bluuebunny/crossref_metadata_2025_split huggingface dataset:
121  The Queen Square tests of auditory cognition: defining hearing deficits and dis- ability in dementia
Authors: Johnson Jeremy , Benhamou Elia , Sivasathiaseelan Harri , Requena-Komuro Mai-Carmen , Nelson Annabel , Rohrer Jonathan , Bamiou Doris-Eva , Hardy Chris , Warren Jason 
Published: May 2022

BackgroundHearing impairment has emerged as a potent association of cognitive decline in dementia and a promising treatment target. To realise this promise, we need to resolve fundamental questions concerning the roles of peripheral versus central auditory deficits in different dementias.MethodsUsing a novel psychoacoustic battery – the Queen Square Tests of Auditory Cognition (QSTAC)– we combined pre-existing and novel measures of peripheral and central hearing functions, to charac- terise discrete ‘auditory phenotypes’ across dementia syndromes. Customised auditory symptom ques- tionnaires (completed by patients’ caregivers) were used to capture daily-life hearing-related disability and care burden. Patient groups: Alzheimer’s disease, frontotemporal dementia, primary progressive aphasia (PPA) and control. Neuroanatomical associations of specific hearing deficits were assessed using voxel-based morphometry.ResultsSyndromic signatures of peripheral and central auditory dysfunction were identified. Alzheimer’s disease was associated with prominent impairments of auditory scene analysis and dichotic listening. PPA syndromes and behavioural variant FTD (BvFTD) were principally associated with deficits of sound pattern analysis, sound identity, emotion recognition and degraded speech perception, which stratified according to sub-syndrome (logopoenic, semantic, nonfluent).ConclusionsTaken together, our findings suggest that major dementias have characteristic and differenti- ated auditory phenotypes, reflecting a complex interplay of peripheral hearing and auditory cognitive dysfunction.jeremy.johnson@doctors.org.uk
How prolonged is a prolonged disorder of consciousness? Longterm follow-up of 71 consecutive admissions
Authors: Allanson Judith , Holland Tony , Pickard John , Kamau Evelyn , Bareham Corinne , Roberts Neil , Stamatakis Emmanuel , Menon David , Hutchinson Peter , Barclay Stephen 
Published: May 2022

There is little Uk data on outcome after Prolonged Disorders of Consciousness(PDOC) and yet, in the light of recent case law and professional guidelines, this is essential for reliable prognostication and thus for best interests discussions about provision of clinically assisted nutrition and hydration.This study reports the very longterm outcome of 69/71 consecutive admissions to a UK fMRI study of PDOC after brain injury. (mean age 47y; 52 male; initially seen at mean 20 m post injury; 47 traumatic brain injury, 18 hypoxia).Status of those alive at follow up (mean 8y7m post injury) was determined after direct examination or use of the Coma-recovery-scale-revised telephone version, with clinicians and families.Mortality data revealed 33/71 (47%) had died naturally at mean of 55m post injury; mean age 49y; this included 27/50 of those initially in Vegetative or Minimally Conscious minus; 21/47 with TBI.Of note 13/69 (19%) who had not emerged at first assessment had recovered to emergence or higher level at followup. 11 were fully active; eg snow-boarding. One regained speech 5 years after injury. 11 were living in domestic settings; 9 with care packages. Only 2/11 with evidence of covert awareness on initial fMRI had emerged.Although these data are from a very selected cohort this data reveals recovery from PDOC can occur very late after injury in those confirmed to be in PDOC after detailed clinical assessment.judith.allanson.1@gmail.com
127  Hypocupraemia-induced anaemia, sensory ataxia and cognitive impairment secondary to zinc-containing dental adhesive
Authors: Dihmis Omar , Jamal Rayyan , Carroll Liam Stuart , Pengas George 
Published: May 2022

A previously fit and well 67 year old male presented with a 5-month history of gradually worsening memory impairment and sensory gait ataxia on the background of recent symptomatic anaemia. He experienced multiple falls and became agitated and socially withdrawn over a 3-week period, resulting in hospital admission. On examination, he had sensory gait ataxia consistent with a dorsal column syndrome. He had a Montreal Cognitive Assessment score of 13. Serum analysis showed normocytic anaemia and leukopenia, severe hypocupraemia, reduced caeruloplasmin and normal zinc levels. Overuse of zinc- containing denture cream was identified as being a cause of excess zinc ingestion and resultant copper deficiency, leading to blood dyscrasia and myelopathy. The cream was withdrawn and IV copper followed by oral supplementation was implemented. Direct questions with regards to excess zinc in the diet and serological testing of copper and zinc should be considered in any patient with a dorsal column syndrome, particularly with concurrent anaemia. Copper deficiency may also have a role in exacerbat- ing pre-existing cognitive impairment.rnj1e16@soton.ac.uk
136  New valproate guidelines and adherence to the pregnancy prevention programme: experience in a tertiary clinic
Authors: Prabhakaran Asmithaa , Coyle Helen , Mohanraj Rajiv 
Published: May 2022

Objectives: To establish the proportion of women of childbearing age on Sodium Valproate (VPA) for epilepsy who met the requirements of the Pregnancy Prevention Programme (PPP) in accordance with the Medicines and Healthcare products Regulatory Agency (MHRA) guidelines, with a view to identifying rates of compliance and the reasons for non-adherence.Methods128 female participants of childbearing age currently on VPA, who had completed an annual risk assessment from Greater Manchester, were included in the study. Patient data was gathered review of Electronic Patient Records.ResultsThe majority of women (n=86, 67%) did not meet the conditions of the PPP: 59 (69%) were on no contraception, and 27 (31%) were on inadequate contraception such as OCP, Depo injection, and condoms. Non adherence to PPP was due to 11 different reasons, the most common (n=27) being learning disability, followed by, no intention of becoming pregnant (n=7), not sexually active (n=13), and patient choice (n=9)ConclusionsPPP does not appear to be relevant to the majority of women of child bearing age pre- scribed VPA. Further patient education about rates of unplanned pregnancies and risks of VPA might help improve adherence to PPP.asmithaa.prabhakaran@student.manchester.ac.uk
142  Ictal asystole case series
Authors: Khalil Mohamed , Shukrallah Arif , Delanty Norman , Elnaggar Hany 
Published: May 2022

Ictal arrhythmias are disturbances of cardiac conduction that occur during clinical or electrographic seizures. Ictal asystole is rare and its incidence can range from 0.3–0.4 % in patients with epilepsy.We reported eleven patients (Seven males and four females) with an age range (31–70 years old) who were monitored in our telemetry unit over the last eight years. Patients were selected based on the history of documented ictal asystole or bradycardia during inpatient VEEG monitoring). In our series the mean latency was 22 seconds and the mean duration of the ictal asystole was 15.8 seconds. During the asystolic phase the seizures may clinically continue or syncopal signs may take over.We found two patterns in ictal semiology in our series. The first group of patients included three patients who experienced a rapid onset of ictal asystole in their seizure and the second group where the latency of ictal asystole was relatively late. Both groups of patients have temporal lobe epilepsy.In our case series all the patients had either left or right temporal lobe epilepsy, six of which were lesional. Ten of our cohort had permanent pace maker following the diagnosis, Six of which had been event free since.dm.neuro@hotmail.com
147  Long-term cenobamate retention in people with focal onset seizures: pooled data from open-label studies
Authors: Sander Josemir W , Alvarez-Baron Elena , Finlan Lee , Toledo Manuel 
Published: May 2022

PurposeMost people with epilepsy receive chronic, long-term treatment with ≥1 anti-seizure medication. Retention rates provide can act as a proxy measure for clinical efficacy/safety over time. We present long-term exposure and retention data from open-label extensions (OLEs) of 3 trials in adults with uncon- trolled focal onset seizures (FOS) receiving adjunctive cenobamate.MethodsOf the three trials, two were OLEs of randomized, placebo-controlled trials (C013 & C017). The third, was a large safety OLE study (C021). Retention rates of cenobamate were estimated using Kaplan- Meier survival analysis.Results1945 patients were exposed to cenobamate during clinical development, of whom 1844 (95%) took part in OLEs. Exposure for the combined double-blind (DB) studies OLEs (C013OLE, C017OLE) was 4.5 years (55 (0.3–94) months (N=504)), and for the C021 (N=1340) 1.9 years (23 (0.03–35 months)). As ofJuly 2019, retention rates at month 94, 69 and 36 were 57%, 59%, and 72% for the three trials (C013OLE, C017OLE, C021). After 1 year, retention rates were 71% (C013OLE), 80%(C017OLE) and 80%(C021) and 65%, 70%, 72% at the end of year 2. The most common reason for discontinuation was withdrawal of consent (19.5%; C013OLE), lack of efficacy (16.6%; C017OLE), and adverse events (12.4%; C021).ConclusionsCenobamate showed high retention rates through an exposure time up to over 7 years (94 months). These results compare favorably with that of other anti-seizure medications.lee.finlan@arvelletx.com
149  Mesial temporal lobe epilepsy with amygdala enlargement: a phenotype of autoimmune epilepsy?
Authors: Glasse Hannah , Hotchkies Angus , Bailey Matt , Mohanraj Rajiv , Cahill Varduhi , Cooper Paul 
Published: May 2022

BackgroundMesial temporal lobe epilepsy with amygdala enlargement (MTLE-AE) is a relatively newly described subtype of focal epilepsy. The aetiology of MTLE-AE remains unclear. We investigated the prevalence of antibodies to neuronal antigens in a cohort of adult patients with MTLE-AEMethodsPatients with MTLE-AE presenting to a tertiary epilepsy clinic were identified. Demographic and characteristic data were collected by review of records. The antibody prevalence in epilepsy (APE2) score was calculated for all patients.Results25 cases of TLE-AE who had undergone antibody testing were identified. 5 cases had positive antibodies (2 VGKC+LGI-1, 1 VGKC alone, 2 GAD). Mean age of epilepsy onset was 46.2 and 35.4 years for antibody positive and negative groups respectively. The antibody positive group had a higher mean APE2 score (6) than the negative group (3.8), partially due to a higher incidence of neuropsychiatric features and prodromal illness. All VGKC positive patients achieved seizure freedom with immunotherapy.DiscussionMTLE-AE may be related to autoimmune processes in a proportion of cases. This potentially treatable cause may be missed in patients with epilepsy, if antibody testing is not undertaken.hannah.glasse@doctors.org.uk
153  Perampanel in patients with a history of psychiatric illness: a post hoc analysis
Authors: Malhotra Manoj , Patten Anna , Kanner Andres M 
Published: May 2022

BackgroundPsychiatric safety data from perampanel randomised controlled trials (RCTs; Studies 304/305/306/335) and open-label extensions (OLEx; Studies 307/335 OLEx) in patients with focal epilepsy with/without psychiatric history were analysed.MethodsTreatment-emergent adverse events (TEAEs) were analysed for patients with/without psychi- atric history.ResultsIn RCTs, 352/2187 (16.1%) patients had psychiatric history; psychiatric TEAEs occurred in 73/244 (29.9%) and 21/108 (19.4%) patients with perampanel and placebo, respectively. Psychiatric TEAEs with perampanel 2 and 4 mg/day were 11.1% and 15.4%, respectively, vs placebo (19.4%). In patients without psychiatric history, psychiatric TEAEs were observed in 157/1325 (11.8%) and 47/510 (9.2%) patients with perampanel and placebo, respectively. Psychiatric TEAEs were more frequent in patients with psychiatric history for all combined doses and placebo (both P<0.01). Most common psychiatric TEAEs with peram- panel: anxiety (5.3%)/insomnia and aggression (both 2.0%) with/without psychiatric history.In OLEx, 283/1895 (14.9%) patients had psychiatric history. Psychiatric TEAEs occurred in 151 (53.4%)/521 (32.3%) patients with/without psychiatric history (P<0.01); most common psychiatric TEAE: irritability (16.3%/10.4%, with/without psychiatric history).ConclusionPsychiatric TEAEs were reported by more patients with psychiatric history and were dependent on perampanel dose irrespective of previous psychiatric illness; 2 mg/day and 4 mg/day doses did not increase psychiatric TEAEs.FundingEisai Inc.manoj_malhotra@eisai.com
157  Efficacy of adjunctive cenobamate: post-hoc analysis in patients grouped by concomitant anti-epileptic drug type
Authors: Brandt Christian , Serratosa Jose , Sanchez-Alvarez Juan , Alvarez-Baron Elena , Finlan Lee , Milanov Ivan , Steinhoff Bernhard J 
Published: May 2022

PurposeThere has been little success with polytherapy for patients with drug-resistant epilepsy. The need for optimizing AED combinations is high. Cenobamate is a novel AED with a unique, dual, complementary mechanism of action (MoA) combining GABA-A positive allosteric modulation (via a binding site different from benzodiazepines) together with broad spectrum sodium channel blockage. Here we assessed the efficacy of cenobamate when combined with AEDs grouped by MoA.MethodsA post-hoc exploratory analysis of the study C017, in adult epilepsy patients with uncontrolled focal onset seizures who had ≥4 seizures/month despite treatment with stable doses of 1–3 AEDs.ResultsIn the maintenance phase, 183/397 (46%) patients were receiving at least one GABA modulator (felbamate, valproate, topiramate, tiagabine, vigabatrin) and 329/397 (82%) a sodium channel blockers (carbamazepine, oxcarbazepine, lamotrigine, lacosamide, eslicarbazepine). Added onto GABA modu- lators, cenobamate 100/200/400mg achieved seizure freedom rates (SFR) of 7.3%/15.6%/30.6% vs 2.1% for placebo; when added onto sodium channel blockers, cenobamate 100/200/400mg/day showed SFR of 2.3%/9.3%/17.5% vs 1.2% for placebo. Both results were statistically significant for 200 and 400mg. A consistent SFR with cenobamate for a subset of patients receiving background levetiracetam (11% 200mg and 25% 400 mg vs 2.5% placebo) as well as those with background benzodiazepines (20% 400 mg vs 0% placebo) occurred.ConclusionsAdjunctive cenobamate achieved significant dose-dependent SFR when combined with AEDs across multiple MoAs in patients with uncontrolled FOS.lee.finlan@arvelletx.com
159  Lessons learned initiating a RCT using an approved drug in a new setting (SPRING Study)
Authors: Grant Robert , Lessels Sarah , Jenkinson Michael , Watts Colin , Marson Anthony , Erridge Sara , Bulbeck Helen , Chisholm Eve Macdonald 
Published: May 2022

BackgroundTrials of approved medications for new indications are becoming increasingly common (repurposing). SPRING – Seizure Prophylaxis IN Glioma is a trial of prophylactic Levetiracetam in adults without prior history of seizure versus no AED. Significant delays were encountered in the set up phase.IssuesLegal contracts between Sponsor and NIHR/UCB (£1.76m) were prolonged.UCB (Belgium) would only transfer drug when ethics had been granted and BREXIT loomed. Company to package levetiracetam required national procurement exercise.Conflicting IRAS advice (Ireland, Scotland, England). Inclusion criteria included patients must have capacity. As patients could lose capacity during study this required Adults with Incapacity REC (Essex), secondary review in Scotland and screening for capacity at each visit. MHRA – mandated monitoring for suicidal ideation at each visit, and detail on contraception during study. HRA – suggested changes to the Patient Information Leaflet and a Schedule of Events Cost Attribution Template – requiring multiple substantial amendments.Neurosurgical centres may feed several oncological departments - site contracts are complex. Electronic eCRF takes time to build and test.ConclusionsConsider planning for longer set up phase in grant submissions. Views expressed are those of the author(s) and not necessarily those of the NHS, NIHR or DOHSC.robin.grant@luht.scot.nhs.uk
Pathological emotionalism following limbic encephalitis: the neural foundations of a novel disorder
Authors: Butler Christopher , Argyropoulos Georgios , Moore Lauren , Loane Clare , Roca-Fernandez Adriana , Lage-Martinez Carmen , Gurau Oana , Irani Sarosh , Zeman Adam 
Published: May 2022

ObjectiveWe investigated pathological emotionalism in a large cohort of patients that had presented with autoimmune limbic encephalitis(a-LE).Methods38 patients in the post-acute phase of a-LE completed questionnaires probing emotion regula- tion. They all underwent structural/functional MRI post-acutely, along with age- and sex-matched healthy controls. We investigated correlations of questionnaire scores with demographic, clinical, neuropsycho- logical and brain MRI data across patients. We also compared patients with pathological emotionalism and those without, along with healthy controls, on grey matter volume, resting-state functional connec- tivity and activity.ResultsPathological emotionalism was reported by 50% of the patients. It was not associated with depres- sion, impulsiveness, or memory impairment. However, it correlated with abnormalities in specific emotional brain networks: volume reduction in the anterior hippocampus, fusiform gyrus and cerebellum, abnormal hippocampal resting-state functional connectivity with the posteromedial cortex and middle frontal gyrus, and abnormal hemodynamic activity in the fusiform gyrus, inferior parietal lobule, and ventral pons.ConclusionsPathological emotionalism is common following a-LE, is not a manifestation of other neu- ropsychiatric disorders, and reflects abnormalities in networks of emotion regulation including, but not limited to the acute hippocampal focus. This condition provides novel insights into the neural basis of emotion regulation and its dysfunction in disease.christopher.butler@imperial.ac.uk
161  Two-centre audit of cannabidiol use in adults with Dravet syndrome
Authors: Silvennoinen Katri , Mantoan Laura , Nashef Lina , Sisodiya Sanjay M , Sidhu Meneka K 
Published: May 2022

BackgroundCannabidiol is a newly-available treatment option for seizures in Dravet syndrome (DS).MethodsAdults in a cannabidiol early access programme at two epilepsy centres were included. Can- nabidiol was titrated up to 20mg/kg, as tolerated. The primary outcome measure was >30% reduction in convulsive seizures assessed at three months of treatment. Secondary outcome measures included later reduction in seizures and incidence of adverse drug reactions (ADRs).ResultsEighteen individuals (seven female; median age 27.5 years) with SCN1A mutation-positive DS took part. Median follow-up was 166 days; nine individuals continued on maintenance treatment. Median maximum dose was 18.6mg/kg/day. Four individuals (22.2%) had a >30% reduction in convulsive seizures by three months; in two, this became evident after three months. ADRs occurred in 14 (77.8%). Commonest ADRs were somnolence and derangement of LFTs (all 18 took concomitant valproate), occurring in eight and seven individuals, respectively. ADRs led to discontinuation in three, including a seizure-free individual. Twelve people (66.7%) required dosage changes to other antiepileptic drugs.ConclusionCannabidiol was effective in a fifth of patients. Two additional patients showed later reduction in seizure frequency, suggesting longer follow-up is warranted. Treatment was complicated by ADRs. Dose adjustments of other antiepileptic drugs may be needed.k.silvennoinen@ucl.ac.uk
162  Cracking the NORSE code
Authors: Midgley Laura , Poole Olivia , Broad Rebecca , Delaj Laura , Flores Lorena , Harikrishnan Sreedharan 
Published: May 2022

This 32 year old Irish traveller presented initially with tremor in his left hand. Blood tests and imaging at the time were unremarkable and he was treated with Botox and Gabapentin to some benefit. Three months later this gentleman presented with status epilepticus requiring intubation and ventilation. Despite escalat- ing anti-epileptic agents in addition to anaesthetic agents he remained in non-convulsive status with an EEG focus in the right temporal-occipital region. MRI showed left posterior parietal, right parietal-occipital and bilateral thalamic signal hyper-intensity. Routine investigations including autoimmune antibodies were unremarkable except for a raised CSF protein and CSF lactate. Crucially, the family later disclosed an extensive family history of epilepsy, including the patient’s niece and nephew, who were both POLG-1 mutation A467T homozygotes. Following initial genetic screening we found our patient to be a POLG-1 mutation A467T heterozygote, which interestingly should not be pathological. Further detailed genetic screening later revealed he was also a POLG-1 W748S heterozygote. As a compound heterozygote this can lead to destabilisation of the linker region of the POLG-1 gene and result in disease, typically causing death in infancy. This gentleman unfortunately remained in non-convulsive status epilepticus despite maximum drug and adjuvant treatments and was subsequently palliated.Laura.midgley1@nhs.net
165  A creepy diagnosis
Authors: Talaei Maryam , MacIver Claire , Pearson Owen R , Pickrell William O 
Published: May 2022

A 44-year-old-female presented with 3 weeks history of sacral anaesthesia, painful left leg paraesthesia and urinary retention requiring intermittent self-catheterisation. A week prior, she had headache, flu-like symptoms and dysuria and received oral antibiotics for E-Coli urinary infection with a negative vaginal swab.She was systemically well. On examination, there was mild left ankle dorsiflexion and plantar flexion weakness, brisk lower limb reflexes and altered sensation in left L5 and bilateral S1 dermatomes.MRI of her whole spine showed subtle signal change in the conus medullaris. CSF revealed 113 white blood cells (80% lymphocytes) with normal protein and glucose and negative oligoclonal bands. Her CT chest,abdomen and pelvis was unremarkable as were: autoimmune and vasculitis screening, serum ACE, vitamin B12, LDH, copper, HIV, syphilis, Lyme, HTLV1&6, Hepatitis B&C, MOG and Aquaporin 4 antibodies.CSF Herpes simplex virus 2 (HSV2) polymerase chain reaction was positive, confirming a diagnosis of HSV2 myeloradiculitis (Elsberg’s syndrome). She was treated with intravenous acyclovir for three weeks with significant clinical response and she was discharged on long-term daily oral acyclovir.Elsberg syndrome is presumed infective (HSV2) acute or subacute bilateral lumbosacral radiculomy- elitis and should be considered in patients with CSF pleocytosis, urologic dysfunction and lumbosacral radiculomyeliitis.maryam.talaei@wales.nhs.uk