bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large single-centre cohort of HSP patients in UK: advantages of deep pheno- typing and longitudinal follow-up
Authors: Price Kitty , Mellor James , Mcnamara Mary , Hewamadduma Channa , Shaw Pamela , Derott Christopher Mc- , Hadjivassiliou Marios 
Published: May 2022

AimTo identify clinical, radiological and instrumented gait correlates predictive of natural history in a cohort of HSP patients.BackgroundHSP is a rare heterogeneous group of neurodegenerative disorders. We present our experi- ence managing a large cohort of HSP patients in the regional centre for HSP. We believe Sheffield Teaching Hospitals to have the largest cohort in the North of England.Methodology and ResultsOur cohort comprises 426 patients, 246 male (57.7%) of which 290 were geneti- cally characterized. The commonest mutation is in SPASTIN (SPG4, 38.3%), whilst REEP1 (SPG31) and SPG11 mutations make up 3.1% and 2.1% respectively. Sheffield also holds the largest cohort of SPG7 patients in the UK (n=54) accounting for 18.6% of genetic HSP. The remainder have mutations in KIF5A, Atlastin, WASHC5, KIAA0196, NIPA1, ARSACS, CYP27A1, CYP7B1, AP4S1, GBA2 and L1CAM. Over 240 patients have had detailed MR imaging which has identified novel features in HSP. Repeated instrumented gait monitoring and cognitive assessments have shown novel clinical markers suggesting disease progression.ConclusionFor rare disorders like HSP, specialised clinics optimise comprehensive longitudinal clinical and radiological data collection for large cohorts. This develops local expertise and helps identify novel radiological and clinically relevant biomarkers, enabling better patient care.klprice1@sheffield.ac.uk
252  Whole exome sequencing in epilepsy: quality of reporting in literature
Authors: Shukralla Arif , Lacey Austin , Naggar Hany El , Cavalleri Gianpiero , Delanty Norman 
Published: May 2022

PurposeWhole exome sequencing is a new rapid and cost effective tool for the diagnosis of the epilepsies.MethodOur primary aim was to assess the quality of reporting of WES. Secondary aims; to compare the quality of studies based on journal type if recent ACMG guideless have made influenced reporting quality; if any outcome reporting biases exist.We analysed studies of whole exome sequencing in epilepsy. We used a self-constructed benchmark to quantitatively analyse studies, explore retrospectively if reporting trends have changed.ResultsTotal of 307 studies was included. Reporting of data was heterogenous with poor reporting of diagnostic yield in 6% of studies, incidental findings in 11%, variants of undetermined significance in 19%. Predictors of poor reporting included: Journal type, proband status and case reports. Pairwise compari- sons of genetics journals versus other journals using relative risks yielded significant differences in reporting of consanguinity status (RR 1.27 CI 1.04–1.55); variant filtering (RR 1.95 CI 1.41–2.7) and determination of pathogenicity (RR 1.35 CI 1.17–1.56).ConclusionReporting of WES data in the medical literature is heterogenous, making comparisons across studies difficult. Formal structured guidelines similar to the CONSORT guidelines are needed to address this issue further.arifshukralla@gmail.com
257  A novel case of a possible genetic orthostatic hypotension syndrome
Authors: Kodali Srikirti , Koay Junie Shiwen , Ingle Gordon Thorpe , Iodice Valeria 
Published: May 2022

A 60-year-old woman was referred to the Autonomic Centre at the National Hospital for Neurology and Neurosurgery (NHNN) due to longstanding history of orthostatic hypotension (OH).She was born of non-consanguineous parents and there was no family history of similar problems. Her tolerance for exercise has been significantly low since childhood.She has a background of schizophrenia, chronic kidney disease and cardiac arrythmias.She was first seen at the NHNN 30 years earlier and investigated with skin biopsy showing loss of tyrosine hydroxylase and neuropeptide Y.During a recent admission, the neurologic examination showed bilateral Horner’s syndrome, OH and parkinsonism (possibly drug induced). Autonomic tests indicated selective impairment of adrenergic sympathetic function. Plasma adrenaline, noradrenaline, dopamine and dopamine beta hydroxylase (DβH) levels were undetectable.The patient is currently being investigated for mutations in genes encoding DβH and CYB561. DβH mutation is unlikely due to the undetectable dopamine. CYB561 gene mutation has been described to interfere with noradrenaline biosynthesis, resembling DβH deficiency.Both disorders are characterised by orthostatic hypotension, recurrent hypoglycaemia and low noradrena- line levels. Establishing the aetiology might have an impact on management given the response to L-DOPS in patients with mutation of genes involved in noradrenaline biosynthesis.16sk0577cam@gmail.com
264  Cognitive and imaging correlates in cerebral amyloid angiopathy subthypes
Authors: Bonifacio Guendalina , Chan Edgar , Islam Afm , Werring David 
Published: May 2022

Common clinical subtypes of CAA are CAA with intracerebral haemorrhage (CAA-ICH), with cognitive decline (CAA-cog), and with Transient Focal Neurological Episodes (CAA-TFNE); most studies of cognition and neuroimaging to date have focussed on CAA-ICH. We therefore evaluated the cognitive and imaging phenotypes across all the CAA subgroups.This is a retrospective cross-sectional study of cognition and imaging in 99 patients; 70 (71%) with CAA and 29 (29%) with presumed hypertensive arteriopathy (non-CAA). We measured impairment across the cognitive domains using a standardised test battery, and we described the imaging biomarkers via visual rating of standardised MRI scans.Most patients had impairment in more than 2 domains (69%). We found impairment in the executive domain in 71% of patients, followed by non-verbal IQ (59%) and verbal IQ (48%). Patients with CAA-TFNE had similar impairments across cognitive domains to CAA-ICH.CAA-cog performed worse than CAA-ICH with verbal recognition memory (p<0.05).With regards to imaging findings, the groups differed significantly for several small vessel disease markers (e.g. moderate to severe cSS in CAA-TFNE compared to CAA-ICH and CAA-cog, >2 lobar CMBs in CAA-ICH and CAA-cog compared to CAA-TFNE).Our findings confirm high rates of cognitive impairment across CAA subtypes, including CAA-TFNE. The cognitive profile of CAA-TFNE was similar to that of CAA-ICH, despite differences in neuroimaging findings. Hence, the effects of CAA on cognition can occur regardless of the presence of ICH.guendabonifacio@gmail.com
267  When investigating stroke is a waste of time
Authors: Cook Sarah , Warner Graham 
Published: May 2022

Young stroke should alert clinicians to investigate for unusual causes.A previously well 43-year-old Caucasian female presented with 2 days of punctuated left sided weakness and sensory inattention. MRI demonstrated multiple territory infarcts, predominantly on the right side. With no vascular risk factors, high dose steroids were commenced assuming primary angiitis of the CNS (PACNS). Blood tests including ESR, HIV, an autoimmune and thrombotic screen and blood cultures were negative. A 24-hour ECG and TOE failed to identify an embolic source, though interval MRIs plus CT angi- ography revealed evolving cerebral and splenic infarcts. A DOAC was added. Retinal angiography did not support PACNS, nor did PET-CT though it did show an avid uptake large pelvic mass. Tumour markers CA 125 and CA 19–9 were markedly raised. Urgent gynaecological review was sought but the patient developed florid aortic regurgitation and further cerebral infarcts despite heparinisation. Repeat echocar- diography this time showed a dysplastic aortic valve. Pelvic mass excision confirmed adenocarcinoma.Non-bacterial thrombotic (marantic) endocarditis (NBTE) is a rare cause of embolic stroke. Systemic wasting from associated malignancy is hinted at in the etymology (Greek.marantikos= to waste away). Our patient remained ‘well’ and only the valve wasted away. Friable valve lesions in NBTE are prone to embolization and removal of the pro-coagulant tumour is the most effective treatment.sarah.cook18@nhs.net
268  Predicting large vessel occlusion using non-contrast CT brain in patients with acute stroke
Authors: Mcverry Ferghal , McCluskey Gavin , Best Elizabeth , McKee Jacqueline , McCarron Mark 
Published: May 2022

IntroductionDetecting large vessel occlusion (LVO)is required to facilitate mechanical thrombectomy in stroke, but angiography is not always routinely available . Hyperdense vessel sign (HVS) and more recently conjugate eye deviation on CT brain have been associated with LVO. Eye deviation and HVS were examined by non-radiologists to determine predictive value for LVO.MethodsPresence of radiological eye deviation and HVS were examined on brain CT for stroke patients with baseline CT angiography. Eye deviation and HVS were compared to angiographic status .Assess- ments were performed blinded to clinical information and angiographic status.ResultsFrom 195 cases 122 had large vessel occlusion. HVS sign predicted LVO with PPV of 90.7, specificity 89.2. Eye deviation predicted LVO with PPV 81.7, specificity 74.3. Presence of both HVS and radiologi- cal eye deviation strongly correlated with LVO ;PPV 98.3, specificity 98.6. Thirty cases with LVO had eye deviation without HVS indicating independent predictive value.ConclusionEye deviation and HVS both show high specificity for LVO, particularly when detected in combination. They are rapidly and reliably detected by non-neuroradiologists on CT brain. Eye deviation on CT ± HVS should prompt consideration of thrombectomy even when angiographic imaging is not available given the likelihood of LVO.– ferghalmcverry@doctors.org.uk
Pre-pregnancy and antenatal care of women with epilepsy
Authors: Miah Taief , Mahmud Mohammad , Vardanyan Robert , Arjomandi-Rad Arian , Dhanjal Mandish , Dassan Pooja 
Published: May 2022

BackgroundEpileptic seizures in pregnancy pose a significant risk to both the mother and fetus. There is little evidence of the impact of pre-pregnancy counselling (PPC) and specialist multi-disciplinary antenatal care on a pregnancy.ObjectivesTo determine critical components of care in preventing seizures and adverse outcomes in pregnancies of women with epilepsy.MethodA retrospective cohort study of pregnant women with epilepsy. Participants were seen in the Neuro-Obstetrics multidisciplinary clinic based in West London from 2012 to 2020.ResultsA total of 150 patients; including 242 pregnancies, were analysed. Of these pregnancies, 69 were reported to have had at least 1 seizure. The anti-epileptic drug profiles and dosages were recorded in each group; 71.5% of pregnancies involved anti-epileptic drugs (AEDs), 68.8% of these patients were on mono-therapy and 22.5% were on dual-therapy. Patients without access to PPC or specialist antenatal care had less frequent monitoring of AED levels, fewer dosage adjustments and a higher seizure frequency during the pregnancy. In 9.1% of pregnancies a new AED was started.ConclusionThese data support the use of PPC in preventing seizures in early pregnancy. The data also shows a reduction in seizure frequency following specialist multidisciplinary antenatal care.mtm116@ic.ac.uk
Neuro patience: report of the 2018/19 national neurology patient experience survey
Authors: Carr Georgina , McIntosh Katharine , Vibert Sarah 
Published: May 2022

The Neurological Alliance’s 2018/19 National Neurology Patient Experience Survey presents a compre- hensive picture of the experiences of people in England living with a neurological condition. The survey ran online and in select neurology clinics between July 2018 and March 2019. The research covers a wide range of topics including diagnosis and information, hospital care, support for mental wellbeing, and access to social care, welfare and employment. With 10,339 responses, it is the largest ever survey of people with neurological conditions in England.The results show that people with neurological conditions are facing long waiting times, poor access to specialists and a lack of personalised care. The survey also found evidence of failings in the social care and welfare systems, and discrimination in the workplace.Overall, the findings suggest that care and support for people with neurological conditions must be:Accessible: the speed of access to specialists must improve overall and should not vary depending on where you livePersonalised and tailored to the needs of each individualHolistic, addressing people’s mental health, social care needs, and their financial security.The results are also broken down to regional (STP) level, revealing wide regional variation across all three themes.georgina.carr@neural.org.uk
COVID-19 and multiple sclerosis: An updated report of the community-based longitudinal UK MS Register study
Authors: Garjani Afagh , Middleton Rodden M , Law Graham R , Tuite-Dalton Katherine , Hunter Rachael , Nair Roshan das , Evangelou Nikos , Nicholas Richard 
Published: May 2022

COVID-19 is a concern in people with multiple sclerosis (MS), mostly because of their long-term physical disabilities and immunomodulatory disease-modifying therapies (DMTs). In this community-based pro- spective longitudinal study, we have been monitoring a cohort of people with MS via the web-based platform of the UK MS Register since the start of the COVID-19 outbreak. We report our findings from 17/03/2020 to 15/01/2021.Out of 7344 participants, 883 (12%) have reported a self-diagnosis of COVID-19 of whom 211 had a confirmed clinical or laboratory-based (n=114) diagnosis. No individual DMT increased the likelihood of contracting COVID-19 (with any of the diagnoses as the outcome). Gender (male: female, adjusted OR: 95% CI [0.94: 0.68–1.3]), web-based Expanded Disability Status Scale score (webEDSS; one-point increase, 0.92: 0.84–1.01), and MS duration (one-year increase, 1: 0.98–1.02) were not associated with contracting COVID-19. Younger age (one-year decrease, 1.04: 1.03–1.06), ethnicities other than white (1.95: 1.13–3.34), and relapsing-remitting MS (versus progressive, 1.72: 2.56–1.16) increased the likelihood of contracting COVID-19. Within a median (interquartile range) of 26 (0–72) days follow-up of participants with COVID-19 (n=532), 69% reported full recovery. A higher webEDSS (one-point increase, 0.84: 0.74–0.96) lowered the likelihood of full recovery. Overall, MS-specific factors do not predispose people with MS to contracting COVID-19, but physical disability can delay recovery.afagh.garjani@nottingham.ac.uk
Improving the early diagnosis of corticobasal syndrome: a large clinico-pathological study
Authors: Lux Danielle , Morris Huw 
Published: May 2022

BackgroundCorticobasal syndrome is associated with a heterogeneous spectrum of pathologies, with low predictive value for Corticobasal degeneration (CBD) pathology. Here, we validate the Armstrong criteria and interrogate clinical features to improve accurate diagnosis ante-mortem.MethodsWe applied Armstrong criteria to all archived cases with a clinical diagnosis of CBS or CBS- overlap syndrome over disease course. Clinical and radiological features were compared by pathologi- cal substrate.Results105 of 123 patients met diagnostic criteria for either Probable or Possible CBS/CBD of whom 38 (36%) had CBD and 79 (75%) had 4-repeat tauopathies (4RT). 3 years from onset, 8/22(36%) of those with Probable CBD and 19/48(40%) Possible CBD had pathology-confirmed CBD, whilst 11/35 (31%) were ‘Armstrong-negative”. Over disease course, PPV for CBD was similar (36%). Criteria were better at predicting 4RT, 82% and 75% within 3 years of onset and over disease course, respectively. Addition of specific language or behavioural abnormalities did not improve PPV. 46% patients met MDS PSP/CBS criteria over disease course, with 92% PPV for 4RT. No individual clinical feature was found to singularly predict underlying pathology.ConclusionThe Armstrong criteria have low predictive value for CBD both in early disease and over disease course. However, it has >80% prediction of 4RT. A combination of more specific biomarkers are required to improve diagnosis.d.lux@ucl.ac.uk
Andersen-Tawil syndrome: multi-system deep phenotyping of a large UK cohort
Authors: Vivekanandam Vinojini , Mannikko Roope , Fialho Doreen , Merve A , Pattni J , Marini-Bettolo C , Savvatis K , Behr ER , Hanna Michael , Matthews Emma 
Published: May 2022

Andersen-Tawil Syndrome (ATS) is a rare channelopathy caused by mutations in the KCNJ2 gene that encodes the ubiquitously expressed Kir2.1 potassium channel. We describe key findings in a large UK cohort of 52 patients, pertinent to the diagnosis and management of ATS. We report a new point prevalence of0.105 per 100 000 (increased from 0.08 per 100 000).While ATS has historically been considered a triad of episodic weakness, cardiac arrhythmias and dys- morphic features, we show that there is considerable variability to this phenotype. Pure cardiac or muscle phenotypes may exist. The absence of dysmorphic features does not exclude the diagnosis. Similarly, a normal long exercise test was seen in five patients.Importantly, we identify that the phenotype includes a significant risk of cardiac morbidity and mortality with 13% of our cohort requiring cardiac defibrillator or pacemaker insertion and an additional 23% reporting syncope. Syncope has been recently associated with an increased risk of life threatening arhythmic events in this cohort. Severe fixed myopathy was seen in a quarter of our cohort with 14% requiring a wheelchair or gait aid.We additionally describe novel neurological features and report eight new KCNJ2 variants with in vitro functional data. We provide key clinical insights and management recommendations. We also identify new features which are interesting areas for future research and collaboration.v.vivekanandam@ucl.ac.uk
SUNFISH Part 2: 24-month efficacy and safety of risdiplam in Type 2/3 SMA
Authors: Baranello Giovanni , Deconinck Nicolas , Mazzone Elena , Vuillerot Carole , Servais Laurent , Gerber Marianne , Kletzl Heidemarie , Yeung Winnie , Martin Carmen ,   et al
Published: May 2022

SUNFISH (NCT02908685) is a multicentre, two-part, randomised (2:1, risdiplam:placebo), placebo-con- trolled, double-blind study in individuals with Type 2/3 spinal muscular atrophy (SMA; inclusion criteria 2–25 years at enrolment). SUNFISH investigates efficacy and safety of risdiplam, a centrally and periph- erally distributed oral survival of motor neuron 2 pre-mRNA splicing modifier. Risdiplam (EVRYSDI™) has been approved by the US Food and Drug Administration for the treatment of individuals with SMA, aged 2 months and older.In Part 1 (N=51) the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels were assessed. Part 2 (N=180) assessed the efficacy and safety of the Part 1-selected dose of risdiplam versus placebo in Type 2 and non-ambulant Type 3 SMA. Individuals received risdiplam or placebo for 12 months; all individuals then received risdiplam until Month 24, when they had the oppor- tunity to enter the open-label extension phase.In Part 2, the primary outcome of the study was met, showing a statistically significant difference in change from baseline in 32-item Motor Function Measure total score at Month 12 between individuals treated with risdiplam (n=120) and placebo (n=60). No treatment-related safety findings leading to withdrawal were reported. Here we present SUNFISH Part 2 data after 24 months’ treatment.g.baranello@ucl.ac.uk16
Beware: adult-onset and fast-progressing Charcot-Marie-Tooth disease chameleons
Authors: Pipis Menelaos , Doherty Carolynne , Skorupinska Mariola , Laura Matilde , Rossor Alexander , Reilly Mary 
Published: May 2022

Differentiating between an acquired and genetic aetiology of peripheral neuropathy poses a challenge to the neurologist. Contributing factors to this include a lack of family history of neuropathy, a rapid progres- sion of the clinical syndrome and/or the presence of features that are considered atypical for inherited neuropathies such as non-length dependent weakness and denervation.We present 6 patients with genetically confirmed CMT (2 NEFH, 3 MME and 1 TFG), who presented in adulthood with a rapid course of disease progression. The mean age of symptom onset was 37.8yrs (range 33–49) and despite an average disease duration of only 12.8yrs (range 7–16), 50% of patients (3/6) required a wheelchair or stick for mobility. All patients developed significant proximal involvement early on in the course of their disease with half of them having persistent evidence of non-length dependent weakness and denervation. All sporadic cases had CSF examinations and investigations for inflammatory causes of neuropathy, 1 patient had 2 courses of IVIG and another was considered for a nerve biopsy prior to achieving a genetic diagnosis.Certain adult onset CMT subtypes may mimic acquired neuropathies and in order to avoid missing treatable causes, the pursuit of both diagnostic avenues is often necessary.m.pipis@ucl.ac.uk
A randomised controlled, trial of the GLP-1 receptor agonist exenatide in idiopathic intracranial hypertension
Authors: Mitchell James , Mollan Susan , Walker Jessica , Lyons Hannah , Yiangou Andreas , torovic Zerin Alimajs- , Grech Olivia , Tsermoulas George , Brock Kristian , Sinclair Alex 
Published: May 2022

BackgroundPre-clinical data demonstrates the ability of Exenatide, a GLP-1R agonist, to reduce CSF secretion and ICP.1 Existing GLP-1R agonists are widely used to treat obesity and diabetes (but do not cause hypoglycaemia).MethodsRandomised, placebo controlled, double-blind trial of Exenatide in women with active IIH. Participants were randomised 1:1 to Exenatide (10mcg twice daily sub-cutaneous) or placebo for 12 weeks. Telemetric, intraparenchymal ICP monitors (Raumedic) recorded ICP over 12 weeks. Analysis was by hierarchical regression, significance level set at p <0.1Results16 participants were recruited, 15 completed the study: BMI 38.1(6.2) kg/m2, ICP 30.6(5.1) cmCSF. ICP, the primary endpoint, fell significantly (2.5 hours -5.7(2.9) cmCSF (p=0.048), 24 hours -6.4 (2.9) cmCSF (p=0.030) and 12 weeks -5.6 (3.0) cmCSF (p=0.058)). Monthly headache days fell in the Exenatide treated cohort (-7.7 (9.2) p=0.069) and vision improved (logMar acuity -0.1 (0.04) p=0.004).ConclusionsExenatide reduced ICP acutely and after chronic dosing. GLP-1R agonists represent a new approach to treat IIH.1. Botfield HF, Uldall MS, Westgate CSJ, Mitchell JL, Hagen SM, Gonzalez AM, Hodson DJ, Jensen RH, Sinclair AJ. A glucagon-like peptide-1 receptor agonist reduces intracranial pressure in a rat model of hydro- cephalus. Sci Transl Med. 2017 Aug 23;9(404):eaan0972. doi: 10.1126/scitranslmed.aan0972.jamesmitchell4@nhs.net20
Yuletide tremor, twitches and tunes
Authors: Talaei Maryam , Ingram Gillian 
Published: May 2022

A 53 year old fit and well female was admitted to hospital with rapidly evolving progressive generalised stimulus sensitive myoclonus, axial rigidity and encephomyelitis over five days, two weeks after confirmed diagnosis of SARS-COV-2 infection. On admission to hospital she had generalised myoclonus involving face, voice, trunk, proximal and distal limbs augmented with tactile and auditory stimulus and voluntary movements. A few days later she developed significant axial rigidity, ocular bobbing and encephalitis as well as a myoclonic storm requiring intubation and ventilation. MRI Brain with contrast and CSF exami- nation were unremarkable and an EEG showed no epileptiform discharges. She was started on high dose intravenous steroids followed by 5 courses of plasma exchange. Her COVID serology was positive and other investigations including Glycine, GAD, amphiphysin and DPPX antibodies were negative. She demonstrated significant improvement and was discharged home a week after plasma exchange with the view to wean off steroids over six weeks. This case demonstrates a patient presenting with a rapidly evolving stimulus sensitive myoclonic storm with rigidity and encephalomyelitis two weeks after SARS-COV2 infection, which responded well to prompt immunomodulatory treatment.maryamtalaei@wales.nhs.uk22