bluuebunny/crossref_metadata_2025 huggingface dataset:
016  Long-term efficacy and safety of perampanel in elderly patients from phase III open-label extension studies
Authors: Marawar Rohit , Leppik Ilo E , Wechsler Robert T , Patten Anna , Ngo Leock Y , Malhotra Manoj
Published: May 2022

Background

The long-term efficacy and safety of adjunctive perampanel was evaluated in patients aged

≥60 years with focal-onset seizures (FOS) with/without focal to bilateral tonic-clonic seizures (FBTCS) who participated in open-label extension Studies 307 (NCT00735397) and 335 (NCT01618695).

Methods

Patients received perampanel 2–12 mg/day during Studies 307 (16-week blinded Conversion; 256-week Maintenance) and 335 (4-week Pre-conversion; 6-week Conversion; ≥46-week Maintenance). Assessments included median per cent reduction in seizure frequency/28 days vs pre-perampanel baseline, 50% responder rates and treatment-emergent adverse events (TEAEs).

Results

The Safety Analysis Set included 71 patients (mean age, 64.0 years). Seizure frequency reductions during Years 1 and 2 were 31.7% (n=71) and 44.5% (n=38) (total FOS), and 95.5% (n=19) and 100.0% (n=9) (FBTCS), respectively. Seizure frequency reductions were observed during Years 3/4 (low patient numbers); over one-third of patients achieved a ≥50% seizure reduction each year. During Years 1, 2, 3 and 4, TEAE incidence was 87.3% (n=62/71), 60.4% (n=29/48), 47.4% (n=9/19) and 57.1% (n=8/14), respectively; most common were dizziness and fall during Years 1/2 and 3/4, respectively.

Conclusion

Perampanel was associated with reductions in seizure frequency over 4 years in elderly patients. The safety profile was consistent with the overall populations.

Funding

Eisai Inc. stella_ngo@eisai.com

33
017  PROVE study 506: perampanel in real-world clinical care of patients based on seizure type
Authors: Wheless James , Patten Anna , Ngo Leock Y , Salah Alejandro , Malhotra Manoj
Published: May 2022

Background

PROVE (NCT03208660) was a retrospective, non-interventional Phase IV study of perampanel during real-world clinical care of patients with epilepsy; we report the efficacy and safety of perampanel in PROVE.

Methods

Data from patients initiating perampanel after 01-Jan-2014 were included. Endpoints included retention rate at 3/6/12/18/24 months (primary), efficacy and safety (secondary). Outcomes were strati- fied by baseline seizure type: focal-onset seizures (FOS) only; generalised seizures only; generalised tonic- clonic seizures (GTCS) only; myoclonic; absence. Patients with FOS and generalised seizures (n=718) were excluded.

Results

In the Safety Analysis Set (n=1703), 24-month retention rates were: 48.1% (FOS only, n=164/341); 47.8% (generalised only, n=120/251); 42.9% (GTCS only, n=27/63); 50.3% (myoclonic, n=100/199); 47.7% (absence, n=84/176). Of 51 patients with seizure data at Months 22–24, median reductions in total seizure frequency/28 days were: 75.0% (FOS only, n=20); 91.6% (generalised only, n=10); 40.0% (GTCS only, n=3); 70.0% (myoclonic, n=7); 100.0% (absence, n=4). Treatment-emergent adverse events occurred in 231/545 (42.4%; FOS only), 185/440 (42.0%; generalised only), 50/110 (45.5%; GTCS only), 117/328 (35.7%; myoclonic) and 154/301 (51.2%; absence) patients; most common were dizziness and aggression.

Conclusion

Perampanel retention rates and safety were generally similar across seizure types. Seizure frequency reductions were observed across subgroups.

Funding.Eisai Inc. stella_ngo@eisai.com
019  Reduced activations within right mesial temporal lobe for visual episodic memory in right temporal lobe epilepsy
Authors: Ramaswamy Arjun , Sablik Maria , Duncan John , Buck Sarah , Sidhu Meneka
Published: May 2022

Rationale: Epilepsy surgery is an effective treatment for Temporal lobe epilepsy (TLE), however memory decline occurs in up to 40% of people. Functional MRI (fMRI) can be used to determine the pre-operative functional anatomy of memory representations to guide surgical decision making and reduce the risk of memory decline.

Methods

22 healthy controls, 8 patients with right TLE (RTLE) and 10 with left TLE (LTLE), performed an overt, word and faces memory-encoding, recognition and recall fMRI paradigm with a baseline of odd-even number decisions. Statistical Parametric Mapping (SPM) was used to investigate specific brain regions associated with encoding and retrieval processes contrasted with the baseline task. One sample and two sample t-Tests were performed between controls and patient groups. Group activations are reported at p<0.001 for extratemporal and p<0.05 for mesial temporal lobe (MTL) activations.

Results

A more specific memory fMRI paradigm showed distinct activations for verbal and visual memory among controls, LTLE and RTLE groups. Particularly for visual memory, the paradigm elicited greater acti- vations in controls within the right anterior MTL and right posterior MTL for face encoding and recognition respectively. These regions have been widely associated with strong encoding and retrieval of visual memory. The reduced activations in RTLE within these regions are indicative of potential visual memory decline after surgery.

arjun.ramaswamy.19@ucl.ac.uk
021  Tics in patients with encephalitis
Authors: Badenoch James , Searle Tamara , Watson Iona , Cavanna Andrea
Published: May 2022

Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in cases of encephalitis resulting from a range of aetiologies. This review aimed to assess the prevalence and characteristics of tics in patients with encephalitis. We conducted a systematic literature review of original studies on the major scientific databases, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In addition to the established association between tics and encephalitis lethargica, our literature search identified reports of tics in patients with immune-mediated pathologies (including autoimmune encephalitides affecting the N-methyl-d-aspartate receptor, voltage gated potassium channels, and glycine receptors) and infective processes (ranging from relatively common viral pathogens, such as herpes simplex, to prions, as in Creutzfeldt-Jakob disease). Tics were most commonly reported in the post-encephalitic period and involvement of the basal ganglia was frequently observed. The association of new-onset tics and encephalitis, in the background of other neuropsychi- atric abnormalities, has practical implications, potentially improving the detection of encephalitis based on clinical features. Future research should focus on the categorisation and treatment of hyperkinetic movement disorders associated with encephalitis.

jxb752@student.bham.ac.uk
Bad altitude
Authors: Kalam Sabrina , Davenport Richard
Published: May 2022

A previously well 15 year old girl presented with recurrent facial weakness associated with air travel. The first event occurred the year before. Mid-flight she developed right facial numbness and weakness with auricular pain resolving within 30 minutes. She remained well and multiple subsequent flights were uneventful. She had an identical episode a year later on the same route, although had flown without incident several times in between. In clinic her neurological examination was unremarkable. Structural imaging was normal and we diagnosed recurrent barotrauma induced transient right facial nerve palsy.

Only 12 cases of facial baroparesis associated with air travel have been reported. These describe transient facial paresis at high altitude with resolution of symptoms within several hours of onset. This phenomenon was previously described as a rare occurrence in divers. The suggested aetiology in both is increased pressure on the tympanic segment of facial nerve within the facial canal, leading to temporary pressure- induced ischaemic neuropraxia. Equalisation of middle-ear pressure relieves symptoms. Most cases require only reassurance although two reported cases underwent surgical management. This case highlights a rare phenomenon that could be mistaken for more sinister disease and is perhaps another (if less com- pelling) reason to reduce air travel…

sabrina_k2005@hotmail.co.uk
041  Posterior reversible encephalopathy syndrome (PRES) in mild and severe COVID-19
Authors: Hayton Philip , Hamdalla Hisham
Published: May 2022

As the COVID-19 pandemic progresses neurological complications are increasingly being reported. Posterior reversible encephalopathic syndrome (PRES) is a clinico-radiological syndrome characterised by headache, visual loss, encephalopathy and seizures, and the development of vasogenic white matter lesions in a classically parieto-occipital distribution. The pathophysiology of PRES is incompletely understood, but both hyperperfusion secondary to hypertension, and endothelial dysfunction leading to vasogenic oedema have been implicated. Here we present a case series of 2 hospitalised COVID-19 patients with markedly different disease severity, both of whom developed PRES. Patient 1 presented with confusion and headache without significant systemic features, on a background of known hypertension. Patient 1 had a single generalised seizure and was managed with levetiracetam and antihypertensives, and showed complete clinical recovery. In contrast, patient 2 presented with respiratory distress, metabolic disturbance and encephalopathy requiring critical care admission. Patient 2 had a protracted admission, developing marked visual disturbance and generalised seizures requiring multiple agents. In both cases initial CT/MRI showed characteristic posterior PRES-like leukoencephalopathy with resolution on follow-up imaging, and CSF biochemistry, cytology and virology were normal. This case series highlights the potential for neurological complications in COVID-19 patients across the spectrum of disease severity.

Philip.hayton@nhs.net
058  Tolosa-Hunt syndrome with features of trigeminal autonomic cephalagia, pituitary enlargement, and non-lateralised headache
Authors: Sim Nicholas Keyi , Liew Sze Yii , Warren Daniel , Hassan Ahamad
Published: May 2022

We present a case of Tolosa-Hunt syndrome with a headache phenotype mimicking a right-sided trigemi- nal autonomic cephalagia (hemicrania continua), and serial MRI imaging showing a stable enlarged pituitary. She was diagnosed initially with common migraine, revised to hemicrania continua, then chronic daily headache, before finally arriving at her diagnosis. She tried multiple anti-migraine therapies and her best response was to indomethacin, discontinued due to gastrointestinal side effects. Her diagnosis was achieved after her headache changed to a left sided headache with a left sided cavernous sinus syndrome, 4 years into her disease course, despite her serial surveillance scans. She responded well to steroids.

This case demonstrates Tolosa-Hunt syndrome may not be side-locked, and the need to consider inflam- matory causes of headache when faced with a patient with persistent headaches and ‘incidental’ pituitary adenoma.

nchlasim@doctors.org.uk

54
063  Improving service provision for patients with suspected idiopathic intracranial hypertension in a joint neuro-ophthalmology clinic
Authors: Dokal Kitt , O’hanlon Ciaran , Castelhano Rute , Yiin Gabriel , Hinze Stephan , Pandit Jyotin , Morrish Paul , Paul Nicola
Published: May 2022

Introduction

Care of patients with suspected Idiopathic Intracranial Hypertension (IIH) involves neurolo- gists and ophthalmologists, however this can be difficult to co-ordinate. Consensus guidelines suggest all patients with suspected IIH should have weight, visual fields, neuroimaging and a CSF opening pressure. The aim of our study was to determine adherence to consensus guidelines.

Methods

We assessed medical notes of consecutive patients attending the new joint neuro-ophthalmol- ogy clinic in the Great Western Hospital, Swindon between 1st September–31st December 2020. Due to the Covid-19 pandemic a neurologist was not always present.

Results

Of 38 patients attending the clinic with suspected IIH, 35(92%) were female. 29(76%) had weight recorded; 14(37%) patients had BMI recorded, 12(32%) had BP recorded; 36(95%)had visual fields recorded, 12(32%) and 17(45%) respectively had whether neuroimaging or lumbar puncture were required. 23(61%) had weight management discussed, 22(58%) had a medication review discussed.

Conclusion

Documentation of weight, BMI, BP, investigation results and management discussions could be improved in the joint neuro-ophthalmology clinic. We aim to address this by introducing an “IIH clinic checklist” for use by clinicians and patients to help improve adherence to consensus guidelines.

kitt.dokal@kcl.ac.uk
075  Secondary syphilis presenting as acute unilateral visual loss in an immunocompetent elderly patient
Authors: Paluri Srinivasa , Arun Tarunya , Prasadh Balaji
Published: May 2022

A 75-year-old lady with a history of hypertension, hypothyroidism and posterior vitreal detachment was admitted with acute reduction of vision and floaters in the left eye.

Fundoscopy revealed optic disc swelling left eye and visual acuity was reduced to finger counting. MRI head and orbits showed micro angiopathic changes only with no optic nerve lesion. A CT Thorax, abdomen and pelvis did not show any abnormalities. Bloods investigations including ESR, CRP ANA, ANCA, dsDNA, ACE, aquaporin and MOG antibodies and serum electrophoresis were normal. Cardiolipin anti- bodies were raised at 101.0 (<10.1). CSF results were bland. Serological investigations revealed a positive RPR, 1:256, we performed a TPPA test to confirm the diagnosis. Fluorescein fundus angiography showed “Leopard spots” suggestive of posterior placoid chorioretinopathy. Subsequent sexual history confirmed recent contact with a new partner. She was treated with doxycycline due to severe penicillin allergy. Visual acuity on the left improved to 6/7.5 in two months’ time.

We report an infrequent case of unilateral optic neuritis as a presenting manifestation of syphilis in an immunocompetent elderly patient. An infectious cause of optic neuropathy needs to be considered at all age groups and it is often completely reversible if intervention is timely.

s.paluri@nhs.net
080  Listen to learn: podcast-series for IMT induction at National Hospital for Neurology and Neurosurgery
Authors: Iqbal Sabahat , Levee Viva , Goh Yee Yen , Parmar Sunjay , Carr Aisling
Published: May 2022

Background

Podcasts are increasingly used as a learning resource in medicine. However, evidence illustrating their impact is limited.

Objective

To assess use and utility of podcasts in IMT induction/introduction to specialist neurology services in NHNN.

Method: A survey of the 2019/20 IMT cohort revealed 85.7% to be ‘not confident’ in the management of patients with neurological disorders at induction. The same proportion had no previous neurology clinical experience. Podcast format, topics and content were derived from this feedback.

We developed 5 open-ended questions on 10 topics (neuropathy, PLEX, DBS, seizure management, IVIg, CSF analysis, MG, GBS, myelopathy and demyelination) and recorded live Q&A sessions with specialist consultants and nurses after approval by UCLH comms team. The podcasts were launched 1 week pre- induction August 2020 on the NHNN education website via a link sent to all new starters. The website is accessible by IMT and specialist trainees after registration with a nhs.net email.

A repeat survey was performed 1month post-induction and download data accessed from the website in January 2021.

Results/Conclusion

85.71% felt ‘confident’ in the management of neurological conditions. The podcasts have been played 560 times in 6 months, 453 times outside London suggesting transferable utility beyond NHNN.

siqbal2482@gmail.com|ABN Bursary

65
094  Measuring neutralising antibodies (NAbs) to interferon-beta (IFNB) for multiple sclerosis (MS): a neglected practice?
Authors: McKee JD , Spence RW , Hughes S , Gray O , Campbell J , Droogan A , McDonnell GV
Published: May 2022

Objective

To determine frequency of testing for NAbs to IFNB in our MS population and adherence to international (EFNS) guidelines.

Background

IFNB was the first approved MS disease modifying therapy (DMT). NAbs diminish efficacy regarding relapse rate, lesion load and disease progression.

Methods

In August 2019, the Northern Ireland (NI) DMT database was interrogated for patients currently or previously receiving IFNB. The NI Electronic Care Record and regional laboratory database were reviewed to verify if NAb testing ever undertaken, results, outcomes of positive results and reasons for treatment cessation.

Results

488 patients were currently on IFNB, 21.6% of the DMT population (IFNB1a intramuscularly - 210, pegylated IFNB1a - 71, IFNB1a subcutaneously - 175, IFNB1b subcutaneously - 32). Overall, 20.1% had NAbs checked (11.2% positive). Additionally, 288 patients had ceased treatment in the past 13 years, 273 having available records, 32 (11.7%) with NAb testing including 7 (21.9%) testing positive. 62/273 patients had discontinued due to relapse or disease progression - only 9 (14.5%) of these had ever had NAbs checked.

Conclusions

These data suggest that guidelines are poorly observed in this population. Improved testing could identify potential treatment failures earlier, avoiding adverse outcomes and facilitating more effective DMT decision making.

jon

mckee@doctors.org.uk

72
095  Remyelination in people with MS due to an RXR agonist is age-dependent
Authors: McMurran Christopher , Mukherjee Trisha , William Brown J , Michell Andrew , Coles Alasdair , Cunniffe Nick
Published: May 2022

Remyelination is a promising strategy to prevent axonal degeneration and progressive disability in people with multiple sclerosis (MS). In animal models, remyelination becomes inefficient with advancing age and much preclinical research is focused on interventions to reverse cellular hallmarks of ageing in remyelinat- ing lesions. However, there is currently limited evidence that human remyelination also declines with age.

We investigated the effect of patient age on treatment response among participants of the CCMR One trial (ISRCTN14265371): a double-blind, placebo-controlled phase 2a study (n=52) that demonstrated the ability of bexarotene, a retinoid-X receptor agonist, to promote remyelination in people aged 25–50 with relapsing remitting MS. For eyes with chronic optic neuropathy (baseline latency >118ms), bexarotene shortened the full-field visual-evoked potential P100 latency maximally in younger patients. The treatment effect diminished by approximately 0.5ms per year, such that older patients receiving bexarotene had a similar P100 latency change to controls. Furthermore, MRI scans of the same patients demonstrated an age-dependent treatment effect on lesion magnetisation transfer ratio, a radiological correlate of remyelination.

These results provide evidence that bexarotene promotes remyelination best in younger patients, rein- forcing the need to address the age-associated decline in remyelination capacity to develop successful remyelinating therapies.

cem73@cam.ac.uk|NIHR Bursary
099  Safety and effectiveness of dimethyl fumarate in multiple sclerosis patients treated over 5 years
Authors: Giles Kathryn , Balashov Konstatin , Macdonell Richard , Windsheimer Joerg , Okai Annette , Martinez Mikel , Mokliatchouk Oksana , Lyons Jennifer , Kapadia Shivani
Published: May 2022

Introduction

In clinical studies, delayed-release dimethyl fumarate (DMF) demonstrated a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies enable char- acterization of risks that may emerge with long-term exposure in clinical practice. ESTEEM (NCT02047097) is an ongoing 5-year study characterizing real-world long-term safety and effectiveness of routinely pre- scribed DMF in MS patients.

Methods

Patients treated with DMF were recruited from ~380 sites. The primary objective was to determine incidence, type, and pattern of serious adverse events (SAEs), and AEs leading to DMF discontinuation.

Results

As of April 3, 2019, 5804 patients had ≥1 dose of DMF. SAEs were experienced by 245 (4.8%) patients, with infections (n=64; 1.3%) and nervous system disorders (n=35; <1%) the most common. There were 1676 (33.0%) permanent treatment discontinuations. Annualized relapse rate over the period of up to 5 years was significantly lower than in the year prior to baseline (risk reduction 88.6% [95% confidence interval: 87.7–89.4]; P<0.0001).

Conclusions

These results reveal low risk of SAE and beneficial therapeutic effects over up to 5 years of real-world DMF use. Updated safety and efficacy results for DMF patients in the United Kingdom will be presented.

Support.Biogen. Disclosures: Included on the poster. Ben.newth@biogen.com
102  Translating logistical challenges into service improvement: MS infusional services during the covid-19 pandemic
Authors: Ramsay Stephen , Magill Fiona , Cartmill Glenn , Goldsmith Grainne , McKee Jon , Kennedy Fiona , Droogan Aidan , Hughes Stella , McDonnell Gavin
Published: May 2022

Background

Providing care to Multiple Sclerosis (MS) patients has been a challenge during the Covid-19 pandemic. Locally, surge plans necessitated an abrupt change of facility for infusional services, now supervised by MS nurses, from an acute site (Royal Victoria Hospital, RVH) to a non-acute site at Musgrave Park Hospital (MPH).

Objective

To assess patient satisfaction with MS infusional therapies at a new, non-acute location and supervision of the service by MS Specialist nurses in comparison with previous arrangements.

Methods

Anonymous patient surveys were developed and collected in order to assess patient demo- graphics and levels of satisfaction across various service domains.

Results

All 120 offered surveys were returned. Overall, 97% recorded a satisfaction score of ≥8/10 (0–10, 10

= extremely satisfied). Key areas of improvement: difficulty parking (0.8% vs 50% in RVH), difficulty of unit access (0.8% vs 38% previously), appointment punctuality (95% on time vs 35% previously), and comfort (83% vs 55% previously). Thematic analysis revealed several key improvement areas: access to MS nursing knowledge, cannulation, and punctuality.

Conclusion

The urgently relocated service, with better access and specialist nursing input, was associ- ated with substantial improvements in patient experience. Despite current unprecedented pressures on healthcare delivery, unique opportunities remain for service improvement.

sramsay03@qub.ac.uk|ABN Bursary

76
005  Infusion associated reactions in ocrelizumab-treated multiple sclerosis patients
Authors: Das Esther , Bewick Claire , Collins Justine , Nash Cynthia , Fisniku Leonora
Published: May 2022

Background and aims

Infusion-associated-reactions (IARs) are a common side effect (SE) of Ocrelizumab, a disease modifying therapy (DMT) licensed for treatment of Multiple Sclerosis (MS). Tolerability is an important factor patients take into account when selecting a DMT. We sought to assess the frequency of IARs in the Ocrelizumab-treated MS-patients at Brighton & Sussex University Hospitals MS-Centre.

Methods

All Ocrelizumab-treated MS-patients data from February 2019 to January 2020 was reviewed. IARs classified as mild, moderate, severe and life-threatening as per Ocrelizumab proforma, during and 1-hour post infusion were recorded. Patients were advised to contact the infusion nurses if they experi- enced further symptoms in the next 24-hours post infusion.

Results

28-patients received Ocrelizumab: 20(71%) females; mean age 41.7 years old (range 25–58); median EDSS 2 (range 0–6). 12(42.8%) patients had received no prior DMTs. 23(82.1) patients reported either nil or mild IARs; 7(25%) patients had mild IAR. 2(7.1%) patients had moderate IAR; 2(7.1%) patients had severe IAR, 1(3.6%) patient experiencing throat pain, swelling, rhinorrhoea and dyspnoea. 1(3.6%) patient experienced significant raised liver enzymes; 1(3.6%) patient had acute respiratory distress syndrome requiring treatment discontinuation.

Conclusion

Our data suggest that Ocrelizumab is generally well tolerated, however caution should be exercised and patient should be monitored closely especially in the initial infusion. Real world data provides useful information to share with patients when they are consented.

leonora.fisniku@nhs.net
119  Long-term effectiveness of natalizumab for RRMS: UK and global interim results from TYSABRI observational program
Authors: Nicholas Richard , Harrower Timothy , Liao Shirley , Vonsy Jean
Published: May 2022

Introduction

The TYSABRI Observational Program (TOP) is an ongoing observational study of natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS) patients. Country-specific data on relapse and disability outcomes, alongside global data, can provide information on natalizumab’s effectiveness in local practice.

Methods

Annualised relapse rate (ARR) was analysed in TOP UK (n=134) and global (N=6320) cohorts using data from July 2007 to November 2020. A subgroup analysis assessed ARR in patients with one prior disease modifying therapy (DMT) in the UK (n=64) and global (n=2795) cohorts. Cumulative probabilities of 24-week confirmed disability worsening and improvement will be presented.

Results

ARR decreased in UK patients from 2.21 in the year before initiation to 0.16 on natalizumab (P<0.0001), consistent with a global decrease from 2.00 to 0.18 (P<0.0001). In patients with one prior DMT, ARR decreased in UK patients from 2.13 in the year before initiation to 0.15 on natalizumab (P<0.0001), similar to the global decrease from 2.03 to 0.16 (P<0.0001).

Conclusions

The reduction in ARR on natalizumab was similar in the TOP UK and global cohorts, including in the subset of patients with one prior DMT. These findings support the real-world effectiveness of natalizumab.

Support.Biogen. Disclosures: Included on the poster. jean.vonsy@biogen.com
122  Neurological manifestations of haemophagocytic lymphohistiocytosis
Authors: Brown Rachel , Amarnani Raj , Flower Luke , Manson Jessica , Carr Aisling
Published: May 2022

Secondary (acquired) haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome which can occur in the context of infection, malignancy or rheumatological disease and is associated with high mortality. Early recognition facilitates access to effective biological therapies and engage- ment with specialist MDTs which focus on managing the underlying trigger. Neurological manifestations are associated with poor prognosis but are not well described.

We retrospectively reviewed 40 cases of secondary HLH in UCLH/NHNN; 25 had neurological compli- cations. Median age at onset: 36 years (range 11–79); 8 females. Causes of HLH were haematological malignancy (14), rheumatological disease (3), infection (2) and other/unknown (6). Neurological involve- ment portended higher morbidity and mortality: 21/40 ICU support; 19/40 in hospital death (15/25 and 16/25 with neurology). Neurological presentations included confusion (10) and reduced consciousness (5), headache (7), neuropathy (3) and myopathy (1). Based on symptomatology, radiological, CSF and metabolic and histological information we propose mechanistic causality of neurological manifesta- tions into: disease infiltration (13/25), metabolic (12/25), iatrogenic (2/25). The role of the cytokine storm in metabolic neurological derangement requires further investigation.

We designed a minimal neurology dataset to improve prospective data collection instituted via the UK HiHASC (Hyperinflammatory and HLH Across Speciality Collaboration). A management algorithm is in development.

rachel

brown@ucl.ac.uk|ABN Bursary

86
126  A case report of the emergence of neurosarcoidosis after COVID-19 infection
Authors: Robinson Rebecca , Nelson Adam , Hughes Stella , Kinney Michael
Published: May 2022

Introduction

Sarcoidosis is a granulomatous disease with protean manifestations. The aetiology is not fully understood. Infectious agents are considered to potentially contribute to its pathogenesis. This case report highlights the emergence of neurosarcoidosis after COVID-19 infection.

Case: A 48 year old female developed cough, myalgia and fatigue and was diagnosed with COVID-19 based on serological testing in April 2020. Post-infection, she developed a reactive arthritis, then presented in June with left facial lower motor neuron weakness, initially treated as a Bell’s palsy with a significant neuralgic component. This pain resolved with steroid treatment. One month later she developed multiple cranial neuropathies and bilateral leg weakness. MRI brain showed bilateral enhancement of the trigeminal and facial nerves. CSF was abnormal (CSF protein 0.95g/L, WCC 9/uL). Leg power rapidly improved with intravenous immunoglobulins, and FDG-PET identified mediastinal and axillary hilar lymphadenopathy. A neck node showed non-necrotising granulomatous inflammation. CSF angiotensin converting enzyme was elevated (2.07umol/min/L). She has since commenced high dose steroids for probable neurosarcoidosis.

Discussion

This case suggests a possible association between COVID-19 and the emergence of sarcoidosis. At present the strength of any association is uncertain and putative mechanisms remain to be determined.

rrobinson17@qub.ac.uk

88
139  Presentation of a rare dysautonomic variant of Guillain-Barré syndrome
Authors: Huang Yun , Baheerathan Aravindhan , Pritchard Jane
Published: May 2022

Guillain-Barré Syndrome (GBS) is an inflammatory disease of the peripheral nervous system. We describe the case of a gentleman who presented with a predominant dysautonomic variant of GBS.

A 55-year-old gentleman presented with a sub-acute onset, progressive syndrome characterised by a combination of ascending distal upper and lower limb paraesthesia, postural dizziness, early satiety and constipation. This was preceded by an upper respiratory tract infection and vaccinations for pneumo- coccus and influenza. On examination, he had length-dependent reduction to pinprick and tempera- ture sensation, normal power, preserved reflexes, with significant orthostatic hypotension. MRI brain and whole spine was unremarkable. Cerebrospinal fluid analysis showed albumino-cytological dissociation and nerve conduction studies was consistent with subacute onset demyelinating polyradiculoneuropa- thy. A diagnosis of pandysautonomic variant of GBS was formulated. He was treated with 5 days of intravenous immunoglobulin (IVIg) (0.4kg/kg/day) with improvements in orthostatic hypotension from day 3 of treatment.

While autonomic instability is common in GBS, a predominant autonomic presentation without motor weakness can represent a rare pandysautonomic variant of GBS. This case illustrates the importance of early detection of autonomic dysregulation in GBS, the requirement for close monitoring and use of IVIg as an effective therapeutic management of autonomic dysfunction.

yun.huang@nhs.net
141  Guillain-Barre as a post-operative syndrome following resection of anaplastic astrocytoma
Authors: Leahy Christopher , Lavin Tim , Gosal David , Herwadkar Amit , D’Urso Pietro , Cahill Varduhi
Published: May 2022

We present a case of Guillain Barre Syndrome (GBS) following resection of a brain neoplasm. A 43 y.o. man presented with diplopia and lower back pain 2 weeks after resection of left mesiotemporal and fusiform gyrus grade III IDH 1 mutant anaplastic astrocytoma. Within a week he was unable to ambulate due to marked leg weakness. Examination showed bilateral weakness of lateral rectus muscles and lower motor bilateral facial weakness. Hip flexion was 1/5 bilaterally, otherwise 0/5. Tone was flaccid. Lower limb reflexes were absent and plantar responses were mute. Imaging showed no evidence of tumour recurrence or drop metastasis. CSF analysis demonstrated raised WCC (43/ul WBCs, <1/ul RBCs), protein was markedly elevated at 4.33 g/l and glucose normal. Cytology was negative for malignancy consist- ently. He was treated 5-days of intravenous immunoglobulin (2g/kg). He walked without assistance on discharge and his recovery was sustained at 6 months follow up. Neurophysiology showed a generalised, non- length dependent, motor> sensory, demyelinating neuropathy. This case highlights the importance of considering GBS as a potential cause of progressive neurological deficit in the postoperative period where “atypical” CSF findings are confounded by the preceding neurosurgical intervention.

christopherleahy@doctors.org.uk
010  Safety and efficacy of long-term dimethyl fumarate treatment
Authors: Gold Ralf , Giovannoni Gavin , Theodore Phillips J , Bar-Or Amit , Fox Robert J , Chen Chongshu , Parks Becky , Kapadia Shivani
Published: May 2022

Introduction

ENDORSE (NCT00835770) evaluated the safety and efficacy of dimethyl fumarate (DMF) treatment for ≥10 years (Y) in relapsing-remitting MS (RRMS) patients.

Methods

Patients treated continuously with DMF 240 mg BID in DEFINE/CONFIRM and ENDORSE were assessed for relapse, confirmed disability progression (CDP), serious adverse events (SAEs), and patient- reported outcomes (PROs): (36-item short form health survey [SF-36]; 5-dimension QoL [EQ-5D]).

Results

Of 618 patients treated for ≥10Y, 38%(192/501) were continuously-treated BID. Mean (SD) age 41.6 (8.7) Y; 68% female. Most (51%[98/192]) patients remained relapse-free or had ≤1 relapse, 73%(141/192); median time-to-first-relapse was 58 weeks. Mean baseline (SD) EDSS score was 2.24 (1.18); patients with EDSS ≤3.5: Y2 89%(164/184), Y8 80%(148/184), Y10 79%(146/184). From Y0–10, 64%(122/191) patients had no CDP. Seventy-seven (40%) patients experienced SAEs; primarily MS relapse 18%(34/192) or infections 6%(12/192). From Y0–10, serious infection incidence did not increase and SF-36 and EQ-5D remained stable.

Conclusions

Patients continuously treated with DMF BID for ≥10Y had low incidence of relapses; the pro- portion of patients with EDSS ≤3.5, patients with CDP, PROs, and incidence of serious infections remained stable over 10Y reinforcing the safety and efficacy of long-term DMF treatment for RRMS patients.

Support

Biogen; disclosures detailed on poster.

g.giovannoni@qmul.ac.uk
020  Long-term efficacy of ocrelizumab in relapsing multiple sclerosis: 6 study years
Authors: Giovannoni Gavin , Kappos Ludwig , Seze Jerome de , Hauser Stephen L , Overell James , Koendgen Harold , Prajapati Kalpesh , Manfrini Marianna , Wang Qing , Wolinsky Jerry S
Published: May 2022

Background

Efficacy/safety of ocrelizumab in relapsing multiple sclerosis were demonstrated in the OPERA I/II (NCT01247324/NCT01412333) double-blind period (DBP). We assessed the efficacy of switching to or maintaining ocrelizumab after 4 years of the open-label extension (OLE).

Methods

At OLE commencement, patients continued ocrelizumab (OCR-OCR) or switched from interferon-β-1a to OCR (IFN-OCR). Adjusted annualised relapse rate (ARR), time-to-onset of 24-week confirmed disability progression (CDP24) and risk of requiring a walking aid (Expanded Disability Status Scale score ≥6.0) from DBP baseline were analysed.

Results

Among IFN-OCR switchers, ARR decreased year-on-year from 0.2 in the pre-switch year to 0.04 in OLE Year 4; OCR-OCR continuers maintained low ARRs (pre-switch, 0.13; OLE Year 4, 0.05). CDP24 was lower year-on-year in OCR-OCR continuers versus IFN-OCR switchers in the pre-switch year (7.7% vs 12.0%) and at OLE Year 4 (19.2% vs 23.7%); p<0.05 all comparisons. Over the DBP and OLE, risk of requiring a walking aid was 44% lower (p=0.004) in OCR-OCR continuers versus IFN-OCR switchers.

Conclusions

After 6 years of follow-up, rates of patients with CDP24 and risk of requiring a walking aid remained lower in earlier initiators of ocrelizumab (OCR-OCR) versus those initially receiving IFN (IFN-OCR), demonstrating maintained benefits of earlier treatment with ocrelizumab.

g.giovannoni@qmul.ac.uk
028  Cladribine to halt deterioration in people with advanced multiple sclerosis (ChariotMS)
Authors: Lieberman David R , Mangat Harpreet K , Schmierer Klaus
Published: May 2022

Background

Disease modifying treatments (DMTs) have transformed the management of people with MS (pwMS). However, patients with an EDSS>6.5 (pwAMS) are considered beyond DMT due to (i) focus on ambulation as outcome measure, (ii) assumption that in pwAMS inflammation plays no role, and

(iii) disregard for potentially length-dependent neuro-axonal damage. Cladribine is a CNS penetrant, effective, convenient and relatively safe DMT. Cladribine effectively depletes B cell subsets, particularly memory B cells, a potential key mechanism of disease control in pwMS.

Aims

To test the efficacy, safety and cost-effectiveness of cladribine tablets in pwAMS (EDSS 6.5–8.5), expand the mechanistic understanding of cladribine in pwAMS and provide evidence for NHS adoption.

Methods

Randomised, double-blind, placebo-controlled phase IIb trial. The primary outcome measure is 9-hole peg test speed at 104 weeks vs baseline. To detect a 15% treatment effect in 9-HPT peg speed with 90% power at 5% significance and 20% drop-out we calculated a sample size of n=200 across 20 UK sites.

Conclusions

ChariotMS will be the first DMT-trial focussing on pwAMS. If successful, ChariotMS would expand the DMT landscape to include pwAMS and provide a platform for potential add-on therapies. ChariotMS is due to start recruitment nationwide from 1 Sep 2020.

david.lieberman@nhs.net
Neuroinflammation and protein aggregation co-localize across the spectrum of frontotemporal dementia
Authors: Bevan-Jones Richard , Cope Thomas , Jones Simon , Kaalund Sanne , Allinson Kieren , Hong Young , Arnold Robert , Patterson Karalyn , O’Brien John , Rowe James
Published: May 2022

Frontotemporal dementia is clinically and neuropathologically heterogeneous, but each major phenotype has been associated with both aggregation of misfolded protein and neuroinflammation. We used positron emission tomography, with [11C]PK-11195 to measure activated microglia, and [18F]AV-1451 to quantify the burden of Tau or TDP-43, in 31 patients with frontotemporal dementia (10 behavioural variant, 11 semantic variant and 10 non-fluent variant) and 15 matched controls, to test the hypothesis that neuroinflamma- tion co-localises with pathological protein aggregation.

Analyses included: (1) region-of-interest binding potentials; (2) pairwise correlation across regions between ligands; (3) principal component analysis of each ligand distribution and (4) multivariate classification of binding distributions.

The analyses converged in showing (a) significant differences in [11C]PK-11195 binding between each patient group and controls in frontotemporal regions; (b) a strong positive correlation between [11C] PK-11195 and [18F]AV-1451 binding in all disease groups, across widespread cortical regions. Thesein vivoresults were confirmed bypost mortemimmunohistochemistry in 12 brains. In addition, we found (c) distinct distributional patterns of [11C]PK-11195 binding associated with different frontotemporal dementia syndromes, that supported more accurate classification of participants than [18F]AV-1451.

Neuroinflammation may be important in shaping the clinical and neuropathological patterns of fronto- temporal dementia, and be a target for disease-modification.

richard.bevanjones@doctors.org.uk
038  Pregnancy outcomes in patients treated with ocrelizumab
Authors: Brex Peter , Oreja-Guevara Celia , Wray Sibyl , Buffels Regine , Zecevic Dusanka , Vukusic Sandra
Published: May 2022

Background

Ocrelizumab is approved for the treatment of relapsing forms and primary progressive multiple sclerosis (MS).

Methods

We report analyses of pregnancies in women who received ocrelizumab in clinical trials/post- marketing sources up to 31/03/2019. Contraceptive requirements for women of childbearing potential were per label (during treatment and for 6/12 months after the last infusion) or adapted in clinical trials (two methods for 6 months or until 48 weeks after the last infusion/until B-cell repletion [whichever longer]). Foetal exposure was defined as the last infusion occurring within 3 months of conception or during pregnancy if the conception date was unknown.

Results

A total of 362 ocrelizumab-exposed pregnancies in women with either MS (N=267), rheumatoid arthritis/systemic lupus erythematosus (N=33) or an unknown indication (N=62) have been reported. Of the 267 pregnancies in women with MS, 118 were considered to have foetal exposure, 47 did not have foetal exposure and 102 had unknown foetal exposure. Preliminary pregnancy outcomes in MS patients include: 62 live births, 86 ongoing pregnancies, 25 elective abortions, 10 spontaneous abortions, 1 stillbirth, 3 ectopic pregnancies, 22 lost to follow-up and 58 unknown/unreported outcomes.

Conclusions

Cases to date do not suggest an increased risk of adverse pregnancy/foetal outcomes with ocrelizumab.

p.brex@nhs.net
The mitogenome of Urnula craterium
Authors: Mukhopadhyay Jigeesha , Wai Alvan , Hutchison Leonard J. , Hausner Georg
Published: May 2022

Urnula craterium (Schwein.) Fr. (1851) has been reported from North America, Europe, and Asia, and can be a pathogen on various hardwood species. In this study, we investigated the mitochondrial genome of U. craterium. The biology and taxonomy of this fungus is poorly studied and there are no mitogenomes currently available for any member of the Sarcosomataceae (Order Pezizales). The complete mitogenome of U. craterium comprises 43 967 bps and encodes 14 protein-coding genes, a complete set of tRNAs and rRNA genes. A novel feature of the mitogenome is the presence of a single subunit DNA polymerase-coding region that is typically associated with linear invertron-type plasmids. The mitogenome may offer insights into the evolution of mitogenomes among members of the Pezizales with regards to gene content and order, mobile elements, and genome sizes.
Skewness-based characterization of silicon photomultipliers
Authors: Vinogradov S.
Published: May 2022

Characterization of SiPMs is an objective of high importance in almost any research, development, and application of these unique photon detectors. Two decades of characterization method developments resulted in a comprehensive and elegant methodology based on a precisely resolved number of fired SiPM cells or the SiPM spectrum. Spectrum fitting procedures are very sensitive to a proper selection of many initial guess values including parameters of minor importance and happen to be unreliable. Moreover, conventional methods are useless for degraded or unresolved SiPM spectra. This challenge was anticipated for SiPM-based detectors of high-luminosity particle calorimeters where a severe radiation degradation of the SiPMs would co-exist with their acceptable performance. To address it, one can measure a mean and variance of SiPM charge responses relying on a priori known Excess Noise Factor of the SiPM but its stability during SiPM degradation is uncertain. This study proposes and evaluates a new approach for the SiPM characterization based on the first three statistical moments (mean, variance, and skewness) of its charge response including skewness. It assumes the Generalized Poisson distribution of the number of fired cells and provides simple closed-form analytical expressions for the parameter estimation. It allows determining a gain, a number of detected photons, and a probability of correlated events directly from raw data. The skewness-based characterization is anticipated to be especially useful for mass testing and continuous monitoring of SiPMs in large-scale experiments due to its simplicity and robustness. Initial evaluations of the method show promising results.
Cosmic dynamics and qualitative study of Rastall model with spatial curvature
Authors: Singh Ashutosh , Singh Gyan Prakash , Pradhan Anirudh
Published: May 2022

We investigate the cosmic dynamics of Rastall gravity in nonflat Friedmann–Robertson–Walker (FRW) space–time with barotropic fluid. In this context, we are concerned about the class of model satisfying the affine equation of state. We derive the autonomous system for the Rastall model with barotropic fluid. We apply the derived system to investigate the critical points for expanding and bouncing cosmologies and their stable nature and cosmological properties. The expanding cosmology yields de Sitter universe at late times with decelerating past having matter and radiation-dominated phases. Investigation of autonomous system for bouncing cosmology yields oscillating solutions in positive spatial curvature region. We also investigate the consequences of setting-up a model of nonsingular universe by using energy conditions. The distinct features of the Rastall model compared to the standard model have been discussed in detail.
Development and cold-test of an RFQ-DTL coupled cavity
Authors: Dou Wei-Ping , Li Chen-Xing , Wang Zhi-Jun , Xue Zong-Heng , Jin Xiao-Feng , Li Zhi-Hui , Li Xiao-Xiao , Wang Chao , Wang Wang-Sheng , Jia Huan , Chen Wei-Long , Zhang Zhou-Li , Qin Yuan-Shuai , Qi Xin , He Yuan
Published: May 2022

With the continuous strengthening of application requirements, neutron sources are becoming more and more compact, integrated and mobile. There are challenges in two aspects. The first is to achieve high transmission efficiency of high beam current physically, the second is to achieve integration and miniaturization technically. The coupling of RFQ and DTL is a feasible way. A preliminary study on the key physical problems in the RFQ-DTL coupled cavity has been accomplished. For the beam dynamics, the compact matching of RFQ and DTL was studied for the coupled cavity. Taking the compact physical design of the RFQ-DTL for deuterium ion beam of 30 mA with the energy of 11 MeV without MEBT as an example, we studied the smooth transition of the phase advance per unit length, the ability of RFQ transition cell to rotate beam in the transverse phase space, the transverse and longitudinal acceptance optimization of DTL. The RFQ and DTL can be matched transversely and longitudinally after removing MEBT, and the transmission efficiency is 98.7%. For direct coupling of four-vane RFQ and CH-DTL, we studied the realization of the coupling, the factors affecting the field amplitude ratio, the tuning of the cavity, and the influence of the superimposed field on the beam transmission. The field amplitude ratio between RFQ and CH-DTL is from 16.5 to 36.2. Under the influence of the superimposed field, the difference in normalized RMS emittance is less than 1%. We have designed, constructed and cold-test the 750 MHz model cavity. The normalized electric field coefficients measured and simulated are basically in agreement.
Dynamics of a Mathematical Model of Cancer and Immunoediting Scenarios Under the Variation of the Immune Cell Activation Rate
Authors: Nova Martínez Manuel Arturo , Granada Díaz Héctor Andrés , Calderón Saavedra Pablo Emilio
Published: May 2022

This article investigates the dynamics of cancer through a coupled system of three nonlinear ordinary differential equations. The evolution of the cancer tumour is examined under the variation of the immune cell activation parameter, and the study determines the values of this parameter that cause changes in the dynamics of this evolution; these changes are a consequence of two transcritical bifurcations and a supercritical Hopf bifurcation that exist in the system. These results reveal the range of immune cell activation for which tumour escape or tumour latency, or oscillatory behavior due to the appearance of limit cycles, is achieved. In addition, an optimal value is distinguished for which a minimum number of active immune response cells is sufficient to bring the tumour to a latent state.