bluuebunny/crossref_metadata_2025 huggingface dataset:
236  Systemic mitochondrial dysfunction in monogenic Parkinson’s disease as a potential biomarker for stratification
Authors: Campbell Philip , Harvey John , Morris Huw , Schapira Anthony
Published: May 2022

To investigate the use of PBMCs as a biomarker of mitochondrial dysfunction in Parkinson disease (PD) fresh peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll gradient separation from PD patients with pathogenic biallelic parkin mutations as well as healthy controls (HC). PBMC mitochondrial function was analysed using Seahorse XF respirometry and flow cytometric assessment of mitochondrial membrane potential (Δψm) using TMRE staining.

Nine parkin PD patients (average age 45.2yrs, 66% male) and 41 healthy controls (average age 57.8yrs, 58% female) were sampled for the study. Parkin patients had increased oxygen consumption related to proton leak, reduced maximal respiration and reduced spare respiratory after correction for age (p<0.01). Additionally Parkin patients were found to have reduced resting Δψm and reduced oxygen consumption related to ATP production (p<0.01). Basal oxygen consumption was similar between Parkin patients and healthy controls.

These findings are in keeping with parkin’s role in removing dysfunctional mitochondria through mitophagy. The finding of normal basal oxygen consumption suggests that dysfunction is most pronounced when cells are under stress, during high ATP demand. This ‘signature’ of mitochondrial dysfunction could be applied to idiopathic PD patients to define a mitochondrial subgroup, in which personalised, stratified therapeutics could be targeted.

p.campbell@ucl.ac.uk
246  Timing is everything: improving inpatient levodopa administration at the National Hospital for Neurology and Neurosurgery
Authors: Ceronie Bryan , Stockford Lindsey , Korlipara Prasad , Foltynie Thomas
Published: May 2022

Background

The mainstay of treatment in Parkinson’s Disease (PD) is levodopa replacement therapy. Variation in the timing of administration can lead to worsening motor fluctuations, falls and medical emergencies.

The National Hospital for Neurology and Neurosurgery treats advanced PD patients with complex medical management and deep brain stimulation, admitting up to 250 neurological and 120 neurosurgical PD patients per year.

Methods

We audited the medication administration of PD inpatients over a two month period, aiming to assess the frequency of clinically significant variations and consider how these might be reduced. We included PD patients on levodopa therapy a minimum of 4 times daily, not self-administering medication and admitted for at least 10 days.

Results

A total of 404 episodes of administration were identified. Across all episodes, 18% of levodopa was given later than 30 minutes and 6.5% given more than 30 minutes early. Variations tended to be greater in the neurosurgical division. Survey of the nursing teams identified a number of barriers to timely administration.

Discussion

We plan to implement change by highlighting PD patients at handover, implementing bedside visual aids with medication timings and encouraging the use of medication alarms. The impact of these changes will be re-audited.

bryan.ceronie@gmail.com
Large single-centre cohort of HSP patients in UK: advantages of deep pheno- typing and longitudinal follow-up
Authors: Price Kitty , Mellor James , Mcnamara Mary , Hewamadduma Channa , Shaw Pamela , Derott Christopher Mc- , Hadjivassiliou Marios
Published: May 2022

Aim

To identify clinical, radiological and instrumented gait correlates predictive of natural history in a cohort of HSP patients.

Background

HSP is a rare heterogeneous group of neurodegenerative disorders. We present our experi- ence managing a large cohort of HSP patients in the regional centre for HSP. We believe Sheffield Teaching Hospitals to have the largest cohort in the North of England.

Methodology and Results

Our cohort comprises 426 patients, 246 male (57.7%) of which 290 were geneti- cally characterized. The commonest mutation is in SPASTIN (SPG4, 38.3%), whilst REEP1 (SPG31) and SPG11 mutations make up 3.1% and 2.1% respectively. Sheffield also holds the largest cohort of SPG7 patients in the UK (n=54) accounting for 18.6% of genetic HSP. The remainder have mutations in KIF5A, Atlastin, WASHC5, KIAA0196, NIPA1, ARSACS, CYP27A1, CYP7B1, AP4S1, GBA2 and L1CAM. Over 240 patients have had detailed MR imaging which has identified novel features in HSP. Repeated instrumented gait monitoring and cognitive assessments have shown novel clinical markers suggesting disease progression.

Conclusion

For rare disorders like HSP, specialised clinics optimise comprehensive longitudinal clinical and radiological data collection for large cohorts. This develops local expertise and helps identify novel radiological and clinically relevant biomarkers, enabling better patient care.

klprice1@sheffield.ac.uk
252  Whole exome sequencing in epilepsy: quality of reporting in literature
Authors: Shukralla Arif , Lacey Austin , Naggar Hany El , Cavalleri Gianpiero , Delanty Norman
Published: May 2022

Purpose

Whole exome sequencing is a new rapid and cost effective tool for the diagnosis of the epilepsies.

Method

Our primary aim was to assess the quality of reporting of WES. Secondary aims; to compare the quality of studies based on journal type if recent ACMG guideless have made influenced reporting quality; if any outcome reporting biases exist.

We analysed studies of whole exome sequencing in epilepsy. We used a self-constructed benchmark to quantitatively analyse studies, explore retrospectively if reporting trends have changed.

Results

Total of 307 studies was included. Reporting of data was heterogenous with poor reporting of diagnostic yield in 6% of studies, incidental findings in 11%, variants of undetermined significance in 19%. Predictors of poor reporting included: Journal type, proband status and case reports. Pairwise compari- sons of genetics journals versus other journals using relative risks yielded significant differences in reporting of consanguinity status (RR 1.27 CI 1.04–1.55); variant filtering (RR 1.95 CI 1.41–2.7) and determination of pathogenicity (RR 1.35 CI 1.17–1.56).

Conclusion

Reporting of WES data in the medical literature is heterogenous, making comparisons across studies difficult. Formal structured guidelines similar to the CONSORT guidelines are needed to address this issue further.

arifshukralla@gmail.com
257  A novel case of a possible genetic orthostatic hypotension syndrome
Authors: Kodali Srikirti , Koay Junie Shiwen , Ingle Gordon Thorpe , Iodice Valeria
Published: May 2022

A 60-year-old woman was referred to the Autonomic Centre at the National Hospital for Neurology and Neurosurgery (NHNN) due to longstanding history of orthostatic hypotension (OH).

She was born of non-consanguineous parents and there was no family history of similar problems. Her tolerance for exercise has been significantly low since childhood.

She has a background of schizophrenia, chronic kidney disease and cardiac arrythmias.

She was first seen at the NHNN 30 years earlier and investigated with skin biopsy showing loss of tyrosine hydroxylase and neuropeptide Y.

During a recent admission, the neurologic examination showed bilateral Horner’s syndrome, OH and parkinsonism (possibly drug induced). Autonomic tests indicated selective impairment of adrenergic sympathetic function. Plasma adrenaline, noradrenaline, dopamine and dopamine beta hydroxylase (DβH) levels were undetectable.

The patient is currently being investigated for mutations in genes encoding DβH and CYB561. DβH mutation is unlikely due to the undetectable dopamine. CYB561 gene mutation has been described to interfere with noradrenaline biosynthesis, resembling DβH deficiency.

Both disorders are characterised by orthostatic hypotension, recurrent hypoglycaemia and low noradrena- line levels. Establishing the aetiology might have an impact on management given the response to L-DOPS in patients with mutation of genes involved in noradrenaline biosynthesis.

16sk0577cam@gmail.com
261  Hearing impairment after subarachnoid haemorrhage
Authors: Ashokumar Monica , Campbell Nicci , Galea Ian
Published: May 2022

Subarachnoid haemorrhage (SAH) results in substantial under-recognized clinical sequelae in survivors, including cognitive deficits and psychological issues. In addition, there is emerging evidence that up to 25% of SAH survivors experience hearing impairment after SAH. In a previous small study of 41 patients, we phenotyped this hearing impairment, and found it to be consistent with an acquired auditory processing disorder. Here we use UK Biobank data to conduct a retrospective case-control study of hearing impairment after SAH (n=245 SAH and 160 523 control individuals). Hearing was assessed with the digit triplet test (DTT), a speech-in-noise test. The effect of age, gender, time since SAH, socioeconomic status, noise exposure and ethnicity on the DTT scores in SAH and control groups was controlled for. The results show that there is a statistically significant difference in DTT scores of SAH survivors versus controls. The findings confirm that individuals with a past history of SAH are at greater risk of hearing difficulty. Screening for auditory deficits, which may affect quality of life, is recommended after SAH. monicaashokumar@gmail.com
264  Cognitive and imaging correlates in cerebral amyloid angiopathy subthypes
Authors: Bonifacio Guendalina , Chan Edgar , Islam Afm , Werring David
Published: May 2022

Common clinical subtypes of CAA are CAA with intracerebral haemorrhage (CAA-ICH), with cognitive decline (CAA-cog), and with Transient Focal Neurological Episodes (CAA-TFNE); most studies of cognition and neuroimaging to date have focussed on CAA-ICH. We therefore evaluated the cognitive and imaging phenotypes across all the CAA subgroups.

This is a retrospective cross-sectional study of cognition and imaging in 99 patients; 70 (71%) with CAA and 29 (29%) with presumed hypertensive arteriopathy (non-CAA). We measured impairment across the cognitive domains using a standardised test battery, and we described the imaging biomarkers via visual rating of standardised MRI scans.

Most patients had impairment in more than 2 domains (69%). We found impairment in the executive domain in 71% of patients, followed by non-verbal IQ (59%) and verbal IQ (48%). Patients with CAA-TFNE had similar impairments across cognitive domains to CAA-ICH.

CAA-cog performed worse than CAA-ICH with verbal recognition memory (p<0.05).

With regards to imaging findings, the groups differed significantly for several small vessel disease markers (e.g. moderate to severe cSS in CAA-TFNE compared to CAA-ICH and CAA-cog, >2 lobar CMBs in CAA-ICH and CAA-cog compared to CAA-TFNE).

Our findings confirm high rates of cognitive impairment across CAA subtypes, including CAA-TFNE. The cognitive profile of CAA-TFNE was similar to that of CAA-ICH, despite differences in neuroimaging findings. Hence, the effects of CAA on cognition can occur regardless of the presence of ICH.

guendabonifacio@gmail.com
267  When investigating stroke is a waste of time
Authors: Cook Sarah , Warner Graham
Published: May 2022

Young stroke should alert clinicians to investigate for unusual causes.

A previously well 43-year-old Caucasian female presented with 2 days of punctuated left sided weakness and sensory inattention. MRI demonstrated multiple territory infarcts, predominantly on the right side. With no vascular risk factors, high dose steroids were commenced assuming primary angiitis of the CNS (PACNS). Blood tests including ESR, HIV, an autoimmune and thrombotic screen and blood cultures were negative. A 24-hour ECG and TOE failed to identify an embolic source, though interval MRIs plus CT angi- ography revealed evolving cerebral and splenic infarcts. A DOAC was added. Retinal angiography did not support PACNS, nor did PET-CT though it did show an avid uptake large pelvic mass. Tumour markers CA 125 and CA 19–9 were markedly raised. Urgent gynaecological review was sought but the patient developed florid aortic regurgitation and further cerebral infarcts despite heparinisation. Repeat echocar- diography this time showed a dysplastic aortic valve. Pelvic mass excision confirmed adenocarcinoma.

Non-bacterial thrombotic (marantic) endocarditis (NBTE) is a rare cause of embolic stroke. Systemic wasting from associated malignancy is hinted at in the etymology (Greek.marantikos= to waste away). Our patient remained ‘well’ and only the valve wasted away. Friable valve lesions in NBTE are prone to embolization and removal of the pro-coagulant tumour is the most effective treatment.

sarah.cook18@nhs.net
268  Predicting large vessel occlusion using non-contrast CT brain in patients with acute stroke
Authors: Mcverry Ferghal , McCluskey Gavin , Best Elizabeth , McKee Jacqueline , McCarron Mark
Published: May 2022

Introduction

Detecting large vessel occlusion (LVO)is required to facilitate mechanical thrombectomy in stroke, but angiography is not always routinely available . Hyperdense vessel sign (HVS) and more recently conjugate eye deviation on CT brain have been associated with LVO. Eye deviation and HVS were examined by non-radiologists to determine predictive value for LVO.

Methods

Presence of radiological eye deviation and HVS were examined on brain CT for stroke patients with baseline CT angiography. Eye deviation and HVS were compared to angiographic status .Assess- ments were performed blinded to clinical information and angiographic status.

Results

From 195 cases 122 had large vessel occlusion. HVS sign predicted LVO with PPV of 90.7, specificity 89.2. Eye deviation predicted LVO with PPV 81.7, specificity 74.3. Presence of both HVS and radiologi- cal eye deviation strongly correlated with LVO ;PPV 98.3, specificity 98.6. Thirty cases with LVO had eye deviation without HVS indicating independent predictive value.

Conclusion

Eye deviation and HVS both show high specificity for LVO, particularly when detected in combination. They are rapidly and reliably detected by non-neuroradiologists on CT brain. Eye deviation on CT ± HVS should prompt consideration of thrombectomy even when angiographic imaging is not available given the likelihood of LVO.– ferghalmcverry@doctors.org.uk
Pre-pregnancy and antenatal care of women with epilepsy
Authors: Miah Taief , Mahmud Mohammad , Vardanyan Robert , Arjomandi-Rad Arian , Dhanjal Mandish , Dassan Pooja
Published: May 2022

Background

Epileptic seizures in pregnancy pose a significant risk to both the mother and fetus. There is little evidence of the impact of pre-pregnancy counselling (PPC) and specialist multi-disciplinary antenatal care on a pregnancy.

Objectives

To determine critical components of care in preventing seizures and adverse outcomes in pregnancies of women with epilepsy.

Method

A retrospective cohort study of pregnant women with epilepsy. Participants were seen in the Neuro-Obstetrics multidisciplinary clinic based in West London from 2012 to 2020.

Results

A total of 150 patients; including 242 pregnancies, were analysed. Of these pregnancies, 69 were reported to have had at least 1 seizure. The anti-epileptic drug profiles and dosages were recorded in each group; 71.5% of pregnancies involved anti-epileptic drugs (AEDs), 68.8% of these patients were on mono-therapy and 22.5% were on dual-therapy. Patients without access to PPC or specialist antenatal care had less frequent monitoring of AED levels, fewer dosage adjustments and a higher seizure frequency during the pregnancy. In 9.1% of pregnancies a new AED was started.

Conclusion

These data support the use of PPC in preventing seizures in early pregnancy. The data also shows a reduction in seizure frequency following specialist multidisciplinary antenatal care.

mtm116@ic.ac.uk
Neuro patience: report of the 2018/19 national neurology patient experience survey
Authors: Carr Georgina , McIntosh Katharine , Vibert Sarah
Published: May 2022

The Neurological Alliance’s 2018/19 National Neurology Patient Experience Survey presents a compre- hensive picture of the experiences of people in England living with a neurological condition. The survey ran online and in select neurology clinics between July 2018 and March 2019. The research covers a wide range of topics including diagnosis and information, hospital care, support for mental wellbeing, and access to social care, welfare and employment. With 10,339 responses, it is the largest ever survey of people with neurological conditions in England.

The results show that people with neurological conditions are facing long waiting times, poor access to specialists and a lack of personalised care. The survey also found evidence of failings in the social care and welfare systems, and discrimination in the workplace.

Overall, the findings suggest that care and support for people with neurological conditions must be:

Accessible: the speed of access to specialists must improve overall and should not vary depending on where you live

Personalised and tailored to the needs of each individual

Holistic, addressing people’s mental health, social care needs, and their financial security.

The results are also broken down to regional (STP) level, revealing wide regional variation across all three themes.

georgina.carr@neural.org.uk
COVID-19 and multiple sclerosis: An updated report of the community-based longitudinal UK MS Register study
Authors: Garjani Afagh , Middleton Rodden M , Law Graham R , Tuite-Dalton Katherine , Hunter Rachael , Nair Roshan das , Evangelou Nikos , Nicholas Richard
Published: May 2022

COVID-19 is a concern in people with multiple sclerosis (MS), mostly because of their long-term physical disabilities and immunomodulatory disease-modifying therapies (DMTs). In this community-based pro- spective longitudinal study, we have been monitoring a cohort of people with MS via the web-based platform of the UK MS Register since the start of the COVID-19 outbreak. We report our findings from 17/03/2020 to 15/01/2021.

Out of 7344 participants, 883 (12%) have reported a self-diagnosis of COVID-19 of whom 211 had a confirmed clinical or laboratory-based (n=114) diagnosis. No individual DMT increased the likelihood of contracting COVID-19 (with any of the diagnoses as the outcome). Gender (male: female, adjusted OR: 95% CI [0.94: 0.68–1.3]), web-based Expanded Disability Status Scale score (webEDSS; one-point increase, 0.92: 0.84–1.01), and MS duration (one-year increase, 1: 0.98–1.02) were not associated with contracting COVID-19. Younger age (one-year decrease, 1.04: 1.03–1.06), ethnicities other than white (1.95: 1.13–3.34), and relapsing-remitting MS (versus progressive, 1.72: 2.56–1.16) increased the likelihood of contracting COVID-19. Within a median (interquartile range) of 26 (0–72) days follow-up of participants with COVID-19 (n=532), 69% reported full recovery. A higher webEDSS (one-point increase, 0.84: 0.74–0.96) lowered the likelihood of full recovery. Overall, MS-specific factors do not predispose people with MS to contracting COVID-19, but physical disability can delay recovery.

afagh.garjani@nottingham.ac.uk
Improving the early diagnosis of corticobasal syndrome: a large clinico-pathological study
Authors: Lux Danielle , Morris Huw
Published: May 2022

Background

Corticobasal syndrome is associated with a heterogeneous spectrum of pathologies, with low predictive value for Corticobasal degeneration (CBD) pathology. Here, we validate the Armstrong criteria and interrogate clinical features to improve accurate diagnosis ante-mortem.

Methods

We applied Armstrong criteria to all archived cases with a clinical diagnosis of CBS or CBS- overlap syndrome over disease course. Clinical and radiological features were compared by pathologi- cal substrate.

Results

105 of 123 patients met diagnostic criteria for either Probable or Possible CBS/CBD of whom 38 (36%) had CBD and 79 (75%) had 4-repeat tauopathies (4RT). 3 years from onset, 8/22(36%) of those with Probable CBD and 19/48(40%) Possible CBD had pathology-confirmed CBD, whilst 11/35 (31%) were ‘Armstrong-negative”. Over disease course, PPV for CBD was similar (36%). Criteria were better at predicting 4RT, 82% and 75% within 3 years of onset and over disease course, respectively. Addition of specific language or behavioural abnormalities did not improve PPV. 46% patients met MDS PSP/CBS criteria over disease course, with 92% PPV for 4RT. No individual clinical feature was found to singularly predict underlying pathology.

Conclusion

The Armstrong criteria have low predictive value for CBD both in early disease and over disease course. However, it has >80% prediction of 4RT. A combination of more specific biomarkers are required to improve diagnosis.

d.lux@ucl.ac.uk
Andersen-Tawil syndrome: multi-system deep phenotyping of a large UK cohort
Authors: Vivekanandam Vinojini , Mannikko Roope , Fialho Doreen , Merve A , Pattni J , Marini-Bettolo C , Savvatis K , Behr ER , Hanna Michael , Matthews Emma
Published: May 2022

Andersen-Tawil Syndrome (ATS) is a rare channelopathy caused by mutations in the KCNJ2 gene that encodes the ubiquitously expressed Kir2.1 potassium channel. We describe key findings in a large UK cohort of 52 patients, pertinent to the diagnosis and management of ATS. We report a new point prevalence of

0.105 per 100 000 (increased from 0.08 per 100 000).

While ATS has historically been considered a triad of episodic weakness, cardiac arrhythmias and dys- morphic features, we show that there is considerable variability to this phenotype. Pure cardiac or muscle phenotypes may exist. The absence of dysmorphic features does not exclude the diagnosis. Similarly, a normal long exercise test was seen in five patients.

Importantly, we identify that the phenotype includes a significant risk of cardiac morbidity and mortality with 13% of our cohort requiring cardiac defibrillator or pacemaker insertion and an additional 23% reporting syncope. Syncope has been recently associated with an increased risk of life threatening arhythmic events in this cohort. Severe fixed myopathy was seen in a quarter of our cohort with 14% requiring a wheelchair or gait aid.

We additionally describe novel neurological features and report eight new KCNJ2 variants with in vitro functional data. We provide key clinical insights and management recommendations. We also identify new features which are interesting areas for future research and collaboration.

v.vivekanandam@ucl.ac.uk
SUNFISH Part 2: 24-month efficacy and safety of risdiplam in Type 2/3 SMA
Authors: Baranello Giovanni , Deconinck Nicolas , Mazzone Elena , Vuillerot Carole , Servais Laurent , Gerber Marianne , Kletzl Heidemarie , Yeung Winnie , Martin Carmen ,   et al
Published: May 2022

SUNFISH (NCT02908685) is a multicentre, two-part, randomised (2:1, risdiplam:placebo), placebo-con- trolled, double-blind study in individuals with Type 2/3 spinal muscular atrophy (SMA; inclusion criteria 2–25 years at enrolment). SUNFISH investigates efficacy and safety of risdiplam, a centrally and periph- erally distributed oral survival of motor neuron 2 pre-mRNA splicing modifier. Risdiplam (EVRYSDI™) has been approved by the US Food and Drug Administration for the treatment of individuals with SMA, aged 2 months and older.

In Part 1 (N=51) the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels were assessed. Part 2 (N=180) assessed the efficacy and safety of the Part 1-selected dose of risdiplam versus placebo in Type 2 and non-ambulant Type 3 SMA. Individuals received risdiplam or placebo for 12 months; all individuals then received risdiplam until Month 24, when they had the oppor- tunity to enter the open-label extension phase.

In Part 2, the primary outcome of the study was met, showing a statistically significant difference in change from baseline in 32-item Motor Function Measure total score at Month 12 between individuals treated with risdiplam (n=120) and placebo (n=60). No treatment-related safety findings leading to withdrawal were reported. Here we present SUNFISH Part 2 data after 24 months’ treatment.

g.baranello@ucl.ac.uk

16
Beware: adult-onset and fast-progressing Charcot-Marie-Tooth disease chameleons
Authors: Pipis Menelaos , Doherty Carolynne , Skorupinska Mariola , Laura Matilde , Rossor Alexander , Reilly Mary
Published: May 2022

Differentiating between an acquired and genetic aetiology of peripheral neuropathy poses a challenge to the neurologist. Contributing factors to this include a lack of family history of neuropathy, a rapid progres- sion of the clinical syndrome and/or the presence of features that are considered atypical for inherited neuropathies such as non-length dependent weakness and denervation.

We present 6 patients with genetically confirmed CMT (2 NEFH, 3 MME and 1 TFG), who presented in adulthood with a rapid course of disease progression. The mean age of symptom onset was 37.8yrs (range 33–49) and despite an average disease duration of only 12.8yrs (range 7–16), 50% of patients (3/6) required a wheelchair or stick for mobility. All patients developed significant proximal involvement early on in the course of their disease with half of them having persistent evidence of non-length dependent weakness and denervation. All sporadic cases had CSF examinations and investigations for inflammatory causes of neuropathy, 1 patient had 2 courses of IVIG and another was considered for a nerve biopsy prior to achieving a genetic diagnosis.

Certain adult onset CMT subtypes may mimic acquired neuropathies and in order to avoid missing treatable causes, the pursuit of both diagnostic avenues is often necessary.

m.pipis@ucl.ac.uk
A randomised controlled, trial of the GLP-1 receptor agonist exenatide in idiopathic intracranial hypertension
Authors: Mitchell James , Mollan Susan , Walker Jessica , Lyons Hannah , Yiangou Andreas , torovic Zerin Alimajs- , Grech Olivia , Tsermoulas George , Brock Kristian , Sinclair Alex
Published: May 2022

Background

Pre-clinical data demonstrates the ability of Exenatide, a GLP-1R agonist, to reduce CSF secretion and ICP.1 Existing GLP-1R agonists are widely used to treat obesity and diabetes (but do not cause hypoglycaemia).

Methods

Randomised, placebo controlled, double-blind trial of Exenatide in women with active IIH. Participants were randomised 1:1 to Exenatide (10mcg twice daily sub-cutaneous) or placebo for 12 weeks. Telemetric, intraparenchymal ICP monitors (Raumedic) recorded ICP over 12 weeks. Analysis was by hierarchical regression, significance level set at p <0.1

Results

16 participants were recruited, 15 completed the study: BMI 38.1(6.2) kg/m2, ICP 30.6(5.1) cmCSF. ICP, the primary endpoint, fell significantly (2.5 hours -5.7(2.9) cmCSF (p=0.048), 24 hours -6.4 (2.9) cmCSF (p=0.030) and 12 weeks -5.6 (3.0) cmCSF (p=0.058)). Monthly headache days fell in the Exenatide treated cohort (-7.7 (9.2) p=0.069) and vision improved (logMar acuity -0.1 (0.04) p=0.004).

Conclusions

Exenatide reduced ICP acutely and after chronic dosing. GLP-1R agonists represent a new approach to treat IIH.

1. Botfield HF, Uldall MS, Westgate CSJ, Mitchell JL, Hagen SM, Gonzalez AM, Hodson DJ, Jensen RH, Sinclair AJ. A glucagon-like peptide-1 receptor agonist reduces intracranial pressure in a rat model of hydro- cephalus. Sci Transl Med. 2017 Aug 23;9(404):eaan0972. doi: 10.1126/scitranslmed.aan0972.

jamesmitchell4@nhs.net

20
Yuletide tremor, twitches and tunes
Authors: Talaei Maryam , Ingram Gillian
Published: May 2022

A 53 year old fit and well female was admitted to hospital with rapidly evolving progressive generalised stimulus sensitive myoclonus, axial rigidity and encephomyelitis over five days, two weeks after confirmed diagnosis of SARS-COV-2 infection. On admission to hospital she had generalised myoclonus involving face, voice, trunk, proximal and distal limbs augmented with tactile and auditory stimulus and voluntary movements. A few days later she developed significant axial rigidity, ocular bobbing and encephalitis as well as a myoclonic storm requiring intubation and ventilation. MRI Brain with contrast and CSF exami- nation were unremarkable and an EEG showed no epileptiform discharges. She was started on high dose intravenous steroids followed by 5 courses of plasma exchange. Her COVID serology was positive and other investigations including Glycine, GAD, amphiphysin and DPPX antibodies were negative. She demonstrated significant improvement and was discharged home a week after plasma exchange with the view to wean off steroids over six weeks. This case demonstrates a patient presenting with a rapidly evolving stimulus sensitive myoclonic storm with rigidity and encephalomyelitis two weeks after SARS-COV2 infection, which responded well to prompt immunomodulatory treatment.

maryam

talaei@wales.nhs.uk

22
A case of encephalopathy following a 10k run
Authors: Carstairs Claire , Jaffer Fatima , Brex Peter
Published: May 2022

We present the case of a 47-year-old man who was admitted with unexplained delirium. He had taken part in a 10km running race three days before. He was admitted to intensive care one year earlier having presented with vomiting, seizures and encephalopathy. This occurred after a road trip in the USA with frequent steakhouse visits. No definitive diagnosis was made. His sister died at 57 from a presumed encephalitis after chemotherapy for breast cancer, but the diagnosis was uncertain. On initial examina- tion the patient was delirious but neurological examination was unremarkable. Blood tests revealed a low-grade neutrophilia with a normal CRP; ammonia was high (340 micromols/L); CK was normal; plasma amino acid profile showed a high glutamine level (1237micromol/L). EEG findings were in keeping with moderate encephalopathy. Genetic testing revealed hemizygosity for the X-linked pathogenic c. 118>T p.(Arg40Cys) mutation, indicating ornithine transcarbamylase (OTC deficiency). The patient’s clinical state improved with supportive measures. He was referred to a specialist metabolic disorder clinic and has remained well. OTC deficiency is a rare but important cause of hyperammonaemic encephalopathy, which can be fatal. Targeted family history in cases of encephalopathy may be helpful. Diagnosis allows genetic counselling and successful management with straightforward methods including diet and exercise modification, dietary supplementation and “SOS” formulas for times of acute illness. We explore investiga- tion and management for under-recognised, important, causes of hyperammonaemic encephalopathy.

claire.carstairs@nhs.net
004  Validation of the diagnostic criteria for sporadic Creutzfeldt-Jakob disease
Authors: Watson Neil , Brandel Jean-Philippe , Green Alison , Hermann Peter , Ladogana Anna , chiari Maurizio Poc- , Smith Colin , Summers David , Zerr Inga , Pal Suvankar
Published: May 2022

Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest form of CJD, a universally fatal and rapidly progressive human prion disease. sCJD typically presents with rapidly progressive dementia but can have diverse manifestations. The diagnosis can be challenging. Diagnostic criteria were revised in 2017 to include the real-time quaking-induced conversion (RT-QuIC) assay and cortical ribboning on magnetic resonance imaging (MRI). The aim of this study is to validate the diagnostic criteria, with the secondary aim of evaluating its impact on classification during life and hence case ascertainment. 501 deceased subjects with post-mortem (PM)-confirmed sCJD between 2017–2019 were included from the national registries of the UK, France, Germany and Italy. A control group of 146 subjects with alternative diagnoses at PM was included. Diagnostic test outcomes were recorded. RT-QuIC was 91.6% sensitive and 100% specific. MRI was the second most sensitive (86.8%) and specific (91.9%) investigation. Codon 129 had a significant impact on MRI changes in sCJD (p<0.001). Subjects were classified during life according to the previous and updated criteria to assess the impact on ascertainment. Revised criteria increased in-life sCJD diagnosis rates by 22.4%. In conclusion, the diagnostic criteria are highly sensitive and specific, allowing effective differentiation of sCJD from potentially treatable mimics, and enhancing in-life sCJD diagnosis.

neil

watson@nhslothian.scot.nhs.uk

27
005  Automated classification of inter-ictal EEG in the diagnosis of epilepsy
Authors: Ahmed Rohan , Pegg Emily , Taylor Jason , Mohanraj Rajiv
Published: May 2022

Background

Diagnosis of epilepsy is based on descriptions of attacks, supported by finding epileptiform activity on EEG. Routine EEG can detect inter-ictal epileptiform discharges (IEDs) in approximately 50% of patients with epilepsy, and approximately 1% of the general population can have IEDs without ever developing epilepsy. The lack of a reliable biomarker is a factor in the high misdiagnosis rate of epilepsy. The EEG carries a wealth of information on brain activity, which cannot be discerned by visual analysis. Advanced EEG analysis with machine learning approaches hold promise in unlocking additional useful information contained in the EEG signal.

Methods

20 patients with idiopathic generalised epilepsy and 20 age-matched controls underwent a 64-channel EEG. After pre-processing, a 20 second epoch of resting state, eyes closed EEG free from IEDs and artefact was used for analysis. Band-pass filtered EEG was used to construct functional connectivity matrices by calculating phase locking value (PLV) between electrode pairs. Connectivity matrices were analysed by a machine learning algorithm to classify patients into epilepsy and controls.

Results

The ML classifier achieved a classification accuracy of 60% between patients with epilepsy and normal controls.

Conclusions

Automated machine learning analysis has the potential to improve the diagnostic utility of EEG in epilepsy. Alternatives to functional connectivity matrices will be explored in future studies with the objective of improving classifier performance.

rohanahmed92@gmail.com
010  Seizure semiology of frontal lobe epilepsy (FLE): a report of two cases with video-telemetry recordings
Authors: Gurney Rowan , Rugg-Gunn Fergus , Sidhu Meneka
Published: May 2022

Frontal lobe seizures can be difficult to distinguish from non-epileptic seizures or sleep disorders. Addition- ally, the ictal EEG is often normal. To illustrate the challenging semiology and frequent misdiagnosis of FLE we discuss two patients, accompanied by video-EEG from the Chalfont Centre for Epilepsy.

Case 1, a 41-year-old man with right frontal lobe focal cortical dysplasia presented with stereotyped nocturnal focal motor seizures that were associated with right frontal epileptic discharges. Seizures manifested as contralateral head version and tonic posturing of the upper limbs; the characteristic “fencing posture” described in seizures involving the supplementary motor area. In some, these evolved to hyperkinetic seizures.

Case 2, a 23-year-old woman with multiple cavernous haemangiomas secondary to KRIT1 gene mutation, presented with stereotyped bipedal cycling movements of the lower limbs and loss of awareness, without associated ictal EEG change. These episodes were previously mis-diagnosed as non-epileptic but were confirmed as epileptic seizures from a right frontal lobe cavernoma.

The unusual semiology of FLE represents a diagnostic challenge, which cannot always be resolved with ictal EEG recordings. FLE should be considered with episodes which are nocturnal, brief, stereotyped, motor predominant with, or without, awareness, and often with bilateral upper limb posturing or hyper- kinetic movements.

rowan

gurney1@nhs.net

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013  Validation of an algorithm identifying epilepsy related hospital admissions from routinely collected administrative data
Authors: Mitchell James , Zammit Louise , Kallis Constantinos , Dixon Pete , Grainger Ruth , Powell Graham , Marson Tony
Published: May 2022

Routinely collected administrative datasets can be used to identify healthcare resource use and inform strategic planning and policy development. We evaluate a new comprehensive epilepsy admission algorithm using ICD-10 coding data from these administrative datasets against a gold standard and existing admission identification algorithms.

All consecutive admissions to a large UK general hospital meeting predefined criteria were identified over a one-month period. Case note review was performed by independent clinicians and admission classi- fied as epilepsy or not epilepsy related. The Liverpool algorithm and a widely used comparator algorithm were applied to the ICD-10 administrative data and compared to clinician classification.

In total 205 admissions were identified. Case-note review (gold standard) identified that 35 cases were epilepsy related admissions, and 156 were not epilepsy related. It was not possible to classify 14 admis- sions due to missing or insufficient data. The Liverpool algorithm incorrectly classified only 17 out of 191 admissions compared to 30 incorrectly classified admissions from a comparator algorithm. The Liverpool algorithm demonstrates sensitivity of 85.7% and specificity of 92.3%.

Whilst no perfect algorithm is likely to exist, the Liverpool algorithm identifies hospital admissions due to epileptic seizures using administrative data with improved sensitivity and specificity compared to previous methods.

james.mitchell@liverpool.ac.uk
015  Long-term (1-year) seizure freedom with adjunctive perampanel in paediatric patients with epilepsy: study 311
Authors: Flamini Robert , Patten Anna , Malhotra Manoj , Ngo Leock Y
Published: May 2022

Background

Long-term (1-year) seizure-freedom rates with adjunctive perampanel were assessed in paediatric patients aged 4–<12 years with focal-onset seizures (FOS) (with/without focal to bilateral tonic-clonic seizures [FBTCS]) or generalised tonic-clonic seizures (GTCS) during Study 311 (NCT02849626).

Methods

Seizure-freedom rates (FOS, FBTCS, GTCS) were assessed in patients who achieved seizure freedom during the Core Study Maintenance Period and then remained seizure free for up to 12 months (calculated from the start of their seizure-free period). Data were stratified by concomitant enzyme- inducing anti-seizure medications (EIASMs) (with and without) and age (4–<7 and 7–<12 years).

Results

For FOS, 6/11 (54.5%) patients remained seizure free for 12 months (with EIASMs, n=2/5 [40.0%]; without EIASMs, n=4/6 [66.7%]; 4–<7 years, n=0/1; 7–<12 years, n=6/10 [60.0%]). For FBTCS, 1/5 (20.0%) patient(s) remained seizure free for 12 months (with EIASMs, n=0/1; without EIASMs, n=1/4 [25.0%]; 4–<7 years, n=0/2; 7–<12 years, n=1/3 [33.3%]). For GTCS, 3/7 (42.9%) patients remained seizure free for 12 months (all 7–<12 years, n=3/6 [50.0%]; no GTCS seizure-free patients received EIASMs).

Conclusion

Despite small patient numbers, seizure-freedom rates are maintained during long-term (1-year) perampanel treatment in paediatric patients, consistent with analyses in adolescents/adults.

Funding.Eisai Inc. stella_ngo@eisai.com
020  Post-operative seizure semiology and scalp EEG changes in a case of right temporal lobe epilepsy
Authors: Sim Nicholas Keyi , Singh Rinki , Maguire Melissa
Published: May 2022

We report a case of changing semiology of intractable right temporal lobe epilepsy. The patient’s semiology of ictal spitting, altered awareness, automatisms and occasional secondary generalization remained stable for many years. 3T MRI head was normal, and subsequent advanced imaging and neu- rophysiology localised the seizure focus to the right temporal lobe and surrounding regions. He received a right temporal lobectomy, with subsequent redo surgery due to incomplete margins. These did not confer seizure freedom. Subsequently his seizure semiology changed to episodic fluent dysphasia with preserved awareness. This was correlated with scalp EEG changes now showing lateralisation to the bilateral temporal lobes.

This case demonstrates that seemingly unilateral temporal lobe epilepsy may arise from bilateral networks, which can manifest for years from one hemisphere. It is also possible that extra-temporal origin seizures (for example from perisylvian, fronto-basal or parietal locations) can manifest with temporal-like semiology and can spread to either temporal lobe, and thus can be a cause of epilepsy surgery failure.

nchlasim@doctors.org.uk

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024  Predicting outcome using patient reported outcomes (PRO) in the UK Parkinson’s disease tissue bank
Authors: Leslie Rebecca , Tilley Benison , Romozzi Marina , Nicholas Edward , Gentleman Steve , Nicholas Richard
Published: May 2022

Background

Prognostic tools in Parkinson’s disease (PD) focus on physician’s assessments. The United Kingdom Parkinson’s disease tissue bank (UKPDTB) has developed a 100-question PRO, the Imperial College London donor questionnaire (ICLDQ).

Objectives

To investigate whether particular ICLDQ questions can predict survival.

Methods

Responses to the ICLDQ Likert scale (scored 0–3) were collected in PD and controls. Using logistic regression modelling we investigated the relationship between responses and survival in PD. Models were tested on an additional sample of PD patients in the UKPDTB.

Results

159 responses in PD and 203 controls were analysed. 75 participants with PD and 0 controls had died since questionnaire completion. Cox regression produced a model of five questions for predicting survival (Concordance=0.751). Questions were divided into symptom categories and two models were generated. One combined sleep and self-care (Concordance=0.661), another combined self-care and autonomic dysfunction (R2=0.1544). When tested on the additional PD sample (n=63), the model combining sleep and self-care was the most effective for predicting survival.

Conclusions

PROs can predict prognosis in PD. High correlation between questions suggests an abbre- viated questionnaire would be beneficial. Difficulties with self-care have been linked with poor survival, our findings support this.

rml1u16@soton.ac.uk

37
025  Keeping time: ward-based interventions improve levodopa administration at the National Hospital of Neurology and Neurosurgery
Authors: Levee Viva , Iqbal Sabahat , Ceronie Bryan , Saifee Tabish , Korlipara Prasad , Foltynie Thomas
Published: May 2022

Background

The National Hospital for Neurology and Neurosurgery admits Parkinson’s disease (PD) patients for medical management and deep brain stimulation, as well as non-PD inpatients on levodopa with dystonia or atypical Parkinsonism. Previous work showed 24.5% of administrations were outside of the recommended 30-minute time window.

Methods

We introduced interventions based on the Leeds Quality Improvement Project “Get it Right on Time”, adapted for local protocols and focused questionnaires. Due to cancellation of elective PD admissions during the SARS-CoV-2 crisis, we included all inpatients on levodopa. We tested differences between pre-intervention and post-intervention groups using Chi-squared (χ2), with post hoc comparisons to examine individual time categories.

Results

We compared 177 post-intervention administration episodes to 404 in the pre-intervention group. Across all time categories, we found a significant change in administration timings between groups (χ2=35.9, p<0.001). This was driven by an increase in levodopa given on time, from 11.4% to 23.2% (p<0.001) and a decrease in levodopa given up to 15 minutes late, from 31.2% to 17.5% (p<0.001).

Conclusion

Ward-based interventions improve timely levodopa administration. Including non-PD patients altered the study population and may have impacted results. Further work includes surveying staff to identify additional interventions and investigating a PD-only cohort.

vivalevee@gmail.com
028  Cortical sensorimotor representations remain normal in musicians’ dystonia despite global deficit in dexterity
Authors: Sadnicka Anna , Wiestler Tobias , Butler Katherine , Edwards Mark , Ejaz Naveed , Diedrichsen Jorn
Published: May 2022

Musicians’ dystonia presents with a persistent loss of motor control during musical performance. The pre- dominant hypothesis is that this loss of motor control is underpinned by maladaptive neural changes to the somatotopic organization of finger representations in primary somatosensory cortex. Here, we tested this hypothesis by investigating the finger-specific activity patterns in the primary somatosensory (S1) and motor cortex (M1) using functional magnetic resonance imaging with state-of-the art multivariate analyses in 11 musicians with dystonia and 9 healthy musicians. We also characterized their dexterous finger control to investigate whether the deficit is strictly limited to musical performance or also generalizes to a non-musical task. We report two key findings. First, during the production of individuated finger presses, musicians with dystonia showed a small, but robust loss of motor control. This deficit was characterized by both a reduction in finger individuation ability, and an exaggeration of mirror movements primarily during use of the clinically identified symptomatic hand, but also to a lesser extent during asymptomatic hand use. Second, we found no evidence of disease-related changes in the corresponding finger representa- tions in S1/M1. Our results contradict the view that abnormalities in sensorimotor finger representations play a role in the pathophysiology of musicians’ dystonia. Our behavioral results also suggest that the loss of finger dexterity in musicians’ dystonia expresses along a spectrum with subtle abnormalities in motor control evident during ordinary dexterous tasks.

asadnick@sgul.ac.uk|ABN Bursary

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031  Left internal carotid artery dissection presenting as an isolated left hypoglossal nerve palsy
Authors: Hanbury Georgina , Baheerathan Aravindhan , Auger Stephen , Patel Maneesh , Gabriel Carolyn
Published: May 2022

A 33 year old male with no significant past medical history presented to the emergency department with an acute onset 4 day history of an odd sensation over his tongue and slurring of his speech. He had noted that his tongue deviated to the left when he stuck it out. There was no headache and no taste disturbance.

Clinical examination revealed a left sided hypoglossal nerve palsy. Sensation of the tongue to pin-prick and taste was normal. There was no Horner’s syndrome.

CT Angiogram of aortic arch and carotid vasculature demonstrated marked irregular calibre and increase in wall thickness of the left internal carotid artery (ICA), just adjacent to the external aperture of the hypoglossal canal, in keeping with a localised left ICA dissection. There was no clinical or radiological evidence of infarction. He was treated with high-dose anti-thrombotic treatment.

An acute isolated hypoglossal nerve palsy as a sequelae of a high ICA dissection is a rare but well docu- mented clinical presentation. The hypoglossal nerve is vulnerable to compression as it passes between the internal jugular vein and internal carotid artery at the skull base. It is crucial that neurologists and stroke physicians swiftly recognise this clinico-radiological syndrome to facilitate prompt, appropriate investigation and commencement of appropriate treatment.

aravindhan.baheerathan1@nhs.net