bluuebunny/crossref_metadata_2025 huggingface dataset:
125  Complex cortical visual impairments following bilateral occipital infarcts after traumatic brain injury
Authors: Lichtblau Nicole , Rich Philip , Griffin Colette
Published: May 2022

Background

Secondary brain damage following acute traumatic brain injury (TBI) contributes to increased morbidity and disability. Intracranial vasospasm is a less common cause for secondary brain damage. We report a case of a 73 year old man in whom post-traumatic vasospasm lead to bilateral occipital infarction.

Case summary

The patient was admitted with a severe TBI following a fall from height causing bilateral fronto-temporal haemorrhagic contusions. Ten days after admission he developed a fluctuating level of consciousness. Repeat cranial CT and angiography showed new bilateral occipital hypodensities and bilaterally multi-level vessel narrowing in the posterior circulation.

The patient suffered from cortical blindness but regained gradually visual perceptual function over the next months. During this time a combination of Balint syndrome (simultanagnosia, oculomotor apraxia and optic ataxia), visual hallucinations and confabulation were observed. Neurorehabilitation was com- plicated by the complex nature of extensive cognitive deficit in combination with the visual impairments but enabled the patient to gain some insight and coping strategies.

Conclusions

This case highlights the complexities of neurorehabilitation following TBI and describes an unusual case of partially reversible cortical blindness. It further highlights the importance of recognising the impact of secondary brain damage after TBI.

nicole.lichtblau@nhs.net
128  White matter fibre loss in Parkinson’s disease hallucinations
Authors: Zarkali Angeliki , McColgan Peter , Leyland Louise-Ann , Rees Geraint , Weil Rimona S
Published: May 2022

Visual hallucinations are common in Parkinson’s (PD) and associated with worse outcomes.1Neuroim- aging shows widespread but non-specific grey matter atrophy in PD-hallucinations1; white matter (WM) loss may be an earlier, more sensitive marker. To detect WM changes in PD-hallucinations we performed diffusion-weighted imaging in 105 patients with PD (n=86 without hallucinations [PD-non-VH], n=19 with hallucinations [PD-VH]), and 35 controls. We performed whole-brain fixel-based analysis,2a novel method that can identify micro- and macro-structural changes at fibre level and examined three measures:

apparent fibre density (FD), sensitive to micro-structural changes,

fibre bundle cross-section (FC), representing macro-structural changes,

combined fibre density and cross-section (FDC).

Groups did not differ in age or gender. PD-VH had higher total UPDRS score [63.5±35.6 vs 43.2±20.6 in PD-non-VH, (p=0.003)]; motor scores did not differ. We found macrostructural changes (FC reduction) within the splenium of the corpus callosum and left posterior thalamic radiation in PD/VH. Whilst there were no significant changes in FD, when using the combined FDC metric, we found large reductions within the splenium in PD-VH (>50% reduction compared to PD-non-VH).

We demonstrate specific WM tract degeneration affecting posterior thalamic tracts in PD-hallucinations, providing direct mechanistic support for attentional models of visual hallucinations.

References

Weil,et al. Visual dysfunction in Parkinson’s disease.Brain2016 Jul 13.

Raffelt,et al. Investigating white matter fibre density and morphology using fixel-based analysis.Neu- roimage2017;144:58–73.

a.zarkali@ucl.ac.uk
Plasma neurofilament light levels as a novel biomarker for neurological involve- ment in Wilson’s disease
Authors: Shribman Samuel , Heller Carolin , Bocchetta Martina , Burrows Maggie , Gillett Godfrey T , Tsochatzis Emmanouil , Zetterberg Henrik , Bandmann Oliver , Rohrer Jonathan D , Warner Thomas T
Published: May 2022

Background

Serum and urine copper levels are used to monitor chelation therapy for Wilson’s disease (WD) but do not reflect neurological involvement. Biomarkers of end-organ damage are needed to optimise chelation therapy and prepare for clinical trials for gene therapy.

Methods

We measured neurofilament light (NfL) levels in plasma samples, Unified WD Rating Scale (UWDRS) scores and brain volumes on T1-weighted MRI at baseline visits for a longitudinal, observational study. Participants were divided into neurological (n=25) and hepatic (n=15) groups according to UWDRS neurological examination (UWDRS-N) scores. Those with new diagnoses (n=2) or recent neurological dete- rioration associated with non-adherence (n=3) were subcategorised as having active disease. Plasma NfL levels were measured in age-matched healthy controls (n=38) for comparison.

Results

Plasma NfL levels were higher in neurological compared with hepatic and healthy control groups (8.6 vs 7.6 vs 7.6 ng/L, p=0.046) and higher in neurological cases with active disease (22.2 vs 8.3 ng/L, p=0.004). In cases without active disease, they correlated with UWDRS-N scores (p=0.003) and cortical grey matter (p<0.001) but not subcortical grey matter (p=0.071) or white matter volumes (p=0.895).

Conclusions

Plasma NfL is a promising biomarker for neurological involvement that, in a small cohort, appears to be associated with neurological disease activity and clinical severity and reflects neuroaxonal injury in cortical grey matter.

s.shribman@ucl.ac.uk
143  Catastrophising cognitions in patients with psychogenic non-epileptic seizures compared to patients with epilepsy
Authors: Whitfield Andrew , Walsh Sean , Levita Liat , Reuber Markus
Published: May 2022

A growing body of evidence suggests more catastrophising cognitions are present in patients with psychogenic non-epileptic seizures (pwPNES) compared to patients with epilepsy (PWE). However, the perseverative aspect of catastrophic thinking including repetitive negative thinking (RNT) has had little attention. In this study pwPNES (n=26) and PWE (n=29) completed self-reported questionnaires including Perseverative Thinking Questionnaire to assess levels of RNT and a modified version of the Safety Behaviors and Catastrophizing Scale to assess catastrophising of seizures. Participants also completed the PHQ-9 and GAD-7 to provide measures of anxiety and depression. Patients with PNES reported significantly higher levels of RNT, catastrophising of seizures, and depression and anxiety than patients with epilepsy. Additionally, the effect of RNT was independent to effects of all other factors in its contribution to PNES suggesting it would serve as a good target for psychological therapy.

ajwhitfield1878@gmail.com
146  Epilepsy, deprivation and mortality in Wales 2005–2017
Authors: Daniels H , Lacey AS , Akbari A , Fonferko-Shadrach B , Hollinghurst J , Rees MI , Sawhney IMS , Powell HR , Kerr MP , Owen Pickrell W
Published: May 2022

Background

Public Health England have recently reported that deaths associated with epilepsy are increasing and are associated with increased deprivation. We investigated comparable Welsh mortality trends and associations between epilepsy mortality and deprivation.

Method

We used routinely-collected health data within the Secure Anonymised Information Linkage (SAIL) Databank. We recorded deaths associated with epilepsy (DAE), epilepsy recorded on death certificates, and deaths in people with epilepsy (DPWE), people with diagnoses of epilepsy and epilepsy prescriptions before death. We compared death rates in different deprivation deciles adjusting for epilepsy prevalence.

Results

During 2005–2017 (41million patient-years) there were 2116 DAE and 7821 DPWE. DAE and DPWE increased from 4.3/100,000/yr and 17.2/100,000/yr in 2005–2007 to 5.7/100,000/yr and 20.9/100,000/yr in 2015–2017. The age-standardised mortality rates (ASMR) in 2006–2008 for DAE and DPWE were 5.3/100,000/yr and 20/100,000/yr respectively, in 2015–2017 they were 5.8/100,000/yr and 20/100,000/yr. DAE were not significantly associated with deprivation when adjusted for epilepsy prevalence.

Conclusion

When adjusting for age, deaths associated wtih epilepsy and deaths in people with epilepsy did not increase significantly in Wales between 2005–2007 and 2015–2017. The association between dep- rivation and deaths associated with epilepsy appears to be explained by higher epilepsy prevalence in areas of higher deprivation.

w.o.pickrell@swansea.ac.uk
154  Crossed cerebellar diaschisis in refractory epilepsy
Authors: Englezou Christina , Hayton Tom , Chelvarajah R , Hughes S , Sawlani Vijay , Shirley Colin , McCorry Dougal
Published: May 2022

Background

Crossed cerebellar diaschisis is the unilateral depression in functional activity of the cerebel- lar hemisphere, caused by a controlateral supratentorial lesion. The phenomenon arises from disruption of neuronal connections between the cerebrum and the cerebellum.

Case report

We present the case of a 42 year old woman with refractory epilepsy since early childhood. Her epilepsy is characterised by focal seizures with no impairment of awareness, and bilateral tonic- clonic seizures. She is currently on triple therapy with topiramate, gabapentin, and lacosamide. Seizure frequency varies with events occurring at least twice a week. MRI brain showed left mesial sclerosis, and PET CT demonstrated marked reduction in glucose uptake in the left temporal lobe, as well as reduction in uptake in the right cerebellar hemisphere. Scalp videotelemetry captured her events and demonstrated onset from the left fronto-temporal region.

Discussion

The epileptogenic focus was localised to the left fronto-temporal region. The PET CT demon- strated the phenomenon of crossed cerebellar diaschisis. It has been said that the phenomenon shows reversibility, but it is a poor prognostic factor, and it could result in cerebellar atrophy.

englezou.chr@gmail.com
158  Non-epilpetic attack disorder admission in the Royal Preston Hospital
Authors: Nwe May , Gall Clarie
Published: May 2022

Background

There is a high number of non-epileptic attack disorder admission rate in the Lancashire teaching hospital which place a high demand on the service. To reduce the number of admission rate, treatment pathway is needed. If effective interventions are implemented there is a potential for the massive cost savings. It has been mentioned that an effective neurology assessment during the consulta- tion and referring to the physiotherapy and psychological services are ways to treat functional neurology disorders. One study highlighted the potential for psychological interventions as a favourable alternative to the current lack of treatment options offered to people with PNES.

Methods

We collated the data from 27 patients who are coded as NEAD for admission in Royal Preston Hospital in 2018.

Result

23–52% had an underlying history of psychological problems such as depression, anxiety and per- sonality disorders.57% had re-admission rate elsewhere. Maximum of 90 times admission as an inpatient in the Royal Preston Hospital.

maythaenwe@gmail.com
166  A not-to-be-missed mimic of TB meningitis
Authors: Dey Kallol , Das Shyamal
Published: May 2022

We present a revelatory case of a TBM mimic highlighting the importance of having a wider differential diagnosis of a familiar clinical scenario.

A 19-year-old lady presented with high grade fever, vomiting and headache for two weeks. Subsequently she developed blurring as well as double vision. She was transferred from a district clinical facility. On examination, she was emaciated, febrile and delirious. There was divergent squint on the left side. On fundoscopic examination, there was papilloedema. There was generalised muscle wasting and tone was normal.There was no neck stiffness and Kernig’s was negative.The DTRs were 1+, plantars flexor. There was mild hepatomegaly. In view of the clinical profile, empirical anti-TB treatment (ATT) with corticosteroid was started, pending CEMRI brain and CSF study. Her labs showed-Hb 10.3, TLC 11,300, Platelets 160,000, malaria parasite- not found, Dengue IgM-unreactive. Her LFTs showed SGOT 110, SGPT 125, ALP 432, Bili 0.63, Gamma GT- 249. She had a CEMRI brain which showed normal brain parenchyma with mucosal thickening in ethmoid sinus. CSF showed 10 cells (all lymphocytes), glucose 58, protein 100.3, normal ADA, RNA TB PCR negative. IgM Scrub typhus was sent because of prolonged fever and it was reactive. Her ATT was stopped but the steroid was continued. She was started on doxycycline 100 mg twice daily. Her fever resolved and the headaches along with sixth nerve palsy resolved swiftly in 48 hours.

drkkdey@gmail.com
Onasemnogene abeparvovec gene therapy for spinal muscular atrophy type 1: phase 3 study update (str1ve-eu)
Authors: Mercuri Eugenio , Baranello Giovanni , Masson Riccardo , Boespflug-Tanguy Odile , Bruno Claudio , Scoto Mariacristina , Servais Laurent , Kauser Imran , Loukes Jonathan , Muntoni Francesco ,   et al
Published: May 2022

Onasemnogene abeparvovec (formerly AVXS-101), a one-time intravenous AAV9-based gene therapy, addresses the genetic root cause of spinal muscular atrophy type 1 (SMA1). We report preliminary data from the phase 3 STR1VE-EU (2017-000266-29/NCT03461289) study evaluating efficacy and safety of onasemnogene abeparvovec infusion. STR1VE-EU is an ongoing, multicenter, open-label, single-arm, single-dose study in SMA1 patients aged <6 months (biallelicSMN1mutations, 1–2xSMN2). Outcomes: independent sitting ≥10 seconds throughout 18 months; survival (no death/permanent ventilation) at 14 months. Enrollment is complete (31 May 2019; N=33, all 2xSMN2). Mean age at dosing: 4.1 (1.4–6) months. Mean baseline CHOP INTEND score: 28 (14–55). Mean time in study: 4.8 (0.4–9.2) months. At baseline, 9/33 (27%) patients required nutritional support and 7/33 (17%) required ventilatory support. Relative to baseline, mean CHOP INTEND score increased 6.4,10.6, and 12.3 points at 1, 3, and 5 months post-dosing, respectively. Overall, 32 patients were surviving without permanent ventilation, including 9/10 patients who reached 10.5 months of age or experienced an event. One patient died (age 6.8 months, hypoxic- ischemic brain injury secondary to respiratory tract infection due to SMA1). Interim data from the ongoing STR1VE-EU study shows that onasemnogene abeparvovec has therapeutic benefit in patients with SMA1.

1ik4ausar078@avexis.com
175  Quality improvement: re-structuring the neurology ‘In-hours’ on-call service at North Bristol Trust
Authors: Hodnett Rebecca , Sarkar Pamela , Tan Melissa
Published: May 2022

Introduction

The joint ABN and RCP 2011 report advocated for changes in planning of local services to improve access to specialist reviews.1At North Bristol Trust (NBT), we restructured our ‘in-hours’ on-call service to enable early neurology review; as Ali et al.2showed, this alters diagnosis and management in up to 79% of cases referred. These changes include an increase in HOT clinic appointments (rapid access service) and pro-active review of Acute Medical Unit (AMU) patients.

Method

From 8th August 2019, two registrars have been placed on-call during ‘in-hours’. One is dedicated to referrals and the other runs the HOT clinics and picks up referrals in AMU. Data was collected from an on-call database and processed on Excel.

Results

>60% reduction in time to review from referral

NBT average of time to review at HOT clinic was 3.44 days

No. of appointments doubled in September compared to June 64% (n=37) of cases were discharged on the day of review

Conclusions

Service improvement shown by significant reduction in delay from referral to review in HOT clinicsProactively picking up referrals increase discharges!Reducing length of stay and investigations reduce costs incurred

Reference

RCP London and the ABN. Local adult neurology services for the next decade. London: RCP, 2011.

Ali E et al. The ‘hidden work’ of a hospital neurologist: 1000 consults later.European Journal of neurology2010 Apr;17(4):e28–32.

melissatan095@gmail.com
180  Outcomes of new referrals to neurology clinics with unexplained symptoms: observational study of 208 patients
Authors: Nikfekr Esmaeil , Ball Nicola
Published: May 2022

Introduction

NHS services are under unprecedented pressure to accommodate more patients. Thirty to 62% of new referrals are patients with non-specific symptoms with estimated cost of approximately 10% of total NHS expenditure in England. This study was conducted to determine prevalence and degree of organocity as well as to characterise neurologically unexplained symptoms in order to explore the feasibility of devising a safe triage system.

Method

556 new referrals was made in on month to Nottingham neurology services, of which 208 eligible patients were retro respectively evaluated for their first encounter and their outcome was prospectively monitored for 12 months. Based on initial assessment they were divided into three categories of 99 patients with Neurologically Unexplained Symptoms, 79 patients as Somewhat Explained and 30 patients with Neurologically Explained Symptoms.

Results

Out of 99 neurologically unexplained patients 53 were investigated of which only one test was positive revealing an organic cause.

Out of 79 patients in the somewhat explained group, 41 patients had tests which led to a diagnosis in 7 patients.

Out of 30 neurologically explained patients, 13 required investigations that revealed a diagnosis in 8 patients.

There were no cases where unexpected neurological condition was diagnosed during the follow up period in any patient.

Conclusion

52% of newly referred patients with neurologically unexplained symptoms had normal inves- tigations without contribution to a diagnosis.

e.nikfekr@yahoo.co.uk
Parkinson’s disease determinants, prediction and gene-environment interac- tions: a UK Biobank study
Authors: Belete Daniel , Jacobs Benjamin Meir , Bestwick Jonathan P , Dobson Ruth , Hardy John , Giovannoni Gavin , Lees Andrew , Schrag Anette , Noyce Alastair J
Published: May 2022

Introduction

Early identification of individuals at high-risk of Parkinson’s disease (PD) may allow for the use of disease modifying treatments. We aimed to define those at risk of incident PD through environmental and genetic risk factors, comorbidities and prodromal symptoms of PD.

Methods

We identified incident cases of PD (n=1276) in the UK Biobank and unmatched controls without a PD diagnosis (n=500,406). Odds ratios for a range of determinants were calculated. A non-genetic model and polygenic risk score (PRS) were constructed. Basic gene-environment interactions were explored.

Results

Strong evidence of association (FDR < 0.05) was found between PD and family history of PD or dementia, not smoking, low alcohol consumption, depression, daytime somnolence, epilepsy and earlier menarche. Individuals in the top PRS decile had an increased risk of PD compared to those in the lowest decline and high scores were associated with an earlier age of diagnosis. There was evidence for a strong interaction between diabetes and PRS.

Discussion

We report the novel finding of a strong association between earlier menarche and increased PD. Analysis of gene-environment interactions found strong evidence that the effect of diabetes is modified by genetic risk. Replication and understanding the mechanism of this observation is an important next step.

d.belete@nhs.net
184  Right data, right care
Authors: Biggin Fran , Knight Jo , Emsley Hedley
Published: May 2022

There is considerable current interest in neurology ‘intelligence’. For example, NHS RightCare uses nation- ally collected data to identify and address variations in care, and the clinically led NHS improvement programme Getting It Right First Time seeks to improve quality of care by reducing variation. Despite this, current neurology ‘intelligence’ strategies lack data on clinic activity because outpatient coding is not routinely done.

In order to determine what insights can be gained from routine data, we have analysed data collected at a neurology outpatient clinic (5902 appointments for 3100 patients) offered by one neurologist (HE) over three years.

We found clear patterns in variables such as age distributions, interval from referral to appointment by conditions, and geographical source of referral. The data can be presented in a format useful for clini- cians and service managers, allowing identification of opportunities for change such as optimal utilisation of alternative pathways for management of primary headache disorders.

In order to be most useful, this type of analysis should be available across all Neurology outpatient services. However various barriers including workforce, non-standardised approaches to outpatient coding, and variation in IT systems hamper implementation. Our ongoing collaborative project seeks to meet these challenges.

f.biggin@lancaster.ac.uk
188  Structural differences in access to neurological healthcare in Northern Ireland: a neurodisparity index
Authors: McCarron Mark , Burns Paul , Forbes Raeburn , McCarron Luke , Mcverry Ferghal
Published: May 2022

Disparities in management of neurological patients should be minimal in a universal healthcare system. Northern Ireland has one neuroscience centre but no neurology centres. We have devised an easily- applied neurodisparity index (NDI) to measure population equity of neurological healthcare. NDI=number of patients managed per 105 population per Trust/number of patients managed per 105 population of the tertiary centre Trust. NDIs <0.75 and >1.25 were arbitrarily designated as neurodisparities.

NDIs were calculated between 2013–2016 for intravenous thrombolysis (eight centres) or mechanical thrombectomy (one centre) for acute ischaemic stroke (AIS), disease modifying drug use for multiple sclerosis (>10 centres) and admissions to a neuroscience neurology ward (n=1) to determine the source and extent of neurodisparity.

Amalgamated NDIs for non-tertiary centre trusts were: 0.36 for mechanical thrombectomy for AIS; 0.79 for intravenous thrombolysis for AIS; 1.1 for disease modifying treatment for multiple sclerosis and 0.48 for patient admissions to the tertiary neurology ward. Individual Trust data demonstrated a geographical gradient for mechanical thrombectomy and regional ward admissions.

Neurodisparities in Northern Ireland are most marked for mechanical thrombectomy and regional neurology ward admissions. Commissioners should be aware that geography and time-dependent man- agement can exacerbate neurodisparities. Extra resources are required to address such neurodisparities.

markmccarron@doctors.org.uk
192  Transitioning: how hard can it really be?
Authors: Kalam Sabrina , Adan Guleed
Published: May 2022

Transition can be ‘challenging’, requiring rapid acquisition of new skills. Though transition in medicine has been studied, transition from senior house officer (SHO) to neurology registrar (NR) specifically has not.

We studied perceptions of NRs on their transition and how core medical training (CMT) impacted this. This was an exploratory study utilising qualitative research methodology. Face to-face interviews were undertaken, gaining in-depth insight into participant perspectives. Four junior NRs in a tertiary teaching hospital in London were interviewed. The data was analysed using inductive thematic analysis.

Three major themes were identified: Transition period, role modelling and clinical training. Overall trainees perceived difficulty in transition and expressed need for a formally acknowledged transition period with teaching on transitioning. Trainees expressed requirement for small-group and bedside teaching. Neurology was also perceived as being an under-taught subject in CMT and thus the expert skill and knowledge required at NR level differed from competencies acquired in CMT.

The transition from SHO to NR is an understudied area. This was a pilot study undertaken just prior to the introduction of the current internal medical curriculum and highlights need for further study in this area in order to further improve training and transitioning in neurology.

sabrina_k2005@hotmail.co.uk
201  Management of an unusual presentation of spontaneous intracranial hypotension (SIH)
Authors: Mohideen Muhammed , Benger Matthew , Mahmood Amira , Hoffman Jan , Goadsby Peter , Stanton Biba , Carlton-Jones Lalani
Published: May 2022

A 49-year-old woman presented with 9 months of progressive cognitive decline and somnolence. In the last few weeks she developed right hand tremor, unsteadiness and urinary incontinence, which improved after lying flat. There was no headache. Examination findings included vertical gaze restriction, hypomimia, right-sided rest tremor, rigidity and bradykinesia, globally brisk reflexes and an unsteady gait. She scored 50/100 on the Addenbrooke’s Cognitive Examination.

Brain MRI showed features consistent with intracranial hypotension with marked ‘brain sag’ but standard imaging did not identify the site of the leak. Two blind blood patches were followed by only transient symptomatic improvement. Initial Digital Subtraction Myelogram (DSM) was non-diagnostic, but repeat DSM identified a leak at C6–7 with an irregular diverticulum/CSF-venous fistula.

A CT-guided fibrin patch injected at C6/7 resulted in transient improvement. Finally, a neurosurgical procedure was performed to coagulate the venous plexus adjacent to the C7 nerve root. This effected a dramatic and sustained improvement in her cognitive and motor symptoms.

SIH is a treatable cause of cognitive decline and parkinsonism. DSM is a novel approach to localising CSF leaks. This is the first reported cognitive presentation of SIH where identification of a CSF leak with DSM led to successful surgical treatment.

saamir.mohideen@nhs.net
203  Outcomes of patients with discordant CSF bilirubin and oxyhaemoglobin xanthochromia Results a retrospective audit
Authors: Day Jacob , Gower Hannah , Gormley Joe
Published: May 2022

Background

Investigation of headaches for possible subarachnoid haemorrhage frequently involves examination of cerebrospinal fluid (CSF) for xanthochromia. If both CSF bilirubin and oxyhaemoglobin are raised it is suggestive of subarachnoid haemorrhage and if both are negative this is reassuring. However, when one of the CSF bilirubin or oxyhaemoglobin is raised in isolation it is unclear what the risk of suba- rachnoid haemorrhage is.

Method

We performed a retrospective audit of all CSF analyses for xanthochromia in a single centre over a 2 year period in 2016–2018. Of the 403 results, 10 had raised CSF bilirubin or oxyhaemoglobin in isolation. 6 had raised oxyhaemoglobin that could impair the ability to detect CSF bilirubin; 4 had raised CSF oxyhaemoglobin which could be due to blood or other causes.

Results

Overall, there was only 1 confirmed subarachnoid haemorrhage and this was traumatic. Of the 9 other cases, 5 were a primary headache, 1 viral meningitis, 1 viral encephalitis, 1 bacterial meningitis and 1 autoimmune encephalitis. In the 18 months since the end of the audit period no patient has re- presented with subarachnoid haemorrhage.

Conclusion

We found no cases of aneurysmal subarachnoid haemorrhage in patients with isolated raised CSF bilirubin or oxyhaemoglobin.

jacobday@doctors.org.uk
228  Testing shortened versions of smell tests to screen for hyposmia in Parkinson’s disease
Authors: Auger Stephen , Kanavou Sofia , Lawton Michael , Ben-Shlomo Yoav , Hu Michele , Schrag Anette , Morris Huw , Grosset Donald , Noyce Alastair
Published: May 2022

Background

Hyposmia is an early feature in neurodegenerative diseases, most notably Parkinson’s Disease (PD). Using abbreviated smell tests could provide a cost-effective means for large-scale hyposmia screening. It is unclear whether short smell tests can effectively detect hyposmia in patient populations.

Objectives

To test the ability of short smell combinations to ‘pre-screen’ for probable hyposmia in people with PD and target administration of more extensive tests, such as the University of Pennsylvania Smell Identification Test (UPSIT).

Methods

We assessed the screening performance of a short 4 smell combination previously derived from use of the 40-item UPSIT in healthy older people and its ability to detect hyposmia in a large cohort of PD patients.

Results

The novel 4 smell combination included Menthol, Clove, Onion and Orange and had a sensitiv- ity of 87.1% (95% confidence interval: 84.9%-89.2%) and specificity of 69.7% (63.3%-75.5%) for detecting hyposmia in patients with PD. A different (also novel) 4-item combination developed using a data-driven approach in PD patients only achieved 81.3% (78.2%-84.4%) sensitivity for equivalent specificity.

Conclusions

A short 4 smell combination derived from a healthy population demonstrated high sensitivity to detect those with hyposmia and PD.

s.auger@outlook.com
232  Organisational impact of upcoming Huntington’s disease treatments in Europe: resource gaps, access to care
Authors: Pedrazzoli Marco , Ponomareva Marina , Moro Mattia , Townson Louisa , Mukelabai Kopano , Levine Aaron , Nordström Anna-Lena , Guttman Mark , Burgunder Jean-Marc , Reilmann Ralf
Published: May 2022

Whilst no disease-modifying-therapies (DMTs) are currently available for Huntington’s disease (HD), the investigational drugs most advanced in clinical development are administered intrathecally, requiring additional resources in HD clinics. We investigated the impact of upcoming DMTs for HD on healthcare systems and the implications of possible resource capacity gaps on access to care.

The capacity to perform intrathecal drug administrations was assessed in 35 HD specialist centres from nine countries. Interviews with >170 healthcare professionals were performed and resources available in each HD centre were compared to the predicted amount of future resources that the estimated eligible patient population would need.

Only 20% of participating HD teams currently have the required resources to perform intrathecal injec- tions: a skilled ‘proceduralist’, one or more nurses to assist in the procedure, and the appropriate space. When considering all resources available in the hospital, only 17% of HD-specialist clinics are estimated to have enough capacity to serve the eligible population. When simulating the additional referral-in of patients from non-HD-specialised clinics, only 6% of HD clinics have enough capacity.

To ensure adequate care, capacity-constrained healthcare systems will need to plan adequately and ensure providers have sufficient training and resources to deliver new intrathecally administered DMTs.

kopano.mukelabai@roche.com
238  Cogniton and mood disorder in cervical dystonia
Authors: Monaghan Ruth , McCormack Derval , Ndukwe Ihedinachi , O’Riordan Sean , Burke Tom , Pender Niall , Hutchinson Michael , O’Keeffe Fiadhnait
Published: May 2022

Background

Cervical dystonia patients have a high prevalence of anxiety and depression which is the main predictor of quality of life. Reports of abnormal cognition in cervical dystonia may be confounded by concurrent mood disorder.

Aim

To assess the relationships between measures of cognition, mood disorder, disease severity, and quality of life in cervical dystonia.

Methods

In 45 cervical dystonia partici- pants, we assessed clinical measures of disease severity, mood disorder using the Beck Anxiety Inventory and Beck Depression Inventory, quality of life by the Cervical Dystonia Impact Profile and Utility Values from the EQ-5D-5L and administered an extensive neuropsychological assessment battery. The outcomes of clinical and neuropsychological variables were compared between participants with and without signifi- cant mood disorder.

Results

Significant anxiety and/or depression were reported in 18 participants (40%); 27 participants (60%) had no prevalent anxiety or depression. Significant deficits in executive function were found in participants with mood disorder in comparison to those without mood disorder; otherwise neuropsychological testing showed no between-group abnormalities. Mood disorder significantly cor- related with measures of executive function and quality of life. Abnormal Social Cognition was found in cervical dystonia, unrelated to prevalent mood disorder.

Conclusion

Mood disorder in cervical dystonia is a significant independent predictor of both measures of executive function and quality of life. Other than in Social Cognition, there was no evidence of any primary cognitive impairment in cervical dystonia.

mhutchin2@mac.com
Review of the clinical spectrum of typical and atypical Lyme neuroborreliosis in southwest England
Authors: Russell Amy Ross , Petridou Christina , Saeed Kordo , Jeppessen Catherine , Sheridan Elizabeth , Okyere Sharon , Lee Mihye , Dryden Matthew , Lovett Joanna
Published: May 2022

Background

Lyme disease is endemic in the UK with a high incidence in southwest England. Neurological involvement occurs in approximately 5% of infected individuals. Previous reviews in southwest England have shown a consistent phenotype in most cases, however anecdotal review suggests a small number of atypical cases, with diverse presentations, which provide a diagnostic challenge, even to experienced neurologists.

Methods

We performed a retrospective, observational study of all identified cases (positive screening ELISA confirmed by immunoblot and neurological symptoms) of neuroborreliosis from six hospitals between January 2015 and December 2017. In addition, we reviewed atypical cases seen over the last decade in the regional neurosciences centre in depth.

Results

72 patients were included in the observational study. 83% had characteristics of Bannwarth’s syndrome (cranial neuropathy, radiculopathy and CSF pleocytosis). Unusual cases included mononeu- ritis multiplex.

Central nervous system involvement was rare. We saw cases presenting with cerebrovascular events, meningitis and encephalitis. Complete resolution of symptoms was reported in 72% of patients. 28% of patients reported residual symptoms, most commonly fatigue and memory problems.

Conclusions

This is the largest UK review of neuroborreliosis. The presentation is usually typical, but atypical presentations vary and can be challenging. The majority of patients recover fully.

amyrossrussell@gmail.com
243  Mood disorder affects age at onset of adult-onset cervical dystonia
Authors: Ndukwe Ihedinachi , O’Riordan Sean , Walsh Cathal B , Hutchinson Michael
Published: May 2022

Introduction

Mood disorder is common in cervical dystonia (CD) and may precede the onset of dystonia. There is controversy as to whether mood disorder is part of the primary process or secondary to the disability.

We assessed the characteristics of CD patients in relation to a past history of mood disorder.

Methods

We collected demographic data, medical history of mood disorder, and prospectively measured prevalence of mood disorder using the BAI and BDI.

Results

In 193 patients (128 women and 65 men) mean age at onset of CD was 43.9 years with mean duration, 17.5 years. Men had earlier age at onset of CD than women(p=0.0037). 53/128 (41%) women with a history of a mood disorder had a significantly earlier median age at onset than 75/128 (59%) women without a history of mood disorder (p=0.005). 33(26%) women with mood disorder prior to CD also had an earlier age at onset than the 75(59%) without such a history (p=0.0154). A history of mood disorder was more common in women(41%) than men(31%). 54/128(42%) women and 21/65(32%) men had current mood disorder symptoms.

Conclusions

The significant differences in the age at onset in women with, and without, a history of mood disorder strongly indicates that anxiety and depression are primary non-motor (and premotor) symptoms of CD.

ihedinachindukwe@gmail.com
263  Neurofilament light chain is a predictor of outcome after aneurysmal subarach- noid haemorrhage
Authors: Garland Patrick , Morton Matthew , Toombs Jamie , Heslegrave Amanda , Durnford Andrew , Gaastra Ben , Zolnourian Ardalan , Zetterberg Henrik , Bulters Diederik , Galea Ian
Published: May 2022

Background

The best predictor of clinical outcome after aneurysmal subarachnoid haemorrhage (aSAH) is the World Federation of Neurological Surgeons (WFNS) score. Yet, this marker of early brain injury only explains 12% of the variance in outcome. Prolonged neurotoxicity via extracellular haemoglobin (Hb) may play a role. Neurofilament light chain (NFL) is released during neuronal damage. We hypothesize that CSF NFL predicts clinical outcome after aSAH and reflects Hb-induced neurotoxicity.

Methods

CSF was collected via an external ventricular drain from 44 high-grade aSAH patients over 14 days post-ictus, and via lumbar puncture from 11 non-haemorrhagic, non-inflammatory neurologi- cal control patients. NFL and Hb were measured using enzyme-linked immunosorbent assay and ultra- performance liquid chromatography respectively. Clinical outcome after aSAH was assessed using the modified Rankin Score (mRS).

Results

NFL was higher in aSAH versus control CSF. High CSF NFL and high WFNS independently predicted worse mRS. CSF NFL was a stronger predictor than WFNS. Post-ictus, NFL and Hb CSF concentration gradually increased over two weeks. Maximum CSF NFL was correlated with maximum preceding CSF Hb, but not WFNS.

Conclusion

The biomarker NFL is a predictor of clinical outcome after aSAH. NFL concentration likely reflects delayed Hb-induced neurotoxicity rather than early brain injury.

pg1p07@soton.ac.uk
White matter hyperintensities and brain microbleeds in ataxia-telangiectasia: the Cambridge cohort
Authors: Tiet May Yung , Nannoni Stefania , Horvath Rita , Markus Hugh S , Hensiek Anke
Published: May 2022

Background

Isolated reports indicate the presence of MRI T2 white matter hyperintensities (WMH) and brain microbleeds (BMB) in ataxia telangiectasia (AT), but this has not previously been assessed in a sys- tematic way. We report the MRI brain findings of a large cohort of adults with variant and classical AT.

Methods

Two investigators independently assessed T2-FLAIR, SWI, GRE sequences of 38 AT patients, for WMH using the Fazekas and modified-Scheltens scales, and for probable BMB using the BOMBs scale.

Results

WMH were observed more frequently in variant AT (81.8% vs 58.3% classic), in the periventricular and deep white matter. Modified-Scheltens score was mean 2.29 (range 0- 11, SD 2.46), without signifi- cant differences between classic and variants (p=0.51); our cohort scored between mean 0.32 (range 0–1, SD 0.47) using Fazekas scale (p=0.25).

BMB were seen more frequently in classic AT (57.1% versus 4.6% variant, p<0.01, SD 33.80) in cortical and subcortical regions. Three classic AT patients had extensive (>100) BMBs.

Conclusions

Mild WMH is a common finding in AT, of which the significance is unknown. The presence of BMBs in a large proportion of patients supports the presence of neurovascular abnormalities in AT, which could contribute to the neurodegenerative process or predispose to cerebral haemorrhage.

myt29@cam.ac.uk
L-arginine and mitochondrial encephalomyopathy, lactic acidosis and stroke- like episodes (MELAS): a systematic review
Authors: Stefanetti Renae , Ng Yi Shiau , Errington Linda , Dlay Jaspreet , Turnbull Doug , McFarland Robert , Gorman Grainne
Published: May 2022

Background

Stroke-like episodes are a neurological emergency associated with MELAS syndrome. Recovery from stroke-like episodes occurs over a variable time period (hours to weeks) and no rigorous natural history studies of the condition have been undertaken. Despite this, L-arginine has been adopted as both acute treatment and prophylaxis. We sought to systematically evaluate the evidence for L-argi- nine use.

Methods

We searched 5 databases published between inception and 15/01/2021. The inclusion criteria were 1) use of L-arginine in acute or chronic management of stroke-like episodes; 2) genetically confirmed mitochondrial disease. GRADE was used to assess the quality of evidence. Prospero registra- tion: CRD42020181230.

Results

Of 3,541 articles identified, 37 were eligible (3 open-label, 1 retrospective cohort, and 33 case reports). All studies were rated as very low-quality evidence. Open-label trials reported clinical response based on the subjective improvement of symptoms within 24 hours of treatment. Thirty-seven patients received L-arginine acutely in other studies. Clinical response was reported over variable time points (27/37); though confounders such as anticonvulsants (19/37) were not considered. Efficacy of chronic L-arginine supplementation cannot be established in most studies.

Conclusion

Evidence for the use of L-arginine in MELAS syndrome is poor, and is associated with a high risk of bias.

yi.ng@ncl.ac.uk

19
When the rhythm moves you
Authors: Doshi Anisha , Midgley Laura , Kyaw Kaung Myat , Tsarouchas Nicholas , Redmond Ian , Harikhrishnan Sreedharan , Memon Shafqat
Published: May 2022

A 47-year-old lady presented with a 6-year history of increasing refractory seizures and scoliosis despite trials of multiple anti-epileptic drugs(AEDs). She described seizures of temporal lobe(TLE) semiology provoked mainly by music which evoked elation. These musicogenic reflex seizures (MRS) were occurring up to twice weekly.

CT and MRI brain, paraspinal EMG, and routine EEG were unremarkable. Provoked EEG captured a gen- eralised seizure with focal left mid-anterior temporal focus with rapid bilateral spreading within 2 minutes of playing a piece of music and lasted for 90 seconds, followed by a prolonged post-ictal phase. Auto- antibody screen revealed persistently elevated and rising serum GAD-Ab(glutamic acid decarboxylase antibodies) at 11618 U/mL with GAD positive on CSF testing. CT body, PET and transvaginal ultrasound revealed no significant abnormalities. Plasmapheresis was trialled with some effect.

We present a rare case of GAD-Ab mediated MRS. MRS are well described, with 9% mediated by GAD-Ab. This mechanistically accounts for the limbic MRS semiology. We highlight the importance of GAD-Ab screening for refractory new onset TLE in an adult, with high serum GAD-Ab titre (≥2000 U/mL) and evidence of intrathecal synthesis. Unlike other immune-mediated epilepsies, GAD-Ab-mediated epilepsy responds poorly to AEDs and may require immunosuppression with rituximab or cyclophosphamide.

References

1. Kaplan, 2003; Falip et al., 2018, 2019; Tseng et al., 2018; Dade et al., 2020; Jesus-Ribeiro et al., 2020

anishadoshi@doctors.org.uk|ABN Bursary
A localisation issue
Authors: Midgley Laura , Broad Rebecca , Poole Olivia , Flores Lorena , Harikrishnan Sreedharan , Lauckaite Kristina , Moran Nicholas
Published: May 2022

A 65 year old lady presented with a one week history of chorea, dysarthria, behaviour change and imbalance. Her condition continued to progress with development of a motor axonal polyneuropathy, affecting mainly the distal upper limbs, and encephalopathy, with a Glasgow Coma Score (GCS) of 6.

MRI head revealed non-specific white matter changes in the cerebral hemispheres. EEG showed a slow background and bifrontal triphasic waves. CSF testing revealed a lymphocytic pleocytosis (34/mm3) with elevated protein (0.88g/L). Extensive microbiological, genetic and autoimmune screening was negative other than positive IgLON5 antibodies (titre 1:1000).

Treatment with intravenous methylprednisolone appeared to be unhelpful, however, plasma exchange was associated with resolution of the encephalopathy and distal upper limb weakness. Intravenous cyclophosphamide was given followed by oral mycophenolate. The patient remains clinically stable at one year after onset.

Anti-IgLON5 disease is typically characterised by central nervous system involvement (sleep disturbance, chorea, gait imbalance and bulbar features) and an uncertain response to treatment. We have presented a case of this rare condition, unusual on account of the peripheral involvement (motor axonal polyneu- ropathy), and apparent improvement with immunosuppression.

Laura.midgley1@nhs.net
001  Machine learning accurately determines the population prevalence of Alzheimer’s disease based on microbiome profile
Authors: Basgaran Amedra , Lymberopoulos Eva , Reis-Dehabadi Maryam , Sharma Nikhil
Published: May 2022

The human microbiome is a complex and dynamic community of microbes, thought to have symbiotic benefit to its host. Influences of the gut microbiome on brain microglia have been identified as a potential mechanism contributing to neurodegenerative diseases such as Alzheimer’s disease (AD), motor neurone disease and Parkinson’s disease. We hypothesise that machine learning applied to the population level gut microbiome will predict the prevalence of AD.

Analyses were performed in R, using two large, open-access microbiome datasets (n=1006 & n >2000) (Lahti et al., 2014; Pasolli et al., 2017). Countries in these datasets were grouped based on AD prevalence and the microbiome profiles compared.

In countries with a high prevalence of AD, there is a significantly lower diversity of the gut microbiome (p<0.001). A PERMANOVA (p<0.05) revealed significant differences between several taxa in countries with high vs low prevalence of AD. Additionally, using machine learning, we were able to predict the preva- lence of AD within a country based on the microbiome profile (Mean AUC 0.935 & 0.870).

We conclude that differences in the microbiome can predict the varying prevalence of Alzheimer’s disease between countries. Our results support a key role of the gut microbiome in neurodegeneration at a population level.

a.basgaran@nhs.net
009  Language decline following white matter tract damage during anterior temporal lobe resection in language dominant hemisphere
Authors: Binding Lawrence , Taylor Peter , Thompson Pamela , Baxendale Sallie , Tisi Jane de , McEvoy Andrew , Miserocchi Anna , Winston Gavin , Duncan John , Vos Sjoerd B
Published: May 2022

Anterior temporal lobe resection (ATLR) for temporal lobe epilepsy (TLE) has remission rates up to 80%, however is underutilised, in part because of the risk of language decline following surgery. Language decline occurs in up to 50% of ATLR in the language dominant side. This can occur despite careful planning with functional MRI (fMRI) language mapping. Several white matter bundles are close to the resection area which could contribute to language decline. Diffusion MRI-based fibre tracking to map the arcuate, uncinate, inferior fronto-occipital, inferior, and middle longitudinal fasciculus was performed on 43 patients. We extracted the left-sided bundles in those temporal lobe epilepsy patients who had left-dominant language based on verbal fluency functional MRI (fMRI) and a left-sided resection. Resection masks were manually drawn and used as exclusion regions. Changes from pre- to post-operative tractography and language ability were measured as percentages. Linear regression revealed that the McKenna Graded Naming test decline was predicted by the arcuate and middle longitudinal fasciculus resection (F(2,41)=5.562, p=0.007) with an adjusted R2 of 0.175. These findings demonstrate that damage to anterior arcuate extensions and the middle longitudinal fasciculus affects picture naming ability.

lawrence.binding.19@ucl.ac.uk