bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

IntroductionMyasthenia 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.MethodsWe reviewed The Christie Hospital database of immunotherapy-related toxicity from 2017–2020. Symptom severity was assessed using the MGFA classification.ResultsSix 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.DiscussionPrevious 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.jamweaver75@gmail.com17
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>Gp. (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

IntroductionSpinal 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).MethodsData 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).ResultsCompared 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.ConclusionMOGAD 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.alijesusalim-marvasti@nhs.net28
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.MethodsWe 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.PreliminaryResults57 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.ConclusionPreliminary 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.HardikBhaskar93@myhunter.cuny.edu29
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.com31
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.zhongbochen@ucl.ac.uk|ABN Bursary36
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

BackgroundCurrent 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.MethodEvaluation 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.ResultsData 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.ConclusionsWe 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

IntroductionGlial 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 PresentationWe 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.DiscussionThis 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

BackgroundImpulse 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.ObjectiveTo compare the frequency of ICBs in patients with iRBD and drug-naive PD.MethodsCross-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.ResultsThe 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.ConclusionsThis 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 Bursary38
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

IntroductionSaliva 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.ObjectiveTo investigate the prevalence of saliva problems in pwMND, their association with clinical factors and their management practice.MethodsWe 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.Results939 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).ConclusionSaliva 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