bluuebunny/crossref_metadata_2025_split huggingface dataset:
WED 203 Vanishing white matter disease due to variant mutations in the EIF2B- 1 gene
Authors: Priya Bangalore , R Berry Ian , John Livingston , Dan Warren , J Nicholl David , Mary O’ Driscoll , Tom Hayton 
Published: October 2018

This otherwise fit and well 25 year old gentleman presented with new onset intermittent stabbing headaches associated with generalised tiredness and one nocturnal seizure. His neurological examination was normal and there were no dysmorphic features. He continues to remain intact neurologically.Initial CT Brain showed periventricular low attenuation changes bilaterally associated with bi-frontal atrophy. MRI Brain confirmed extensive periventricular White Matter T2 high signal changes in keeping with Leukomalacia and generalised cerebral atrophy.Genetic testing revealed 2 variant mutations in the EIF2B1 gene, of which one has been previously reported pathogenic and the other is a frame shift variant – likely pathogenic consistent with a diagnosis of vanishing White Matter Leukodystrophy.VWM leukodystrophy is an autosomal recessive disorder characterized by variable neurologic features, including progressive cerebellar ataxia, spasticity, and cognitive impairment associated with WM lesions on brain imaging. The prevalence is unknown; and age at onset can range from early infancy to adulthood. Rapid neurological deterioration can occur following minor head trauma, infections and stress. Mutations in EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5 genes cause leukoencephalopathy with Vanishing White Matter.
THUR 213 An unusual case of cluster acetylcholine receptor antibody positive myasthenia gravis
Authors: Conor Kavanagh , James Lilleker , Rajiv Mohanraj , Thomas Smith 
Published: October 2018

A 73-year-old builder presented with fatigable ptosis and ophthalmoplegia. He was started on pyridostigmine for presumed ocular myasthenia gravis (MG). Despite making an initial improvement he subsequently developed dysarthia, dysphonia and a head drop within 3 weeks. At this time, he also had mild proximal weakness and marked asymmetrical distal weakness of the upper limbs and mild distal lower limb weakness.Conventional serological screening for acetylcholine receptor (AChR) and muscle specific kinase antibodies were negative. However, extended testing using a cell-based cluster assays demonstrated AChR antibody positivity. Repetitive nerve stimulation demonstrated significant decrement more prominent in distal muscles.Despite high dose prednisolone, azathioprine, several courses of IV Immunoglobulins and plasma exchange the patient has had frequent admissions to the high dependency and intensive care setting with respiratory failure.Cluster AChR antibody positive MG has been described only within the last decade and is usually mild and treatment responsive. This is the first case reported to have required intubation and ventilation due to respiratory failure. This case highlights the importance of extending the routine panels for antibody testing in patients with ‘seronegative’ MG and the need to remain vigilant in patients with cluster-AChR positive disease.
THUR 216 Myasthenia gravis, thymoma and good’s syndrome
Authors: Sophie Elands , Gordon Ingle 
Published: October 2018

Myasthenia gravis (MG) is in 15% of cases a paraneoplastic phenomenon secondary to a thymoma. A subset of these will have both a thymoma and associated immunodeficiency known as Good’s syndrome. Immunological features include hypogammaglobulinaemia, a reduction in peripheral B cells, CD4+ lymphopenia, and reversal of CD4/CD8 ratio.We present two cases followed by a literature review:52 year–old man presented with dysphagia, diagnosed as MG. He was found to have a stage 4a thymoma (histology B2), subsequently resected. He was noted to have a reduction in peripheral B cells and CD4+ lymphopenia suggestive of Good’s syndrome. He has also had chronic diarrhoea and recurrent pulmonary infections with Pseudomonas, Klebsiella and Mycobacterium abscessus. Current immunotherapy includes prednisolone.42 year–old woman presented with a myasthenic crisis requiring ITU admission. She was found to have a thymoma (histology B3), treated with resection and adjuvant radiotherapy. Peripheral B cell reduction led to a diagnosis of Good’s syndrome. She is currently in remission on prednisolone, mycophenolate mofetil and 6–weekly immunoglobulin infusions.These cases illustrate that Good’s syndrome is an important differential when managing patients with myasthenia gravis, especially as the immunodeficiency may precede or occur after the diagnosis of a thymoma.
THUR 217 Salmonella gives you wings
Authors: Mahima Kapoor , Mary M Reilly , Michael J Devine , Aisling Carr 
Published: October 2018

A 35-year-old British man based in Pakistan presented with a febrile illness, associated with hepatosplenomegaly. Salmonella paratyphi A was isolated from blood cultures and he was treated with oral and intravenous cephalosporins. 3 weeks later, he developed polyarthralgia and right scapular winging. 5 weeks after the initial episode, fevers recurred with new right upper limb neuropathic pain. Examination showed weakness of right serratus anterior, deltoid and triceps, and reduced sensation in left lateral cutaneous nerve of forearm (LCNF) distribution. Neurophysiology showed abnormal sensory responses in the left LCNF and right superficial peroneal nerve, and abnormal EMG in right serratus anterior and right pronator teres. MRI brachial plexus showed no abnormal enhancement in the plexus. CSF was normal. Salmonella paratyphi A was again cultured from blood and he was re-treated. 10 months’ later, he has residual, mild weakness of right deltoid.Salmonella typhi has been associated with Guillain-Barre syndrome, and can have neuropsychiatric manifestations. The association with a post-infectious polyneuropathy has not previously been reported.
WED 222 Hawkes sign: a novel test for carpal tunnel syndrome
Authors: Christopher Hawkes 
Published: October 2018

BackgroundIn carpal tunnel syndrome (CTS) patients often report symptoms when elevating the arms, as in driving or phoning.In Hawkes test both forearms are squeezed firmly about 50 mm (2 inches) proximal to the patient’s wrist while simultaneously elevating the subject’s hands just above shoulder height. When positive there is tingling in a median nerve distribution within a few seconds.MethodsFifteen patients with suspected CTS were evaluated by a) Tinel’s, Phalen’s and Hawkes’ manoeuvres b) routine nerve conduction tests (NCT) then graded positive or negative and compared with NCT.ResultsPositive signs were present for Tinel in 14/15; Phalen in 8/10 and Hawkes in 15/15. NCT supported CTS in 9/15. Where NCT were abnormal Tinel and Hawkes signs were always positive but Phalen was negative in 2/7. Where NCT was normal (6/15) the negative/positive rates were: Tinel 1/5; Phalen 3/3; Hawkes 0/6.ConclusionAll three procedures, particularly Tinel and Hawkes had a high positive rate for CTS, but confirmed by NCT in only 6/15. However, NCT may be falsely negative especially in mild cases. The proposed arm elevation/compression test permits useful initial assessment of CTS although the false positive rate is probably high.
THUR 231 Developing a new rating scale for ocular myasthenia gravis
Authors: Wong Sui H , Miranda Eduardo , Lee Helena , Eggenberger Eric , Cornblath Wayne , Barnett Carolina 
Published: October 2018

Ocular Myasthenia Gravis (OMG) causes ptosis and diplopia, which can be disabling. For this study, OMG is defined as MG patients who have ocular symptoms only and no generalised involvement. A robust way of assessing the severity of OMG symptoms is important for research, to assess treatment and outcome. The rating scales recommended for MG research have a predominant focus on generalised disease, and are insufficiently sensitive for OMG due to the limited number of ocular questions. This study aims to create a new rating scale for OMG that is sensitive, reliable and clinically usable. We present our proposal of such a rating scale, which incorporates physician- and patient-rated components. We report the preliminary results of this pilot observational cohort study, in 60 patients with OMG. We compare the results of this with the MG composite scale.Future work is planned to validate this rating scale and to develop this alongside the MG Impairment Index (MGII). For future phases of this study we plan to assess the usability of this rating scale by Neurologists without specialist Neuro-ophthalmology.We invite feedback from Neurologists at the ABN.
WED 236 Skeletal muscle channelopathies and sudden infant death syndrome
Authors: Emma Matthews , Roope Mannikko , Leonie Wong , Dimitri Kullmann , Sanjay Sisodiya , Peter Fleming , Elijah Behr , Michael Hanna 
Published: October 2018

BackgroundSkeletal muscle channelopathies are rare genetic disorders causing periodic paralysis and myotonia. They are generally considered debilitating but not life-threatening. However cases of life-threatening respiratory muscle crises have recently been reported in infants requiring ITU support. We hypothesised muscle channelopathy gene variants may contribute to the risk of sudden infant death.MethodsWe analysed the SCN4A gene for rare variants in 278 cases of sudden infant death (SIDS) and 729 ethnically matched controls. Biophysical characterisation was performed using a heterologous expression system.ResultsFour of the 278 SIDS cases (1.4%) had an ultra-rare, functionally disruptive SCN4A variant compared to 0/729 ethnically matched controls (p=0.0057). The degree of channel perturbation associated with these four variants was qualitatively similar to the SCN4A variants previously implicated in infants with life-threatening apnoeic events.ConclusionsRare SCN4A variants that directly alter channel function occur in sudden infant death cases. These variants are predicted to significantly alter muscle membrane excitability compromising respiratory and laryngeal function. Data on pregnancy/post-natal complications is now being collected from parents with genetically confirmed sodium channelopathies via clinic and on-line registry. Laryngospasm has recently been implicated in SUDEP - analysis of SCN4A variants in SUDEP cases is also underway.
WED 237 Phosphorodiamidate morpholino oligomers for treatment of duchenne muscular dystrophy
Authors: Kate Maresh , May Tiet , Michela Guglieri , Joana Domingos , Volker Straub , Thomas Voit , Francesco Muntoni 
Published: October 2018

Exon skipping is a novel, mutation-specific approach to treating patients with Duchenne muscular dystrophy (DMD). Phosphorodiamidate morpholino oligomers are nucleic acid analogues that selectively redirect pre-mRNA splicing to enable production of internally truncated dystrophin.In exon 51 skipping (eteplirsen; n=36) and exon 53 skipping (golodirsen; n=25) clinical studies, internally shortened dystrophin mRNA was observed in all treated patients (per reverse transcription polymerase chain reaction). Eteplirsen increased dystrophin expression 15.5-fold, 11.6-fold, and 2.4-fold vs untreated controls (percent dystrophin-positive fibres, Western blot, and immunohistochemistry intensity, respectively; all, p≤0.007) in a 180 week study, and 2.8-fold (Western blot; p=0.008) in a 48 week study. Golodirsen increased dystrophin expression 10.7-fold (Western blot) over baseline following 48 weeks of treatment. Over 4 years, versus comparable external controls, eteplirsen slowed ambulatory decline (6 min walk test difference, 165 m; p=0.001) and cumulative risk of losing ambulation (83% vs 17%). In 2 clinical studies that included non-ambulatory patients, eteplirsen slowed pulmonary decline versus natural history data (assessed by spirometry).Eteplirsen and golodirsen demonstrated clinical and biochemical effects in patients with DMD; ongoing studies of these compounds are further characterising their effects in various patient populations.
WED 238 Do we follow the abn myaesthenia guidelines?
Authors: Jacob Roelofs , Rose Bosnell , Geraint Fuller 
Published: October 2018

BackgroundThe ABN treatment guidelines1 for myasthenia Gravis (MG) have recently been published.AimWe reviewed the records of patients with MG to assess how well the ABN guidelines are being followed in a district general hospital based neurology centre.MethodsAll patients who had positive anti-AchR antibody tests from 2014–2017 and clinicians were asked to identify further patients. Retrospective review of electronic patient record, clinic letters and laboratory data reviewed.Results59 patients; 24 ocular and 35 generalised (by type - II: 17, III:15, IV:1, V:1, unclear:1). 63% male, average age 64 (range 18–91). 22/35 (62.8%) generalised MG patients were in remission off pyridostigmine. 13 on steroids, 17 azathioprine, 5 mycophenolate; 3 methotrexate. 2 patients were admitted to ITU, 16 patients had inpatient admissions, 11 patients had IVIG.14/24 (58.3%) with ocular MG were in remission off pyridostigmine; 5 on steroids, 6 azathioprine. 2 patients had been admitted. 7 of 23 patients on AZT (30.4%) did not have a TMPT level recorded, with only 19 (79%) having sufficiently regular bloods monitoring.DiscussionTreatment for most patients followed the ABN guidelines. The most common difficulties related to testing for TMPT and blood monitoring.Reference1. Sussman J, Farrugia ME, Maddison P, et al. Myasthenia gravis: Association of British neurologists’ management guidelines. Practical Neurology2015;15:199–206.
WED 241 Clinical relevance of regular blood monitoring in IG treatment
Authors: Khalil A , Compton L , Kapoor M , Groves J , Nihoyannopoulos L , Gosal D , Rossor A , Reilly MM , Carr AS , Lavin T 
Published: October 2018

BackgroundABN immunoglobulin (Ig) guidelines advise routine FBC and U and E monitoring with every treatment episode and screening for IgA deficiency. AimsWe audited compliance in inflammatory neuropathy patients on longterm treatment in two UK Neurology departments. We looked for evidence of clinically relevant haematological or AKI Ig-related events.MethodsData was collected from Nov 2015 to Nov 2017. Accepted definitions for clinically and/or biochemically significant haemolysis, neutropenia, thrombocytopenia and AKI were used.Results1919 treatment episodes in 90 patients were analysed. Mean age (SD)=57.6 (14.4)years, 69.1% male, 74% CIDP (26% MMN), 94% IVIg (6% SCIg). Mean dose=1.57 (0.74) g/kg/month or 97.1 (37.3) g/infusion. No clinically significant episodes of haemolysis, neutropenia, thrombocytopenia or AKI occurred in relation to Ig treatment. An asymptomatic drop of >10 g/L Hb occurred in 68/1919 episodes in 38 individuals (3.5%); mean reduction 17.7 g/L, lowest Hb 99 g/L. Two patients with CRF (stage 3) received 28 (IV) and 104 (SC) infusions respectively without impact on eGFR. Two individuals with relative IgA deficiency (0.38 g/L, 0.4 g/L) received 16 infusions over 1.5 years without complications.ConclusionsNo clinically significant Ig-related events were identified in this representative cohort. We suggest annual screening or clinically indicated testing as safe and more appropriate in longterm IVIg use.
WED 242 A challenging case of periorbital swelling
Authors: Aginor Spanoulis , Papastergiou Yalatia , Mitropoulou Panagiota , Burke Georgina 
Published: October 2018

A 54 year old lady was referred with a eighteen month history of slowly progressive, asymmetric, periorbital and facial oedema. She was thought to have inflammatory orbital pseudotumour.During this time, she had also developed a dry mouth, joint pains and enlarged salivary glands. A salivary gland ultrasound scan was suggestive of Sjogren’s disease although antinuclear antibody and rheumatoid factor were negative. She had recently been prescribed omeprazole for mild dysphagia and hoarse voice from vocal cord oedema.Past medical history included Hashimoto thyroiditis for which she was taking levothyroxine.Clinical examination revealed peri-orbital and facial oedema causing proptosis of the right globe and complete lid closure. Visual acuity, eye movements and visual fields of the left eye were normal. Her voice was hoarse and she had mouth ulcers. She had a widespread erythematous rash that was thought to be a drug reaction to omeprazole.Apart from mild lymphopenia and mildly deranged liver function, blood tests, including inflammatory markers and thyroid function, were unremarkable.MRI of the brain and orbits revealed diffuse oedema of facial structures, including the orbital muscles. A CT body scan was unremarkable.A temporalis muscle biopsy confirmed a high grade NK/T cell lymphoma.
WED 258 Stroke mimic diagnoses on a centralised hyperacute stroke pathway
Authors: Stefaniak James D , Heartshorne Rosie , Punter Martin , Molloy Jane 
Published: October 2018

IntroductionStroke is highly prevalent, with an estimated 25.7 million occurring worldwide in 20131. In an effort to reduce mortality and length of hospital stay2, hyperacute stroke services have been fully centralised in Greater Manchester since 2015 such that all possible strokes within 48 hours of onset are transferred for assessment at one of three stroke centres. However, there have been concerns regarding the transfer of stroke mimic diagnoses along such pathways.MethodsA retrospective analysis was performed of patients assessed by the hyperacute stroke team in the Emergency Department of the Comprehensive Stroke Centre (Salford Hospital) in December 2015.ResultsIn December 2015, 309 patients with queried stroke were assessed by the Comprehensive Stroke Centre hyperacute stroke team. Of these, 82% had been redirected or transferred from another hospital. 47% had a non-stroke diagnosis at discharge or repatriation, resulting in a combined 331 days of stay at Salford hospital by patients without a stroke. The five most common non-stroke diagnoses were TIA, migraine, infection, seizure and functional neurological disorder.ConclusionsThe optimal clinical care of non-stroke patients should be considered when planning centralisation of hyperacute stroke services.References1. Benjamin EJ, Blaha MJ, Chiuve SE, et al. (2017). Heart disease and stroke statistics-2017 update: A report from the American Heart Association. Circulation 135:0. doi:10.1161/CIR.00000000000004852. Morris S, Hunter RM, Ramsay AIG, et al. Impact of centralising acute stroke services in English metropolitan areas on mortality and length of study: Difference-in-differences analysis. BMJ 2014;349:4757.
THUR 021 Transforming acute neurology: a 4 year study
Authors: Arani Nitkunan , Bridget Macdonald , Ajay Bhoodoo , Medina Southam , Caitlyn Smyth , Andrew Tomkins , Fred Schon 
Published: October 2018

We present a novel approach to acute neurological care. The key is an acute neurology triage nurse, based in the medical admission unit as well as an epilepsy specialist nurse seeing every patient referred with fits on the day of admission, a designated acute neurology consultant and acute neurophysiology and neuroradiology links. We have designated this group, a hyperacute neurology team (HANT).This study compares all admissions in 2014, the year before the team was established with 2015–2017. The total number of referrals has increased from 720 in 2014 to 1248 in 2017. The percent of patients seen on the day of referral has risen from 59% in 2014 to 92% in 2017.Average length of stay for patients with a primary diagnosis of epilepsy has gone down from 4.1 days in 2014 to 3.4 in 2017. Multiple admissions for epilepsy has reduced from 28 in 2014 to 21 in 2017. Patients suitable for early discharge are seen in consultant or nurse «outpatient hot clinics» or nurse telephone clinics.The cost of establishing this service has been relatively small (£106,000) and the service benefits enormous. We feel this model is worthy of wider debate.
285 Piloting and implementing an acute neurology service
Authors: Peukert Thomas 
Published: October 2018

Over the past decade, the number of patients attending the emergency department (ED) at the Royal Victoria Hospital Belfast, with neurological symptoms, has doubled. Typically, over 50% of these patients would subsequently be admitted to hospital. In 2013, a pilot project was conducted with the aim of evaluating the effectiveness of a rapid access neurology clinic on reducing such admissions.A dedicated neurology clinic was set up offering 12 slots per week. Patients were seen within 10 days of ED staff booking them into the clinics. Early results indicated that within the first month 28 admissions were avoided. As a result rapid access neurology clinics were rolled out. Two acute neurologists were appointed and since 2015, 3 rapid access clinics run per week (15 slots). In addition to the rapid access clinics, the acute neurology team also offer two additional services:Reviewing all patients who have been admitted under the medical take with neurological symptomsPatients who attend ED overnight but require urgent evaluation/tests can be sent home and will be seen the next morning by the acute neurology teamAnalysis indicates approximately 1250 admissions are avoided each year with an estimated cost saving of over £2 million.
290 CSF chitinases as novel biomarkers for MND
Authors: G Thompson Alexander , Elizabeth Gray , Marie-Laetitia Thézénas , D Charles Philip , Samuel Evetts , T Hu Michele , Kevin Talbot , Roman Fischer , M Kessler Benedikt , R Turner Martin 
Published: October 2018

The development of biomarkers for amyotrophic lateral sclerosis (ALS, the commonest phenotype of MND) is a priority to reduce diagnostic delay, allow earlier assessment of therapeutic activity, and provide pathogenic insight.Liquid chromatography tandem mass spectrometry with label-free quantification was used to quantify CSF proteins in individual participant samples. A longitudinal cohort comprised patients with ALS (n=43) and primary lateral sclerosis (PLS, n=6). A cross-sectional cohort comprised healthy (n=20) and disease control patient CSF samples (Parkinson’s disease n=20, MND mimic disorders n=12).Among 773 identified proteins, significantly elevated levels of three macrophage-derived chitinase proteins were detected in the ALS group, specifically chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1) and chitinase-3-like protein 2 (CHI3L2). Levels correlated with rate of disease progression (CHIT1 r=0.56, p<0.001; CHI3L1 r=0.31, p=0.028; CHI3L2 r=0.29, p=0.044), and levels of the axonal degeneration marker phosphorylated neurofilament heavy chain (r=0.62, p<0.001; r=0.49, p<0.001; r=0.41, p<0.001). Levels of CHI3L1, but not CHIT1 or CHI3L2, increased over time in those with low initial values (gradient=0.005 log abundance units/month, p=0.001).Microglial activation has been implicated in the pathogenesis of MND and neuroinflammatory pathways are a major target of therapeutic interest. CSF chitinases may be potential pharmacodynamic as well as diagnostic biomarkers.