bluuebunny/crossref_metadata_2025 huggingface dataset:
137  Accuracy of using administrative data to identify epilepsy cases: a systematic review of validation studies
Authors: Mbizvo Gashirai K , Bennett Kyle , Schnier Christian , Simpson Colin R , Duncan Susan E , Chin Richard FM
Published: May 2022

Purpose

To ascertain the accuracy of using administrative healthcare data to identify epilepsy cases.

Method

We searched MEDLINE and Embase from 01/01/1975–03/07/2018 for studies evaluating the diagnostic accuracy of administrative data in identifying epilepsy cases using any disease coding system. Two authors independently screened studies, extracted data, and quality-assessed studies. We assessed PPV, sensitivity, NPV, and specificity. The primary analysis was narrative.

Results

Thirty studies were included between 1989–2018. Risks of bias were low, high, and unclear in four, 14, and 12 studies, respectively. Coding systems included ICD-9, ICD-10 and Read Codes, with or without antiepileptic drugs (AEDs). PPVs included ranges of 5.2–100% (Canada), 32.7–96.0% (US), 47.0–100% (UK), and 37.0–88.0% (Norway). Sensitivities included ranges of 22.2–99.7% (Canada), 12.2–97.3% (US), and 79.0–94.0% (UK). Nineteen studies contained ≥1 algorithm with a PPV >80%. Sixteen studies contained ≥1 algorithm with a sensitivity >80%. PPV was highest in algorithms consisting of disease codes (ICD-10 G40–41, ICD-9 345) in combination with ≥1 AED. The addition of symptom codes to this (ICD-10 R56, ICD-9 780.3, 780.39) lowered PPV. Sensitivity was highest in algorithms consisting of symptom codes with ≥1 AED. Whilst using AEDs alone achieved high sensitivities, the associated PPVs were low. Most NPVs and specificities were >90%.

Conclusion

In the first global systematic review of this topic, we conclude that it is reasonable to use administrative data to identify people with epilepsy in epidemiological research.

mbizvogkm@gmail.com
144  Brain tumour related epilepsy with co-existing non epileptic attacks: characteristics of a clinically challenging cohort
Authors: Samarasekera Shanika , Liang Di
Published: May 2022

Background

The co-existence of non epileptic attacks (NEAD) in patients with brain tumour related epilepsy (BTRE) is poorly described. Non epileptic attacks (NEAD) co-occur in up to 30% of patients with epilepsy (PWE) [SS1] . Adverse life events are associated with development of NEAD; their co-occurrence in those with BTRE is potentially un-surprising .

Methods

Clinical trajectories of patients with BTRE and co-existing NEAD were characterised. The diagnosis of NEAD was based on specialist’s observation of attacks and/or capture of attacks on video. Patients had been referred because of persisting symptoms in spite of escalating antiepileptic therapy.

Results

Of seven patients, six developed NEAD following development of BTRE. One developed NEAD de novo following tumour biopsy. Onset of NEAD was not temporally linked with the diagnosis of a brain tumour. In five, NEAD onset occurred when seizures were controlled (< 1 seizure/month). All seven nev- ertheless reported fear of developing uncontrolled seizures and identified their NEAD as more disabling than their epilepsy.

Six were initially misdiagnosed with escalating seizures. Patients were eventually managed with polytherapy (two found adjunctive clobazam helpful) and behavourial strategies including mindfulness.

Conclusion

NEAD can co-occur with BTRE and should be considered where seizure type symptoms are escalating.

[SS1]S.R. Benbadis, W.A. HauserAn estimate of the prevalence of psychogenic non-epileptic seizures.

Seizure, 9 (2000), pp. 280–281 shani@doctors.org.uk
Atomoxetine and citalopram alter brain network organisation in Parkinson’s disease
Authors: Borchert Robin , Rittman Timothy , Rae Charlotte , Passamonti Luca , Jones Simon , Vatansever Deniz , Rodríguez Patricia Va´zquez , Ye Zheng , Rowe James ,   et al
Published: May 2022

Recent evidence has shown potential cognitive benefits in Parkinson’s disease from restoring neuro- transmitter deficits including noradrenergic and serotonergic transmission. Here, we study global and regional brain network organization using task-free imaging, which minimizes performance confounds and the bias towards predetermined networks. Thirty-three patients with idiopathic Parkinson’s disease were studied three times in a double-blinded, placebo-controlled crossover design, following placebo, 40mg oral atomoxetine or 30mg oral citalopram. Seventy-six controls were scanned without medication to provide normative data. Relative to controls, patients on placebo had executive impairments, which was reflected in dysfunctional network dynamics in terms of reduced clustering coefficient, hub degree and hub centrality. In patients, atomoxetine improved fluency in proportion to plasma concentration (P=0.006, r2=0.24), and improved response inhibition in proportion to increased hub Eigen centrality (P=0.044, r2=0.14). Citalopram did not improve fluency or inhibitory control, but its influence on network integration and efficiency depended on disease severity: clustering (P=0.01, r2=0.22), modularity (P=0.043, r2=0.14) and path length (P=0.006, r2=0.25) increased in patients with milder forms of Parkinson’s disease, but decreased in patients with more advanced disease (UPDRSIII>30). This study supports the use of task-free imaging of brain networks in translational pharmacology of neurodegenerative disorders. We propose that hub connectivity contributes to cognitive performance in Parkinson’s disease, and that noradrenergic treatment strategies can partially restore the neural systems supporting executive function.

robinborchert@gmail.com
152  Automating the assessment of first seizure care pathways and clinical outcomes using electronic patient records
Authors: Shek Anthony , Theochari Evangelia , Searle Thomas , Kraljevic Zeljko , Viana Pedro , Bruno Elisa , Teo James , Dobson Richard , Richardson Mark P
Published: May 2022

Purpose

Electronic Patient Records (EPR) are ideal sources of information to provide evidence for the optimisation of health management. However, beyond direct patient care, their use for secondary purposes such as research or service improvement has been limited.

Aims

We aimed to explore the feasibility of using novel patient data analytics tools (CogStack & MedCAT) at King’s College Hospital trust (KCH) to identify suspected first seizure patients and compare their man- agement against NICE guidelines.

Method

We utilised CogStack to search 1.4 billion EPR documents at KCH to identify suspected first seizure patients. We then retrieved their subsequent records, and used a combination of manual extraction and a natural language processing tool (MedCAT), to extract information about their symptomatic presenta- tion, final diagnosis, timing of investigations, and specialist appointments.

Results

226 patients attended the emergency department with suspected first seizures. MedCAT could be feasibly trained with expert knowledge to increase the accuracy of automatically extracting relevant textual information from EPR. Our analysis of patient records identified steps in the clinical pathway that frequently fell short of the NICE guidelines.

Conclusion

EPR are feasible to be mined at scale for the rapid analysis of service demand and monitoring patient health trajectories. The insights of this study have been used to improve first seizure management in KCH, demonstrating the value of NLP application in healthcare.

anthony.shek@kcl.ac.uk

107
168  Asymptomatic dengue illness complicated by Guillain Barre syndrome
Authors: Siddiqui Sarah , Midgley Laura , Poole Olivia , Redmond Ian , Alkufri Fadi , Harikrishnan Sreedharan , Moran Nicholas
Published: May 2022

Arboviral infection Dengue can cause a spectrum of disease varying from asymptomatic illness to dengue fever to the severe dengue hemorrhagic fever. Neurological complications are rarely reported in the lit- erature (0.5–6%), mostly from dengue-endemic areas in tropics and subtropical regions. We report a case of a 59-year-old man who returned from a recent work-related travel from India. Three weeks following a mild viral prodrome, he developed bilateral lower motor neuron facial palsy with absent deep tendon reflexes. CSF showed albuminocytologic dissociation and electrophysiological studies showed demyeli- nating neuropathy. Routine GBS screen for common etiological viruses was negative and subsequently additional testing based on recent travel was performed which showed positive Dengue IgM and RNA in serum. The patient was treated with plasma exchange for 5 days and his facial weakness improved to a great extent.

This case demonstrates the importance of considering arboviral infections such as Dengue in patients with GBS particularly in people living in or travelling from endemic areas. Additionally, like many other viral illnesses, there may not be clear clinical evidence of Dengue fever and the prodrome may go unnoticed and undiagnosed, hence a high index of suspicion is required.

s_hasan_s@yahoo.com
169  Adult brainstem glioma mimicking as a neuro-infectious process: case report and literature review
Authors: Wu Kit , Coulden Amy , Mahmood Amira , Kentley Jonathan , Salam Sharfaraz , Ghosh Rhia , Reisz Zita , Bodi Istvan , Britton Tom
Published: May 2022

Background andAim

Brainstem gliomas are rare, accounting for less than 2% of adult gliomas. They are difficult to diagnose and challenging to treat [Hu et al, 2016]. Here, we report a patient with an unusual clinical presentation of brainstem glioma, supported by radiological and histopathological findings.

Clinical presentation

A 61-year old male retired diver presented with 2-month history of worsening occipital headache, described as a constant pressure worse on lying down with migrainous features of nausea and light-sensitivity, and intermittent episodes of double vision and poor balance.

Neurological examination on admission was normal. He progressed to develop double vision, left-sided weakness and worsening swallowing and respiratory function.

Investigations

Blood tests for infections and vasculopathy were negative. Two CSF samples taken showed high protein (1.7g and 3.25g respectively) with the first showing 100% lymphocytes and the latter 56% monocytes and 42% lymphocytes. There were no malignant cells on immunophenotyping.

MRIs demonstrated progressive of ring-enhancing lesions in brainstem in keeping with inflammatory con- ditions. Biopsy was not possible due to the centrally-located lesions. Despite receiving wide spectrum antimicrobials, steroids and respiratory support, he died 2 months later. Autopsy of the brain showed a glioblastoma with brainstem infiltration and cystic necrosis in the pons.

Gliomatosis pattern and leptomeningeal and nerve root spreading of brainstem glioblastoma can be misleading signs with neuro-infections as a differential. Early neurosurgical intervention may aid diagnosis.

kitwu@doctors.org.uk
171  Systemic infections and acute admission in long-term neurological conditions
Authors: Saldanha Ramos Ana Rita , Varatharaj Aravinthan , Galea Ian
Published: May 2022

Background

People living with a long-term neurological condition (LTNC) make up nearly one-fifth of hospital admissions in the UK. Though LTNCs are diverse, the common trigger for deterioration is often systemic infection. More data on the problem is required to inform service planning.

Methods

The case notes of 157 consecutive patients with an LTNC presenting to University Hospital South- ampton for urgent care, were reviewed, as part of an ongoing and prospective service evaluation. Data was collected on mode of presentation, acute diagnosis, specialty input, length of stay, complications, and change in social needs.

Results

Dementia (43%) and stroke (27%) were the most common LTNCs. Systemic infection was the trigger for admission in 52% of patients. The mode of presentation was most commonly deterioration in func- tional abilities and cognition. Mean length of stay was 5.7 days. Care needs increased in 11% of patients.

Conclusion

This data provides a snapshot of the urgent care needs of people with LTNCs, which should help inform future service planning. In particular, the impact of systemic infection is significant and strate- gies to mitigate this are discussed.

ritaramos.jc4@gmail.com
172  Quality improvement project on the peri-procedural management of lumbar punctures
Authors: Mousele Christina , Gillingham Alexandra , Mummery Catherine , Carr Aisling
Published: May 2022

Introduction

Cancellation rate of elective lumbar punctures (LPs) due to inappropriate management of antithrombotic medications and lack of adequate training of junior doctors in the peri-procedural man- agement of LPs encouraged us to conduct a quality improvement project aiming to address these issues.

Methods

Retrospective review of day case elective LPs (01/10/2018 - 01/01/2019) Junior doctor surveys aiming to assess LP related knowledge and confidence

Results

37.5% (75/200) of the scheduled LPs were cancelled due to mistakes in the pre-procedural man- agement of patients’ blood-thinning medication. Junior doctors’ knowledge of consent and antithrom- botic management was suboptimal. As was self-reported confidence and competency in independent performance of LPs at CMT/SHO level.

Change implemented

Implementation of Trust-approved Guidelines on peri-procedural management of LPs based on systematic review of literature

LP training clinic

Re-audit.LP cancellation rate fell to 8% after implementation of these measures (15/04/2019 - 15/07/2019) with meaningful improvement in LP knowledge/confidence of junior doctors. christinamousele92@gmail.com
177  Outpatient letter writing in the neurology department
Authors: Lock Felicity , Wardle Mark
Published: May 2022

Objective

As a predominantly outpatient-based specialty, neurology clinic letters are a vital, yet often overlooked, communication tool. This study aims to evaluate whether current Neurology outpatient letters in University Hospital of Wales meet the standards suggested by the Academy of Medical Royal Colleges and the Professional Records Standards Body.

Methods

An assessment proforma was created based on the standards. A retrospective sample of consult- ant letters from General Neurology, Epilepsy and Multiple Sclerosis outpatient clinics throughout January 2019 were assessed. 2–4 letters were randomly selected from each clinic, aiming for equal numbers of follow-up and new cases.

Results

187 clinic letters were assessed, from 12 different anonymised consultants. Letters universally achieved ‘mandatory’ PRSB headings, fewer meeting non-mandatory headings. There was a wide variety in style and content, with consultants’ mean word counts ranging from 89 to 537. Turnaround delay between clinic and typing ranged from 0 to 79 days, with 79.7% of letters copied to the patient.

Conclusion

Though mandatory content was achieved, consistency and clarity often lacked. Present- ing the results at audit meeting prompted much interest and discussion. Many supported implementing a departmental letter structure and exploring reducing turnaround delay to improve the quality and efficiency of outpatient letters.

LockFJ@cardiff.ac.uk
179  Improving respiratory screening and NIV assessment in motor neuron disease
Authors: Rice-Wilson Daniel , Ealing John
Published: May 2022

Motor neurone disease (MND) commonly causes death from respiratory muscle weakness. Non-invasive ventilation (NIV) is currently the most life-prolonging treatment, and its inclusion in NICE guidelines has increased respiratory function testing, respiratory referrals and usage. Earlier referral to respiratory services results in more hospital appointments before NIV initiation. We aimed to assess whether patients were receiving NICE-compliant respiratory screening and calculate the NIV uptake rate of those referred. We also sought to measure the effect of NIV on survival. We retrospectively examined 194 patient records from the SRFT MND care centre between 1st January and 31st December 2016. A Kaplan-Meier analysis was used to calculate survival. All appropriate patients received NICE-compliant respiratory screening, with 27% patients referred for NIV. Of those referred 33% were started on NIV at initial assessment, and 12% during follow up. Non-invasive ventilation increased survival by 265 days. The result of NICE-compli- ant practice is a low rate of NIV uptake, burdening patients and services with extra appointments. NIV significantly increases life expectancy and patients must receive it as soon as it is indicated. We plan to incorporate NIV assessment by respiratory physicians within the MND clinic to complement the screening process and reduce unnecessary referrals.

daniel.rice-wilson@nhs.net
185  An assessment of perceived gender disparity in platform and poster presenters at ABN conferences
Authors: Patel Faheemah , Lawrence Joanne
Published: May 2022

Background anecdotal observation of Edinburgh 2019 platform presenters suggested reduced repre- sentation of female neurologists. We compared the gender distribution of authors with the 2018/19 RCP Census1; 33% of consultant and trainee neurologists were female, but this varied with status (29% consult- ant, 44% trainee neurologists being female1).

Method

2015–2019 authors sorted by position, then gender attributed to first names using online databases including genderize.io. The proportions of first, last and other female authors were compared with RCP data1 for consultant and trainee neurologists.

Results

In 2019, women accounted for 39% of all abstract authors, 41% of first authors and 29% last authors. Gender distribution generally reflected that of the RCP census*, particularly when adjusted for status, given the dominance of early career researchers (ECR) as first authors and consultant neurologists as last authors. Female first author numbers peaked in 2018 (50% of first authors for all abstracts, 55% for all ECR abstracts, 49% for ECR platforms) but fell to 41%, 45% and 35% respectively in 2019.

Conclusion the gender distribution of ABN abstract authors typically correlates well with that of UK neurolo- gists reported in the RCP census*. However Edinburgh2019 saw a significant drop in abstracts submitted by women. Contributing factors for investigation include the influence on attendance of accessibility from other neuroscience centres.

faheemah.patel@abn.org.uk
187  Variation in training: Results from a survey of UK neurology trainees
Authors: Ross Russell Amy L , Zarkali Angeliki , Shribman Samuel , Alexander Sian K , Warner Thomas T , Jones Matthew , Pereira Anthony , Hughes Tom AT , Kipps Christopher , Mummery Catherine J
Published: May 2022

Background

Neurology training in the UK is governed by a national curriculum defining the outcomes every trainee must achieve. However, the delivery of neurology training and trainee satisfaction differs significantly across the UK1.

The Association of British Neurologists Trainees (ABNT) recently completed a qualitative study of the highest and lowest performing trusts for neurology training across the UK and identified key indicators associated with trainee satisfaction2.

Aim

To establish the variation in these indicators across the country.

Methods

We conducted a survey of UK neurology trainees to audit regional performance against the indicators identified in the previous qualitative study.

Results

We had responses from 50 trainees, covering all deaneries.

There was consultant supervision reported >98% of the time. 56% of supervising consultants were on-site during working hours, and 66% were present during clinics. In 74% of cases, the supervising consultant for inpatient referrals also had pre-booked clinics.

Adaptation of daily roles according to trainee level was only reported by 26% of trainees, with <20% reponses reporting variation in clinic lists, or examples of ST3 shadowing.

52% of trainees were required to relocate during training.

There was significant variation within deaneries, suggesting these factors are often determined at a trust level.

1. Shribman S, Alexander SK, Zarkali A, et al. doi:10.1136/practneurol-2018–002129 amyrossrussell@gmail.com
190  Placebo – to use or not to use? Survey on the use of placebo treatments
Authors: Huys Anne-Catherine ML , Franklin Hannah D , Bhatia Kailash P , Stone Jon , Edwards Mark J
Published: May 2022

Patients´ and healthcare professionals´ attitudes to deceptive and open-label placebo treatments in clinical practice were evaluated by means of an anonymous survey.

The overall attitude to deceptive placebo treatments was favourable amongst the 310 neurological patients and 100 medical patients/healthy participants taking part in the survey. The 90 healthcare pro- fessionals and 140 patients with a functional neurological disorder were more conservative, with equal numbers being in favour and against.

An even more crucial factor is the considerable percentage being strongly opposed to deceptive placebo

– 16% of neurological patients and 30% of patients with a functional neurological disorder.

The majority of healthcare professionals had never used deceptive placebo, with an even smaller pro- portion ever having used open-label placebo. There was marked scepticism with regards to open-label placebo in all groups, with the general underlying belief that open-label placebo is fairly ineffective

The prohibition of deceptive placebo use in the UK seems to be in line with general concerns and oppo- sition to placebo. Future studies will show if the negative attitude to open-label placebo is justified or if this ethically viable option deserves more consideration.

The survey is ongoing (to take part, visit https://is.gd/hcp_placebosurvey). The final numbers and conclu- sions may thus change.

anne-catherine.huys.15@ucl.ac.uk
Quantitative volumetric analysis of piriform cortex on MRI and its clinical correla- tion in drug-refractory TLE
Authors: Iqbal Sabahat , Rojas-Leon Jose , Galovic Marian , Vos Sjoerd B , Hammers Alexander , Tisi Jane De , Koepp Mathias J , Duncan John S
Published: May 2022

Introduction

In animal studies, an area known as the piriform cortex (PC) has been implicated to be a critical area of epileptogenesis. However, this has seen limited translation to human studies.

Objective

To understand the degree of damage to PC in patients with temporal lobe epilepsy (TLE) as well as to correlate clinical characteristics of TLE with PC volumetry.

Methods

Manual segmentation of the PC on structural MR images of 60 consecutive adults with drug- refractory unilateral TLE and 20 age matched control subjects was performed. Univariate and multivari- ate regression models were employed to examine the relationship of PC and hippocampal volumes with clinical variables collected.

Results

In controls, consistent asymmetry between the left and right PC was found. The right PC was consistently larger than the left across all study groups. Notably, the inter-rater and intra-rater variability were in good agreement. This study found that both the ipsilateral (r=-0.291, p=0.012) and contralateral (r=-0.338, p= 0.008) PC volumes have a negative correlation with the duration of epilepsy. Therefore, evidencing the damage of PC in mesial TLE. The temporal atrophy of the PC correlated with temporal atrophy of the hippocampus. This study could not strongly establish the correlation between any other clinical variable studied.

Conclusion

Further longitudinal studies are required to confirm the findings of this study to enable the PC to be considered in treatment strategies for patients with drug-refractory TLE.

siqbal2482@gmail.com
193  Factors that promote well-being in 5 long-term neurological conditions: a patient and carer perspective
Authors: Head Claudia , Fearn Sarah , Kipps Christopher
Published: May 2022

Background

Neurological long-term conditions (LTCs) are associated with decreased psychological well-being. Identifying factors that promote well-being is crucial for improving quality of life. Existing research has identified common well-being factors, but investigating patient/carer perspectives allows for personalised insight into less-recognised factors.

Aims

To identify and analyse well-being factors across 5 neurological LTCs - Parkinson’s disease (PD), multiple sclerosis, (MS) motor neuron disease (MND), Huntington’s disease (HD) and epilepsy

Methods

Qualititative data was analysed from the NeuroLTC study for 1,490 participants who were asked what factors helped maintain their well-being. A total of 2405 well-being factors, identified from 846 free-text responses were categorised using inductive thematic analysis, and then analysed by condition. PD responses (n=387) were further analysed to determine whether patient gender or disease progression affected well-being factors cited.

Results

Social support, exercise, lifestyle and supportive equipment were the most common well-being factors across all conditions. Less-recognised factors (patient attitude, diet, alternative therapies) were also noted. Response frequencies in MND were the most dissimilar to other conditions. In PD, analysis showed the evolution of relevant well-being factors over time, whereas no notable difference was found between factors cited by each gender.

Conclusion

This study of patient/carer perspectives on well-being factors, found variation across neuro- logical conditions and disease progression (for PD). This could inform advice given by healthcare profes- sionals to promote patient well-being.

ckipps@nhs.net
196  Evidence and the assisted suicide debate
Authors: Nath Uma , Regnard Claud , Lee Mark , Wiblin Lou , Lloyd Kiran
Published: May 2022

Assisted Suicide (AS) inspires strong opinions on all sides of the debate. There is no consensus around the terminology. When medical policy on PAS (physician assisted suicide) is being considered in several countries, as it is at present, there is a need for high quality evidence

A Medline search for Assisted Suicide brings up 5,550 results, but a large proportion of these are com- mentaries, opinions, case reports and discussion. There are relatively few objective studies on its practice that have been published in peer reviewed journals. For example, there are very few studies published on complication rates of the drugs used in AS. There is little comparative data on the quality of life in AS and non AS deaths. There are several official data sources in areas where AS is legal but the extent and quality of the data collected varies considerably with much missing data. In Oregon, data regarding complications in AS cases is missing in 63% of cases. All areas where AS is legal, use retrospective monitor- ing systems. It can be difficult to gather accurate information. The lack of well-conducted, high quality objective research is a challenge for all those involved in the AS debate.

uma.nath@btinternet.com
197  Window of opportunity to save cost, rationalise use and improve monitoring of IVIG: a tertiary-care-audit
Authors: Sherman Danielle , Packwood Shirley , Hewamadduma Channa
Published: May 2022

Background

IVIG is now widely used to treat immune-mediated neurological conditions with annual expenditure on IVIG within Neurosciences directorates exceeding several millions of pounds. IVIG use is strictly monitored by the Department of Health (DOH) due to its cost-burden and supply shortages. This audit evaluates large tertiary centre IVIG use in line with DOH guidelines.

Methodology and Results

The paper and electronic records of the 57 patients receiving regular IVIG for a chronic neuromuscular condition were reviewed against the set criteria and standards. In the last year only: 79% of the patients had an annual review of IVIG therapy; 39% had ³1 clinical outcome measure checked to assess effectiveness of IVIG; and 37% of those classified as clinically stable/improved had an attempt at dose/frequency reduction of IVIG. This audit raised issues of requiring greater monitoring visits to ensure compliance and enforce trial of dose down-titration.

Conclusion

Our data demonstrate a definite opportunity for optimisation of monitoring and rationalisa- tion of IVIG use in order to reduce the treatment burden on patients and reduce IVIG expenditure. To achieve these objectives and to increase efficient use of consultant clinics, a best practice algorithmic protocol driven by a nurse-led IVIG monitoring service is proposed.

daniellerachael@googlemail.com
200  A randomized, placebo-controlled study of galcanezumab in patients with treatment-resistant migraine: double-blind results from CONQUER
Authors: Mulleners Wim , Kim ByungKun , Láinez Miguel , Lanteri-Minet Michel , Aurora Sheena , Nichols Russell , Wang Shufang , Tockhorn-Heidenreich Antje , Pain Andrew
Published: May 2022

Objective

CONQUER assessed galcanezumab efficacy and safety in patients with episodic or chronic migraine who had multiple migraine preventive treatment failures.

Methods

In this phase 3, double-blind study, patients (aged 18–75 years) met criteria for migraine, had 4–29 monthly migraine headache days, and 2–4 migraine preventive medication category failures in the past 10 years. Patients were randomized to receive galcanezumab 120mg/month (with 240-mg loading dose; N=232) or placebo (N=230). Primary endpoint: overall mean change from baseline in number of monthly migraine headache days across Months 1–3. Key secondary endpoints: ≥50%, ≥75%, or 100% reduction in monthly migraine headache days and change on Migraine-Specific Quality of Life-Role Function Restrictive domain.

Results

Galcanezumab-treated patients averaged 4.1 fewer monthly migraine headache days from a baseline of 13.4 versus placebo patients’ average of 1.0 fewer from a baseline of 13.0 (between-group difference 3.1; p<0.0001; 95%CI: -3.9, -2.3; effect size=0.72). Galcanezumab was superior to placebo on all key secondary endpoints and did not differ from placebo in terms of safety.

Conclusion

Galcanezumab was superior to placebo in preventive treatment of migraine and was safe and well tolerated in patients with previous failures to standard-of-care preventive treatments.

pain_andrew@lilly.com
Ethnic and socioeconomic determinants of dementia risk: a nested case-con- trol study in East London
Authors: Bothongo Phazha , Jitlal Mark , Parry Eve , Foote Isabelle , Waters Sheena , Dobson Ruth , Noyce Alastair , Bestwick Jonathan , Marshall Charles
Published: May 2022

Background

The influence of ethnicity and socioeconomic status on dementia risk remain incom- pletely understood. We addressed this issue using data from over a million people in the diverse population of East London (<50% White and >50% in the most deprived UK quintile).

Methods

We identified 4137 cases of dementia, and matched on age and gender to controls with ratio 1:4. We calculated odds ratios (ORs) for ethnicity and Index of Multiple Deprivation (IMD), before and after adjustment for established risk factors (diabetes, hypertension, smoking, BMI, depression and hearing loss). We calculated weighted population attributable fractions (PAF) for each factor.

Results

Risk of dementia was higher for Black and South Asian groups than White (ORs Black 1.43, South Asian 1.17). Risk of dementia was reduced in all IMD quintiles relative to most deprived (ORs 2nd 0.71, 3rd 0.52, 4th 0.71, 5th 0.59). The effects of ethnicity and deprivation persisted after adjusting for known risk factors. Weighted PAFs for modifiable risk factors were notably higher in this popu- lation for depression (9.2%) and diabetes (6.2%) than those estimated in the Lancet Commission meta-analyses (4% and 1.2% respectively).

Conclusions

Ethnicity and socioeconomic deprivation are important determinants of dementia risk, with effects larger than many of the more established risk factors. Depression and diabetes are of greater relative importance, and should be prioritised as targets for dementia prevention efforts in more diverse and deprived populations.

drcharlesmarshall@gmail.com
205  Is it a brain tumour? Assessment on performance of the CNS two week wait pathway
Authors: Shanmugalingam Thurkaa , Quattrocchi Graziella
Published: May 2022

Background

In June 2015, NICE published updated two week wait (2WW) referral guidelines for general practitioners (GPs) for patients with suspected central nervous system (CNS) tumours. These include guidance on relevant clinical information and recommendations for using brain imaging. We reviewed all cases referred to Lewisham and Greenwich (L&G) NHS Trust sites (University Hospital Lewisham (UHL) and Queen Elizabeth Hospital (QEH)) through this pathway with the aim of identifying the appropriate- ness of referrals and reflect on ways to improve this pathway.

Methods andResults

A total of 233 cases were referred onto the 2WW pathway for suspected CNS cancer across L&G NHS Trust between April and October 201; of which 62 were referred to UHL and 161 to QEH. Electronic records and clinic letters were reviewed. Demographics, reason of referrals, target times, and clinical outcome were recorded. 97.7% of these referrals were seen within the target wait of two weeks. Headache was the most common cause for referral.

Discussion

The annual GPs consultation for headache is 4.4 per 100 patients, of which 2% are referred to secondary care. Compliance may be improved by implementing educational programmes in the primary care setting or redesigning the form to optimise referrals.

thurkaa.shanmugalingam@doctors.org.uk
206  Use of non-invasive vagal nerve stimulation in a tertiary headache service
Authors: Lowe Michael , Gorrie George , Dani Krishna , Selvarajah Johann , Tyagi Alok
Published: May 2022

Introduction

Non-invasive vagal nerve stimulation (nVNS) is a novel treatment modality for primary headache disorders. There is some clinical trial evidence to support its use, both as an abortive and pre- ventative treatment, in cluster headache and migraine. We evaluated the use of this novel treatment in a regional tertiary headache service.

Methods

A retrospective analysis of case notes of all patients currently using nVNS in our service was undertaken. Other current and previous headache treatments were recorded. A subjective assessment of response to nVNS was made based on available clinical data.

Results

21 patients currently using nVNS were identified. Diagnoses were chronic cluster headache (n=12), episodic cluster headache (n=1), migraine (n=4), hemicrania continua (n=3) and SUNCT (n=1). All current users reported some degree of positive response to nVNS, with 14 (67%) assessed as having a large improvement. The most frequently reported improvement parameter was reduction in headache frequency (15, 71%). Those reporting a large improvement used significantly fewer concurrent preventa- tive medications (median 0 vs. 2.5, p=0.033).

Conclusions

In this small group of patients with a variety of headache diagnoses nVNS has been an effective treatment; this appears to be due to efficacy as a preventative treatment.

michaelcmlowe@gmail.com
207  OnabotA for CM: benefits beyond headache-day reduction
Authors: Blumenfeld Andrew M , Diener Hans-Christoph , Lipton Richard B , Dodick David W , DeGryse Ronald E , Adams Aubrey Manack , Sommer Katherine , Silberstein Stephen D
Published: May 2022

Objective

Evaluate the impact of onabotulinumtoxinA treatment in adults with chronic migraine.

Methods

Post-hoc analysis of pooled data from the 24-week, placebo-controlled, PREEMPT (NCT00156910,NCT00168428) and single-arm, 108-week COMPEL (NCT01516892) studies. Percentages of participants meeting responder status at 24, 48, or 108 weeks for clinically meaningful changes in headache days (≥50% reduction), Headache Impact Test (HIT-6; ≥5-point improvement), Migraine-Specific Quality-of-Life Questionnaire Role Function-Restrictive (MSQ-RFR; ≥10.9-point improvement), and either Average Daily Headache Severity (ADHS; ≥1-point improvement; PREEMPT) or Migraine Disability Assessment Scale (≥5-point improvement) were calculated.

Results

Participants (N=1384) were randomized to onabotulinumtoxinA (n=688) or placebo (n=696) in PREEMPT; 716 participants were enrolled in COMPEL. In PREEMPT, significantly more participants treated with onabotulinumtoxinA than placebo met responder criteria for change in headache days (44.8% vs 34.2%), HIT-6 (40.8% vs 25.3%), MSQ-RFR (59.0% vs 40.2%), and ADHS (35.5% vs 22.4%) scores at 24 weeks (all

P<0.001). At least 1 domain was met by 72.1% and 56.6% of PREEMPT participants treated with onabotu- linumtoxinA and placebo, respectively (P<0.001), and 87% of onabotulinumtoxinA-treated participants at year 2 in COMPEL.

Conclusions

OnabotulinumtoxinA-treated participants demonstrated clinically meaningful improvements across multiple domains in the PREEMPT studies and up to 2 years in COMPEL.

Sommer_Kathrine@Allergan.com
211  The prevalence and characteristics of multiple sclerosis-associated uveitis in UK biobank
Authors: Taylor Thomas , Jacobs Benjamin , Giovannoni Gavin , Dobson Ruth
Published: May 2022

Background

Uveitis describes intraocular inflammation of the uveal tract. It may be associated with auto- immune diseases (e.g. ankylosing spondylitis), inflammatory diseases (e.g. Crohn’s), infections (TB, toxoplas- mosis) or it may be idiopathic, however an association with Multiple Sclerosis (MS) has also been observed.

Methods

2151 individuals with MS were identified within UK Biobank via ICD-10 code G35 and self-reported diagnosis, and compared to the remainder of the Biobank cohort. Uveitis was defined using ICD-10 codes H20, H30, and H22.1 along with self-report. We used multivariate logistic regression to model uveitis diagnosis on MS status and control for confounding factors (age, sex, and socio-economic status).

Results

Uveitis prevalence in people with MS was 0.60%, compared to 0.18% in controls. 3 individuals with MS and uveitis had an additional diagnosis associated with uveitis (ankylosing spondylitis and sarcoid) and were excluded, leaving a prevalence of 0.48%. The odds ratio (OR) of uveitis in MS was 2.73, 95%CI 1.46–5.10, p = 0.0068. 90% people with dual diagnosis were female. 30.0% were DRB1*15 heterozygotes, while 70.0% carried no copies of the DRB1*15 risk allele.

Conclusions

These findings support the suggested association of these two conditions and demonstrate a comparable predominance of white females with both conditions.

thomasrptaylor@gmail.com
217  Histiocytes and the brain: a rare case of Rosai-Dorfman disease responsive to trametinib
Authors: Hawken Jonathan , Hu Mo , Johnston Ann , Edwards Marc
Published: May 2022

Rosai-Dorfman Disease (RDD) is a rare heterogenous systemic condition caused by histiocyte over-prolif- eration within various organ systems, which may manifest with neurological symptoms.

We report the case of a 70-year-old female who presented with pan-hypopituitarism, and was found to have leptomeningeal enhancement and an infundibular mass lesion on MRI. Brain biopsy confirmed a histological diagnosis of RDD, and initially she was managed conservatively.

Four years later her cognition, gait and level of functioning deteriorated. Serial MRIs showed slow progres- sion of the lesions. Treatment with pulsed methylprednisolone followed by an oral taper proved ineffec- tive. A multi-disciplinary team decision was made to start treatment with Trametinib (1mg once daily).

A repeat MRI after 6 months showed a reduction in enhancing lesions with no new lesions. Her mobility and cognition also improved objectively. Treatment is ongoing and has been well tolerated with only a mild skin rash as a possible adverse reaction.

Trametinib is an inhibitor of mitogen-activated extracellular signal regulated kinase enzymes (MEK1 and MEK2). It is typically used for melanoma, but there is emerging evidence of its effectiveness in RDD. Optimal treatment duration is not yet clearly established, and further research is needed to elucidate underlying disease mechanisms.

drhawken@outlook.com
218  Cerebral lipiodol embolisation following lymphangiography – a rare neurologi- cal presentation
Authors: Batcheller Lisa , Thaller Mark , Wright Benjamin
Published: May 2022

Presentation

A 73-year-old gentleman was admitted for 2 stage oesophagectomy (laparascopic abdominal and open thoracic) which was reported as uneventful. The tumour was subsequently confirmed T2N0M0 therefore cured by the operation. 3 days post operation increasing chest drain output was noted, this became milky with coarse creps on auscultation and this was confirmed later as a chyle leak.

Intervention

Interventional radiology performed lymphangiography under local anaesthesia on day 26 post op.

Complication

The day after the procedure his GCS dropped with bilateral miotic pupils, increased tone and double incontinence. Initial bloods, arterial blood gas and glucose were normal. Naloxone was given with limited response. His surgical team requested CT head and neurology review.

Results

CT head showed patches of high density throughout basal ganglia, cortex and cerebellum but no infarct in keeping with embolization of lipiodol contrast medium. MRI head confirmed maturing ischaemic cortical and subcortical change.

Management

The neurological picture showed an encephalopathy with more left sided upper motor neuron signs than on the right. He was managed initially in intensive care with supportive management however prognosis was unclear with no evidence-based treatment. There was also risk of late inflamma- tory reaction analogous to arachnoiditis seen post myelography.

Outcome

He subsequently had thoracotomy with clipping/suturing of the left thoracic duct. He was discharged home after three months in hospital.

lisabatch1@gmail.com
220  Cochrane review of interval brain imaging in adults with cerebral glioma
Authors: Thompson Gerry , Lawrie Tess , Kernohan Ashleigh , Jenkinson Michael , Grant Robert
Published: May 2022

Background

It is not known whether imaging at pre-specified time points after glioma diagnosis and treatment leads to better outcomes than triggered imaging performed in response to new or worsening symptoms.

Objectives

To systematically review the effect of different imaging strategies on health and economic outcomes for adults with cerebral glioma (grade 2 to 4).

Methods

CENTRAL, MEDLINE and Embase were searched up to 18/06/2019 for relevant RCTs and non- randomised studies comparing imaging strategies in adults with glioma. The NHS Economic Evaluation Database (EED) was also searched for relevant economic evaluations. We used standard Cochrane review methodology.

Findings

We included one retrospective study comparing early post-operative imaging (within 48 hours) with no early post-operative imaging among 125 adults with glioblastoma. Evidence suggested little or no difference in survival between approaches at one year (RR 0.86, 95% CI 0.61 to 1.21; 48% vs 55% died, respectively) and two years after diagnosis (RR 1.06, 95% CI 0.91 to 1.25; 86% vs 81% died, respectively) but was assessed as very low quality. No economic evaluations were found.

Conclusions

The effect of different imaging strategies on survival and other health outcomes remains largely unknown. Existing imaging schedules seem to be pragmatic rather than evidence-based.

robin.grant@luht.scot.nhs.uk
224  Parkinson’s UK – connecting the Parkinson’s research community and increase participation
Authors: Hursey Amelia
Published: May 2022

Before Parkinson’s UK went through its rebrand in 2010, we asked our members how we were perceived. The results highlighted the need for us to communicate, collaborate and involve people affected by Parkinson’s in more areas of our work. Today everything we do as an organisation includes people affected by Parkinson’s.

Within the research directorate we have focused on 3 key initiatives over the last decade; the Research Support Network (RSN), Research Involvement and Participation. The Parkinson’s UK RSN is an online network of currently over 6000+ people affected by Parkinson’s who are interested in research.

We surveyed our RSN membership and 70% of them wanted to take part in research but only 24% had. Many Parkinson’s research trials have failed to recruit participants to time and target, causing the research to go over budget and sometimes fail to reach significance. Data from the 2018 Parkinson’s audit report found only 20% of people affected by Parkinson’s are told about research by their health care profes- sional. By working with people affected by Parkinson’s, Health Care Professionals and Researchers, we developed the Participation work stream to address this discrepancy. The tools we’ve created help researchers to connect with potential participants, patients to take control and health care professionals to signpost people to find research in their area using our Take Part Hub, improving outcomes for patients and research performance.

ahursey@parkinsons.org.uk
225  A rare case of recurrent unsteadiness due to Miller Fisher syndrome
Authors: Levinson Gavriella , Wei Diana , Warner Graham
Published: May 2022

A 71-year-old male presented to the emergency department with unsteadiness, blurred vision, slurred speech and sensory changes. He had progressive loss of reflexes. After initial horizontal nystagmus he developed bilateral ophthalmoplegia with bilateral ptosis and impaired coordination with an ataxic gait. This was preceded by productive cough and loose stools.

The patient was diagnosed with Miller Fisher Syndrome (MFS), with a positive anti-GQ1b antibody and CSF albuminocytologic dissociation supporting the diagnosis. This was the patient’s second episode of MFS. The first had occurred twenty-seven years earlier with a similar presentation and examination findings.

This poster then reviews the clinical presentation, management and recurrence of Miller Fisher Syndrome. gavriella.levinson@nhs.net
233  Working towards an adaptive trial platform for Parkinson’s disease
Authors: Zeissler Marie-Louise , Dominey Thea , Morris Huw , Bandmann Oliver , Schrag Annette , Foltynie Tom , Carroll Camille
Published: May 2022

Background

No intervention for Parkinson’s disease (PD) has been unequivocally proven to be neuro- protective. Setting up phase 2 and 3 clinical trials in isolation is costly, time consuming and inefficient. An adaptive trial design may allow streamlining clinical evaluation, with interim analyses allowing for early detection and replacement of ineffective arms. We were interested to explore the practicalities of developing an adaptive trial for PD.

Method

We consulted with experts in disease areas where adaptive trials have been initiated and sought support from national and international Parkinson’s experts, charities, and input from patient advocates.

Results

Following consultation, we have adapted the process successfully employed by the multiple sclerosis (MS) Society in the development of the STOP MS initiative. Initial steps involve a review of recent trial methodologies and a Delphi study involving multi-organisational stakeholders, including patients and international experts. These results will inform the function of working groups responsible for drug selection, trial design, outcome measure selection and infrastructure.

Conclusions

Developing a adaptive trial for PD is challenging. However, we now have a process to take this forward, building on the success of similar initiatives in other neurodegenerative diseases.

marie-louise.zeissler@plymouth.ac.uk