bluuebunny/crossref_metadata_2025_split huggingface dataset:
134 Predictors of serum vitamin D level in multiple sclerosis
Authors: Kuri Ashvin , Vickaryous Nicola , Jacobs Benjamin Meir , Awad Amine , Dobson Ruth 
Published: August 2022

BackgroundLow serum 25(OH)D3 (vD) in early disease may be associated with worse prognosis in multiple sclerosis (MS). Determinants of serum vD concentration are established in healthy individuals, but poorly studied in people with MS (pwMS). Unpicking the determinants of vD concentration in pwMS may have important preventative and therapeutic implications.MethodsWe recruited a study cohort of pwMS from the UK MS Register (n=315) and matched controls (n=232). We measured serum 25(OH)D3 and genotyped six vD-associated SNPs. We developed a weighted genetic risk score (GRS) using these SNPs and validated it in 373,357 UK Biobank participants. We then assessed predictors of vD levels in our cohort and constructed multivariable models to assess the influence of GRS.ResultsThe GRS was well-validated, being strongly associated with vD status in the Biobank cohort (p<2x10-16). In our study cohort, taking vD supplementation, having MS, lower BMI, increased age and supplementation dose were associated with higher vD levels (false discovery rate, FDR<5%). In multivariable models adjusting for these confounders, GRS was strongly associated with vD level in non-supplementers (p=0.004), but not in supplementers (p=0.47).ConclusionsOur findings suggest vD supplementation is the most important determinant of vD level in pwMS, and genetic determinants may play a relatively minor role.
139 Characterising DARC (Detecting Apoptosing Retinal Cells) spots in optic neuritis
Authors: Choi Soyoung , Maddison John , Nicholas Richard , Cordeiro Francesca 
Published: August 2022

PurposeOptic neuritis (ON) is a common feature of Multiple Sclerosis (MS). DARC is an intravenous fluo- rescent-tagged annexin V (ANX776) identifying cell stress and apoptosis with retinal imaging. We aimed to differentiate DARC spots in ON from healthy subjects using descriptive measures (DM) of DARC spots identified by a convolutional neural network-aided algorithm (CNN-AA).MethodsDARC spots were identified from anonymised DARC images obtained from ON (n=12; mean age=46) and healthy (n=68; mean age=48) participants after ANX776 administration using the CNN-AA (ISRCTN10751859). DM characteristics: mean, standard deviation (std), skew, kurtosis, coefficient of variation (cv), Euclidean distance from the nearest blood vessel (bvdist) and the 7Hu moments, were analysed on ON (n = 357) and healthy (n = 2457) eyes using two-tailed student t-tests. Distributions of spot metrics were analysed using two-sample Kolmogorov-Smirnov test.ResultsThe mean, cv and kurtosis (p £ 0.0001) and hu1 and std (p £ 0.001) were found to be significantly different between DARC spots in ON and healthy controls. Distributions of the individual DM metrics analysed, showed a significant difference (p £ 0.0001) between ON and healthy spots for the same variables (mean, cv, kurtosis, hu1 and std).ConclusionDM of DARC spots distinguish ON and healthy subjects. Further studies with larger ON groups are needed to replicate this finding.
160 Ophthalmological involvement in m.3243A>G-related mitochondrial disease
Authors: Devine Helen , Ng Yi , McFarland Robert , Gorman Grainne , Browning Andrew 
Published: August 2022

BackgroundThe m.3243A>G mtDNA is the most common pathogenic mtDNA variant and has a very varied clinical phenotype. Vision has a high metabolic demand and there are large numbers of mito- chondria in the retina, particularly in the photoreceptors and the retinal pigmented epithelial layer. Little is known about the heteroplasmic/phenotypic correlations of retinopathy in patients with m.3243A>G- related mitochondrial disease.ObjectiveThe overall aim of the study was to explore retinal involvement in patients with m.3243A>G- related mitochondrial disease. Specifically, to describe the retinal and optic nerve changes and to determine whether the presence of maculopathy and/or optic nerve changes predict the development of CNS involvement in patients with the m.3243A>G mutationMethodsPatients with genetically confirmed m.3243A>G-related mitochondrial disease were identified from the UK Mitochondrial Disease Patient Cohort; a registry of patients under active follow up at one of the three UK Mitochondrial Centres (Newcastle, London and Oxford). Participants underwent detailed clinical and ophthalmological examination. Ophthalmological phenotype was correlated with a validated clinical rating scale score (NMDAS) and m.3243A>G heteroplasmy levels.ResultsRetinal defects were common in m.3243A>G-related mitochondrial disease with subgroups of patients demonstrating maculopathy or optic nerve involvement.ConclusionCharacteristic retinal defects are common in m.3243A>G-related mitochondrial disease.
163 Immunosuppression guidelines ongoing implementation project
Authors: Japzon Nicole , Gurney Rowan , Basgaran Amedra , Compton Laura , Lunn Michael , Carr Aisling 
Published: August 2022

In 2016, a hospital approved guideline on first line immunosuppression was introduced. This included evidence-based guidance on consent, prescription, dosing, safety and efficacy monitoring of corticos- teroid, azathioprine, methotrexate, mycophenolate, IVIg, SCIg, rituximab and cyclophosphamide use in common inflammatory neuromuscular diseases. It was accompanied by drug-specific patient information booklets and disease-specific clinical outcome measurement tools. The centre for neuromuscular diseases has not recorded any serious adverse events associated with these medications since its introduction.With junior doctors rotating in 3-6 monthly cycles, we identified the need for recurrent implementation efforts to maintain guideline impact. With an iterative process of four sequential cycles we:1) performed a survey of adequacy of admission/discharge documentation,2) created electronic patient record (EPR) proformas for admission/discharge,3) included a training session at changeover hospital induction,4) added a training session to mid-rotation peer-led teaching rota.This process resulted in optimal admission/discharge documentation (as per guidelines) of: Cycle 2) 61%/96%; Cycle 3) 100%/70%; Cycle 4) 86%/100%.Here we highlight the potential for loss of compliance with guideline use by junior medical staff over multiple changeovers, demonstrate the need for ongoing implementation efforts and underline the benefit of integrated electronic proformas (content in poster).
169 An audit into the management of functional neurological disorder in Salford
Authors: Houston James , Cooper Paul 
Published: August 2022

BackgroundFunctional neurological disorder (FND) is a debilitating condition impacting all aspects of life. Poor understanding of FND, and lack of clinical service pathways, may result in poor management, compared to recent NICE (2021) Quality Standards. We audited patients diagnosed with FND after admission to Salford Royal, including the care pathways used.MethodsSalford Royal electronic patient records were accessed to populate an existing data collection tool used for analysis of neurological services. Patients admitted over a 4 month period were identified using ICD-10 coding (F44.5), with appropriate inclusion and exclusion criteria. We excluded patients with non-epileptic seizures as their prime diagnosis.ResultsWe identified 64 admitted patients, with 10 excluded. Of 54 patients analysed, 91% had a motor deficit, 53% had a sensory deficit, many therefore presenting with functional motor disorders, often with impaired mobility, and likely to benefit from a multidisciplinary team approach. 44% of patients had no documented management plan for their FND at discharge, and in 80% of patients follow-up plans were unclear. (It is acknowledged that limited access to outpatient letters from community services may have impacted results.)ConclusionFND patients are being failed by our services, which are not meeting NICE Quality Standards. The unit is currently developing a multidisciplinary service for FND patients, which has proved challenging in the present climate. We plan to repeat the audit once our proposed service is established.
170 Commencing novel therapies for adult SMA patients: experience from a hybrid clinic
Authors: Cader Zahra , Nevin Katie , Maidment Lindsay , Packwood Shirley , Chilimina Nyaose , Monks Kimberley , Hewamadduma Channa 
Published: August 2022

Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder that affect both adults and children. Two novel therapies were approved for patients in England by NICE (Nusinersen via Management Access Agreement (MAA) and Risdiplam via Early Access to Medicine scheme (EAMS)). Setting up baseline assessments, designing new pathways, acquiring personnel and resources have been challenging. We present a pathway analysis of the new clinic set-up, process of patient choice, risk minimisation in intro- ducing the two novel therapies, and the impact therapies have had on adult cohort of SMA patients.Total of 58 patients included (31 had type 2 SMA and 27 had type 3[only 11/27 were ambulant]. The average age of patients with type 2 and 3 SMA was 25 and 33 respectively. 19 patients chose risdiplam (oral) and 22 are on nusinersen (intra thecal). We analysed factors that govern patients’ treatment decisions.We report factors that helped early success in our hybrid clinic set-up. Set criteria on each scheme; but potential side effects, information availability, route of administration (mainly previous spinal surgery), speed at treatment initiation but not COVID directed many patients’ treatment decisions. A battery of outcome measures were analysed to establish treatment impact at 12 months.
175 A case series of anti-HMGCR immune mediated necrotizing myopathy: the West Midlands data
Authors: San Pyae Phyo , Davies Nicholas , Srinivasan Venkataramanan , Samra Amrit , Paluri Srinivasa , Ubben Simon , Kumar Prateek , Kiolachidis Konstantinos , Dhar Saikat , Moor Carl-Christian 
Published: August 2022

BackgroundAmong immune mediated myopathies, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) immune mediated necrotizing myopathy (IMNM) has been increasingly rec- ognised over the last two decades.Majority are associated with statin exposure and typically present with hovering high creatinine kinase (CK) and/or progressive proximal myopathy despite discontinuation of statin.MethodWe analysed the data of 18 cases of anti-HMGCR IMNM from West Midlands region from 2016 to 2022.Results16 had statin exposure. Only 1 was asymptomatic but the rest experienced progressive proximal myopathy. Strikingly, two-thirds reported dysphagia and 3 required Intensive Unit admissions.Anti-HMGCR antibody was positive in all cases. CK levels remained high (mean=9053IU/l) despite dis- continuation of statin. A trend of persistently high ALT, lowering creatinine and weight loss reflected smouldering muscle loss.The asymptomatic patient did not need treatment. Significant improvement/remission was achieved spontaneously in 1, with steroids or IVIG alone in 10 and with combined immunotherapies in the rest. 1 patient died despite improvement in CK level.ConclusionAnti-HMGCR IMNM, especially when associated with statin, responds well to immunotherapy. We suggest having a low threshold for checking anti-HMGCR antibody in patients with persistently high CK levels and/or proximal limb/pharyngeal muscle weakness, especially in the presence of statin exposure.
192 Tacrolimus-induced chronic inflammatory demyelinating polyradiculoneuropa- thy (CIDP): a case series
Authors: Evans Matthew , Dahdaleh Sam , Karunaratne Kushan , Pritchard Jane , Rinaldi Simon , Viegas Stuart 
Published: August 2022

IntroductionCalcineurin inhibitors are used for immunosuppression after solid organ transplantation, and tacrolimus is the most commonly agent used. It is associated with several adverse effects including oppor- tunistic infection, nephrotoxicity, diabetes and increased cancer risk, but less well known is its association with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). Case series: We describe 7 cases of patients developing CIDP following tacrolimus treatment post transplantation. There were 3 cardiac, 3 lung and 2 renal transplants. Time since starting tacrolimus to development of CIDP varied widely from 5 months to 14 years. All cases were clinically consistent with CIDP with demyelinating neuropathy on neurophysiology. Intravenous immunoglobulin (IVIg) was tried in 6/7 cases but only showed clinical effec- tiveness in 2 patients, who required long-term treatment 2-monthly while continuing tacrolimus. In 3 of the IVIg non-responders (and 1 patient not trailed on IVIg), immunosuppression was switched to an alternative agent (sirolimus) with long-term resolution of neuropathy. Some cases were confounded: 1 associated with EBV and another CMV viraemia.ConclusionVarious case reports have demonstrated a possible association between tacrolimus and CIDP, but this is the largest case series to date. IVIg responsiveness alone is generally poor, but resolution is possible when switching to alternative agents.
193 Unusual presentation of hereditary neuropathy with liability to pressure palsies (HNPP)
Authors: Foo Eng Chuan , Al-Samak Ali , Lwin Khine Khine , Thura Myat , Tun Shwe Zin 
Published: August 2022

IntroductionHNPP is an autosomal dominant disorder with estimated prevalence between 0.84- 16/100,000, commonly presenting as mononeuropathies involving pressure-prone areas. Presentation as both a brachial plexopathy and spinal accessory neuropathy is rare, and previously unreported.Case ReportA 30-year old female with no known medical co-morbidities presented with a 3-month history of right shoulder pain and weakness, and intermittent numbness of the elbow and hand. Examina- tion showed wasting of right trapezius and spinati muscles, shoulder droop, and weakness involving the right sternocleidomastoid, shoulder, and median and ulnar-supplied hand muscles. Nerve conduction studies and electromyography revealed axonal-loss pattern neuropathy of right suprascapular and spinal accessory nerves. Focal demyelination was seen in bilateral median and ulnar nerves across the wrists and elbows. Needle EMG showed denervation changes in right infraspinatus and trapezius muscles. Sub- sequent genetic testing of patient and her mother revealed deletion of chromosome 17p11.2 including PMP22. She improved clinically following a period of intensive physiotherapy.ConclusionHNPP typically affects pressure-prone sites such as the median, ulnar or peroneal nerves. Brachial plexopathy is uncommon, and involvement of spinal accessory nerve is very rare. Recognition of symptoms, with appropriate targeted electrodiagnostic and genetic investigations is important in achieving an accurate diagnosis and management.
194 CANVAS-related sensory ganglionopathy without severe ataxia – the importance of muscle afferents in proprioception
Authors: McKenna Mary Clare , Kinsella Justin , Houlden Henry , Connolly Seán 
Published: August 2022

BackgroundSensory ganglionopathy is typified by selective peripheral sensory axonal loss on nerve conduction studies (NCS) and can occur with CANVAS (cerebellar ataxia with neuropathy and bilateral vestibular areflexia) syndrome.Case: A 53-year old woman had a 4-year history of some unsteadiness, slurred speech and distal sensory symptoms. She also reported a daily cough over the past 10 years. Clinically, she had dysarthria and mild sensory ataxia. Proprioception and deep tendon reflexes were preserved.Results of Investigations: NCS demonstrated markedly reduced sensory nerve action potential (SNAP) amplitudes in upper and lower limbs with normal motor NCS. The tibial H-reflexes were strikingly retained. Genetic testing confirmed biallelic RFC1 intronic repeat expansion mutation consistent with CANVAS syndrome.DiscussionThe retained H-reflexes (and tendon reflexes) indicates relative sparing of the group Ia muscle afferents that originate from muscle spindle primary endings and are known to contribute significantly to proprioception. This accounts for the relatively mild gait ataxia in the setting of CANVAS syndrome despite marked sensory NCS abnormalities.
205 Relationship between thrombin generation and micro-embolic signals in moderate-severe asymptomatic and symptomatic carotid stenosis patients
Authors: Subramanian Arun , Murphy Stephen , Smith Deirdre , Tierney Sean , Egan Bridget , Rushe Hannah , O’Sullivan Jamie , O’Donnell James , Hamilton George , McCabe Dominick 
Published: August 2022

BackgroundData are limited on thrombin generation biomarker profiles in carotid stenosis patients with or without cerebral micro-embolic signals (MES).Aims andMethodsIn this prospective, multi-centre, observational study, plasma thrombin generation parameters were compared in patients with ≥50-99% asymptomatic(N=34) vs. symptomatic carotid stenosis in the early (≤4 weeks; N=39) and late phases (≥3 months; N=31) after TIA/ischaemic stroke. Nested longitudinal follow-up was performed in symptomatic patients. Transcranial Doppler ultrasound classified patients as MES+ve or MES-ve.ResultsThere were no significant differences in thrombin generation parameters between early or late symptomatic vs. asymptomatic patients (P≥0.17). In symptomatic patients with matched data at each timepoint, peak thrombin production (365.1 vs. 327.2nM; P=0.003) and endogenous thrombin potential (2242.6 vs. 2078.4 nM*min; P=0.048) decreased between the early and late phases overall. The fall in peak thrombin during follow-up was significant in symptomatic subgroups who underwent revascularisation (N=26; P=0.007) and who were MES-ve (N=14; P=0.029), but not in those on optimal medical therapy alone (N=5; P=0.19).DiscussionThrombin generation decreases over time and following revascularisation in TIA/stroke patients with moderate-severe symptomatic carotid stenosis, including those who are MES-ve. These data improve our understanding of haemostatic/thrombotic biomarker profiles in patients with carotid stenosis.
Parallel Session 1: Muscle, nerve and quality| Wed 18 May, 1115 – 1230|04 Project NeuroSafe: safety practice in neurology services
Authors: Kipps Christopher , Mummery Catherine 
Published: August 2022

BackgroundHow do we show that neurological services and neurological practice are safe? We aimed to identify the range of safety practices in neurology, develop a means of measuring safety practice activity at individual, service and national levels, assess safety culture across UK neuroscience centres and create benchmarks to allow future comparison of safety practice. We intend that this will provide information for service improvement and individual revalidation.MethodsItems assessing safety practice were collated from medical literature and direct experience of ABN Quality and Service Committee members. These were combined into a pilot survey for distribution to ABN Advisory Groups and ABN Committee members.Results18 questions on individual practice and 15 service-level questions were identified for the pilot. Results of the pilot will be presented and delegates will be asked for feedback during the meeting on the safety questions and their use in appraisal and revalidation.ConclusionA suite of individual metrics can be combined to evidence safety practice at a personal and service level in neurology.
Idiopathic intracranial hypertension: evaluation of births and fertility through the hospital episode statistic dataset 2002–2020
Authors: Thaller Mark , Mytton Jemma , Wakerley Benjamin , Mollan Susan , Sinclair Alexandra 
Published: August 2022

IntroductionIdiopathic intracranial hypertension (IIH) predominantly affects women of reproductive age with obesity with a distinct profile of hyperandrogenism and insulin resistance. Polycystic ovary syndrome (PCOS) has an established adverse fertility phenotype that typically affects obese women. IIH may impact reproductive health.MethodsProspective cohort study of women with IIH aged 18-45 years from the English Hospital Episode Statistic dataset between 1st April 2002 and 31st March 2019. Comparison made to PCOS and general population controls. Main outcome measures were pregnancies, gestational complications, and method of delivery.ResultsData was collected from 17587 IIH, 199633 PCOS, and 10947012 general population patients. The live birth rate, adjusted for age, was significantly lower amongst women with IIH (54.1%) compared to PCOS (67.9%), p<0.0001 and general population (57.7%), p<0.0001. Pre-eclampsia and gestational diabetes risks were higher following a diagnosis of IIH (5.3-fold and 2.7-fold respectively, p<0.0001) compared to general population controls. Following a diagnosis of IIH, elective caesarean section rates were more than twice that of general population (OR 2.4).ConclusionsThis data indicates there are lower age-adjusted total pregnancy rates, increased risk of pre-eclampsia and gestational diabetes and a doubling of elective caesarean section rates in those with a diagnosis of IIH.
West is best – a strongman with numb feet
Authors: Edwards Marc , Powell Robert 
Published: August 2022

A 64-year-old post office worker presented with several years of progressive unsteadiness and tingling sensation in his feet. He was an enthusiastic bodybuilder and had been regularly taking anabolic steroids since his 20s.On examination he had a broad based gait and Romberg’s test was positive. There was mild dysarthria, dysmetria and an intention tremor. There was wasting evident in his right hand related to a known right ulnar neuropathy. Power was full throughout all limbs but reflexes were reduced. Pin-prick sensation was reduced to the knees and proprioception and vibratory sense were reduced distally.Neuroimaging revealed cerebellar atrophy and nerve conduction studies an axonal peripheral neuropa- thy. On further questioning the patient disclosed his dietary regime of 4 cans of blended tuna daily for the past 25 years. Mercury levels were significantly raised at 256nmol/l (normal range <25nmol/l). He was advised to stop eating tuna and was prescribed dimercaptosuccinic acid. The level subsequently dropped to 48nmol/l.Chronic mercury toxicity can present in a variety of ways due to its deposition in different organs (kidneys, liver, brain). In this case, excessive exposure to organic mercury in tuna fish led to a peripheral neuropathy and cerebellar ataxia.
Cryptic confusion
Authors: Vonberg Frederick , Dawson Angelo , Scott Gregory 
Published: August 2022

Neurotoxicity is often a late consideration, particularly if the neurotoxic agent is given with therapeutic intent, because the poisoning occurs without the diagnostic clues typical of an intentional attack. We present the case of a 76 year old woman with renal failure, who was admitted with confusion and hal- lucinations. Several days previously, she had started Aciclovir because of a vesicular rash. Her condition was attributed to varicella zoster encephalitis and she was switched from oral to intravenous Aciclovir. Two days later, and after peritoneal dialysis, she had deteriorated further, becoming completely unre- sponsive with upper limb myoclonus.The 9-Carboxymethoxymethylguanine (CMMG) level was elevated at 21.2 mg/L (normal <2mg/L). A diagnosis of Aciclovir-induced neurotoxicity (AIN) was made. Aciclovir was stopped, the patient received haemodialysis, and she made a significant recovery.AIN occurs almost exclusively in patients with renal failure. Reduced excretion of Aciclovir, or its prodrug Valaciclovir, results in the toxic accumulation of CMMG. Critically, peritoneal dialysis has little effect on removing Aciclovir. AIN is characterised by triad of hallucinations, involuntary movements, and delusions of death, including Cotard’s syndrome. Diagnosis is challenging as AIN can resemble viral encephalitis. AIN should be considered in encephalopathic patients with renal failure who are taking Aciclovir.