bluuebunny/crossref_metadata_2025 huggingface dataset:
UK Multiple Sclerosis service audit of 70 centres: access to neuroradiology
Authors: Rog David , Hobart Jeremy , Matthews Joela ,   Raising the Bar 4 MS UK MS Study Group
Published: May 2022

Introduction

The UK MS service audit builds upon GIRFT’s recommendation for disease-specific data. Here, we address access to Neuroradiology and Neuroradiologists.

Aim

To document the variability in access to Neuroradiology support, for UK MS Teams.

Methods

We asked all MS services to complete service questionnaires, supplemented with individual clinician interviews. Specifically, we asked about access to specialist Neuroradiologists, timeliness, out- sourcing and quality of MRI reporting and impact upon care.

Results

70 MS centres contributed MS service data, encompassing over 105522 people with MS, ≈85% of the UK MS population.

76% of respondents felt at least half of MRI scans were reported in a timely manner, however 46% felt lack of access to MRI impacted upon the care they could offer. 68% of centres had scans reported by a neuroradiologist, however 63% of centres outsourced reporting and 69% of centres were concerned about reporting quality and the necessity for re-reporting.

Conclusions

Significant variability exists in the reporting of MS scans in the UK. This could impact upon access to, and use of, DMTs in centres and is increasingly important, given the availability of high efficacy DMTs, their sequencing and their potential adverse events.

We recommend partnership working between MS Teams and Neuroradiologists to maximise dissemina- tion of expertise and minimise inefficiency in access to, reporting and discussion of, MS scans, at local, regional network and national levels.

david.rog@srft.nhs.uk
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

Background

This 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.

Methods

CD4+ 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.

Results

Paired 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%.

Conclusion

We 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

Introduction

SORD 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).

Methods

We present nine cases of SORD-related neuropathy.

Results

Nine 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%).

Conclusions

The 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

Objective

Our aim was to report neurological manifestations of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS).

Methods

Patients (<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.

Results

New-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).

Conclusions

Children 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.

zhongbo

chen@ucl.ac.uk

18
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

Objective

The IIH weight trial (IIH: WT) aimed to compare the efficacy of bariatric surgery with a community weight management intervention (CWI) in active IIH.

Methods

This 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.

Results

Sixty-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 Relevance

In 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.

Investigations

NCS/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.

Diagnosis

A 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.

Conclusion

We report a unique FOSMN case with some overlap features of PSP, not previously described. daniel.rice-wilson@nhs.net

23
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

Introduction

MRI 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.

Methods

We 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.

Results

We 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.

Conclusions

MRI 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.

danielle

sequeira@nhs.net|ABN Bursary

26
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

Background

Early 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.

Methods

We 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.

Results

VBM 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).

Conclusion

Genetic 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

Background

This 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.

Methods

During 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).

Results

Overall, 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.

Conclusion

These data suggest adjunctive perampanel does not worsen myoclonic/absence seizures in adult/adolescent/paediatric patients.

Funding

Eisai Inc. stella_ngo@eisai.com

32
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

Background

A standard cut-off of ≥2 CSF-specific OCBs is used in multiple sclerosis but some studies suggest ≥3 CSF OCBs maybe more specific.

Aim

To determine if a cut-off of ≥2 or ≥3 CSF OCBs should be used in MS

Materials and Methods

Oligoclonal 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.

Results

CSF 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.

Conclusion

Detection 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

Introduction

Seizures 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?

Methods

Setting

137 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.

Results

For 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.

Conclusions

There 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.uk

34
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

Background

The 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.

Methods

Individuals were examined using the motor part of Unified PD Rating Scale (MDS-UPDRS-III) after a minimum of 5-year follow-up.

Findings

We 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.

Conclusions

This 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 Bursary

40
035  Vestibular syndrome: a single centre experience of acute dizziness
Authors: Mahmud Mohammad , Prendergast Mabel , Dixon Luke , Seemungal Barry
Published: May 2022

Dizziness accounts for 2–5% of emergency department presentations. Vestibular syndrome, one cause of dizziness, can present secondary to an acute stroke of the brainstem and cerebellar (posterior circula- tion), a life-threatening condition that has potential time dependent treatments.

We conducted a retrospective case note analysis using Imperial NHS Trust patient records from January to September 2020. We looked at presentations of all presentations of vestibular syndrome requiring MRI head imaging. Retrospective ethics were obtained from local ethics committee.

116 patient encounters (54% female) were included with a mean (SD) age of 62 (±18). DWI-positive stroke was confirmed in 23% of patients presenting with acute dizziness. Of these DWI-positive stroke patients, a further 23% presented with isolated vertigo. The mean NIHSS score of isolated vertigo patients was 0 and none underwent thrombolysis. Only 14% of patients had a complete HINTS examination and none were referred to the Neuro-Otology Unit. The isolated vertigo patients who were DWI-negative had no definitive diagnosis in 45% of the patient encounters.

Major deficiencies exist in the care of patients presenting with dizziness, especially stroke patients. There is a need for stroke clerking to include dizziness and for doctors to be aware of stroke presenting as isolated vertigo.

mabel.prendergast18@imperial.ac.uk
037  New insight into dysautonomia in GFAP astrocytopathy
Authors: Goh Yee Yen , Koay Shiwen , Goodall Jack , Oommens Grace , Ingle Gordon , Parris Victoria , Iodice Valeria , Swanton Josephine , McNamara Patricia
Published: May 2022

A 17yo Filipino man presented with a rapid onset meningoencephalitic illness, dysautonomia (cardiovas- cular and genitourinary), neuropsychiatric, myoclonus and cerebellar symptoms. Examination revealed lower limb proprioceptive loss and areflexia.

CSF showed lymphocytosis, hypoglycorrachia and glial fibrillary acidic protein (GFAP) antibodies. MRI head was normal on D4 and D11, but repeat imaging (D25) showed a reversible splenial T2 hyperintensity, which improved by D40. Neurophysiology showed a sensory neuronopathy. Autonomic function testing confirmed sympathetic cardiovascular failure. Pupillometry showed bilateral Horner’s indicating further sympathetic deficit. Dynamic sweat testing showed evidence of post-ganglionic sudomotor dysfunction.

He received treatment with IV methylprednisolone followed by a prednisolone taper with good response.

GFAP is an intracytoplasmic protein, found in astrocytes, unmyelinated nerve fibres as well as dorsal root ganglia, in keeping with our patient’s clinical presentation. However, literature review shows signifi- cant heterogenicity in presentation and pathogenicity of the GFAP antibody is unclear, as it could be a bystander protein.

Dysautonomia is reported in 24–57% of GFAP astrocytopathy, but has not been well-characterised. We describe the first in-depth autonomic testing in GFAP astrocytopathy which shows sympathetic cardio- vascular failure and evidence of sudomotor post-ganglionic dysfunction.

yeeyen.goh@nhs.net|ABN Bursary
043  A case of cerebral air embolism from giant pulmonary bulla during air travel
Authors: Matthews Rachael , Ahmed Rohan , Mohanraj Rajiv
Published: May 2022

Cerebral air embolism following pulmonary barotrauma during flight in patients with giant pulmonary bullae is rare, with only five reported cases. We aim to highlight and better understand this unusual condition.

A 47-year-old male airline passenger with a primary lung bulla experienced an inflight cerebral air embolism resulting in hypoxic brain injury. On landing, he was found unconscious and developed seizures. He was admitted to intensive care, requiring invasive ventilation. CT brain demonstrated diffuse oedema. Sub- sequent MR brain imaging demonstrated bilateral hypoxic injury, characteristic of air embolism. Chest CT revealed a giant pulmonary bulla.

Air embolism occurs in patients with pulmonary bullae during flight due to pulmonary barotrauma. Pressure change during ascent causes expansion of bullae, resulting in tears in the pulmonary vasculature, with air leakage and embolisation to the arterial cerebral circulation. No British Thoracic Society air travel guide- lines extend to advice regarding risk of rupture of bulla given the rarity of this presentation.

Neurological deficit in cerebral air embolism is variable, and some cases can be reversible. Our patient had modest improvement in clinical status and was discharged to a neurorehabilitation facility. Patients with known giant pulmonary bullae should be counselled on the risks associated with air travel.

rachaelmatthews@doctors.org.uk
053  Intracranial pressure determines headache morbidity in idiopathic intracranial hypertension
Authors: Mollan Susan , Wakerley Ben , Alimajstorovic Zerin , Mitchell James , Ottridge Ryan , Yiangou Andreas , Thaller Mark , Grech Olivia , Brock Kristian , Sinclair Alex
Published: May 2022

Objective

Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure (ICP).

Methods

IIH:WT was a randomised controlled parallel group multicentre trial investigating weight manage- ment methods in IIH. Participants with active IIH (evidenced by papilloedema) and a body mass index (BMI) ≥35kg/m2 were recruited. At baseline, 12 months and 24 months headache characteristics and quality of life outcome measures were collected and lumbar puncture measurements were performed.

Results

Sixty-six women were included (mean age 32.0 years (SD ± 7.8)), and mean body mass index of

43.9 ± 7.0 kg/m2. The headache phenotype was migraine-like in 86%. Headache severity correlated with ICP) at baseline (r=0.285; p=0.024); change in headache severity and monthly headache days correlated with change in ICP at 12 months (r=0.454, p=0.001 and r=0.419, p=0.002 respectively). Cutaneous allodynia was significantly correlated with ICP at 12 months. (r=0.479, p<0.001). Boot strap analysis noted a positive association between ICP at 12 and 24 months and enabled prediction of change in headache severity and monthly headache days. ICP was associated with significant improvements in quality of life (SF-36).

Conclusions

We demonstrate a positive relationship between ICP and headache and cutaneous allodynia, which has not been previously reported in IIH. Those with the greatest reduction in ICP had the greatest reduction in headache frequency and severity.

soozmollan@doctors.org.uk
054  Tolerability of fremanezumab in migraine patients with cardiovascular medica- tion use at baseline: a pooled analysis
Authors: Coppola Gianluca , Cohen Joshua , Ning Xiaoping , Kessler Yoel , Janka Lindsay , Riaz Sajjad , Barbanti Piero
Published: May 2022

Objective

To evaluate adverse events (AEs) in a subgroup of migraine patients with baseline cardiovas- cular (CV) medication use in this pooled analysis of three phase 3 trials of fremanezumab.

Methods

This analysis included data from the HALO EM, HALO CM, and FOCUS studies, in which patients were randomized 1:1:1 to subcutaneous quarterly or monthly fremanezumab or matched placebo over 12 weeks. AEs were evaluated for patients with baseline CV medication use.

Results

Overall, 280 of 2,842 patients (9–11% across treatment groups) in this pooled population were receiving CV medications at baseline, most commonly agents acting on the renin-angiotensin system (3–4%) and beta-blockers (3–4%). In the placebo, quarterly fremanezumab, and monthly fremanezumab groups, respectively, 53%, 66%, and 64% of patients reported at least 1 AE, and the most common AEs were injection-site-related (pain [19%, 29%, and 20%], erythema [10%, 20%, and 13%], and induration [8%, 18%, and 24%]). Cardiovascular AEs (CVAEs) were infrequent; no individual CVAE was reported for >1 patient in any treatment group. No safety signals were identified.

Conclusion

In this pooled analysis, fremanezumab treatment was well tolerated over 12 weeks, with low incidences of CVAEs, comparable to placebo, in patients with migraine using CV medications at baseline.

JMarzella@cellohealth.com

52
062  A case of autosomal dominant optic atrophy plus syndrome
Authors: Brennan Declan , Langan Yvonne , Redmond Janice
Published: May 2022

Autosomal dominant optic atrophy plus syndrome is a rare cause of blindness and sensorineural deafness, usually presenting with insidious onset in childhood. Other clinical manifestations are variable but include, peripheral neuropathy, myopathy, opthalmoplegia, ataxia and spastic paraparesis.

We present a 50-year-old gentleman brought to clinic with a history of a slowly progressive gait difficulty. He was blind and deaf since childhood but no diagnosis had been made. He had no relevant family history. Examination revealed bilateral optic atrophy on fundoscopy. He was unable to stand unassisted and had reduced reflexes in the lower limbs. MRI brain and spine, together with routine bloods including neuropathy screen were unremarkable. Nerve conduction studies/EMG showed evidence of a large fibre sensorimotor axonal peripheral neuropathy, which was worse in the lower limbs. Given his constel- lation of symptoms, genetic testing was arranged and revealed a heterozygous pathogenic variant in OPA1 gene. This was consistent with a diagnosis of autosomal dominant optic atrophy plus syndrome.

This condition is rare and often first detected in childhood. Diagnosis can be challenging due to variable clinical phenotypes and markedly variable expression of disease within families. There is a need for strong clinical suspicion for the disease in any patient with a history of blindness.

declan

brennan.1@ucdconnect.ie

56
076  What is the cost? An audit of investigations sent before and during lumbar puncture (LP)
Authors: Andrews Michael , Delaney Milo , Schmierer Klaus , Dobson Ruth , Marshall Charles
Published: May 2022

Background

Unnecessary investigations are an important source of wasteful healthcare spending. We studied rates of inappropriate tests performed for patients having elective lumbar punctures in a large regional neurosciences centre.

Methods

We analysed 127 consecutive elective lumbar punctures during a four-month period. We audited whether pre-procedure blood tests were performed in each patient, and whether these were indicated according to ABN guidelines. We then compared the CSF tests requested at the time of procedure to the tests specified by the referring consultant.

Results

114/127 (90%) patients had pre-procedure blood tests for platelets and/or clotting, whereas only 5.8% of these were required according to established guidelines. The total cost of these unnecessary blood tests was £1766. 55 unnecessary CSF tests were sent in 36 patients, at a total cost of £5,233.00. The combined annual cost of unnecessary blood and CSF tests for this patient group at our centre was estimated at £15,699.

Conclusions

Unnecessary blood and CSF tests are a significant source of wasteful spending in our centre. We have designed a quality improvement project comprising an educational component and redesign of electronic documentation. We will present the results of a reaudit after this intervention.

mikeandrews91@hotmail.co.uk

63
084  Reducing the environmental impact of junior doctors at Queen Square
Authors: Wilkins Dominic
Published: May 2022

Objective

To demonstrate that realistic, targeted interventions can reduce the negative environmental impact of the neurology SHO cohort (12 ST1/2-grade doctors) at the National Hospital for Neurology and Neurosurgery (NHNN), using QI methodology.

Method: Improvement priorities were identified using UCLH Sustainability Steering Group guidance, and refined with a focus group of stakeholders (NHNN SHOs). 3 sub-projects were planned in parallel, using PDSA cycles. A SMART framework generated predictions for outcome and process measures. Data was collected via surveys at three timepoints. Results were used to plan further intervention.

Results

The waste reduction sub-project demonstrated a 35% reduction in paper use for patient lists, saving 72 sheets a month or 8% of one tree a year.

The emission reduction sub-project demonstrated a change in commute behaviour, leading to an estimated 54% reduction in commute-related emissions.

The culture change sub-project demonstrated increased confidence in reducing environmental impact, with 85.7% of SHOs taking action to do so.

Conclusions

This project demonstrates the potential for meaningful benefit through scalable interven- tions. The most encouraging aspect was the engagement of the SHO cohort, representative of a gen- eration of young healthcare professionals with the potential to lead neurology and the NHS to a more sustainable future.

dominic

wilkins.14@ucl.ac.uk

67
086  A UK multicentre audit on the use of MRI in multiple sclerosis
Authors: Allen Christopher , Fernandes Linford , Williams Thomas , Chataway Jeremy , Evangelou Nikos , Tallantyre Emma , Ford Helen ,   UK MS Registries,   Trials Group
Published: May 2022

The contemporary use of MRI in the care of 2567 persons with multiple sclerosis (MS) was audited in 25 MS centres, from all four UK nations. Variation in practice has an impact on patient care and implica- tions for service design.

Routine monitoring of all MS patients accounted for 45% of MRI scans, and the mean inter-scan interval varied by centre from 12 to 32 months, a wide variation in practice. For routine monitoring scans, the detection of one new MS lesion was associated with 30% of patients subsequently changing disease- modifying treatment (DMT); this increased to 52% when ≥2 new lesions were reported.

Unfortunately, only half of patients requiring progressive multifocal leukoencephalopathy surveillance were scanned at the recommended frequency.

Most MRI scans are performed within ten years of diagnosis. With DMT now available for all stages of MS, this will lead to significant additional MRI utilisation. Spinal imaging was included in half of routine moni- toring scans; this had no measureable impact on DMT decision-making. Neither did it have any impact on detection of radiological dissemination in time for diagnostic scans. This suggests that its use could be safely restricted to help meet the additional capacity required.

christopher

allen@nottingham.ac.uk|ABN Bursary

68
087  Paramagnetic rims are a specific biomarker in multiple sclerosis
Authors: Allen Christopher , Meaton Isobel , Altokhis Amjad , Clarke Margareta , Sinnecker Tim , Wuerfel Jens , Evangelou Nikos ,   MAGNIMS study group
Published: May 2022

Paramagnetic rims appear as a hypointense border around the edge of Multiple Sclerosis (MS)4

lesions when visualised on phase sensitive imaging such as T2*, FLAIR* or SWI. They are likely due to immune cell uptake of liberated iron following the destruction of oligodendrocytes. While rarer than the central vein sign, initial reports suggest they are a specific marker of MS. However, disagreement remains with different groups reporting varying prevalence, location, persistence over time and association with expanding lesions, disease stage and disability.

Eight centres in the MAGNIMS (Magnetic Resonance Imaging in Multiple Sclerosis) study group contrib- uted phase imaging of 562 people. They included patients with MS, clinically isolated syndrome, migraine, NMOSD, CNS vasculitis, small vessel ischaemia, diabetes mellitus, and cluster headache along with healthy controls. In patients with MS and clinically isolated syndrome 129 lesions with a paramagnetic rim were detected. The prevalence was 23% and 26% of patients respectively, suggesting this biomarker may be present across all MS stages. Only one paramagnetic rim lesion was found in the rest of the cohort, in a patient with diabetes mellitus, confirming its exceptionally high specificity of 99.7%.

christopher.allen@nottingham.ac.uk|ABN Bursary
093  Improving care of multiple sclerosis-associated uveitis in a tertiary referral centre in Northern Ireland
Authors: Logan John , Ramsay Stephen , Kennedy Fiona , Hughes Stella , McDonnell Gavin , McAvoy Clara
Published: May 2022

Introduction

Multiple sclerosis can be associated with uveitis. A cohort of patients were characterised using standard uveitis nomenclature and a series of recommendations to improve their care introduced.

Methods

Data was collected retrospectively for patients with consultant diagnosed multiple sclerosis from the local adult uveitis database.

Results

25 patients were identified according to inclusion criteria (71% female). The primary location of uveitis at presentation was 52% intermediate, 24% panuveitis, 12% posterior and 12% anterior. Subtypes of multiple sclerosis were 76% relapsing-remitting, 16% secondary progressive and 8% primary progressive. Average age of presentation to uveitis clinic was 39 (range 12–69). Average age of onset of demyelinating symptoms was 36 (range 16–68). Uveitis presented before demyelinating symptoms in approximately half (52%) of cases with a mean time difference of 7 years (range 0–29). Three patients (developed symptoms consistent with demyelination whilst on anti-TNFα agents for treatment of their uveitis (one intermediate, one posterior, one panuveitis).

Conclusions

After collaboration between ophthalmology and neurology it was recommended to:

Enquire about neurological symptoms in all patients with uveitis.

Perform neurological imaging and referral where there is clinical suspicion of multiple sclerosis.

Ensure no neurological symptoms have developed since first presentation of uveitis prior to commenc– ing anti-TNFα agents as a treatment for uveitis.

Collaborate between departments in cases of multiple sclerosis-associated uveitis to use treatments which can be beneficial to both pathologies.

johnlogan95@hotmail.co.uk
003  Systemic inflammation, erythrocyte fragility and multiple sclerosis
Authors: Stuart Charlotte M , Howard Sarah , Chouhan Joe , Varatharaj Aravinthan , Teeling Jessica L , Galea Ian
Published: May 2022

In an unbiased proteomic assay, extracellular haemoglobin was the only serum protein which correlated with brain atrophy in secondary progressive MS. Increased erythrocyte osmotic fragility is reported in individuals with relapsing remitting multiple sclerosis (RRMS) versus control individuals and in active versus quiescent RRMS. Erythrocyte fragility has not been measured in progressive MS patients. Here we measure erythrocyte osmotic fragility in individuals with progressive MS versus control individuals. In a murine experimental model of systemic infection, we prove that systemic inflammation causes erythrocyte osmotic fragility. In summary, it is possible that extracellular hae- moglobin released during systemic infections contributes to MS pathology by entering the brain through a leaky blood-brain barrier.

c.stuart@soton.ac.uk
096  COVID-19 in MS: clinically reported outcomes from the UK MS register
Authors: Middleton Rod , Craig Elaine , Rodgers William , Tuite-Dalton Katie , Garjani Afagh , Evangelou Nikos , Hunter Rachael , DasNair Roshan , Nicholas Richard
Published: May 2022

Background

The UK MS Register (UKMSR) has been capturing longitudinal clinical and patient reported outcomes (PROs) since 2011. As the UK population ‘locked-down’ in March 2020 it became important that clinicians could record hospitalised MS patients due to COVID-19 and record outcome. The UKMSR provided an electronic case return form, designed collaboratively by the community.

Aim

Impacts of disability, age and treatment on mortality in pwMS with COVID-19

Method

Linear modelling and standardised hypothesis testing were performed on an outcome of died or not, impact of disability (EDSS), disease modifying therapies and age.

Results

N=132 PCR confirmed COVID-19 patients submitted, 14 missing EDSS, leaving n=118. Female n=80, n relapsing =74, n progressive = 44, mean age 49.2. Median EDSS = 5.0. Linear regression for age was found to be most significant for outcome (p=0.002). Univariate analysis found that the outcome was not independent of EDSS (ChiSq p=0.0008), DMT (ChiSq p=0.006) and MSType (ChiSq p=0.0006). In the multivariate model only, age remained significant.

Conclusions

Only age remained as a marker of poor outcome multivariate analysis. No MS Specific characteristics were found to be significant. We would encourage continued data collection from UK neurology centres to increase the utility of this data.

r.m.middleton@swansea.ac.uk

73
101  The importance of the multidisciplinary team (MDT) in the management of patients with multiple sclerosis
Authors: Ramsay Stephen , Spence Robert , Robinson Rebecca , Bhattacharya Debarata , Nelson Adam , Flynn Peter , Droogan Aidan , Hughes Stella , Kennedy Fiona , McDonnell Gavin
Published: May 2022

Background

Clinical decision-making for patients with MS relies heavily on the expertise of radiologists. In June 2018 we developed a monthly MDT meeting with neuroradiology to review complex cases. In this study, we assess the rate and clinical significance of variance between original MRI reports and those following MDT review.

Methods

A 6-month retrospective study was performed. Data focused on the frequency of scan report revisions and subsequent impact on clinical management.

Results

We analysed 157 cases. Of these, 68% had confirmed MS whilst 32% were under investigation. Of the 157, 64% were originally reported by a general radiologist and 36% by neuroradiology. Following neuroradiology review, 63 cases (40%) had the original report amended; of these, 81% were originally authored by a non-neuroradiologist. MDT review amended 64% of original reports from general radiology. The most frequently occurring revision was identification of additional, originally unreported inflammatory lesions. Of the 63 report revisions, 29% resulted in a change in clinical management. Overall, 4% of patients with a diagnosis of MS had this diagnosis questioned or reversed following MDT review of their imaging.

Conclusions

This study demonstrates a high rate of variance in MRI reporting between general and neuroradiologists. This has clear implications for patient management, confirming the importance of dedicated MDTs involving specialist neuroradiology.

sramsay03@qub.ac.uk|ABN Bursary