bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual dysfunction predicts cognitive impairment and white matter degenera- tion in Parkinson’s disease
Authors: Zarkali Angeliki , McColgan Peter , Leyland Louise-Ann , Lees Andrew , Weil Rimona
Published: May 2022

Introduction

Visual dysfunction predicts Parkinson’s dementia but whether this translates to structural change is not known. We aimed to identify longitudinal white matter changes in Parkinson’s with low visual function and those who developed mild cognitive impairment(MCI).

Methods

We used fixel-based analysis to examine longitudinal white matter change in Parkinson’s. Diffusion MRI and clinical assessments were performed in 77 patients (22 low/55 high visual performers; and 13 MCI/51 normal cognition) and 25 controls at baseline and after 18 months. We compared micro-structural changes in fibre density, macro-structural changes in fibre cross-section and combined fibre density and cross-section across white matter, adjusting for age, gender and intracranial volume.

Results

Parkinson’s with low visual performance showed worse cognition at follow-up (r=-0.386, p-0.024) and were more likely to develop MCI than those with normal vision (p=0.008). Parkinson’s with poor visual function showed diffuse micro-structural and macro-structural changes at baseline, whereas those with MCI showed fewer baseline changes. At follow-up, Parkinson’s with low visual function showed wide- spread macrostructural changes with up to 22% further reductions in fibre cross-section, involving the fronto-occipital fasciculi, external capsules, and middle cerebellar peduncles bilaterally. No longitudinal change was seen in baseline MCI or in MCI converters, even when combining the two groups.

Conclusions

Parkinson’s with poor visual function show increased white matter damage over time, providing further evidence for visual function as a marker of imminent cognitive decline.

a.zarkali@ucl.ac.uk
Good outcomes after aggressive treatment of immune checkpoint inhibitor related myasthenia gravis: a case series
Authors: Weaver Jamie , Dodd Katherine , Hameed Hasan , Roberts Mark , Lilleker James , Lorigan Paul , Cooksley Timothy
Published: May 2022

Introduction

Myasthenia gravis (MG) is a rare but potentially life-threatening complication of immune- checkpoint inhibitor (ICI) therapy and often co-presents with myositis and myocarditis. We present a series of six patients from a tertiary oncology center.

Methods

We reviewed The Christie Hospital database of immunotherapy-related toxicity from 2017–2020. Symptom severity was assessed using the MGFA classification.

Results

Six patients with ICI-related MG were identified. The median number of preceding immunotherapy doses was 2. Common initial presenting complaints were ptosis (100%) and diplopia (50%) with 2/6 patients showing severe (MGFA > II) symptoms. Five patients had concomitant myositis and myocarditis. AChR or MuSK autoantibodies were positive in three patients. Two patients required advanced respiratory support.

All patients received urgent treatment with intravenous methylprednisolone and mycophenolate. Five also received intravenous immunoglobulin and a single patient was treated additionally with abatacept and rituximab. No patient died from MG-related complications. All were successfully discharged following the acute episode.

Discussion

Previous case series of ICI-related MG have reported high mortality rates, particularly in those with overlapping myositis/myocarditis. In our cohort we demonstrate good outcomes associated with early aggressive treatment with IVIG, IVMP, and mycophenolate. An agreed national treatment protocol or clinical discussion forum would be beneficial.

jam

weaver75@gmail.com

17
Detailed evaluation of cognitive performance in idiopathic intracranial hyper- tension and relevance of intracranial pressure
Authors: Grech Olivia , Clouter Andrew , Mitchell James , Alimajstorovic Zerin , Ottridge Ryan , Yiangou Andreas , Shapiro Kimron , Mollan Susan P , Sinclair Alexandra J
Published: May 2022

Idiopathic intracranial hypertension (IIH) is an increasingly prevalent disease, characterised by raised intracranial pressure (ICP). Cognitive impairments have been reported in IIH, however evidence support- ing these deficits are scarce and contributing factors have not been defined. Using a bespoke battery of cognitive tests, we identified multiple domains of deficiency in a case-control prospective study of 66 female adult IIH patients. Attention networks (executive function) and sustained attention were impaired compared to a body mass index and age matched control group of 25 healthy female participants. These deficits were not permanent as participants exhibited improvement in several domains over 12 months which were associated with reduction in ICP. Cognition was evaluated before and after a lumbar puncture, with acute reduction in ICP and noted significant improvement in executive function. The impact of comorbidities was explored, with headache severity during cognitive testing, co-morbid depression and markers of obstructive sleep apnoea adversely associated with cognitive performance. Deficits were also significantly associated with impaired reliability to perform visual field tests, the cornerstone of monitoring vision in IIH. Our findings propose that cognitive impairment should be recognised as a clinical manifestation of IIH and treating comorbidities could improve cognitive performance.

livgrech@googlemail.com
A man with Erb’s disease
Authors: Leddy Sara , Jaffer Fatima , Lipnicka-Khan Monika , Nigel Leigh P
Published: May 2022

A man, currently aged 72, developed a spastic paraparesis without sensory abnormalities progressing to wheel-chair dependence and late urinary incontinence over 14 years. Apart from a history of type 2 diabetes mellitus, he was otherwise well. Extensive blood and CSF investigations including screening for HIV, HTLV1, syphilis, and Lyme disease were normal or negative. There was no evidence of neuropathy or denervation on EMG. MRI showed mild non-specific white matter signal change in both cerebral hemi- spheres. A provisional diagnosis of primary lateral sclerosis (PLS) was revised with the finding of elevated Very Long Chain Fatty Acids (VLCFAs). Genetic testing revealed a novel missense variant c.1771C>G

p. (Arg591Gly) in exon 7 of the ABCD1 gene. Mutation in ABCD1 transporter leads to accumulation of VLCFAs in the peroxisomes and cytosol which is toxic, causing oxidative stress and demyelination in the CNS and PNS. Literature review did not reveal reports of AMN mimicking PLS. Our patient highlights the importance of screening VLCFAs (abnormal in ~99% of men with AMN) in suspected PLS, a diagnosis of exclusion. Diagnosis of ALD/AMN allows genetic counselling, screening for adrenal failure, and access to stem cell therapy for children with asymptomatic cerebral onset ALD.

sara.leddy1@nhs.net
Spinal cord involvement in MOGAD, AQP4-Ab NMOSD & MS
Authors: Mariano Romina , Messina Silvia , Roca-Fernandez Adriana , Cavey Ana , Everett Rosie , Leite Maria Isabel , Kong Yazhuo , Palace Jacqueline
Published: May 2022

Introduction

Spinal cord involvement is important in aquaporin-4(AQP4) antibody(Ab)-positive neuro- myelitis optica spectrum disorder(NMOSD), myelin-oligodendrocyte glycoprotein-Ab disease(MOGAD) and multiple sclerosis(MS).

Methods

Data from adults with spinal cord involvement and MOGAD(n=46) or AQP4-Ab(n=69) were retrospectively analysed. An additional c-spine MRI (3DT1,3DT2,2D axial T2*,DTI,MTR) was performed and analysed using SCT and FSL on 20 patients from each cohort, together with 20 MS and 20 healthy volunteers(HV).

Results

Compared to AQP4-Ab, MOGAD patients had more short lesions(p≤0.0001) and multiple lesions(p≤0.001). In AQP4-Ab, age was the most important factor affecting long-term outcome; while in MOGAD it was the presence of a brainstem lesion at the time of the myelitis. In the cervical cord MRI study, the MOGAD group had no residual lesions, and did not show a significant reduction in either CSA, FA or MTR, but showed a reduction of grey matter volume in those with cervical cord involvement(p=0.0229). The AQP4-Ab group showed a significantly reduced CSA(p=0.0288) and FA(p=0.0085) and a reduced MTR compared to both HV(p≤0.0001) and MOGAD(p=0.0096). This was driven by those with cervical cord lesions. The MS group had a significantly reduced FA(p=0.0204), GM(p=0.0133) and MTR(p=0.0106). FA associated with EDSS(p=0.02,R2=0.25) in the corticospinal tract and pain in the spinothalamic tract(p≤0.01,R2=0.32). Overall, CSA was the strongest predictor of EDSS.

Conclusion

MOGAD may predominantly affect the grey matter. AQP4-Ab disease shows the most severe, localised cord damage. MRI metrics do not discriminate these conditions but show clinical significance.

romina.mariano@ndcn.ox.ac.uk
006  Seizure focus prediction from seizure semiology: data-driven cortical probabilis- tic heatmaps from 4643 patients
Authors: Alim-Marvasti Ali , Romagnoli Gloria , Pérez-García Fernando , Geranmayeh Fatemeh , Scott Gregory , Shahrbaf Sadegh , Chowdhury Fahmida Amin , Diehl Beate , Clarkson Matthew , Duncan John
Published: May 2022

Seizure semiology is important in the evaluation of patients with drug resistant focal epilepsy to help later- alise and localise the seizure onset zone for curative resection. The localising values of initial semiology are widely variable. We created the Semiology-to-Brain Database and 3D Visualisation Tool (SVT) to objectively localise the seizure focus, from an individual-participant systematic review, as per PRISMA guidelines. This yielded 11230 localising and 2391 lateralising semiology datapoints from 4643 patients across 309 studies.

We integrated SVT into the freely available 3D-Slicer software with a graphical user interface, enabling visualisations of semiologies as probabilistic cortical heatmaps.

We used SVT to predict the seizure-focus for a random retrospective patient: a 28-year-old right-handed gentleman. He had nocturnal generalised seizures from age 12yrs and subsequently developed stereo- typed head and eye versions to the right, tonic left leg extension and raising of the left arm with speech arrest. Ictal scalp EEG was non lateralising and interictal EEG showed bitemporal sharp waves. MRI showed cortical dysplasia in the left superior frontal gyrus and ictal SPECT highlighted the superior more than middle frontal gyrus. After intracranial EEG, a limited resection including the supplementary motor area resulted in complete seizure-freedom (ILAE 1) for four years of follow up.

We demonstrate that the SVT prediction, blinded to MRI and EEG data, is congruent with the actual resection.

alijesus

alim-marvasti@nhs.net

28
007  Management of convulsive status epilepticus in Swansea
Authors: Avo Cameron , Powell Robert
Published: May 2022

Objectives

(1) To evaluate adherence to local status epilepticus (SE) guidelines. (2) To characterise patients with SE and identify causes and predisposing factors.

Methods

We reviewed notes of patients presenting to Morriston Hospital with SE in 2019/20. The cause of SE and compliance with local guidelines were evaluated, and it was documented whether SE patients with previous epilepsy (SEPE) had been reviewed in the 12 months prior to admission.

PreliminaryResults

57 cases were identified. Of the 13 reviewed so far, 11 correctly received an initial ben- zodiazepine. 5 of the 9 patients who did not respond to two doses of benzodiazepines correctly received levetiracetam. Those who failed to respond to medication were intubated. 4 of the 9 patients requiring a second intervention were intubated where guidelines recommend levetiracetam. Of the SEPE cases, 50% were reviewed in the 12 months pre-admission. The commonest causes of SE were cerebrovascular disease, background epilepsy, and alcohol withdrawal.

Conclusion

Preliminary findings suggest that 61.5% of patients received treatment in compliance with local guidelines, and further work will evaluate whether deviations have impacted outcomes. After iden- tifying common causes of SE and evaluating how patients are reviewed, we can consider implementing improvements in its management.

950448@swansea.ac.uk
008  Association of COVID-19 infections with new-onset and breakthrough epileptic seizures
Authors: Bhaskar Hardik , Singh Neeraj
Published: May 2022

Since the advent of the COVID-19 pandemic, anecdotal reports have indicated a possible relationship between COVID-19 infections and novel seizures. This study explores the relationship between COVID-19 infections and novel or breakthrough seizures in a single New York-based hospital system with the largest patient sample to date. We analyzed 426 patients admitted with COVID-19 infections and administered antiepileptic medications between 1 February and 30 June 2020. Patients were divided into those with and those without a known history of epilepsy. The incidences of new-onset seizures and the mortality rates were compared between these groups by employing Pearson’s chi-squared test, and their statisti- cal significance was measured by Fisher’s exact test. Novel seizures were more likely to occur in patients without a known history of epilepsy than in patients with one (p=0.0004). There was no difference between the mortality rates of patients who had novel seizures and those who did not (p=0.1253). There was also no difference in mortality rates between patients who had a history of epilepsy and those who did not (p=0.9048). These results indicate that COVID-19 infections may cause novel seizures in patients without epilepsy, and would warrant further exploration into this pathophysiology.

Hardik

Bhaskar93@myhunter.cuny.edu

29
012  Structural connectivity informed stereoelectroencephalography (SEEG) electrode targeting in suspected pseudotemporal and temporal plus epilepsy
Authors: Khosropanah Pegah , Costanza Martina Della , Li Kuo , Mancini Matteo , Vos Sjoerd , Winston Joel , Sparks Rachel , Ourselin Sebastien , Duncan John S , Vakharia Vejay
Published: May 2022

Long-term seizure-free outcome failure following Antero-Mesial Temporal (AMT) resection in drug-resistant Mesial Temporal Lobe Epilepsy (MTLE) patients may arise from extra-temporal regions termed pseudotem- poral epilepsy (pTLE) or alternatively, the epileptogenic zone may extend beyond the AMT termed tem- poral-plus epilepsy (T+E). Insula (INS), Orbito-Frontal (OF) cortex, cingulum (CI), temporo-parieto-occipital junction are Candidate Brain Regions (CBRs) that can be involved.

Stereoelectroencephalography (SEEG) can distinguish T+E and pTLE from MTLE if the electrodes are accu- rately placed to sample the CBRs. We study the structural connectivity from the amygdalohippocampal complex (AHC) to sub-segmented parcels of the CBRs to identify differential connectivity that may guide SEEG planning. Whole-brain connectomes were generated in 25 patients with hippocampal sclerosis (12 right) that underwent SEEG. Connectivity of the AHC was calculated as a normalized t-score map and the regions with the greatest connectivity are shown in Table 1.

Results suggest parcels of the CBRs show preferential connectivity to the AHC which occasionally differ between the left and right HS. Further studies are required to identify if structural connectivity-based SEEG- targeting can improve the detection of pTLE and T+E.

khosropanahpegah7@gmail.com

31
022  Functional genomics and transcriptomics further characterise and potentially improve diagnostic yield of hereditary ataxias
Authors: Chen Zhongbo , Cipriani Valentina , Zhang David , Tucci Arianna , Vestito Letizia , Smedley Damian , Houlden Henry , Botia Juan , Ryten Mina
Published: May 2022

Up to 60–74% of patients with hereditary ataxia (HA) remain undiagnosed even following whole genome sequencing. We leveraged publicly-available -omics data to generate 299 genic features, capturing information about: gene structure/complexity; genetic variation; tissue-specific, cell-specific and tempo- rally-relevant gene expression/co-expression and protein products. Using existing age-of-onset informa- tion, we categorised HA-linked genes as childhood-onset, adult-onset and those overlapping both. By comparing the properties of childhood- and adult-onset genes, we demonstrated: (i) an unexpectedly high short tandem repeat (STR) density within childhood-onset genes suggesting that we may be missing pathogenic STRs within this cohort; (ii) significant similarities in annotation across the groups suggesting adult- and childhood-onset patients should be screened for mutations using a common gene set. We tested the latter hypothesis within the Genomics England 100,000 Genomes Project by assessing the burden of potentially pathogenic variants among childhood-onset genes in adult-onset HA patients and vice versa. This demonstrated a significantly higher burden of rare potentially pathogenic variants in the childhood-onset HA genes POLR3A and SACS amongst individuals with adult-onset HA. Thus, our analysis would suggest that a broader testing strategy for HAs particularly in adult-onset patients could increase diagnostic yield and highlights genic features of interest to explore in an unsolved cohort.

zhongbo

chen@ucl.ac.uk|ABN Bursary

36
023  Evaluating a home-based care pathway for people with Parkinson’s disease
Authors: King Emma , Inches Jemma , Edwards Emma , Rideout Jane , Whipps Sue , Holley Martha , Gorst Terry , Carroll Camille
Published: May 2022

Background

Current care pathways for people with Parkinson’s (PwP) are not tailored to need. In line with the NHS Long Term Plan, together with PwP, we have co-developed, piloted and evaluated an innovative care pathway, ‘Home Based Care (HBC)’, based on supported self-management, triggered contacts and digitally-enabled remote monitoring.

Method

Evaluation was performed at baseline and 6-monthly of motor (UPDRS II and accelerometer) and non-motor (NMSQ, PDSS2, HADS) symptoms, acceptability and self-management efficacy. Care was audited using Parkinson’s UK national audit standards. Process measures captured feasibility.

Results

Data are available for 93 patients at baseline and 38 at 6m. Compared with baseline, after 6m on HBC, fewer PwP had uncontrolled bradykinesia (55.3% vs 63.4%), severe non-motor symptom burden (32.4% vs 50.6%), depression (2.9% vs 15.9%) and anxiety (17.1% vs 23.2%); median UPDRS II improved from 12.0 to 9.0; PwP felt more involved in care (70% vs 42%), listened to (72% vs 48%) and treated as an individual (81% vs 58%), as well as having increased PD understanding (57% vs 38%) and ability to self- manage (45% vs 34%). HBC met 93% of national audit criteria.

Conclusions

We have demonstrated acceptability, feasibility and effectiveness of our novel Parkinson’s care pathway.

e.king6@nhs.net|NIHR Bursary
Confused and tetraplegic: examine your ICU patient
Authors: Aslanyan Aram , Herwadkar Amit , Sharaf Nazar , Jones Matthew , Kobylecki Christopher , Lavin Tim , Cahill Varduhi
Published: May 2022

Introduction

Glial Fibrillary Acidic Protein (GFAP) astrocytopathy can manifest as a combination of meningitis, encephalitis or myelitis syndrome, which makes the diagnosis challenging, especially in the Intensive Care setting.

Case Presentation

We present a case of 43-year-old male who presented to ED with headache, fever, myalgia and acute confusion complicated by respiratory failure attributed to aspiration pneumonia in need of ventilatory support. CSF findings were remarkable for lymphocytic pleocytosis (WCC 197, 95% lymphocytes) and markedly elevated protein of 3.52g/L resulting in the diagnosis of meningoencephalitis. Following a sedation hold he was found to have flaccid quadriparesis and a truncal sensory level, which was not present on admission. An MRI brain showed linear perivascular radial enhancement while the cervicothoracic spine showed longitudinally extensive transverse myelitis. Extensive investigations rendered positive CSF GFAP antibodies. The patient was treated with intravenous Methylprednisolone and plasma exchange followed by a tapering dose of oral steroids. Upon his discharge to a rehabilitation facility the patient was a manual wheelchair user.

Discussion

This case demonstrates the importance of a thorough assessment of ICU patients for the timely detection of an evolving neurological deficit. A high index of suspicion for GFAP-mediated inflammation is warranted in patients presenting with meningoencephalomyelitis.

aram.aslanyan@srft.nhs.uk
026  Impulse control disorders in idiopathic REM sleep behaviour disorder and drug-naive Parkinson’s disease
Authors: Otaiku Abidemi
Published: May 2022

Background

Impulse control disorders and compulsive behaviours (ICBs) in Parkinson’s disease (PD) are predominantly related to dopamine replacement therapy. However, drug-naive PD patients can also experience ICBs. It has been suggested that REM sleep behaviour disorder (RBD) is associated with increased ICB risk in PD, but this remains controversial. Although patients with idiopathic RBD (iRBD) commonly experience neuropsychiatric problems, ICBs have not previously been characterised in this prodromal population.

Objective

To compare the frequency of ICBs in patients with iRBD and drug-naive PD.

Methods

Cross-sectional analysis of baseline data of 38 iRBD patients and 231 age- and sex-matched PD patients from the Parkinson’s Progression Markers Initiative cohort, who were evaluated with the the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s disease.

Results

The presence of ≥1 ICB was significantly higher in patients with iRBD (31.6%), compared to patients with PD (18.2%). Hobbyism (13.2%), hypersexuality (7.9%), eating (7.9%), and punding (7.9%) were the most frequent ICBs in iRBD.

Conclusions

This is the first study to demonstrate that patients with iRBD experience ICBs more frequently than patients with drug-naive PD. ICBs should be recognised as common and distinct neuropsychiatric features in iRBD. RBD may additionally represent an important determinant of ICBs in PD.

a.otaiku@nhs.net|NIHR Bursary

38
027  The prevalence and management of saliva problems in motor neuron disease
Authors: Pearson Iona , Glasmacher Stella , Newton Judith , Mehta Arpan , Beswick Emily , Davenport Richard , Chandran Siddharthan , Pal Suvankar
Published: May 2022

Introduction

Saliva problems are common in people with motor neuron disease (pwMND). Despite guide- lines for assessment and treatment, management of saliva problems has received little research attention.

Objective

To investigate the prevalence of saliva problems in pwMND, their association with clinical factors and their management practice.

Methods

We conducted an analysis of pwMND diagnosed between January 2015 and October 2019 using the Scottish MND Register (CARE-MND). The association between clinical factors and saliva problems was investigated using univariate and multivariable logistic regression. A survey of relevant healthcare professionals was performed to contextualise findings.

Results

939 pwMND were included. Saliva problem prevalence was 37.5% (294). Bulbar onset (P<0.001) but not age, sex, time to diagnosis and MND subtype were independently associated with presence of saliva problems in multivariable regression. 60.3% (155) pwMND with saliva problems received pharmacological management. The most used medications were hyoscine, amitriptyline, carbocisteine, glycopyrrolate and atropine. Evidence-base (72.7%) and local guidelines (90.9%) were cited as the most important factors influencing treatment decision by survey respondents (n=11).

Conclusion

Saliva problems are associated with bulbar onset MND. Many pwMND with saliva problems did not receive recommended treatments. Future research is required to determine the relative efficacy of individual pharmacological treatments.

s1505898@ed.ac.uk
029  Postural instability in DYT-TOR1A dystonia dynamically dependent on sensory feedback
Authors: Sadnicka Anna , Dennis Elena , Bhatia Kailash , Rothwell John , Chen Xiuli , Galea Joseph
Published: May 2022

Dystonia is clinically defined as a disorder of posture yet there has been little systematic exploration of postural control in the laboratory. Patients with DYT-TOR1A dystonia held the handle of a planar robotic arm to make point-to-point reaching movements with their symptomatic right arm. Reaches were made from a central start box to eccentric targets (15°, 135°, 225° or 315°). Position was then held within the target box for 10s. Estimation of arm position was dependent on proprioceptive and visual feedback (experimentally manipulated with balanced pseudo-randomization: cursor visible or not visible). During the hold phase, in the dystonia group, mean velocity did not resolve to zero in either feedback condition with increased fluctuations (movements associated with a velocity peak ) consistently interrupting postural stability. By the end of the hold phase, in the dystonia group, a performance segregation across feedback conditions occurred; with visual feedback (high accuracy, low variability, in line with controls); with no visual feedback (low accuracy, high variability, significant deficit). To gain insight into mechanism a reinforcement learning model was able to reproduce empirical data if noise parameters for sensory feedback and central motor instability were varied. By using DYT-TOR1A as a prototype for dystonia, our results refine aetiological models, assist the design of biomarkers and inform rehabilitation strategies.

asadnick@sgul.ac.uk|ABN Bursary
033  GLP-1RAs reduce stroke incidence in patients with type 2 diabetes mellitus: a meta-analysis
Authors: Maskery Mark , Wall Jasmine , Holscher Christian , Jones Stephanie , Price Christopher , Strain David , Watkins Caroline , Werring David , Emsley Hedley
Published: May 2022

Background

Patients with Type 2 Diabetes Mellitus (T2DM) are at a relatively higher risk of severe stroke. Glucagon like peptide-1 receptor agonists (GLP-1RAs) are licensed for the management of T2DM. Cardio- vascular outcome trials (CVOTs) have demonstrated that GLP-1RAs can be safely administered to T2DM patients but have also indicated a trend towards a reduction in non-fatal stroke incidence compared to placebo.

Methods

We searched the literature to identify all GLP-1RA CVOTs. We performed a meta-analysis of the incidence of non-fatal stroke and presented the outcomes by Odds Ratio (OR) with 95% confidence intervals (CI).

Results

We identified 7 GLP-1RA studies. SUSTAIN-6 and REWIND reported statistically significant reductions in non-fatal stroke incidence, whilst LEADER demonstrated a similar, non-significant trend. ELIXA, EXSCEL, HARMONY and PIONEER-6 did not report a reduction in stroke incidence. Meta-analysis of 7 studies, totalling 56,004 participants yielded a significant reduction in non-fatal stroke incidence in patients receiving GLP-1RAs when compared with placebo (OR 0.85, 95% CI 0.76 – 0.94).

Conclusions

This data supports the value of GLP-1RAs in reducing stroke incidence in patients with T2DM. There is potential value in prospective, randomised controlled trials adequately powered to establish the value of GLP-1RAs in stroke prevention in T2DM patients.

mark.maskery@doctors.org.uk|ABN Bursary
036  A rare subtype of a rare type of stroke – sulcal artery syndrome
Authors: Win Myat , Hernandez Ana Campos , Fox Robin , Harikrishnan Sreedharan , McWilliam Matthew
Published: May 2022

A 78 year old man was woken from sleep by a sudden excruciating neck pain. The pain was accompa- nied by left arm and leg weakness and paraesthesia which progressed to maximum intensity over hours. His past medical history was significant for ischaemic heart disease and type 2 diabetes. On examination there was an incomplete Brown-Sequard syndrome localising to the left hemicord. MRI of the cervical spine showed intramedullary T2 hyperintensity and restricted diffusion in the left hemicord at C2-C3 level. CT angiogram of the vertebral arteries excluded dissection.

We diagnosed acute spinal cord infarction due to a sulcal artery occlusion, and treated with antiplatelets and secondary stroke prevention. The neurological deficit improved significantly over the following days.

Spinal cord strokes are diagnostic challenges and account for only 1.25% of all strokes. Sulcal artery syndrome is a rare cause of spinal cord infarction, involving the territory of the sulcal arteries, which are paired penetrating branches of the anterior spinal artery and perfuse the anterior two-thirds of half the spinal cord. An acute onset with pain is an important clue - otherwise the hemi-distribution and short segment of signal change may be misdiagnosed as an inflammatory lesion.

myat

win@nhs.net

43
039  Cerebral venous sinus thrombosis and COVID-19: causation or coincidence?
Authors: Crawford James , Taylor Hannah , Iftikhar Hajira , McKee David , Chaouch Amina
Published: May 2022

Since early in the pandemic, it has been recognised that coronavirus disease 2019 (COVID-19) is associ- ated with an increased risk of thromboembolic complications. Several recent case reports have identified cases of cerebral venous sinus thrombosis (CVST) occurring in conjunction with COVID-19. Given these patients’ increased risk of thromboembolic events, some authors have hypothesised that there may be a causative association between the two conditions.

To examine this hypothesis, we collected a retrospective case series of patients with CVST presenting to a large tertiary neurology centre and surrounding trusts in the North West of England between January 2019 and December 2020. The catchment area serves approximately 3.2 million people, of which all confirmed cases of CVST are discussed with tertiary services. We identified 46 cases of CVST during 2020, 5 of which were identified as having been positive for COVID-19 RNA or antibodies at the time of CVST diagnosis (10.87%). A comparative 52 cases of CVST were identified during 2019.

We suggest our findings do not provide evidence for an association between CVST and COVID-19 based on overall incidence trends. However, we also suggest that further research should be undertaken regarding this potential association, with particular emphasis on COVID-19 antibody testing.

jamiecrawford1995@gmail.com
HTLV-1 encephalomyelitis; a case report of a treatable manifestation of HTLV-1 infection
Authors: King-Robson Josh , Taylor Graham P
Published: May 2022

Introduction

Human T-cell lymphotropic virus type-1 (HTLV-1) infection remains asymptomatic in >90% of the 20-million people infected worldwide. However in 3%, chronic inflammation within the thoracic spinal cord leads to progressive spastic paraparesis; HTLV-1 associated myelopathy (HAM). This pathological process is not limited to the thoracic cord. We present a case of HTLV-1 encephalomyelitis.

Case

A 53-year-old woman with HAM of 9 years duration presented with subacute cerebellar dysfunc- tion, being unable to feed herself, 3-months after cessation of methotrexate. Investigations demonstrated extensive T2-hyperintensity within the brainstem, cortical and subcortical white matter with punctate contrast enhancement; lymphocytic CSF; and high blood (36%) and CSF (72%) HTLV-1 proviral load (DNA copies per 100 lymphocytes). We diagnosed HTLV-1 encephalomyelitis and commenced high dose methylprednisolone with slow steroid taper following which functional independence in the upper limbs was regained.

Discussion

Risk of HAM rises exponentially once HTLV-1 proviral load exceeds 1%, while CSF:blood proviral load ratio ≥2:1 indicates CNS infiltration of HTLV-1 infected lymphocytes. This patient’s high HTLV-1 proviral load and widespread MRI changes indicated HTLV-1 associated inflammation of the brain and spine. Prompt immunosuppression resulted in significant recovery and highlights the importance of early rec- ognition and management of extraspinal manifestations of HTLV-1 infection.

j.king-robson@nhs.net
048  Cannabis-based medicinal products for neurological disorders: a study of 75 patients
Authors: Weatherall Mark
Published: May 2022

Cannabis-based medicinal products (CBMPs) were approved for use by specialist medical practitioners in the UK in 2018. Licensed indications for CBMPs are limited, but studies have suggested potential benefits from the use of CBMPs across a number of neurological conditions. I present details of 75 neurology patients presenting to a UK-based CQC-registered medical cannabis clinic between December 2019 and January 2021.

The most common reason for presentation was epilepsy (22 patients), followed by migraine (19), and MS (12). Small numbers of patients were seen with other neurological disorders. 23 patients had never used cannabis or cannabis-based products; 29 had taken OTC products, 17 had used cannabis recreationally, and 6 patients had previous taken prescribed CBMPs.

15 patients were not prescribed CBMPs. Of these 5 were deemed unsuitable because other licensed treatment options had not been sufficiently explored. CBMPs were generally well tolerated, only 4 patients experiencing adverse effects from THC (somnolence, nausea).

Of 60 patients treated, follow-up is available for 46. Of these, 23 (50%) found CBMPs helpful in treating their neurological symptoms, and 11 (24%) found CBMPs helpful in improving their general quality of life. 12 (26%) patients did not find CBMPs helpful.

In a real world setting, therefore, patients can find CBMPs helpful for improving neurological conditions, and quality of life. Further studies would be helpful to determine optimal dose and timing schedules for future clinical trials.

mark

weatherall1@nhs.net

49
050  Evaluation of 3 month data for the use of erenumab for chronic migraine in Glasgow
Authors: Dani Krishna , Murray Lesley , Benchiheub Anissa , Gorrie George , Selvarajah Johann , Sharma Sandeep , McKenzie Michael , McCorkell Laura , Rankin Christine , Tyagi Alok
Published: May 2022

Background andMethods

Erenumab, a monoclonal antibody to CGRP, is a new treatment option for preventive treatment of migraine. We audited 3 month outcome data of erenumab for prevention of chronic migraine in Glasgow. Patients are offered erenumab 140mg if they fail 4 migraine prophylactic agents in addition to Botox. Erenumab is continued for a further 9 months if effective at 3 months (≥30% reduction in total headache days or ≥50% reduction in severe headache days, using data from the “best month”). A 3 month extension is occasionally considered if there is a trend for improvement.

Results

Data were available for 93 patients (86% female). Previous treatments included: all 4 prespecified prophylactics (76%); flunarizine(63%); GON block(51%); Botox(95%); neuromodulation(25%); dihydroergot- amine infusion (19%). Erenumab was continued in 81% (53% continued for reduction in headache days, 28% for reduced severity/clinical discretion) and discontinued in 19% for dramatic improvement (2%), side effects (2%), and inefficacy (15%). Side effects included constipation(23%), hair loss(3%) injection site reactions, fatigue, cramps, itch (all 2%), itch, blistering, restless legs, rash, nausea, diarrhoea, insomnia, flushes (all 1%).

Conclusion

A surprisingly high response rate was observed at 3 months. Twelve month data are required to determine if the effect is sustained.

krishna

dani@icloud.com

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051  Peripheral nerve blocks in combination with onabotulinum toxin A treatment to improve migraine outcomes
Authors: Germain Lewis , Hilton James , Amores Fred , Fernandes Linford , Randall Marc , Idrovo Luis
Published: May 2022

There is no evidence base on the efficacy of onabotulinum toxin A treatment and peripheral nerve blocks (PNBs) when used in combination to treat chronic migraine. This retrospective single centre evaluation looked at outcomes from 198 headache service users who had been managed with onabotulinum toxin A treatment alone (n=97), PNBs alone (n=43) or both treatments in combination (n=58). 85% of patients who had PNBs alone considered them effective in reducing their headache burden on follow-up, compared to 71% of patients who had onabotulinum toxin A treatment only. In patients who received both headache treatments, due to increased headache burden, 84% of patients found PNBs effective, while 41% of patients found onabotulinum toxin A treatment effective, suggesting that PNB respond- ers don’t always respond to onabotulinum toxin A treatment. There were also differences in the type of headache outcomes reported, with patients who received PNBs more likely to report a reduction in headache severity compared to patients who received onabotulinum toxin A treatment (69% vs. 50%). Patient who received onabotulinum toxin A treatment were more likely to report a reduction in headache days (47% vs 0.31%). Complications rates and side effects were also evaluated.

linford.fernandes@nhs.net|ABN Bursary
052  How much weight loss is required to reduce intracranial pressure in idiopathic intracranial hypertension?
Authors: Mollan Susan , Mitchell James , Ottridge Ryan , Yiangou Andreas , Cartwright David , Grech Olivia ,   IIH WT investigators, Tahrani Abd , Brock Kristian , Sinclair Alex
Published: May 2022

Background

The amount of weight loss required in idiopathic intracranial hypertension to reduce intrac- ranial pressure (ICP) has not been established.

Methods

Using the IIH:weight trial data from 66 active patients randomised to bariatric surgery or community weight management intervention (CWI) (1:1) a linear hierarchical regression model was used to fit to the trial outcomes, adjusted for time, treatment arm, and body weight. This enabled prediction of ICP.

Results

The greater the reduction in ICP was predicted with greater weight loss, with 24% weight loss resulting in normalisation of ICP in this population. The effect on ICP further improves between 12 to 24 months as the participants continue to lose weight. For expected ICP values to cross the threshold for normal, at 25cmCSF within 2 years, it is generally required that the patient would be allocated to the bariatric surgery arm and achieve a weight of 110kg. Those with a higher starting weight needed to lose more weight to meaningfully reduce ICP. This model also demonstrated that in the CWI arm if no or little weight loss was achieved in those with a high baseline weight an increase in ICP would be expected.

Conclusions

There should be care when exposing women with IIH and BMI≥35kg/m2 to repeated cycles of lifestyle interventions that fail to achieve adequate weight loss, as this approach is unlikely to achieve sustained remission of disease.

soozmollan@doctors.org.uk

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Concurrent sodium channel myotonia and amyotrophic lateral sclerosis supports shared pathogenesis
Authors: Franklin John , Cooper-Knock Johnathan , Baheerathan Aravindhan , Moll Tobias , Heverin Mark , Hardiman Orla , Mannikko Roope , Shaw Pamela , Hanna Michael
Published: May 2022

Amyotrophic lateral sclerosis (ALS) is an invariably fatal adult-onset neurodegenerative disorder; 10% of ALS is autosomal dominant but even sporadic ALS exhibits significant heritability. Dysfunctional voltage- gated sodium channels (NaVs) have been implicated in both sporadic and familial forms of the disease, but it is unclear whether these are an upstream cause or a downstream consequence. Rare missense mutations in the SCN4A gene, encoding NaV1.4, disrupt membrane excitability and cause autosomal dominant muscle channelopathies such as myotonia and hypo/hyperkalaemic periodic paralysis. We report two patients with congenital SCN4A channelopathy due to p.S1159P and p.R672H mutations who developed ALS in later life. Based on our finding we hypothesised that ALS may be linked to genetic mutations in other voltage gated ion channels. Rare-variant burden testing using whole genome sequenc- ing data from 4,495 ALS patients and 1,925 controls within the superfamily of voltage-gated ion channels (Accession: ssf81324) identified one gene, SCN7A, which passed multiple testing correction (p=0.0002, Firth logistic regression) consistent with an enrichment of ALS-associated mutations. We propose that genetic mutations within NaVs leading to neuromuscular excitotoxicity are an upstream cause of ALS. Early identification of ALS patients carrying NaV mutations might lead to personalised therapy with a sodium channel-blocking agent such as riluzole.

j.franklin@doctors.org.uk
055  Insights into a secondary care headache service
Authors: Scott James , Bateman Karen , Cottam Rachel , Muddle Lynne , Young Emma , Ridha Basil , Ganesalingam Jeban
Published: May 2022

Background

Headache is an extremely common presentation to primary care, with some patients requiring referral to general neurology or specialist headache services.

Aims

Here we describe the cohort of patients who are referred to secondary care for management of headaches.

Methods

Neurology outpatient clinics at Brighton and Sussex University Hospitals NHS during June 2019 were retrospectively analysed using electronic records.

Results

Of the 538 patients seen, 123 (23.4%) presented with headache. 48 patients were new referrals and 75 were follow up. 38% of new patients required a follow up appointment.

26 patients (21%) had 2 simultaneous headache disorders. 77 patients (63%) presented with migraine while cervicogenic (n=9), cluster (n=8) and idiopathic intracranial hypertension (n=6) were the next most prevalent.

22 patients with migraine were initiated on a preventative medication while 7 had a dose adjustment. 11 were prescribed an abortive treatment. 1 patient was prescribed simple analgesia. 10 patients received greater occipital nerve block while 6 received Erenumab. For 9 patients, their headache had resolved by the time they attended clinic.

Conclusion

As new treatments such as monoclonal antibodies become available for migraine, ongoing discussion will be vital to ensure headache services can adapt and deliver these therapies effectively.

j.scott3@uni.bsms.ac.uk|ABN Bursary
056  Efficacy of fremanezumab in chronic migraine patients with inadequate response to ≥3 preventive medication classes
Authors: Lambru Giorgio , Dhiraj Dalbir , Ning Xiaoping , Campos Verena Ramirez , Barash Steve , Sherwin Eoin , Cohen Joshua
Published: May 2022

Objective

To evaluate efficacy of fremanezumab in a subgroup of chronic migraine (CM) patients with inadequate response to ≥3 migraine preventive medication classes (CM ≥3 inadequate responses subgroup) from the double-blind, phase 3b FOCUS study.

Methods

In FOCUS, patients with inadequate response to 2–4 migraine preventive treatment classes were randomized (1:1:1) to quarterly fremanezumab, monthly fremanezumab, or placebo for 12 weeks. Changes in monthly migraine days (MMD), 6-item Headache Impact Test (HIT-6) score, and monthly days using acute headache medication and response rates (≥30% reduction in MMD), were evaluated in CM

≥3 inadequate responses subgroup.

Results

Of 838 randomized patients, 293 were included in this analysis. Change from baseline in MMD over 12 weeks was significantly greater with fremanezumab (LSM[SE]: quarterly, −4.0[0.56]; monthly, −4.1[0.56]) versus placebo (−1.0[0.59]; P<0.0001), as was ≥30% response rate (44% and 46% vs 18%; P<0.0001). Signifi- cantly greater reductions from baseline were observed in HIT-6 scores during 4 weeks after third study- drug dose with quarterly (−3.8[0.70]) and monthly (−4.9[0.71]) fremanezumab versus placebo (−1.7[0.75]; P<0.01). Reductions in acute medication use days were significantly greater with fremanezumab versus placebo (P<0.0001).

Conclusions

In CM patients with inadequate response to ≥3 migraine preventive medication classes, fremanezumab was well tolerated and effective.

mknagge@cellohealth.com

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060  Calcitonin gene-related peptide monoclonal antibody treats headache in patients with active idiopathic intracranial hypertension
Authors: Yiangou Andreas , Mitchell James , Vijay Vivek , Grech Olivia , Bilton Edward , Lavery Gareth , Fisher Claire , Edwards Julie , Mollan Susan , Sinclair Alexandra
Published: May 2022

Background

Headache is the dominant factor for quality of life related disability in idiopathic intracranial hypertension (IIH) and typically has migraine-like characteristics. There are currently no evidence-based therapeutics for headache in IIH, and consequently this is an important unmet clinical need.

Case series

We report a series of seven patients in whom headaches were the presenting feature of IIH the headaches had migraine-like characteristics, as is typical in many IIH patients. Papilloedema settled (ocular remission) but headaches continued. These headaches responded markedly to erenumab, a monoclonal antibody targeted against the calcitonin gene related peptide (CGRP) receptor. Of note, there was a recurrence of raised ICP, as evidenced by a return of the papilloedema, however the headaches did not recur whilst treated with erenumab.

Conclusions

Those with prior IIH who have their headaches successfully treated with CGRP therapy, should remain under close ocular surveillance (particularly when weight gain is evident) as papilloedema can re-occur in the absence of headache. These cases may suggest that CGRP could be a mechanistic driver for headache in patients with active IIH.

a.yiangou@bham.ac.uk|NIHR Bursary

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061  A retrospective cohort study of cavernous sinus/orbital apex syndromes presenting to Imperial College London
Authors: Baheerathan Aravindhan , Huang Yun , Dixon Luke , Everitt Alex
Published: May 2022

Introduction

The differential diagnosis of patients presenting with cavernous sinus (CSS) or orbital apex syndromes (OAS) are broad and can be challenging with regards to both diagnosis and treatment.

Methods

We performed a retrospective cohort study of such presentations at our institution from 2015–2021, collecting demographics, investigations and their yield, final diagnosis and management & outcomes.

Results

30 patients

Mean age 50 ± 18.3 years

Prominent pain in 87%

Raised ESR in 27% which subsequently normalised

IgG4 subsets raised in 7%

Matched oligoclonal bands and raised CSF protein were the commonest CSF anomalies

All had cross-sectional imaging

2 patients with an initially normal MRI had a repeat diagnostic MRI within 2 weeks

30% of patients had either lymph node or retro-orbital tissue biopsy

76% had idiopathic retro-orbital inflammation, 7% neurosarcoidosis and 7% IgG4 disease

10% had a neoplastic process

Good recovery seen for idiopathic retro-orbital inflammation treated with IVMP and steroid taper

Conclusion

A high number of patients in our cohort with CSS/OAS have a presumed inflammatory aetiology but with excellent clinical outcome. When clinical suspicion remains high, patients should have interval MR imaging. Bloods & lumbar puncture generally demonstrate non-specific abnormalities and a tissue diagnosis should be obtained if possible for diagnostic security.

aravindhan.baheerathan1@nhs.net