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Bickerstaff’s Brainstem Encephalitis (BBE) is a condition causing impairment of sensorium in association with ophthalmoplegia and ataxia. Here we present a case of BBE presenting with bilateral vocal cord paralysis.A 35-year-old female presented with a sore throat and shortness of breath in the context of a fall and ankle injury the previous day. She became confused and agitated in hospital. Several hours after pres- entation she was found cyanosed with stridulous breathing (with normal saturations). Fibre-optic nasola- ryngoscopy revealed bilateral vocal cord palsy. She was intubated and transferred to ICU. Investigations including a full infection screen, CSF analysis and MRI were normal and non-diagnostic. Examination during a sedation hold revealed a unilateral third, fourth, and bilateral sixth and seventh cranial nerve palsies. She had flaccid quadriparesis and was globally areflexic. Nerve conduction studies showed a motor predominant polyneuropathy. A diagnosis of BBE was made based on the clinical findings with acute confusion. She was treated with plasma exchange and immunoglobulins and was discharged with almost complete recovery.There are no previous case reports of vocal cord paralysis being the presenting feature of BBE. Neurologi- cal disease accounts for only 12% of cases of bilateral cord palsy. These causes may be systemic such as myasthenia gravis or diphtheria, or focal affecting the nucleus ambiguus in the medulla. However, clini- cians must recognise these cases promptly to ensure adequate investigation and treatment.

IntroductionThis audit of existing neuropharmacists shows how the role has grown over the years to help look after tasks suited to their skill set such as governance, introduction of new medication and path-way design, which has helped neurology teams in utilising the skills of each member of the team appropriately.AimTo showcase the growing role of the neuropharmacist.MethodsA survey of existing neuropharmacists about their current roles and duties was undertaken, utilising the network of 50 neuropharmacists across the UK.ResultsThe role of the neuropharmacist has grown with subspecialism occurring in areas such as MS, headache, epilepsy and parkinsons disease. Patient facing clinics, leading on governance for the neu- roscience team, introduction of new medication to pathways and taking part in research across the healthcare economy (ie with primary care) are all areas that the neuropharmacist has been involved.ConclusionsThe role of the neuropharmacist is diverse and can be utilised by the neurology team to ensure appropriate skill set are used to deliver the best care to patients. It is hope this work will help teams that do not have a neuropharmacist to develop business cases and redesign patient and disease pathways to include other members of the team.

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

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

RG6102 is a bispecific 2+1 monoclonal antibody (mAb) under development for the treatment of Alz- heimer’s disease (AD). It combines the anti-amyloid beta antibody gantenerumab with a transferrin receptor 1-binding “Brain Shuttle” module, enabling active receptor-mediated transport across the blood–brain barrier.In preclinical studies, RG6102 has shown superior distribution, target engagement and amyloid plaque clearance compared with gantenerumab. In a human Phase Ia study, there was a markedly increased cerebrospinal fluid (CSF)/plasma ratio for RG6102 compared with typical mAbs.Brainshuttle AD is a 28-week, randomised, global, multicentre, double-blind, placebo-controlled, parallel- group Phase Ib/IIa study evaluating the safety, tolerability, immunogenicity and pharmacokinetics/phar- macodynamics (PK/PD) of RG6102. Multiple-ascending intravenous doses of RG6102 are administered every 4 weeks to patients with prodromal or mild-to-moderate AD. The study consists of a screening period, a double-blind treatment period and a safety follow-up period.The primary objective is to evaluate the safety and tolerability of RG6102. Secondary outcome measures include the change from baseline in brain amyloid load, plasma and CSF concentration of RG6102 and incidence of anti-drug antibodies to RG6102. Exploratory endpoints include the clinical effect of multiple doses of RG6102 on clinical outcome measures and on various PD biomarkers.Recruitment for Brainshuttle AD is currently ongoing.

IntroductionOrthostatic hypotension (OH) and supine hypertension (SH) are prevalent in alpha-synucle- inopathies, posing a therapeutic dilemma as OH treatment may worsen SH. We aimed to characterise SH in pure autonomic failure (PAF), multiple system atrophy (MSA), and Lewy body disorders (LBD: Parkinson’s disease and Dementia with Lewy bodies).Methods166 patients (72 PAF, 59 MSA, 35 LBD) underwent cardiovascular autonomic testing and 24hr- ambulatory blood pressure monitoring (24hr-ABPM). Demographic, clinical features, medications and cardiovascular autonomic biomarkers were compared.ResultsSH was present in more than half of patients with PAF, MSA and LBD (56%, 51% and 50%, respec- tively) without anti-hypotensive medications. Supine pre-stand BP during 24hr-ABPM detected SH with 60% sensitivity and 86% specificity [area under the curve 0.73 (95%CI 0.66-0.81)]. Supine noradrenaline levels were significantly higher in MSA vs PAF and LBD (268 vs 183 and 210 pg/ml, p<0.01). There was a strong correlation between OH, SH and nocturnal hypertension after adjusting for age, anti-hypotensive medications and supine noradrenaline levels (R2=0.48, p<0.01).ConclusionsSH and nocturnal hypertension commonly co-exist and are independently associated with OH in alpha-synucleinopathies. 24hr-ABPM is useful in detecting SH in these patients. The pathophysiology of SH is likely to be heterogeneous and not entirely explained by residual sympathetic tone.

IntroductionSporadic CJD (sCJD) is universally fatal. While median survival is 5 months, there is consider- able heterogeneity with some surviving weeks while others survive several months or years. We sought to evaluate characteristics influencing disease duration, and the performance of latest diagnostic criteria incorporating cortical ribboning on MRI brain and the RT-QuIC assay.Methods501 autopsy-confirmed cases from surveillance centres in the UK, France, Germany and Italy were stratified into short (<75 days), typical (75-222 days) and long (>222 days) survival groups. We evaluated clinical features, investigation results, and diagnostic criteria classification.ResultsShort survival was associated with male sex (p=0.02) and older age (p=0.004). Prion protein gene codon 129 polymorphism status greatly influenced duration (p=<0.001, with longest survival in methionine- valine heterozygotes). Extrapyramidal features were most frequent in long survivors (p=0.04). EEG and 14-3-3 were most sensitive with short survival (p<0.001), RT-QuIC with typical survival (p=0.03) and MRI sen- sitivity did not vary (p=0.4). Previous diagnostic criteria lacked sensitivity in long survivors (p=0.001) while updated criteria were equivalent between groups (p=0.19): sensitivity for long survivors increased 27.7%.ConclusionsThis study demonstrates important factors influencing survival and associated phenotypes. The latest diagnostic criteria for sCJD have significantly enhanced diagnosis in long survivors.

Anti-viral vaccination has rarely been associated with Guillain-Barré syndrome(GBS). We performed a population-based study of NHS England data and a UK multicentre surveillance study to investigate the relationship between COVID-19 vaccination and GBS.We linked GBS cases from England’s National Immunoglobulin Database(NID) with COVID-19 vaccina- tion data from December 2020–July 2021. GBS temporally associated within a 6-week risk window of any COVID-19 vaccine was identified.We prospectively collected incident UK GBS cases January–November 2021 regardless of vaccine exposure.The NID recorded 996 English GBS cases January–October 2021. A spike of cases above the 2016-2020 average occurred March–April 2021. 198 cases occurred within 6 weeks of first-dose COVID-19 vaccina- tion (0.618cases/100,000vaccinations: 176 ChAdOx1 nCoV-19, 21 tozinameran, 1 mRNA-1273). First-dose ChAdOx1 nCoV-19 accounted for the excess of 98-140 GBS cases with a peak 24 days post-vaccination. First-dose tozinameran and second-dose any vaccination showed no excess GBS risk. The UK multicen- tre surveillance dataset (121 patients) identified no phenotypic or demographic differences between vaccine-linked and unlinked cases.First-dose ChAdOx1 nCoV-19 vaccination is associated with excess GBS risk 0.576 (95%CI 0.481-0.691) cases/100,000 doses. No specific features are associated with vaccination-related GBS cases. The mechanism of immunogenicity of ChAdOx1 nCoV-19- warrants further study.

Queen Elizabeth HospitalIntroductionCannabidiol (CBD) is approved for the treatment of refractory epilepsy associated with Dravet and Lennox-Gastaut syndromes. Affected individuals have co-morbid intellectual disability, making serum monitoring challenging. Those prescribed CBD at the Queen Elizabeth Hospital underwent at least one face to face appointment in the twelve months preceding treatment. Many were initiated on CBD remotely, in keeping with trust guidance to reduce the burden of face-to-face consultations during the Pandemic.NICE recommends liver function test (LFT) monitoring in those prescribed CBD at baseline, 1, 3 and 6 months, then periodically thereafter 2. All patients initiating CBD were offered LFT on site, with a recom- mendation to GPs to continue LFT monitoring in the community.Aim To assesses whether CBD patients undergo LFT monitoring in keeping with NICE guidance.ResultsOf thirty patients prescribed Cannabidiol for a minimum of six months, sixteen (53%) had LFTs undertaken at least once. Twelve (75%) were conducted by their GP. Three patients had abnormal LFT at some stage which normalised within six months of initiation of treatment.RecommendationsRegular liaison with community healthcare providers about LFT protocols and access to finger prick testing (both on site and community) would potentially facilitate regular serum monitoring.

BackgroundVaccination is a recognised trigger of ADEM and approximately 50% paediatric cases have antibodies to MOG. The SARS-CoV-2 mass vaccination programme could therefore trigger cases of MOGAD. Neuromyelitis optica (NMO) is an autoimmune inflammatory condition of the CNS associ- ated with antibodies to AQP4.MethodTen patients (ages 22 – 65 years) with antibodies to MOG or AQP4 were referred to the NHS England NMO service having developed acute onset CNS inflammation within 8 weeks of vaccination.ResultsEight patients had MOGAD, seven of whom received the AstraZeneca vaccine (AZV) and one the Pfizer vaccine (PV). Only the post-PV MOGAD patient presented with typical adult-onset phenotype of isolated ON. All post-AZV MOGAD patients presented atypically; 85.7% had LETM and 71.4% had intrac- erebral lesions, resembling ADEM more commonly seen in paediatric MOGAD. The atypical presentation supports a causative role of AZV, but the role of PV is less convincing.Two patients had AQP4-NMOSD with typical demographic features. Both received AZV. Less typically, one young adult presented with LETM rather than characteristic young adult ON, the other had a silent short segment myelitis, which is rarely seen in AQP4-NMOSD. Both patients achieved good outcomes.ConclusionWe discuss the potential causation and pathophysiological mechanisms.