bluuebunny/crossref_metadata_2025 huggingface dataset:
15.09 Examining the neurological consequences of new psychoactive substances -‘legal highs’
Authors: Jones Rebekah , Kelleher Charles , Tanti Matthew , Cosgrove Jeremy , Maguire Melissa
Published: March 2023

Background

New psychoactive substances (NPS) are of global concern accounting for increasing deaths in the UK. We conducted a retrospective analysis of patients attending Leeds Teaching Hospitals NHS Trust with NPS abuse during 2016–2017 and report neurological presentations and outcomes.

Methods

We identified 227 records of NPS attendances through electronic searches using Symphony electronic software. Demographic and clinical data were obtained from case-note review.

Results

Average age was 34, 82% were male. Two thirds were unemployed, 17% prisoners, 9% students and 4% prison workers. ‘Spice’ accounted for the majority of presentations (90%). 4-methyl methcathinone (‘MCAT’) accounted for 8% of presentations. The remainder reported nitrous oxide (NOS) use. In the spice subgroup, 52% had low GCS, 20% had seizures. Ventilatory support was required in two cases (1%). In the MCAT subgroup, average GCS was 14 and 20% of patients presented with seizure. Psychiatric disturbance was higher in MCAT group (30%). Most patients (62%) were observed in the emergency department and then discharged. Only 3% were referred to the drug and alcohol team.

Conclusions

Spice accounted for the majority of NPS presentations. Unemployed single men were particularly at risk. Low GCS and seizures were the commonest presentations, with most requiring observation only.
225 Sporadic inclusion body myositis: a longitudinal observational study investigating outcome measures for clinical trials
Authors: Sangha Gina , Skorupinska Iwona , Germain L , Bellin A , Parton Matthew , Hanna Michael , Miller James , Hilton-Jones David , Freebody Jane , Machado Pedro
Published: March 2023

Background

Sporadic inclusion body myositis (IBM) is the most common age-related acquired myopathy. Our aim was to longitudinally evaluate clinical, quantitative and functional characteristics of the disease to develop statistical models of progression that can be used in clinical trials.

Methods

In a prospective cohort study, we recruited 205 patients with a diagnosis of IBM across three centres (London, Oxford and Newcastle).

Patients underwent bilateral manual muscle testing (MRC scale), quantitative muscle testing and disability scoring (IBM Functional Rating Scale) at each follow up visit. The time at which a patient first required a mobility aid was recorded.

Linear multilevel models were fitted to investigate the progression of these scores over time. Cox proportional hazards regression was used to model time to use of a mobility aid.

Results

In the preliminary analyses we have generated reliable multilevel models of disease progression using those muscle groups that are worst affected by the disease over time. We have also modelled the progression of IBMFRS over time. These models can be used to predict/monitor disease progression.

Conclusion

This study will be the largest prospective observational study in IBM to date and will reveal useful outcome measures that can be used in clinical trials.
226 Quantitative strength profiling in inclusion body myositis
Authors: Lilleker James B , Oldroyd Alexander , Chinoy Hector , Miller James AL
Published: March 2023

Background

Inclusion body myositis (IBM) is a rare idiopathic inflammatory myopathy subtype. Our study aimed to describe the disease progression rate in IBM using measures of muscle strength and functional assessment tools.

Methods

Retrospective analysis of quantitative muscle strength data and functional assessment tool results (IBM Functional Rating Scale [IBM-FRS] and the Neuromuscular Symptom and Disability Score [NSS]), systematically collected from verified IBM cases (July 2003 to March 2015) at a UK neuromuscular clinic. Yearly rate of strength change was estimated for each muscle group and associations between with the IBM-FRS/NSS were examined using simple linear regression.

Results

Data from 80 IBM cases (44% female) were analysed, a total of 232 person-years and a median 2.3 years (IQR 0.6, 4.4) follow-up. Similar rates of deterioration were found for right and left sided muscle groups. Annual rate of strength loss was greatest for grip, pinch and knee extension (-5.5% [95% CI -6.3, -4.6], -16.0% [-18.4, -13.5] and -7.1% [-7.6, -6.5]). The rate of strength loss was greatest for males. Increased strength measurements were associated with improved IBM-FRS/NSS scores for most muscle groups.

Conclusion

This is the first long-term study to comprehensively demonstrate quantitative strength change in a large IBM cohort. We provide valuable natural history data to support discussions regarding prognosis, focus effective choice of outcome measures and inform required study numbers for future clinical trials.
227 An audit of adherence to ABN guidelines in myasthenia gravis diagnosis and management
Authors: Hutchcroft Christopher , Boix-Codony Marc , Hamid Shahd
Published: March 2023

Introduction and aims

We identified previously-audited shortfalls in myasthenia gravis diagnostic and management practice, notably in ensuring appropriate bone protection and making sure that patients were followed up in prompt time. We aimed to reaudit practice at The Walton Centre and identify adherence to ABN guidelines.

Methods

Patients investigated for suspected myasthenia presenting October 2017 to September 2018 who were subsequently managed at the Walton Centre.

Results

43 patients identified. Anti-AChR at first appointment: 42/43 (97%) Serum anti-MuSK if anti-AChR is negative: 9/10 (90%) MR brain for ocular MG if serology and neurophysiology negative: 1/1 (100%) Thymus imaging for all patients: 38/41 (93%). Neurophysiology if serology negative: 7/7 (100%) First follow-up within six weeks: 38/41 (44%). Second follow-up within 12 weeks: 22/40 (55%) Generalised MG admitted unless symptoms mild: 9/10 (90%) Pyridostigmine started at the time of diagnosis: 35/36 (97%) Glucocorticoids started if no remission on pyridostigmine: 22/22 (100%) Bone protection if on glucocorticoids: 19/21 (90%)

Conclusion

We found that adherence had improved regarding bone protection when on steroids, but follow-up times remained a problem. Additionally, anti-MUSK and EMG were largely used when indicated, but also often unnecessarily used in the presence of positive AChR antibodies.
229 Dysregulated axonal homeostasis in C9orf72 iPSC-derived motor neurones
Authors: Mehta Arpan , Selvaraj Bhuvaneish , Dando Owen , Burr Karen , Hardingham Giles , Chandran Siddharthan
Published: March 2023

Dysregulated axonal homeostasis is a potential pathomechanism in ALS, but its relevance to the commonest known genetic mutation in ALS – the C9orf72 repeat expansion – remains unclear. We performed unbiased transcriptomics of cell-autonomous C9orf72 motor neurone (MN) perturbations in a humanised model using patient-derived induced pluripotent stem-cell lines against an isogenic background generated by CRISPR/Cas9 and studied the functional consequences of downstream axonal hits. Differential gene expression analysis examined the intersection in differentially expressed genes between the mutant-isogene pairs, revealing 215 genes: 95 up and 120 down. Pathway analysis showed an axonal signature, with upregulation of pathways involved in cytoskeletal organisation, axon guidance, and Trk receptor signalling, and downregulation of pathways involved in the mitochondrial electron transport chain and axon guidance. Significantly dysregulated genes were confirmed using real-time quantitative PCR. This led to two hypotheses examining for aberrations in axonal length and transport. Axonal length was measured using manual tracking of SMI-312 labelled axons. Axonal transport was determined by tracking Ds-Red2 labelled mitochondrial movement using a live-imaging setup and analysed using KymoToolBox. Both axonal length and transport were reduced in the mutants compared to their isogenic counterparts. Further experiments are underway to determine whether common pharmacological manipulations can rescue both phenotypes.
235 Epidemiology of motor neurone disease in wales
Authors: Saad Toni , Dawson Ken , Hirst Claire , Baker Idris , Lowman Andrea , Wardle Mark , Harding Katharine ,   on behalf of the South Wales Motor Neurone Disease
Published: March 2023

Background

National registries of patients with rare disease such as motor neurone disease (MND) can lead to more reliable epidemiological estimates.

Methods

The South Wales MND Network records clinical data on all patients referred to the specialist MND clinics in south Wales and diagnosed with MND. Anonymised data was accessed for analysis. The prevalence date was 23/6/2016, and all patients registered with the South Wales MND Network, alive and resident in the region on that date were included. Population estimates were obtained from Welsh Government data.

Results

There were 202 people with MND on the prevalence date, of whom 122 (60.4%) were male. The median time from onset to diagnosis was 1.4 years (interquartile range 0.9–2.4 years). Prevalence in the region was 8.8 per 100,000. This varied by local health board, with the highest prevalence seen in Aneurin Bevan University Health Board (12.1 per 100,000), and the lowest in Abertawe Bro Morgannwg University Health Board (7.0 per 100,000). Male:female ratio was similar for all local health boards (χ2=3.6, p=0.46).

Conclusions

Our estimates of prevalence are in keeping with other European countries. Future investigation into variation in MND prevalence may provide insights into underlying mechanisms of disease.
237 SLC25A46 mutations cause a spectrum of disorders including CMT2 with optic atrophy
Authors: Doherty Carolynne , Pipis Menelaos , Cortese Andrea , Poh Roy , Polke James , Pitceathly Robert , Rossor Alexander , Reilly Mary
Published: March 2023

Case

A 20-year-old female had symptom onset age 7 of bilateral foot drop and distal lower limb atrophy. Nerve conduction studies demonstrated a length dependent axonal motor and sensory neuropathy. At 16 her vision deteriorated to 3/36 right, 6/60 left. Visual evoked potentials were borderline compatible with bilateral optic atrophy. Metabolic and structural causes were excluded.

Examination

At age 18 examination demonstrated bilateral foot drop and a positive knee bob sign. There was asymmetrical distal limb atrophy. Fundi were pale. Reflexes were brisk in upper limbs and knees with absent ankles and mute plantars.

Results

The 56-gene Bristol axonal neuropathy panel revealed a non-pathogenic TRPV4 mutation. Mutations in OPA1, OPA3, POLG, ATPase 6 and 8 were not identified. Exome sequencing in the research setting demonstrated compound heterozygous SLC25A46 mutations. One mutation was confirmed in each of her parents.

Discussion

Mutations in SLC25A46 are associated with spectrum of disorders encompassing pontocerebellar hypoplasia (including lethal congenital cases), Leigh Syndrome, Progressive myoclonic ataxia with optic atrophy and neuropathy, and hereditary motor and sensory neuropathy type 6B, sometimes with associated features such as cerebellar ataxia and spasticity. We present a case of CMT2 with optic atrophy due to heterozygous mutations and discuss the literature.
240 A case of fulminant guillain-barré syndrome mimicking brain death
Authors: Sivagnanasundaram Jananee , Broad Rebecca , Tague Lucy , Quaresma Catarina , Dittrich Richard , Alkufri Fadi , Harikrishnan Sreedharan
Published: March 2023

Guillain-Barré syndrome (GBS) encompasses a spectrum of acute immune-mediated polyneuropathies. Rarely, in its fulminant form, it can rapidly progress to mimic brain death. We present a case with diagnostic challenges due to a limited history.

A 58-year-old gentleman presented generally unwell and within hours of admission choked on his dinner and suffered a cardiorespiratory arrest. Review on ITU revealed absent brainstem reflexes apart from a weak pupillary light response.

EEG showed slowing with subtle reactivity, MRI Brain was normal, and CSF revealed albuminocytological dissociation.

On day 27 of admission, he was found to follow commands with eye movements, appearing to be in an incomplete locked-in state. Nerve conduction studies confirmed a severe axonal sensorimotor neuropathy with sural sparing. He was treated with plasma exchange and intravenous immunoglobulins and continues to make significant motor improvements each week.

This case highlights the crucial recognition of this extreme presentation of GBS, as a misdiagnosis of brain death may lead to the withdrawal of ventilatory support. In a third of reported similar cases there has been a good recovery and in the majority (as in our case) serum ganglioside antibodies have been negative, raising the possibility of alternative nodal and paranodal target antigens.
246 Refractory seizures: a case of post-partum pyridoxine dependent epilepsy
Authors: Chaudhuri Shreya , Ball Joanna , Murphy Elaine , Muhammed Kinan
Published: March 2023

A 29 year old woman underwent a planned Caesarean delivery. She denied any pre-existing medical conditions. 72-hours later she developed multiple generalised tonic-clonic seizures requiring sedation and intubation. Brain imaging revealed long standing enlargement of the ventricles. Urinary protein and blood pressure were normal. She continued to have frequent seizures confirmed on EEG despite treatment with multiple anti-epileptics.

Collateral history from family revealed seizures as an infant but none since aged 6 months and that she was not taking anticonvulsants. Further inquiries confirmed a regular prescription for Vitamin B6 (Pyridoxine) which she had stopped during pregnancy. In the context of refractory seizures and the imaging findings, the possibility of Pyridoxine-dependent epilepsy was raised. Pyridoxine 100 mg twice daily was started. After the first dose, the patient’s seizures stopped and she was extubated, anticonvulsants were stopped and she had no further seizures.

Pyridoxine dependent epilepsy is an autosomal recessive condition. Clinical features include refractory seizures in the first few months of life. It is caused by mutations in the ALDH7A1 gene which codes for α-aminoadipic semialdehyde dehydrogenase (α-AASA, Antiquitin), an enzyme involved in the breakdown of lysine within the brain resulting in raised levels. Diagnosis involves genetic testing and elevated plasma and urine levels of α-AASA. Treatment is lifelong daily pyridoxine supplementation.

Pabrinex containing Pyridoxine should be considered in all patients who have ongoing seizures not responding to multiple anti-epileptic medication.
247 Autosomal recessive spinocerebellar ataxia type 10 (SCAR10); a rare diagnosis courtesy 100,000 genome project
Authors: Zafar Hassan W , Gutowski Nicholas J
Published: March 2023

Background

Autosomal recessive spinocerebellar ataxias (ARCAs) can involve both central and peripheral nervous systems as well as other organ systems and so frequently pose a diagnostic challenge due to significant overlap in clinical presentation.

Objective

We report a case of a Caucasian lady who presented with ataxia, dysarthria and vertical gaze nystagmus. Genetics revealed a mutation in the ANO 10 gene confirming a diagnosis of Spinocerebellar Ataxia Type 10 (SCAR 10).

Methods

A 67 year old lady presented 25 years ago with unsteady gait, dysarthria and vertical gaze nystagmus. Her symptoms gradually progressed and she has used a wheelchair for 5 years. Extensive biochemical, imaging and genetic investigations remained unrevealing. MRI showed marked cerebellar atrophy. She had a male sibling with a similar cerebellar syndrome, he died 8 years ago. There is no consanguinity and no other family history. She underwent whole genome sequencing (WGS) as part of the 100,000 Genome project.

Results

WGS revealed heterozygous mutations in the ANO 10 gene confirming Spinocerebellar Ataxia Autosomal Recessive 10 (SCAR 10).

Conclusions

Gene panel coverage varies with time and rare ARCAs may remain undiagnosed. This case demonstrates the value of the 100,000 Genome project, and by inference WGS, for rare genetic disorders.
248 A 57-year-old man with deteriorating mobility and deafness
Authors: Stavrou Maria , Yeo Jing Ming , Richard Davenport
Published: March 2023

A 57-year-old man re-presented to the neurology clinic in August 2014 with a 20-year history of progressive gait decline, and a 2-year history of requiring crutches and a wheelchair. Recently, he had also developed numbness below his knees. His upper limb function had remained normal. He wore bilateral hearing aids for sensorineural deafness, had a 10-year history of red–green colour blindness and suffered from bladder dysfunction for several years. His neurological symptoms had been previously investigated but without a diagnosis, and he had been lost to follow-up for several years. In 2017, with the advent of next-generation sequencing gene panel, he was screened for 20 spastic paraparesis genes. This identified a mutation inSPG7in the form of a homozygous variant c.1529C>T/p.Ala510Val, consistent with autosomal-recessive HSP.

This man’s diagnosis was made by molecular genetic testing nearly 20 years after his symptoms began. This was achieved by the astonishing progress over the last decade in identifying HSP genes coupled with the introduction of high-throughput sequencing approaches. These advances provide benefits to HSP families including diagnostic certainty, avoidance of time-consuming and expensive investigations, genetic counselling and optimisation of care. A step forward would be to establish an international database of people with this condition to characterise genotype/phenotype correlations, elucidate the natural history and to facilitate clinical trials focusing on effective interventions.
251 Economic burden of spinal muscular atrophy type 1 (SMA1)
Authors: Dabbous Omar , Seda Jennifer , Kausar Imran , Droege Marcus , Sproule Douglas M
Published: March 2023

Background

SMA1 is a rapidly progressing disease resulting in muscle weakness, respiratory failure, and early death. This retrospective analysis estimated the economic burden of SMA1 using QuintilesIMS’s PharMetrics Plus Health Plan Claims Database.

Methods

SMA1 infants (N=119) were matched (1:1) with a random sample of infants by age, gender, index year, and Charlson Comorbidity Index. Healthcare resource utilization (HCRU) and costs incurred during the post-index/follow-up period (≥30–360 days, February 2011–November 2016) were compared.

Results

Significantly more SMA1 patients had ≥1 all-cause HCRU claims vs. matched patients (98.3% vs. 54.6%, P<0.0001). Mean per-patient-per-month (PPPM) all-cause HCRU was higher for SMA1 infants: pharmacy (1.43 vs. 0.37 prescriptions); outpatient (14.10 vs. 2.17 services); inpatient (0.23 vs. 0.003 admissions) (all, P<0.0001). Mean PPPM hospital admissions (0.23 vs. 0.003), length of hospital stay (6.93 vs. 0.09 days), procedures/admission (1.49 vs. 0.03), and readmissions (0.04 vs. 0.00) were also significantly greater for SMA1 infants (all, P<0.0001). Pharmacy, outpatient, and inpatient costs PPPM were greater in SMA1 infants ($371 vs. $20; $4,192 vs. $232; and $22,500 vs. $22 [all, P<0.0001]), resulting in extrapolated all-cause total annual costs of $324,751 (SMA1 cohort) vs. $3,294 (matched cohort).

Conclusions

The economic burden of SMA1 is substantial.
252 Speed to treatment effect in spinal muscular atrophy type 1
Authors: Droege Marcus , Dabbous Omar , Feltner Douglas , Novack Aaron , Kausar Imran , Menier Melissa , Sproule Douglas
Published: March 2023

Background

Spinal Muscular Atrophy type 1 (SMA1) is a rapidly progressing disease resulting in death/permanent ventilation by 2 years of age. In ENDEAR, ∼10% of patients died/required permanent ventilation within 2 months after therapy initiation; 39% died/required permanent ventilation by 6 months. This may reflect a non-immediate therapeutic impact related to loading dose schedule. This study explored the rapidity of therapeutic effect of onasemnogene abeparvovec (AVXS-101) gene-replacement therapy (phase 1 study) relative to nusinersen (phase 3 study, ENDEAR).

Methods

SMA1 patients were treated with a one-time intravenous AVXS-101 injection (NCT02122952; cohort 2; N=12; 24 months follow-up). Outcomes were event-free survival (EFS, no death/permanent ventilation [AVXS-101: ≥16 hours ventilation/day for >2 weeks; ENDEAR: tracheostomy or ≥16 hours ventilation/day for >21 days]) and motor function improvements (CHOP-INTEND).

Results

All patients treated with AVXS-101 survived event-free 24 months post-dose, while 49/80 nusinersen patients showed EFS. Rapid increases in CHOP-INTEND of 9.8 and 15.4 points were observed at 1- and 3-months post–AVXS-101 dose (nusinersen: ≤5-point increase at 2 months after initiation).

Conclusions

AVXS-101 appears to improve survival and induce more rapid motor function improvements relative to nusinersen, consistent with rapid restoration of survival motor neuron expression in motor neurons with a single dose.
253 Idiopathic intracranial hypertension causing back pain and visual loss without headache
Authors: Cheema Sanjay , Cooper Sarah
Published: March 2023

Idiopathic intracranial hypertension (IIH) usually presents in overweight young women with headache and visual disturbance.

We report a case in a slim young woman, who described six months of increasingly severe lower back pain, worse on lying flat and often waking her at night. Despite a significantly elevated cerebrospinal fluid (CSF) opening pressure of 55cm CSF, at no point did she experience a headache.

The back pain entirely resolved as CSF pressure was treated. No secondary cause was found on brain or spinal imaging and CSF constituents were normal. She sustained some early and permanent visual loss and required a shunt procedure to control the raised intracranial pressure and ongoing visual deterioration. She has remained well, 20 months since the original presentation.

Our patient had pre-existing ocular hypertension, which did not resolve after effective treatment of the raised intracranial pressure and may have affected the presentation of papilloedema.

This case highlights that IIH should be considered in patients with visual symptoms and back pain, even in the absence of headache, and acts as a reminder that patients with IIH are not necessarily overweight.
254 Visual inversion illusion in a patient with multiple sclerosis
Authors: Cheema Sanjay , Mahmud Mohammad , Cooper Sarah
Published: March 2023

Background

It is possible to suddenly and temporarily experience the illusion that the world is upside down.

This visual inversion illusion is rare, but has previously been reported in patients with migraine, posterior circulation stroke, traumatic brain injury, and multiple sclerosis (MS).

The same illusion can be provoked in neurologically-normal aircraft pilots or astronauts under certain circumstances; and in experiments involving wearing vision-inverting goggles.

Case history

We report a patient with secondary progressive MS, who for the past six months reported that ‘when I get tired my eyes see everything upside-down’. These episodes occurred most evenings and resolved after a night’s sleep.

On examination there was evidence of previous optic neuritis and intranuclear ophthalmoplegia. MRI brain showed multiple lesions in the brainstem and visual pathways.

Discussion

This case adds to the small number of reports of this phenomenon in the context of MS, and the first where it is related to fatigue.

The precise anatomical substrate is unknown. It has been reported in patients with single lesions in the brainstem, vestobulocerebellum, and right parieto-occipital region.

The illusion may occur due to disrupted sensory integration between visual input and other verticality signals, for example from the vestibular system.
262 Consequence or coincidence? Migraine and stroke
Authors: Oo Aung
Published: March 2023

A 52-year-old female was admitted following 1-week history of headache, and 1-day history of vertigo.

Her only past medical history was migraine. She is a non-smoker. She is not on any medications including contraceptive pills.

The headache was like her usual throbbing headache- on the right side of head, associated with nausea, and photophobia. Visual flickering had already resolved on admission. This was not relieved by over-the-counter painkiller.

She experienced vertigo on the day of admission which was new for her.

Clinical examination revealed normal neurological examination apart from ataxia. Other cerebellar signs were notably absent.

She was initially treated for migraine with aspirin, prochlorperazine and sumatriptan with no success.

MRI head revealed small acute infarct in right cerebellum. MRA showed no aneurysm or dissection. All young stroke diagnostic work-up were unremarkable.

Discussion

Migraine may mimic stroke. It is also known to increase the risk of stroke, particularly in women who have migraine with aura. There is an association between migraine with aura and silent infarct-like lesions on brain MRI located mainly in the posterior circulation white matter or cerebellum. Thus in this case, migraine is likely to be a cause of stroke, although coincidental occurrence cannot be ruled out.
264 A rare cause of young stroke diagnosed by intracranial MR vessel wall imaging
Authors: Aggarwal Veena , Benjamin Laura , Simister Robert
Published: March 2023

Current stroke guidelines do not facilitate the expedient diagnosis of inflammatory stroke. At UCLH, we have integrated intracranial vessel wall imaging (iVWI) into our stroke pathway to overcome this barrier. We present a case, where iVWI facilitated the diagnosis and helped us interpret a further asymptomatic stroke event.

A 36-year-old man presented with left sided facial weakness. He had type 2 diabetes, hypertension, obesity, and hypercholesterolaemia. CT showed a right MCA/ACA infarct with severe bilateral ICA stenosis. MRI confirmed a borderzone infarct. The patient was treated with anti-platelets, a statin and continued ramipril and amlodipine. iVWI imaging identified an unexpected inflammatory vasculopathy. His CSF was supportive of CNS inflammation, and thus, commenced on prednisolone and empirical valaciclovir. His 3-month interval scan showed new asymptomatic borderzone infarcts that were concordant with hypoperfusion injury, and temporally linked with the initiation of indapamide by his GP, this was subsequently stopped. His vasculopathy remained static. A six-month interval scan showed no new lesion, and improvement of his inflammatory vasculopathy. Using iVWI, we were able to diagnose an inflammatory vasculopathy that could have been missed. The case also highlighted that excessive early reduction of blood pressure can contribute to hypoperfusion related stroke.
265 Stroke-like symptoms on the coronary care unit: consider contrast induced encephalopathy
Authors: Paul NLM , Hyde T
Published: March 2023

A 71 year old right-handed female with acute heart failure, type 2 diabetes and renal failure underwent percutaneous coronary intervention (PCI) and stenting of the right coronary artery as an urgent elective procedure. During the procedure, she was hypotensive which improved with supportive treatment. Within hours of the procedure, she had sudden onset of left hemiweakness and speech difficulty. On examination she was mute with a left hemianopia, left hemiparesis, right arm weakness and left hemisensory loss. CT head showed multiple areas of high attenuation bilaterally in multiple vascular territories, without clear artery occlusion. The next day, the hemiweakness had almost completely resolved, she had fluent speech with amnesia for recent events and subtle cognitive difficulties. Diffusion weighted MRI showed tiny areas of acute cortical infarction in the right hemisphere without any haemorrhage. At the time of hospital discharge, she had recovered completely. We suggest contrast-induced encephalopathy (CIE) as a differential in the diagnosis of stroke-like symptoms and cognitive difficulties after percutaneous coronary intervention. CIE is a reversible neurological complication associated with contrast administration. In acute stroke the abnormalities persist on follow-up imaging, whereas they resolve in CIE. CIE after PCI is rare but recognition is important to avoid the risks associated with erroneous treatment of acute ischaemic stroke or intracerebral haemorrhage.
1 Asymptomatic meningiomas: not so indolent after all?
Authors: Christopher Edward
Published: March 2023

The incidental discovery of asymptomatic meningiomas and their conservative management are becoming more common with the growth in accessibility and use of neuroimaging. These asymptomatic meningiomas may predispose patients to certain risks, some of which can potentially be fatal.

This case describes a 75-year-old woman with known asymptomatic meningiomas and recent history of urosepsis who initially developed recurrent focal motor seizures before rapidly decompensating into super-refractory status epilepticus (SRSE) requiring general anaesthesia. MRI demonstrated the formation of abscess secondary to an infected meningioma (meningioma abscess). She underwent abscess resection and was managed with antibiotics and maintenance antiepileptic drugs post-operatively. The meningioma abscess culture grew the same organism as the urine culture from the preceding urosepsis, suggestive of haematological seeding. She was neurologically and clinically stable and remained seizure-free at three months follow up.

Only ten cases of meningioma abscesses have been reported to date. Risk factors or recent history for infection can be found in all cases. The three joint most common symptoms are fever, headache, and seizures. Our case illustrates the most potentially fatal sequela of meningioma abscess reported to date.

Meningioma abscess is an important differential/complication to recognise in patients with known meningioma in the context of systemic infection. This is becoming increasingly important as the incidental discovery of asymptomatic meningiomas and the proportion of elderly patients with comorbidities and immunosuppression continue to increase. Early suspicion and setting low thresholds for imaging can lead to timely management, improve prognosis, and avoid potentially fatal complications such as SRSE.
2 Meningitis management audit at a single centre: further support for culture-independent techniques in diagnosing meningitis
Authors: Williams Simon , Hassan-Smith Ghaniah
Published: March 2023

Objective

Rapid identification of meningitis and initiation of rational treatment is critically important. We reviewed whether our management was consistent with recent recommendations, for patients treated August 2015-July 2018.

Methods

Patients aged ≥16 coded as having meningitis/meningoencephalitis/specific meningitides (total codes=27) at QEHB over this period (n=497) were identified by informatics and data analysed using electronic records. Specific patient groups were analysed including post-neurosurgical and community-acquired meningitis.

Results

183 patients met the inclusion criteria, for community-acquired meningitis (n=118) or post-neurosurgery (n=65). Within the A&E subgroup (n=92), 80% received neuroimaging pre-LP despite 78% not having contraindication to LP. Median time to LP was 19hours (IQR:11.0–31.0); none performed within 1hour. Antibiotics were administered prior to LP in 72% cases. No neurosurgical patients had meningococcal/pneumococcal serum or CSF PCR sent. Serum PCR was sent in 11% of community-acquired meningitis patients - 23% were positive. CSF PCR was sent in 28% - 22% were positive. None of these cases had positive CSF culture.

Conclusions

Despite BIA recommendations, time-to-LP was delayed and culture-independent techniques such as serum/CSF PCR for bacterial pathogens were under-utilised, despite out-performing CSF culture. The emergence of novel culture-independent methods, including targeted point-of-care and unbiased-metagenomic sequencing, are likely to become increasingly relevant.
09.12 Hu dunnit? Anti-Hu associated paraneoplastic longitudinally extensive transverse myelitis, secondary to small-cell lung cancer
Authors: Mehta Puja R , Sibtain Naomi A , Norwood Fiona , Brex Peter A
Published: March 2023

We describe a 62-year-old smoker, presenting with a 6-week evolving history of progressive weakness of his legs and right hand, with sphincter disturbance. Past medical history included latent tuberculosis aged 25, which was treated. MRI whole-spine revealed longitudinally extensive transverse myelitis (LETM) spanning C4-T1. CSF examination revealed WCC 43 (93% lymphocytes), protein 844 mg/L, normal paired glucose, unmatched CSF oligoclonal bands, negative viral PCR, AFB, and mycobacterial culture, and cytology in keeping with chronic inflammation. He was treated with intravenous steroids with an oral taper; however, he made no improvement. Aquaporin-4 and anti-MOG antibodies were negative. Anti-Hu antibodies were strongly positive. CT thorax revealed a right hilar mass with mediastinal lymph node enlargement. Whole-body FDG PET-CT was in keeping with a primary lung malignancy. EBUS-guided fine needle aspiration confirmed a histological diagnosis of small-cell lung cancer. Oncology MDT deemed the tumour to be inoperable and he was treated with palliative chemotherapy. To our knowledge, this is the first reported case of paraneoplastic LETM, secondary to small-cell lung cancer, associated with positive anti-Hu antibodies. This case highlights that a paraneoplastic work-up should be considered early in LETM, particularly in older patients and those with risk factors for cancer.
09.48 Acute psychosis in a young woman
Authors: Gorgoraptis Nikos , Kolanko Magda , Petridou Christina , Patel Sachin , Singh-Curry Victoria , Davies Nicholas , Irani Sarosh , Carswell Christopher
Published: March 2023

NMDA receptor (NMDA-R) encephalitis may occur as a post-infectious syndrome following HSV encephalitis. Borrelia burgdorferi is not a well-established infective trigger of NMDA-R antibody encephalitis. There is one previous report of NMDA-R antibodies in association with Lyme disease.

We report the case of a 27-year-old woman who presented with acute psychosis. She had a history of tick bite in Slovenia two months previously, followed by headache, flu-like symptoms and diplopia two weeks later. She then developed behavioural disturbance, with disinhibition, disordered thought and paranoia, resistant to antipsychotic medication. MRI brain revealed multiple white matter lesions and diffuse cranial nerve enhancement. CSF was active. Lyme serology (Borrelia IgG and IgM immunoblot) was positive. NMDA-R antibodies were positive (serum and CSF; fixed- and live-cell assays). Infective, autoimmune and neoplastic workup was otherwise unremarkable. She received antimicrobial treatment for neuroborreliosis as well as a course of intravenous immunoglobulin, with gradual resolution of the neuropsychiatric disturbance, normalisation of her neuropsychological assessment and improvement of the MRI appearances. Repeat NMDA-R antibody testing upon convalescence was negative in the serum and CSF (live-cell assay).

This is the second reported case of NMDA-R antibody positivity with clinical features of NMDA-R antibody-associated encephalitis in serologically confirmed Lyme disease.
11.42 The scottish epilepsy deaths study (SEDS): identifying avoidable epilepsy-related deaths
Authors: Mbizvo Gashirai K , Schnier Christian , Simpson Colin R , Chin Richard FM , Duncan Susan E
Published: March 2023

Purpose

Quantify avoidable epilepsy-related mortality in adults (aged ≥ 16 years).

Method

We identified adult epilepsy-related deaths occurring between 01/01/2009–2016 in Scotland by linking death certificates to administrative primary and secondary care datasets. International Classification of Disease (ICD-10) codes (G40–41, R56.8), Read Codes (F25..), and antiepileptic drugs (AED) were examined in the linked dataset to identify potential epilepsy patients, using clinical data from medical records as a diagnostic reference to calculate positive predictive values (PPV). EPRDs were determined from death certificates (including post-mortem indicators) and medical records, estimating their standardised mortality ratio (SMR) and mortality rate (MR). The Office for National Statistics’ Revised Definition of Avoidable Mortality Causes 2016 was used to identify potentially avoidable EPRDs.

Results

Combining AED prescription with death certificate epilepsy codes G40–41 had the highest PPV (99%) for epilepsy diagnosis. There were 2,149 EPRDs. Age-standardised MR per 100,000 ranged between 6.8 (95%CI 6.0–7.6) in 2009 and 9.1 (95%CI 8.2–9.9) in 2015. SMR was higher in young adults (≤55 years), peaking at 6 (95%CI 2.3–9.7) in the 16–24-year-old group. There were 579 EPRDs in those aged ≤55 years. 31% were SUDEP, 26% respiratory causes (mainly aspiration pneumonias), and 15% mental disorders (mostly alcohol-related). 79% of all EPRDs were potentially avoidable. Commonest modifiable factors were absent epilepsy specialist input, poor patient education, and drug errors.

Conclusion

The burden of avoidable epilepsy-related mortality remains high, particularly in young adults.
12.30 Do anticholinergic drugs increase alzheimer’s pathology in parkinson’s patients? A retrospective post-mortem investigation
Authors: Liu Alan King Lun , Lim Yau Mun , Pearce Ronald KB , Gentleman Steve M
Published: March 2023

Introduction

Recent studies have highlighted the accumulated use of anticholinergic drugs is associated with an increased risk of dementia, and many of those are used for symptomatic management in Parkinson’s disease (PD). Unfortunately, the only available post-mortem study investigating the effect of anticholinergic agents on Alzheimer’s pathology burden suffers from several methodological limitations. Therefore, we aimed to validate if cumulative use of anticholinergic medication will increase Alzheimer’s pathologies in the post-mortem PD brains.

Material and methods

Retrospective case note analysis was carried out on 54 selected PD cases from the Parkinson’s UK Brain Bank and cases were stratified into no, low and high anticholinergic burden using literature-based anticholinergic scores. Association of anticholinergic burden and Alzheimer’s pathology in post-mortem tissues was analysed with logistic regression modelling.

Results

A higher anticholinergic burden is associated with a greater tau burden in entorhinal cortex in PD cases (OR=2.21). Interestingly, a high anticholinergic burden decreases the odds of amyloid-beta presence in the anterior hippocampus (OR=0.127), entorhinal cortex (OR=0.124) and frontal cortex (OR=0.113) of PD cases.

Conclusion

We have demonstrated that anticholinergic drugs have varying effect on Alzheimer’s pathology in post-mortem PD brain tissues. Complex mechanism is probably involved and require further studies.
11.54 Current challenges in the assessment and diagnosis of optic disc swelling and idiopathic intracranial hypertension
Authors: Ransley George , Vijay Vivek , Grant Laura , Bahra Anish
Published: March 2023

Optic disc swelling is a challenging presentation with a wide differential including potentially life-threatening diagnoses alongside benign causes. In this retrospective review, we assess over 33,000 referrals to an Eye Treatment Centre between 2014 and 2018. We identify 167 referrals for ‘optic disc swelling’ or similar terms. The overall rate of referrals to the ETC remained stable throughout this period, however the rate of referrals for optic disc swelling increased almost threefold from 2016 onwards. This was primarily due to a large increase in the number of referrals from Opticians, which correlates chronologically with the case of missed papilloedema resulting in a criminal conviction of the optometrist in question, Honey Rose.

77 patients were confirmed to have papilloedema, and in this group the most common final diagnosis was Idiopathic Intracranial Hypertension (IIH). 74 patients were diagnosed with pseudopapilloedema, the most common cause of which was drusen. Of note, over one-fifth were found to have normal optic discs on examination.

Pathways for the workup of patients with suspected IIH were examined. A large proportion of patients experienced delays of up to 31 months awaiting essential imaging or lumbar puncture. Importantly, 37% never had venography.
12.06 Gait symptoms correlate with cognitive problems in parkinson’s
Authors: Tilley BS , Romozzi M , Hession CM , Shiwani T , Goldfinger MH , Gentleman SM , Nicholas R
Published: March 2023

The akinetic-rigid (AR) subtype of Parkinson’s disease (PD), characterised by rigidity, akinesia and gait impairment, is associated with cognitive impairment unlike the tremor dominant (TD) subtype. It is unknown which symptoms in AR-PD drive this relationship, and whether individual symptoms are better predictors of cognitive impairment than motor subtype.

Methods

Using a 100 item questionnaire, self-rated symptom severity data on PD-related symptoms sampled when the person signed up to the Parkinson’s UK Tissue Bank. Multivariate regression analysis was used to assess individual symptom scores as predictors of cognitive impairment severity, measured using composite scores of the cognitive symptom questionnaire items.

Results

Gait disturbance was the only motor symptom predicting increasing cognitive impairment score (β=0.4025; p=0.0003). Additional significant predictors included: neuropsychiatric symptom score (β=0.2952; p=0.001), anosmia score (β=0.627; p=0.0004) and hallucination score (β=0.7586; p<0.0001).

Discussion

Gait disturbance, hallucinations, neuropsychiatric symptoms and anosmia are associated with cognitive impairment in PD. Gait disturbance is unique among PD motor symptoms, in its relationship to cognitive impairment. Individual motor symptoms are of greater prognostic value than motor subtypes.
017 When the (genetics) penny drops…
Authors: Sutton Fiona , Mattoscio Miriam , Rosser Elisabeth , Silva Rajith de
Published: March 2023

Background

Drop attacks are commonly referred to Neurologists and their differential diagnosis is wide. The family history and clinical examination proved critical in establishing the (very rare) cause here.

Clinical case

A 21-year-old man was seen with drop attacks provoked by auditory stimuli. He had global developmental delay, and dysmorphic features- traits shared by his mother, sister and brother (none of whom had neurological complaints or severe learning disability [LD]). Examination revealed hypertelorism, low slanting palpebral fissures, ‘fleshy’ hands & tapering fingers and kyphoscoliosis. His mother and sister had similar hands.

An archived genetic test confirmed the presence of a mutation in RPS6KA3, supporting the diagnosis of Coffin-Lowry syndrome (CLS). CLS is rare (1:50,000) and X-linked dominant. In addition to LD and dysmorphic features (as here), stimulus-induced drop attacks (responsive to Clonazepam, usually) are common.

CLS affects women less severely, due to the ameliorating effect of the non-mutated allele in females. The mildly affected brother of the proband has Klinefelter’s syndrome.

Our patient’s attacks were completely abolished with Clonazepam.

Key points

The differential diagnosis of drop attacks is wide.

Don’t forget the family!

Genetic testing, as well as elucidating diagnoses, can point to effective therapies.
018 Lost in translation: documentation of on call neurology advice and the clinical impact of discrepancies
Authors: Mahmood Ammad , Davidson Amy , Dani Krishna
Published: March 2023

Background

On-call neurology advice in the West of Scotland is centralised to one site handling 128±19 calls during working hours weekly. Telephone advice is documented at the regional centre by the neurologist and in patients’ notes by the referrer. Errors in transcription can result in patient harm.

Methods

Neurologists’ documentation was compared retrospectively to patients’ notes to identify discrepancies which were classified as major or minor based on potential for harm. Analysis was undertaken for one week in November 2016. A change in practice was implemented with all neurologists’ documentation uploaded electronically to the patients’ case record. The analysis was repeated in November 2018.

Results

53 cases were analysed before intervention and 63 afterwards. Post intervention the following improvements were seen: proportion of unsatisfactorily documented cases reduced from 21%→13% (undocumented cases increased 8%→13%, incomplete/inaccurate cases reduced 13%→0%); number of major and minor cases reduced (3→1 and 6→1 respectively); proportion of patients not receiving recommended treatment reduced from 20%→0%. The proportion of patients not undergoing recommended investigations increased from 10%→14%.

Conclusion

In a regional service, neurologists documenting on-call advice in a manner accessible to all care providers led to reduced potential for patient harm, particularly in patients receiving recommended treatment.
019 A rare cause of oculomotor nerve palsy
Authors: Jones Andrew , Williams Toby , Herwadkar Amit , McKee David , Kobylecki Chris
Published: March 2023

Introduction

Behçet’s disease is a multisystem inflammatory disease of unknown aetiology characterised by oral and genital ulceration, vascular lesions, and ocular, cutaneous and neurological manifestations. Many disease features are due to vasculitis and it is particular for its involvement of all sizes of blood vessels on both sides of the circulation.

Case report

We present a report of a 43-year-old female with a background of severe neurological complications of Behçet’s disease (previous rhombencephalitis) presenting with left-sided headache, neck pain, photophobia, diplopia, nausea and vomiting. Complete left third nerve palsy developed during admission. MR brain imaging excluded acute parenchymal disease but was suggestive of a left posterior communicating artery aneurysm, confirmed on CT angiogram. Urgent catheter angiography demonstrated a 5×3 mm left anterior choroidal artery aneurysm, which was occluded by coiling. Two months later, left oculomotor nerve palsy had resolved and follow-up imaging at six months showed stable appearances.

Discussion

Intracranial aneurysms are a rare but potentially life-threatening complication of Behçet’s disease. Intracranial aneurysms are potentially treatable and should be considered in Behçet’s patients presenting with intracranial pathology.
11.15 ABN survey 2016: geographic variations in service provision
Authors: Fernandes Peter , Mummery Cath
Published: March 2023

Introduction

The 2016 ABN Acute Neurology survey provides a wealth of data on geographic variations in the provision of neurological services. In this abstract we discuss differences in access to neurological care and services with respect to the 19 ABN regions.

Methods

2016 ABN survey data were analysed by region with bed data obtained from ONS records. Missing data were checked where possible but otherwise assumed to be negative responses.

Results

Across the UK there are 263 beds/FTE consultant, ranging from 455 (Wales) to 154 (SW Thames). Neurology inpatients as a proportion of total patients differ 16-fold between South West (0.016) and Wales (0.001). There are wide variations in acute neurological services (ward consultants, acute clinics, MAU ward-rounds). Only East Anglia and Northern Ireland regions have on-site stroke thrombolysis in all hospitals. Involvement in acute stroke thrombolysis ranges from 2.5 neurology consultants/hospital (Wessex) to 0 (NW Thames and Mersey). Access to investigations differs widely for 24/7 MRI (35% all hospitals, regional ranges 0% to 83%); EEG (61% [38%-85%]); NCS/EMG (57% [20%-85%]); and on-site neuro-radiology (38% [17%-71%]).

Conclusion

These data show considerable differences in a variety of metrics between ABN regions, with implications for equitability of care.