bluuebunny/crossref_metadata_2025_split huggingface dataset:
225 Sporadic inclusion body myositis: a longitudinal observational study investigating outcome measures for clinical trials
Authors: Sangha Gina , Skorupinska Iwona , Germain L , Bellin A , Parton Matthew , Hanna Michael , Miller James , Hilton-Jones David , Freebody Jane , Machado Pedro 
Published: March 2023

BackgroundSporadic inclusion body myositis (IBM) is the most common age-related acquired myopathy. Our aim was to longitudinally evaluate clinical, quantitative and functional characteristics of the disease to develop statistical models of progression that can be used in clinical trials.MethodsIn a prospective cohort study, we recruited 205 patients with a diagnosis of IBM across three centres (London, Oxford and Newcastle).Patients underwent bilateral manual muscle testing (MRC scale), quantitative muscle testing and disability scoring (IBM Functional Rating Scale) at each follow up visit. The time at which a patient first required a mobility aid was recorded.Linear multilevel models were fitted to investigate the progression of these scores over time. Cox proportional hazards regression was used to model time to use of a mobility aid.ResultsIn the preliminary analyses we have generated reliable multilevel models of disease progression using those muscle groups that are worst affected by the disease over time. We have also modelled the progression of IBMFRS over time. These models can be used to predict/monitor disease progression.ConclusionThis study will be the largest prospective observational study in IBM to date and will reveal useful outcome measures that can be used in clinical trials.
226 Quantitative strength profiling in inclusion body myositis
Authors: Lilleker James B , Oldroyd Alexander , Chinoy Hector , Miller James AL 
Published: March 2023

BackgroundInclusion body myositis (IBM) is a rare idiopathic inflammatory myopathy subtype. Our study aimed to describe the disease progression rate in IBM using measures of muscle strength and functional assessment tools.MethodsRetrospective analysis of quantitative muscle strength data and functional assessment tool results (IBM Functional Rating Scale [IBM-FRS] and the Neuromuscular Symptom and Disability Score [NSS]), systematically collected from verified IBM cases (July 2003 to March 2015) at a UK neuromuscular clinic. Yearly rate of strength change was estimated for each muscle group and associations between with the IBM-FRS/NSS were examined using simple linear regression.ResultsData from 80 IBM cases (44% female) were analysed, a total of 232 person-years and a median 2.3 years (IQR 0.6, 4.4) follow-up. Similar rates of deterioration were found for right and left sided muscle groups. Annual rate of strength loss was greatest for grip, pinch and knee extension (-5.5% [95% CI -6.3, -4.6], -16.0% [-18.4, -13.5] and -7.1% [-7.6, -6.5]). The rate of strength loss was greatest for males. Increased strength measurements were associated with improved IBM-FRS/NSS scores for most muscle groups.ConclusionThis is the first long-term study to comprehensively demonstrate quantitative strength change in a large IBM cohort. We provide valuable natural history data to support discussions regarding prognosis, focus effective choice of outcome measures and inform required study numbers for future clinical trials.
227 An audit of adherence to ABN guidelines in myasthenia gravis diagnosis and management
Authors: Hutchcroft Christopher , Boix-Codony Marc , Hamid Shahd 
Published: March 2023

Introduction and aimsWe identified previously-audited shortfalls in myasthenia gravis diagnostic and management practice, notably in ensuring appropriate bone protection and making sure that patients were followed up in prompt time. We aimed to reaudit practice at The Walton Centre and identify adherence to ABN guidelines.MethodsPatients investigated for suspected myasthenia presenting October 2017 to September 2018 who were subsequently managed at the Walton Centre.Results43 patients identified. Anti-AChR at first appointment: 42/43 (97%) Serum anti-MuSK if anti-AChR is negative: 9/10 (90%) MR brain for ocular MG if serology and neurophysiology negative: 1/1 (100%) Thymus imaging for all patients: 38/41 (93%). Neurophysiology if serology negative: 7/7 (100%) First follow-up within six weeks: 38/41 (44%). Second follow-up within 12 weeks: 22/40 (55%) Generalised MG admitted unless symptoms mild: 9/10 (90%) Pyridostigmine started at the time of diagnosis: 35/36 (97%) Glucocorticoids started if no remission on pyridostigmine: 22/22 (100%) Bone protection if on glucocorticoids: 19/21 (90%)ConclusionWe found that adherence had improved regarding bone protection when on steroids, but follow-up times remained a problem. Additionally, anti-MUSK and EMG were largely used when indicated, but also often unnecessarily used in the presence of positive AChR antibodies.
235 Epidemiology of motor neurone disease in wales
Authors: Saad Toni , Dawson Ken , Hirst Claire , Baker Idris , Lowman Andrea , Wardle Mark , Harding Katharine ,   on behalf of the South Wales Motor Neurone Disease
Published: March 2023

BackgroundNational registries of patients with rare disease such as motor neurone disease (MND) can lead to more reliable epidemiological estimates.MethodsThe South Wales MND Network records clinical data on all patients referred to the specialist MND clinics in south Wales and diagnosed with MND. Anonymised data was accessed for analysis. The prevalence date was 23/6/2016, and all patients registered with the South Wales MND Network, alive and resident in the region on that date were included. Population estimates were obtained from Welsh Government data.ResultsThere were 202 people with MND on the prevalence date, of whom 122 (60.4%) were male. The median time from onset to diagnosis was 1.4 years (interquartile range 0.9–2.4 years). Prevalence in the region was 8.8 per 100,000. This varied by local health board, with the highest prevalence seen in Aneurin Bevan University Health Board (12.1 per 100,000), and the lowest in Abertawe Bro Morgannwg University Health Board (7.0 per 100,000). Male:female ratio was similar for all local health boards (χ2=3.6, p=0.46).ConclusionsOur estimates of prevalence are in keeping with other European countries. Future investigation into variation in MND prevalence may provide insights into underlying mechanisms of disease.
237 SLC25A46 mutations cause a spectrum of disorders including CMT2 with optic atrophy
Authors: Doherty Carolynne , Pipis Menelaos , Cortese Andrea , Poh Roy , Polke James , Pitceathly Robert , Rossor Alexander , Reilly Mary 
Published: March 2023

CaseA 20-year-old female had symptom onset age 7 of bilateral foot drop and distal lower limb atrophy. Nerve conduction studies demonstrated a length dependent axonal motor and sensory neuropathy. At 16 her vision deteriorated to 3/36 right, 6/60 left. Visual evoked potentials were borderline compatible with bilateral optic atrophy. Metabolic and structural causes were excluded.ExaminationAt age 18 examination demonstrated bilateral foot drop and a positive knee bob sign. There was asymmetrical distal limb atrophy. Fundi were pale. Reflexes were brisk in upper limbs and knees with absent ankles and mute plantars.ResultsThe 56-gene Bristol axonal neuropathy panel revealed a non-pathogenic TRPV4 mutation. Mutations in OPA1, OPA3, POLG, ATPase 6 and 8 were not identified. Exome sequencing in the research setting demonstrated compound heterozygous SLC25A46 mutations. One mutation was confirmed in each of her parents.DiscussionMutations in SLC25A46 are associated with spectrum of disorders encompassing pontocerebellar hypoplasia (including lethal congenital cases), Leigh Syndrome, Progressive myoclonic ataxia with optic atrophy and neuropathy, and hereditary motor and sensory neuropathy type 6B, sometimes with associated features such as cerebellar ataxia and spasticity. We present a case of CMT2 with optic atrophy due to heterozygous mutations and discuss the literature.
240 A case of fulminant guillain-barré syndrome mimicking brain death
Authors: Sivagnanasundaram Jananee , Broad Rebecca , Tague Lucy , Quaresma Catarina , Dittrich Richard , Alkufri Fadi , Harikrishnan Sreedharan 
Published: March 2023

Guillain-Barré syndrome (GBS) encompasses a spectrum of acute immune-mediated polyneuropathies. Rarely, in its fulminant form, it can rapidly progress to mimic brain death. We present a case with diagnostic challenges due to a limited history.A 58-year-old gentleman presented generally unwell and within hours of admission choked on his dinner and suffered a cardiorespiratory arrest. Review on ITU revealed absent brainstem reflexes apart from a weak pupillary light response.EEG showed slowing with subtle reactivity, MRI Brain was normal, and CSF revealed albuminocytological dissociation.On day 27 of admission, he was found to follow commands with eye movements, appearing to be in an incomplete locked-in state. Nerve conduction studies confirmed a severe axonal sensorimotor neuropathy with sural sparing. He was treated with plasma exchange and intravenous immunoglobulins and continues to make significant motor improvements each week.This case highlights the crucial recognition of this extreme presentation of GBS, as a misdiagnosis of brain death may lead to the withdrawal of ventilatory support. In a third of reported similar cases there has been a good recovery and in the majority (as in our case) serum ganglioside antibodies have been negative, raising the possibility of alternative nodal and paranodal target antigens.
246 Refractory seizures: a case of post-partum pyridoxine dependent epilepsy
Authors: Chaudhuri Shreya , Ball Joanna , Murphy Elaine , Muhammed Kinan 
Published: March 2023

A 29 year old woman underwent a planned Caesarean delivery. She denied any pre-existing medical conditions. 72-hours later she developed multiple generalised tonic-clonic seizures requiring sedation and intubation. Brain imaging revealed long standing enlargement of the ventricles. Urinary protein and blood pressure were normal. She continued to have frequent seizures confirmed on EEG despite treatment with multiple anti-epileptics.Collateral history from family revealed seizures as an infant but none since aged 6 months and that she was not taking anticonvulsants. Further inquiries confirmed a regular prescription for Vitamin B6 (Pyridoxine) which she had stopped during pregnancy. In the context of refractory seizures and the imaging findings, the possibility of Pyridoxine-dependent epilepsy was raised. Pyridoxine 100 mg twice daily was started. After the first dose, the patient’s seizures stopped and she was extubated, anticonvulsants were stopped and she had no further seizures.Pyridoxine dependent epilepsy is an autosomal recessive condition. Clinical features include refractory seizures in the first few months of life. It is caused by mutations in the ALDH7A1 gene which codes for α-aminoadipic semialdehyde dehydrogenase (α-AASA, Antiquitin), an enzyme involved in the breakdown of lysine within the brain resulting in raised levels. Diagnosis involves genetic testing and elevated plasma and urine levels of α-AASA. Treatment is lifelong daily pyridoxine supplementation.Pabrinex containing Pyridoxine should be considered in all patients who have ongoing seizures not responding to multiple anti-epileptic medication.
247 Autosomal recessive spinocerebellar ataxia type 10 (SCAR10); a rare diagnosis courtesy 100,000 genome project
Authors: Zafar Hassan W , Gutowski Nicholas J 
Published: March 2023

BackgroundAutosomal recessive spinocerebellar ataxias (ARCAs) can involve both central and peripheral nervous systems as well as other organ systems and so frequently pose a diagnostic challenge due to significant overlap in clinical presentation.ObjectiveWe report a case of a Caucasian lady who presented with ataxia, dysarthria and vertical gaze nystagmus. Genetics revealed a mutation in the ANO 10 gene confirming a diagnosis of Spinocerebellar Ataxia Type 10 (SCAR 10).MethodsA 67 year old lady presented 25 years ago with unsteady gait, dysarthria and vertical gaze nystagmus. Her symptoms gradually progressed and she has used a wheelchair for 5 years. Extensive biochemical, imaging and genetic investigations remained unrevealing. MRI showed marked cerebellar atrophy. She had a male sibling with a similar cerebellar syndrome, he died 8 years ago. There is no consanguinity and no other family history. She underwent whole genome sequencing (WGS) as part of the 100,000 Genome project.ResultsWGS revealed heterozygous mutations in the ANO 10 gene confirming Spinocerebellar Ataxia Autosomal Recessive 10 (SCAR 10).ConclusionsGene panel coverage varies with time and rare ARCAs may remain undiagnosed. This case demonstrates the value of the 100,000 Genome project, and by inference WGS, for rare genetic disorders.
248 A 57-year-old man with deteriorating mobility and deafness
Authors: Stavrou Maria , Yeo Jing Ming , Richard Davenport 
Published: March 2023

A 57-year-old man re-presented to the neurology clinic in August 2014 with a 20-year history of progressive gait decline, and a 2-year history of requiring crutches and a wheelchair. Recently, he had also developed numbness below his knees. His upper limb function had remained normal. He wore bilateral hearing aids for sensorineural deafness, had a 10-year history of red–green colour blindness and suffered from bladder dysfunction for several years. His neurological symptoms had been previously investigated but without a diagnosis, and he had been lost to follow-up for several years. In 2017, with the advent of next-generation sequencing gene panel, he was screened for 20 spastic paraparesis genes. This identified a mutation inSPG7in the form of a homozygous variant c.1529C>T/p.Ala510Val, consistent with autosomal-recessive HSP.This man’s diagnosis was made by molecular genetic testing nearly 20 years after his symptoms began. This was achieved by the astonishing progress over the last decade in identifying HSP genes coupled with the introduction of high-throughput sequencing approaches. These advances provide benefits to HSP families including diagnostic certainty, avoidance of time-consuming and expensive investigations, genetic counselling and optimisation of care. A step forward would be to establish an international database of people with this condition to characterise genotype/phenotype correlations, elucidate the natural history and to facilitate clinical trials focusing on effective interventions.
251 Economic burden of spinal muscular atrophy type 1 (SMA1)
Authors: Dabbous Omar , Seda Jennifer , Kausar Imran , Droege Marcus , Sproule Douglas M 
Published: March 2023

BackgroundSMA1 is a rapidly progressing disease resulting in muscle weakness, respiratory failure, and early death. This retrospective analysis estimated the economic burden of SMA1 using QuintilesIMS’s PharMetrics Plus Health Plan Claims Database.MethodsSMA1 infants (N=119) were matched (1:1) with a random sample of infants by age, gender, index year, and Charlson Comorbidity Index. Healthcare resource utilization (HCRU) and costs incurred during the post-index/follow-up period (≥30–360 days, February 2011–November 2016) were compared.ResultsSignificantly more SMA1 patients had ≥1 all-cause HCRU claims vs. matched patients (98.3% vs. 54.6%, P<0.0001). Mean per-patient-per-month (PPPM) all-cause HCRU was higher for SMA1 infants: pharmacy (1.43 vs. 0.37 prescriptions); outpatient (14.10 vs. 2.17 services); inpatient (0.23 vs. 0.003 admissions) (all, P<0.0001). Mean PPPM hospital admissions (0.23 vs. 0.003), length of hospital stay (6.93 vs. 0.09 days), procedures/admission (1.49 vs. 0.03), and readmissions (0.04 vs. 0.00) were also significantly greater for SMA1 infants (all, P<0.0001). Pharmacy, outpatient, and inpatient costs PPPM were greater in SMA1 infants ($371 vs. $20; $4,192 vs. $232; and $22,500 vs. $22 [all, P<0.0001]), resulting in extrapolated all-cause total annual costs of $324,751 (SMA1 cohort) vs. $3,294 (matched cohort).ConclusionsThe economic burden of SMA1 is substantial.
252 Speed to treatment effect in spinal muscular atrophy type 1
Authors: Droege Marcus , Dabbous Omar , Feltner Douglas , Novack Aaron , Kausar Imran , Menier Melissa , Sproule Douglas 
Published: March 2023

BackgroundSpinal Muscular Atrophy type 1 (SMA1) is a rapidly progressing disease resulting in death/permanent ventilation by 2 years of age. In ENDEAR, ∼10% of patients died/required permanent ventilation within 2 months after therapy initiation; 39% died/required permanent ventilation by 6 months. This may reflect a non-immediate therapeutic impact related to loading dose schedule. This study explored the rapidity of therapeutic effect of onasemnogene abeparvovec (AVXS-101) gene-replacement therapy (phase 1 study) relative to nusinersen (phase 3 study, ENDEAR).MethodsSMA1 patients were treated with a one-time intravenous AVXS-101 injection (NCT02122952; cohort 2; N=12; 24 months follow-up). Outcomes were event-free survival (EFS, no death/permanent ventilation [AVXS-101: ≥16 hours ventilation/day for >2 weeks; ENDEAR: tracheostomy or ≥16 hours ventilation/day for >21 days]) and motor function improvements (CHOP-INTEND).ResultsAll patients treated with AVXS-101 survived event-free 24 months post-dose, while 49/80 nusinersen patients showed EFS. Rapid increases in CHOP-INTEND of 9.8 and 15.4 points were observed at 1- and 3-months post–AVXS-101 dose (nusinersen: ≤5-point increase at 2 months after initiation).ConclusionsAVXS-101 appears to improve survival and induce more rapid motor function improvements relative to nusinersen, consistent with rapid restoration of survival motor neuron expression in motor neurons with a single dose.
253 Idiopathic intracranial hypertension causing back pain and visual loss without headache
Authors: Cheema Sanjay , Cooper Sarah 
Published: March 2023

Idiopathic intracranial hypertension (IIH) usually presents in overweight young women with headache and visual disturbance.We report a case in a slim young woman, who described six months of increasingly severe lower back pain, worse on lying flat and often waking her at night. Despite a significantly elevated cerebrospinal fluid (CSF) opening pressure of 55cm CSF, at no point did she experience a headache.The back pain entirely resolved as CSF pressure was treated. No secondary cause was found on brain or spinal imaging and CSF constituents were normal. She sustained some early and permanent visual loss and required a shunt procedure to control the raised intracranial pressure and ongoing visual deterioration. She has remained well, 20 months since the original presentation.Our patient had pre-existing ocular hypertension, which did not resolve after effective treatment of the raised intracranial pressure and may have affected the presentation of papilloedema.This case highlights that IIH should be considered in patients with visual symptoms and back pain, even in the absence of headache, and acts as a reminder that patients with IIH are not necessarily overweight.
254 Visual inversion illusion in a patient with multiple sclerosis
Authors: Cheema Sanjay , Mahmud Mohammad , Cooper Sarah 
Published: March 2023

BackgroundIt is possible to suddenly and temporarily experience the illusion that the world is upside down.This visual inversion illusion is rare, but has previously been reported in patients with migraine, posterior circulation stroke, traumatic brain injury, and multiple sclerosis (MS).The same illusion can be provoked in neurologically-normal aircraft pilots or astronauts under certain circumstances; and in experiments involving wearing vision-inverting goggles.Case historyWe report a patient with secondary progressive MS, who for the past six months reported that ‘when I get tired my eyes see everything upside-down’. These episodes occurred most evenings and resolved after a night’s sleep.On examination there was evidence of previous optic neuritis and intranuclear ophthalmoplegia. MRI brain showed multiple lesions in the brainstem and visual pathways.DiscussionThis case adds to the small number of reports of this phenomenon in the context of MS, and the first where it is related to fatigue.The precise anatomical substrate is unknown. It has been reported in patients with single lesions in the brainstem, vestobulocerebellum, and right parieto-occipital region.The illusion may occur due to disrupted sensory integration between visual input and other verticality signals, for example from the vestibular system.
262 Consequence or coincidence? Migraine and stroke
Authors: Oo Aung 
Published: March 2023

A 52-year-old female was admitted following 1-week history of headache, and 1-day history of vertigo.Her only past medical history was migraine. She is a non-smoker. She is not on any medications including contraceptive pills.The headache was like her usual throbbing headache- on the right side of head, associated with nausea, and photophobia. Visual flickering had already resolved on admission. This was not relieved by over-the-counter painkiller.She experienced vertigo on the day of admission which was new for her.Clinical examination revealed normal neurological examination apart from ataxia. Other cerebellar signs were notably absent.She was initially treated for migraine with aspirin, prochlorperazine and sumatriptan with no success.MRI head revealed small acute infarct in right cerebellum. MRA showed no aneurysm or dissection. All young stroke diagnostic work-up were unremarkable.DiscussionMigraine may mimic stroke. It is also known to increase the risk of stroke, particularly in women who have migraine with aura. There is an association between migraine with aura and silent infarct-like lesions on brain MRI located mainly in the posterior circulation white matter or cerebellum. Thus in this case, migraine is likely to be a cause of stroke, although coincidental occurrence cannot be ruled out.
264 A rare cause of young stroke diagnosed by intracranial MR vessel wall imaging
Authors: Aggarwal Veena , Benjamin Laura , Simister Robert 
Published: March 2023

Current stroke guidelines do not facilitate the expedient diagnosis of inflammatory stroke. At UCLH, we have integrated intracranial vessel wall imaging (iVWI) into our stroke pathway to overcome this barrier. We present a case, where iVWI facilitated the diagnosis and helped us interpret a further asymptomatic stroke event.A 36-year-old man presented with left sided facial weakness. He had type 2 diabetes, hypertension, obesity, and hypercholesterolaemia. CT showed a right MCA/ACA infarct with severe bilateral ICA stenosis. MRI confirmed a borderzone infarct. The patient was treated with anti-platelets, a statin and continued ramipril and amlodipine. iVWI imaging identified an unexpected inflammatory vasculopathy. His CSF was supportive of CNS inflammation, and thus, commenced on prednisolone and empirical valaciclovir. His 3-month interval scan showed new asymptomatic borderzone infarcts that were concordant with hypoperfusion injury, and temporally linked with the initiation of indapamide by his GP, this was subsequently stopped. His vasculopathy remained static. A six-month interval scan showed no new lesion, and improvement of his inflammatory vasculopathy. Using iVWI, we were able to diagnose an inflammatory vasculopathy that could have been missed. The case also highlighted that excessive early reduction of blood pressure can contribute to hypoperfusion related stroke.