsWe derived an optimised AD polygenic risk score (AD-PRS) using imputed genotype data from 488,377 participants in UK Biobank. We examined the structural brain correlates of AD-PRS in 27,496 healthy UK Biobank participants using voxel-based morphometry (VBM) and additionally performed regression analyses using image-derived phenotypes (IDP) from T1-weighted and diffusion-weighted magnetic resonance images.ResultsVBM revealed that high AD-PRS was associated with reduced grey matter volume (GMV) in bilateral hippocampus and putamen (family wise error correction, p<0.05). IDP analysis further revealed a bihemispheric limbic network incorporating hippocampus, parahippocampal gyrus, ventral striatum, orbitofrontal cortex, and thalamus, as well as with reduced white matter integrity in the major white matter tracts of this network (fornix, cingulum hippocampus, and thalamic radiation).ConclusionGenetic liability to AD is associated with preclinical neurodegeneration in grey and white matter components of the limbic system. Integrity of this network could serve as a marker of preclinical AD and an outcome measure in prevention trials.cameron.watson@qmul.ac.uk|ABN Bursary
011  Progressive myoclonic epilepsy due to rare mitochondrial ND6 mutation, m.14487T>C
Authors: Khoo Anthony , Naidu Saadnah , Wijayendran Surapi , Merve Ashirwad , Bremner Fion , Sidhu Meneka 
Published: May 2022

We report the case of a 43-year old man with adult-onset drug-resistant epilepsy, cortical myoclonus and bilateral optic neuropathies. Serial MRI scans over a two year period demonstrated the interval devel- opment of bihemispheric stroke-like lesions. Giant somatosensory evoked potentials and short-duration myoclonic jerks with craniocaudal spread on surface-EMG were consistent with cortical myoclonus. Optical coherence tomography showed bilateral symmetric thinning of the nerve fibre layer in the pap- illomacular bundles. Muscle biopsy was non-diagnostic, however next-generation whole mitochondrial gene sequencing identified a pathogenic m.14487T>C mitochondrial gene mutation. This gene is most commonly implicated in cases of infantile-onset Leigh syndrome, although a broader phenotypic spectrum including migraine with aura and progressive myoclonic epilepsy have recently been described. Bilateral optic neuropathies consistent with Leber hereditary optic neuropathy are commonly seen with other ND6 mitochondrial gene mutations and were in our case a striking feature. Debilitating right-sided facial myoclonus affecting speech and swallowing remained highly drug-resistant however symptomatic benefit was derived from targeted onabotulinum toxin A injections (80 units orbicularis oculi, 10 units nasalis, 10 units risorius, 20 units levator anguli oris, 60 units platysma) administered every three months.anthony.khoo@sa.gov.au|ABN Bursary
014  Efficacy and safety of perampanel for myoclonic and absence seizures: studies 332, 311 and 232
Authors: Brandt Christian , Ben Renfroe J , Ngo Leock Y , Patten Anna , Malhotra Manoj 
Published: May 2022

BackgroundThis post hoc analysis assessed the efficacy and safety of adjunctive perampanel in adult/adolescent/paediatric patients with myoclonic and absence seizures during Phase II/III clinical studies.MethodsDuring Study 332 (NCT01393743), patients aged ≥12 years with generalised tonic-clonic seizures (GTCS) received placebo/adjunctive perampanel 8-mg/day. In Study 311 (NCT02849626), patients aged 4–<12 years with focal-onset seizures/GTCS received perampanel ≤16-mg/day. In Study 232 (NCT01527006), patients aged 2–<12 years with epilepsy received perampanel ≤0.18-mg/kg/day. Data from patients with baseline myoclonic and/or absence seizures were pooled. Assessments included median percent change in seizure frequency/28 days and treatment-emergent adverse events (TEAEs).ResultsOverall, 66/393 patients had myoclonic seizures (placebo, n=23; perampanel, n=43) and 72/393 had absence seizures (placebo, n=33; perampanel, n=39); patients with both seizure types are counted twice. Reductions in seizure frequency/28 days were observed with placebo and perampanel: myoclonic, 52.5% and 24.6%; absence, 7.6% and 25.1%, respectively. TEAEs with placebo and perampanel occurred in 18 (78.3%) and 36 (83.7%) patients with myoclonic seizures, and 25 (75.8%) and 34 (87.2%) patients with absence seizures, respectively; most common TEAEs with perampanel were dizziness and fatigue.ConclusionThese data suggest adjunctive perampanel does not worsen myoclonic/absence seizures in adult/adolescent/paediatric patients.FundingEisai Inc. stella_ngo@eisai.com32
Do we still need OCBs in MS diagnosis and how many?
Authors: Campagna Giovanna , Birch Katherine , Gibbons Emily , Jackson Edward , Chadwick Carrie , Ellul Mark , Jacob Anu , Huda Saif 
Published: May 2022

BackgroundA standard cut-off of ≥2 CSF-specific OCBs is used in multiple sclerosis but some studies suggest ≥3 CSF OCBs maybe more specific.AimTo determine if a cut-off of ≥2 or ≥3 CSF OCBs should be used in MSMaterials and MethodsOligoclonal bands were tested using standardised methods incorporating iso- electric focussing. Samples sent between July 2018-June 2019 were included. CSF OCB number (1, ≥2,≥3, or unclear) was assessed by two blinded raters and case records were reviewed.ResultsCSF OCBs were detected in 196/746 (26%) samples (CSF OCB=1; 14/196 (7%), ≥2=182/196 (93%), ≥3=169/196 (86%). Clinical data were available in 157 patients (MS=101, other inflammatory=37, unclear significance=19). Excluding CSF OCB results, 68/101 (67%) cases fulfilled MS diagnostic criteria. Of patients with 1, ≥2 and ≥3 CSF OCBs, 1/8 (12%), 100/182 (55%) and 98/169 (58%) had MS respectively. The positive predictive value of 1, ≥2, and ≥3 OCBs was 0.35, 0.89 and 0.92 respectively in CNS inflammatory disease.ConclusionDetection of CSF OCBs was necessary to fulfil MS diagnostic criteria in approximately 30% of cases. Detection of ≥3 OCBs marginally improved the likelihood of an MS diagnosis. Overall measures of sensitivity, specificity and receiver operator curves will be presented.giovanna.campagna@thewaltoncentre.nhs.uk
018  The national audit of seizure management in hospitals: round 3 (NASH 3)
Authors: Powell Graham , Taylor Claire , Dixon Pete , Pearson Mike , Tudur-Smith Catrin , Marson Tony 
Published: May 2022

IntroductionSeizures are a common presentation in the Emergency Department (ED). Previous rounds of NASH (2011 and 2013) identified major deficiencies in the provision of care and a disconnection between acute medicine and neurology services. Has there been any improvement?MethodsSetting137 Hospital sites across the UK. Participants: 4132 attendances between 01/06/2018– 30/06/2019 were assessed, 61% had a prior diagnosis of epilepsy and 23% presented with suspected first seizure. Outcome Measures: Data were recorded to assess prior care, the acute presentation and subsequent care including referral for specialist review.ResultsFor patients presenting with first seizure an attempt was made to contact an eyewitness in 70.4%. CT Brain was requested in the ED in 66%, which has increased from 45% in NASH 1. Onward referral for specialist review was requested in 64%.For patients with epilepsy 55% had not seen an epilepsy specialist in the previous 12 months. CT Brain was requested in 30%, increasing from 17% in NASH 1. Specialist review was requested for 35% who had not seen a specialist in the previous 12 months and for 44% who had.ConclusionsThere has been little improvement in the past decade. Improvements are urgently needed to improve the wellbeing of patients presenting with seizures, patients with epilepsy and the efficiency of the healthcare system.gpowell@liv.ac.uk34
030  Emerging parkinsonism in the PREDICT-PD cohort after 5-year follow-up
Authors: Simonet Cristina , Bestwick Jonathan , Schrag Anette , Lees Andrew , Noyce Alastair 
Published: May 2022

BackgroundThe PREDICT-PD study is a web-based study which aims to identify individuals aged 60–80 at risk of future Parkinson’s disease (PD) from the UK general population. Soon after enrolment, representative groups of individuals that were classified as higher risk (HR) or lower risk (LR) (highest and lowest 15% of risks scores) were reviewed ‘in person’ with HR group being more likely to show subtle motor impairment compared with the LR group.MethodsIndividuals were examined using the motor part of Unified PD Rating Scale (MDS-UPDRS-III) after a minimum of 5-year follow-up.FindingsWe reviewed 132 participants (HR:33, LR:99). HR subjects were predominantly male (74.2%) and older (77.2yo vs 73.6yo, p<0.001). At 5-year follow-up a bigger change in MDS-UPDRS-III was seen amongst HR individuals compared to LR group (36% vs 13% increasing > 5 points in the motor scale). In contrast to the baseline analysis, where there were no significant differences on a keyboard tapping test (BRAIN test), HR participants performed worse than LR participants (43.7key/sec vs 53.9key/sec, p<0.001) after 5 years. Two participants received a PD diagnosis during follow-up with respective motor signs demonstrated 2 and 5 years before fulfilling clinical diagnosis criteria.ConclusionsThis study identifies early motor features and their evolution during PD pre-diagnostic phase. Remotely administered tools may be capable of detecting subtle motor dysfunction at early stages of PD.c.simonet@qmul.ac.uk|NIHR Bursary40