bluuebunny/crossref_metadata_2025 huggingface dataset:
081 Impact of co-morbid PCOS on IIH outcomes
Authors: Thaller Mark , Homer Victoria , Wakerley Benjamin , Mollan Susan , Sinclair Alexandra
Published: August 2022

Introduction

Idiopathic intracranial hypertension (IIH) and Polycystic ovary syndrome (PCOS) affect women of reproductive age with obesity but have different hyperandrogenic profiles. The prevalence of comorbid PCOS in IIH patients is highly variable in the literature; and the longitudinal impact on visual and headache outcomes are unknown.

Aims and Methods

Assess the prevalence in a prospective IIH cohort (IIH Life database (2013-2021)) based on Rotterdam criteria from questionnaire and routine clinical practice data. Secondary aim to evaluate the impact of PCOS on IIH outcomes (visual and headache).

Results

382 females with IIH were followed up for a median 10 (0-87) months and had presence or absence of PCOS documented. Prevalence of PCOS in IIH was 20.4% (78/382) by the Rotterdam criteria, with additional 15.2% (58) describing hyperandrogenism alone.

Females with IIH and comorbid PCOS did not have significantly different visual or headache outcomes (including mean deviation and optical coherence tomography papilloedema measures).

Conclusions

Symptomatic hyperandrogenism is common in IIH patients who have previously been noted to have elevated levels of testosterone. Diagnosing co-morbid PCOS is important as it can impact fertility and long-term cardiovascular risk. From an IIH management aspect, comorbid PCOS does not confer worse visual or headache outcomes.
097 Transcranial sonography in the prodromal phase of PD
Authors: Rees Richard , Simonet Cristina , Gill Aneet , Giovannoni Gavin , Lees Andrew , Bestwick Jonathan , Noyce Alastair J , Schrag Anette
Published: August 2022

Introduction

Transcranial sonography (TCS) has been shown to be a reliable imaging biomarker in patients with Parkinson’s disease (PD). 90% of patients with PD have enlarged nigral hyperechogenicity (SN+) compared to 10% healthy controls (HC).

Objective

To assess the relationship between SN+ and motor and non-motor features of prodromal PD.

Methods

Higher-risk (HR) and lower-risk (LR) age- and gender-matched controls from the PREDICT-PD study were compared alongside PD patients. TCS was performed with a cut-off of 0.20cm2 for SN+. Validated scales were used to assess motor and non-motor features. All assessments were undertaken blind to risk of PD determined by the PREDICT-PD algorithm. PREDICT-PD participants were compared according to enlarged or normal SN echogenicity.

Results

47 PREDICT-PD participants and 13 PD patients were compared. 40/47 PREDICT-PD participants and 12/13 PD patients had good quality sonographic appearances on at least one side. 24 PREDICT-PD participants had enlarged SN+ and 23 were normal. SN+ participants had higher MDS-UPDRS III scores than those with normal SN (mean 6 vs 4, p=0.036), but did not differ in any other domain. There was no relationship between SN+ and risk of PD.

Conclusion

Despite evidence for use around the time of PD diagnosis in individuals with motor features of PD, we found no convincing evidence to support the use of TCS in the prodromal phase.
099 Thrombotic and haemorrhagic complications associated with PLEX, reducing the risks
Authors: Japzon Nicole , Han Ruth , Sacks Benjamin , Levee Viva , Rosser Sinead , Samaroo Yasmine , Westwood John Paul , Zambreanu Laura , Lunn Michael P , Spillane Jennifer
Published: August 2022

Background

Plasma Exchange (PLEX) is an increasingly used therapy for various immune-mediated neu- rological diseases. Treatment can be complicated by potentially life-threatening clots and bleeds but there is limited data available regarding these risks.

Method and Intervention: A retrospective audit of the records of patients receiving PLEX in the NHNN for neurological disease from May 2019 – October 2020 was performed to identify thrombotic and haemor- rhagic complications. A multi-disciplinary PLEX working group was created to set guidelines for all aspects of the PLEX process including mode of vascular access, use of prophylactic heparin and fluid replace- ment. The service was subsequently re-audited.

Results

46 patients were treated with plasma exchange between May 2019 and Oct 2020. 11% developed a thrombus requiring anticoagulation. 41% developed a haemorrhage, 42% of which required intervention.

Following protocol change a review of 32 patients between November 2020 to October 2021 showed that there was a reduction of 27% in the incidence of thrombus and a 17% reduction in the incidence of haemorrhage.

Conclusion

PLEX is integral to the treatment of disabling and potentially fatal immune-mediated neuro-logical diseases. Careful consideration of all aspects of the PLEX process, reduces risks associated with treatment and improves patient safety.
107 Short term neuropsychiatric outcomes of STN – DBS using directional vs conven- tional ring mode stimulation
Authors: Hammersley Beth , Bonello Michael , Fahad Salam , Costa Antonio Da , Mullin Jenny , Farah Jibril , Alusi Sundus
Published: August 2022

Achieving the best outcome from STN stimulation for the treatment of Parkinson’s disease depends on ideal electrode placement and optimum stimulation settings. Motor symptoms are known to respond well to stimulation of the dorsolateral nucleus of the subthalamus and avoidance of tissue activation of the surrounding structures that may give rise to unwanted side effects including slurred speech, gait problems and neuropsychiatric symptoms. The recent development of multidirectional stimulation systems has enabled electrical current steering to activate the desired tissue areas in order to achieve effective neuromodulation.

In this audit of 16 patients who underwent STN-DBS, we looked at the short-term neuropsychiatric outcomes in patients in whom current steering was deployed to achieve the best motor control to those in whom control was achieved by conventional ring mode stimulation. The patients’ symptoms were assessed at baseline and at 12 months using validated scales for anxiety, depression, apathy, and impulsivity. There was no statistical difference in the neuro-psychiatric outcomes between the two groups. However, the number of patients in this study was small and larger studies for longer periods are required to evaluate the potential benefit of this new development in minimising the neuropsychiatric complications of this treatment.
111 Factors that affect care needs in people with Parkinson’s disease: a patient perspective
Authors: Fearn Sarah , Viana Clara Mencio , Bartolomeu-Pires Sandra , Kipps Christopher
Published: August 2022

Background

The care that people with Parkinson’s (PwP) require varies over the course of the disease. A patient perspective on the factors determining care needs over time has been lacking.

Aim

1) To identify the relative importance of factors that affect care needs of PwP from a patient per- spective. 2) To identify whether the relative importance of different factors varies by demographic and clinical characteristics.

Method: 392 PwP completed a 5-point Likert scale to score the importance of 6 different factors that affect care needs. Means scores were obtained and factors were compared by participant age, gender, living alone, disease progression, and presence of co-morbidities.

Results

From a patient perspective, mobility was the most important factor for assessing care needs, followed by dexterity, eating and drinking, communication, cognitive function, and mental health. This ranking was constant across demographic and clinical characteristics. However, younger patients, females, those living alone, more progressed patients, and those with co-morbidities tended to produce higher mean scores of importance suggesting a larger impact at an individual level.

Conclusion

This study determined which factors patients consider to most affect the care they require, enabling healthcare professionals to provide more personalised care to PwP.
114 Pain and objectively measured cognitive performance in adults with multiple sclerosis: a systematic review
Authors: Brown Fraser , Glasmacher Stella , Taylor Daniel , Jenkins Ruth , Chandran Siddharthan , Gillespie David , Foley Peter
Published: August 2022

Background

Pain and cognition are important symptoms in multiple sclerosis (MS). Cognitive processes contributing to pain experience are increasingly documented. Any relationship between pain and objectively measured cognitive performance (OMCP) in MS, including potential mediating factors such as fatigue and medication, remains unclear. Understanding this relationship may facilitate targeted treatment strategies.

Objective

Determine the relationship between pain and OMCP in MS.

Methods

We conducted a systematic review, following a pre-registered protocol, of clinical studies examining relationships between pain and OMCP in MS. We searched MEDLINE, Embase and PsychInfo. We assessed confounders and described findings using neuropsychologist-assigned cognitive domains. Risk of bias was assessed using a modified Newcastle-Ottawa Scale.

Results

10 studies were included. Eight studies identified a relationship between pain and OMCP. In six studies, worse pain scores were associated with worse cognition. However, no evidence was available for several cognitive domains. Studies infrequently controlled for confounders. Most studies were judged to be at risk of bias.

Conclusions

While several studies suggest that pain in MS is related to worse objective cognitive perfor- mance, conclusions are limited by study design and limited evidence in many cognitive domains. Future studies should better establish this relationship and delineate the neurological substrate underpinning it.
121 The ADAMS project: protocol and baseline results
Authors: Jacobs Benjamin , Giovannoni Gavin , Noyce Alastair , Morris Huw , Dobson Ruth ,   et al
Published: August 2022

Genome-wide association studies (GWAS) of Multiple Sclerosis (MS) have focussed on populations of European ancestry. Studying MS genetics in other ancestries is necessary to ensure the generalisability of these findings.

We report the design of a new collaborative MS genetics project – ‘ADAMS’. Individuals with MS from non-White-British ethnic backgrounds will be recruited either via a website – https://app.mantal.co.uk/ adams – or in-person at a participating site. We will collect demographic and phenotypic data using a combination of a baseline questionnaire and subsequent healthcare record linkage. We will collect DNA from up to 1000 participants using saliva kits (Oragene-600) and genotype individuals using the Illumina Global Screening Array version 3. Genotypes will be combined with large ancestrally-matched control datasets (UK Biobank and East London Genes and Health).

We have recruited 91 participants within the first eight weeks of the study. Of this initial cohort, 73.9% are female, 84.5% were born in the UK, 32.4% identified as Asian or Asian British, 28.2% as Black, African, Caribbean or Black British, and the remainder identified as having mixed, other, or White backgrounds. 51% stated they were unlimited in their mobility. 84.7% of participants have relapse-onset forms of MS and 76.1% have ever had disease-modifying therapy. The median age at diagnosis is 30.5 and the median age at recruitment 36.7. Further recruitment and genetics results will follow over the next 3 years.
123 Oxidative stress responses – potential biomarkers in multiple sclerosis
Authors: Minton Thomas , Hares Kelly , Kemp Kevin , Scolding Neil , Rice Claire
Published: August 2022

Introduction

Oxidative stress is implicated in the pathophysiology of multiple sclerosis (MS). To investigate their potential as MS biomarkers, we compared plasma levels of two master regulators of antioxidant processes nuclear factor erythroid 2 related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α), as well as downstream antioxidant enzymes superoxide dismutase 1 (SOD1) and catalase.

Methods

Plasma levels of Nrf2, PGC1α and SOD1 were measured using enzyme-linked immunosorbent assay (ELISA). Plasma catalase levels were measured using a catalase activity assay. The results were analysed using a multiple regression model.

Results

Plasma PGC1α concentrations were higher in people with MS compared to controls and lower in patients with primary progressive MS than those with relapsing remitting MS. Plasma Nrf2 levels were increased in those on disease modifying therapy with Dimethyl fumarate, which was most pronounced 6 weeks post-initiation. Plasma Nrf2 levels fell in patients commencing Ocrelizumab. Plasma catalase activity was higher in patients with MS when compared to control, and higher in patients with progressive MS phenotypes. No statistically significant changes in plasma SOD1 levels were observed.

Conclusions

Our findings support further investigation of the potential for plasma PGC1α, Nrf2 and catalase as disease biomarkers in MS.
135 The UK MS pregnancy register: baseline data from the first fifty enrolled patients
Authors: Iyer Priyanka , Craig Elaine , Brex Peter , Ford Helen , Hughes Stella , Middleton Rod , Murray Katy , Pearson Owen , Rog David , Dobson Ruth
Published: August 2022

Background

We present baseline data on the first 50 participants recruited to the UK MS Pregnancy Register.

Methods

Data collected via questionnaires from consenting participants until 20th December 2021 were included.

Results

50 participants (all with relapsing remitting MS; mean age at diagnosis 28.0 years; mean age at recruitment 33.0 years) were included. Median EDSS was 2.5 (n=16). Gestation at recruitment ranged from 2 to 40 weeks. 78% had discussed their pregnancy in advance with their MS team. 90% of patients had ever taken DMT. Of the patients that stopped DMT (n=23), 16 reported stopping for pregnancy-related reasons. Of these, 39% stopped before pregnancy and 30% following conception. 15 women are continuing DMT during their current pregnancy, taking the following DMT: Glatiramer acetate (n=5), natalizumab (n=7), Peginterferon beta-1a (n=2), not recorded (n=1). In those with prior pregnancies, 61% (14/23) reported pregnancy loss with 1 case of a rare genetic condition in the baby. None of the prior pregnancy losses happened whilst on DMT. One participant reported previous PPH and foetal macrosomia and another reported previous pre-eclampsia.

Conclusions

These results show that a patient-facing pregnancy MS registry is feasible and can collect previous adverse pregnancy outcomes. Future results will inform clinicians and women about the safety of DMT and adjunctive medication during pregnancy and postpartum.
137 Impact of absolute lymphocyte count (ALC) frequency on detection of dimethyl fumarate–associated lymphopenia
Authors: Brownlee Wallace , Hadipour-Rahimabadi Shooka , Davies Heather , Belviso Nick , Shen Changyu , Kapadia Shivani , Levin Seth , Li Hanyue
Published: August 2022

Introduction

Lymphopenia is a known adverse event of dimethyl fumarate (DMF) with treatment dis- continuation recommended for patients with severe prolonged (≥6 months) lymphopenia. Because of the COVID-19 pandemic burden on healthcare systems, we retrospectively examined the impact of absolute lymphocyte count (ALC) monitoring frequency (every-3-months vs every-6-months) on lym- phopenia detection.

Methods

Samples from patients enrolled in phase 3 trials (DEFINE/CONFIRM) and the extension study (ENDORSE) were retrospectively analysed using 3-month or 6-month intervals. Lymphopenia was defined as ALC <0.91x109/L and severe lymphopenia as ALC <0.5×109/L. Times to the first lymphopenia event and first severe lymphopenia event were estimated using Kaplan-Meier methods.

Results

The analysis included 741 patients. There were 355 lymphopenia cases (76 severe) with 3-month monitoring, and 314 cases (70 severe) with 6-month monitoring. Over 120 months, incidence of first lympho- penia event was significantly different for 3-month vs 6-month monitoring (difference range: 2.64%–6.54%; P=0.0088). Incidence of first severe lymphopenia event was not significantly different for the two intervals (P=0.5866). Proportions of patients with severe prolonged lymphopenia with 3-month and 6-month moni- toring were similar (4.0% vs 4.2%).

Conclusions

The results of this study may be informative to clinicians managing pandemic-related health- care resource burdens. Support: Biogen. Disclosures on poster.
142 Discordance between neurologists and people with MS on the presence and burden of cognitive impairment
Authors: Penner Iris Katharina , Heras Virginia de las , Jones Eddie , Castro Patricia Dominguez , Bezlyak Vladimir , Piani-Meier Daniela , Lines Carol
Published: August 2022

Introduction

Approximately 34%-65% of people with multiple sclerosis (pwMS) develop cognitive impair- ment (CI). CI often encompasses information processing speed, memory problems, difficulty concentrat- ing, and problems using executive functions effectively. This study explores the perception of the presence of CI from the perspectives of pwMS and neurologists.

Methods

US, UK and EU retrospective data analysis from the 2011-2019 Adelphi Multiple Sclerosis Disease- Specific Programme (MS-DSP). The MS-DSP is a database where neurologists provide data on the next 10 pwMS to have a consultation, patient record form (PRF), integrated with pwMS self-reported data, patient self-completion form (PSC). Neurologists and pwMS were asked about the presence of problems concentrating.

Results

25,374 pwMS had a PRF. 11,220 pwMS had a PRF and PSC, of these 4294 answered the cognition section, with 62% (n=2,643) reporting CI (mild 36.8%, moderate 18.6, or extreme 6.1% problems concen- trating) in the past two weeks. For the same pwMS, neurologists reported 27% (n=1,158) currently having CI (mild 19.9%, moderate 6.8%, or severe 0.3% problems concentrating).

Conclusions

A clear discordance is observed between neurologists and pwMS on their perception of the presence and severity of CI with neurologists clearly underestimating the existence. Funding: Novartis Pharma AG, Basel, Switzerland.
143 Effect of siponimod on disability progression measured by ambulation score: post hoc analysis of EXPAND
Authors: D’Souza Marcus , Giovannoni Gavin , Vermersch Patrick , Maca Jeff , Ansari Soudeh , Karlsson Goeril , Piani-Meier Daniele , Kappos Ludwig
Published: August 2022

Background

In the Phase 3 EXPAND study, siponimod reduced the Neurostatus-EDSS-measured risk of 3/6-month (M) confirmed disability progression versus placebo by 21%/26%, with more pronounced effects (31%/37%) in active SPMS (aSPMS). Here we evaluated the contribution of the Ambulation Score (AS) to measuring siponimod’s effect on disability progression.

Design/Methods

This post-hoc analysis included the overall population (OP); siponimod/placebo n=1099/546) and aSPMS/non-active (naSPMS) patients (siponimod, n=516/557; placebo, n=263/270). Outcomes included change from baseline in Neurostatus-EDSS/AS, time-to-first worsening on AS (3M/6M confirmed worsening [3M/6MCW]) by ≥1/≥2-points and categorical analysis (proportion of patients with 3M/6MCW or confirmed improvement [CI] by ≥1-point during the core study [median(range): 21(0.2–37.0) M]).

Results

In the OP, the Neurostatus-EDSS, and more prominently, AS change from baseline, favored siponimod versus placebo at all visits (M6-M30); most pronounced at M18 (EDSS: 0.13 versus 0.23;p=0.003; AS: 0.50 versus 0.81;p=0.001). Siponimod significantly reduced the risk of 3MCW (≥1-point, HR=0.78,p=0.0046;

≥2-point, 0.71,p=0.0007) and 6MCW in AS (≥1 point, 0.74, p=0.0023).In aSPMS, pronounced effects were observed in 3MCW (≥1-point, HR=0.68,p=0.002; ≥2-point, 0.60,p=0.0005); 6MCW (≥1-point, HR=0.63,p=0.0007), with fewer patients worsening/more improving on siponimod and a trend for fewer patients worsening in naSPMS.

Conclusions

More pronounced effects on the Neurostatus-EDSS and AS were observed in aSPMS. Funding: Novartis Pharma AG, Basel, Switzerland.
145 Long-term safety of ofatumumab in patients with relapsing multiple sclerosis
Authors: Hauser Stephen , Cross Anne , Winthrop Kevin , Wiendl Heniz , Nicholas Jacqueline , Meuth Sven , Giacomini Paul , Saccà Francesco , Su Wendy , Kappos Ludwig
Published: August 2022

Objective

To assess the long term safety and tolerability of ofatumumab treatment in patients with relapsing multiple sclerosis (RMS)

Methods

Patients completing the core ASCLEPIOS I/II, APOLITOS and APLIOS trials could enter ALITHIOS, an ongoing, open-label, extension trial. Here, we analyze the cumulative data for up to 4 years of ofa- tumumab treatment (data cutoff: 25-Sep-2021) in the overall (N=1969), continuous (ofatumumab in core+extension; N=1292) and newly-switched (teriflunomide core and ofatumumab extension; N=677) groups. Laboratory parameters including neutrophils, lymphocytes, and serum immunoglobulin (Ig) G and IgM levels will be analyzed.

Results

In data reported from ALITHIOS (cut-off of 29-Jan-2021), representing ofatumumab treatment for up to ~3.5 years, 83.8% of patients had ≥1 AEs (exposure-adjusted incidence rate [EAIR], 148.7) and 9.7% had ≥1 serious AEs (EAIR, 4.8) with a low incidence of serious infections (2.9%; EAIR, 1.4) and malignancies (0.3%; EAIR, 0.3). Updated safety data representing continuous ofatumumab treatment for up to 4 years will be presented at the congress.

Conclusion

Safety findings for up to 3.5 years show ofatumumab treatment to be generally well-tol- erated with no new safety risks identified. This additional safety data will help confirm ofatumumab’s longer-term safety profile. Funding: Novartis Pharma AG, Basel, Switzerland.
156 Association of locus of control with clinical and psychosocial aspects of living with multiple sclerosis
Authors: Rothman Isaac , Tennant Alan , Mills Roger , Young Carolyn
Published: August 2022

Aim

Health Locus of control (LOC) refers to the individual’s beliefs regarding control over their life outcomes. This study aimed to determine the influence of LOC on clinical and psychosocial aspects associated with multiple sclerosis (MS).

Methods

5059 participants with MS completed a questionnaire pack as part of the ongoing Trajectories of Outcome in Neurological Conditions (TONiC) study. Associations between predominant LOC, measured by the Multidimensional Health Locus of Control Scale, and a range of sociodemographic and clinical variables were explored.

Results

Each LOC predominance was found to be significantly associated with all of the clinical variables and age, but not gender or educational level. When controlling for level of disability, Chance (CLOC) was associated with higher self-efficacy and quality of life than Powerful Others (PLOC), while Internal (ILOC) had no influence on the variables. A change in LOC away from ILOC was found with disease progression.

Conclusions

In MS, believing that health is controlled mainly by chance, rather than healthcare profes- sionals or one’s self, confers the most benefit with regards to quality of life. The observed shift away from internality of LOC with MS progression may not be maladaptive, but rather a protective adaptation to reduce psychological distress.
162 Use of brain imaging and EEG for prognostication in post-cardiac arrest coma
Authors: Carey Charles , Rogers Tobias , Mohanraj Rajiv
Published: August 2022

Introduction and Aims

Accurate prognostication for comatose patients following out of hospital cardiac arrests (OOHCA) remains challenging. This study aimed to evaluate the use of CT-scans and EEGs for neuro-prognostication in comatose OOHCA patients admitted to ICU in 2 major cardiac centres.

Methods

Records of 71 patients admitted to ICU following OOHCA in 2019 were reviewed. Use of CT-scans and EEGs were compared with the European Resuscitation Council (ERC) guidelines.

Results

46 (64.8%) patients had withdrawal of life support (WLS) during admission. 60 (84.5%) patients had reported CT-brains, of which 26.7% showed either generalised oedema or a loss of grey-white matter distinction and 73.3% showed other ischaemic changes or normal results. 100% of patients with general- ised oedema or a loss of distinction and 59.1% patients with other ischaemic changes or normal scans had WLS during admission. EEGs were performed in 21 patients (29.6%), 18 (85.7%) of which had WLS. 22 (31.0%) patients had WLS within 72 hours of arrest. 90.9% of these patients had CT-heads and 0% had EEGs performed.

Conclusion

EEGs were used infrequently for neuro-prognostication and cerebral oedema and a loss of grey-white matter distinction were more often associated with WLS.
Effectiveness of COVID-19 vaccines in multiple sclerosis patients receiving disease-modifying therapies in England
Authors: Garjani Afagh , Patel Sameer , Law Graham R , Bharkhada Dhiren , Rashid Waqar , Coles Alasdair , Evangelou Nikos
Published: August 2022

Studies have measured the immunological response to COVID-19 vaccines among multiple sclerosis (MS) patients receiving disease-modifying therapies (DMTs), but its clinical relevance is unclear. We aim to understand how MS DMTs affect the clinical effectiveness of COVID-19 vaccines.

We analysed data of all MS patients receiving DMTs in England from December-2020 to January-2022. We calculated post-vaccination (≥14 days following second dose) incidence of infection (positive COVID-19 test) and COVID-19 related hospitalisation (within 0-28 days of a positive test and >1 day). We used merged datasets of the NHS England and NHS Improvement and the UK Health Security Agency.

A total of 38,039 MS patients on DMTs (90%) had at least two COVID-19 vaccines. Post-vaccination incidence of infection was 24% (859/3624) for ocrelizumab, 22% (819/3797) for fingolimod, and ranged from 11% to 16% for other DMTs. Hospitalisation rate among infected patients was 7% (n=61) for ocreli- zumab, 4% (n=33) for fingolimod, and ranged from 1% to 4% for other DMTs.

Patients on ocrelizumab have higher rates of COVID-19 related infection and hospitalisation compared to other DMTs using current vaccination protocols. Patients on fingolimod also have higher rates of post- vaccination infection but their hospitalisation rate is similar to other DMTs. Further analysis including demo- graphics, booster vaccines, unvaccinated, and mortality is ongoing to be presented at the meeting.
171 Urinary P75: a novel biomarker for motor neuron disease?
Authors: Chapman Laura , Shepheard Stephanie , Verber Nick , Turner Martin , Malaspina Andrea , Rogers Mary-Louise , Shaw Pamela
Published: August 2022

Motor neuron disease (MND is a progressive and fatal disease. The urinary neurotrophin receptor p75 extracellular domain (p75ECD) has previously been reported as a potential disease biomarker.

This study measured urinary p75ECD using an enzyme-linked immunoassay and normalised the results against urinary creatinine. Participants were recruited via the Multicentre Biomarker Resource Strategy in ALS (AMBroSIA) programme. Study participants included 97 MND patients, 24 of whom were studied longitudinally, and 27 healthy controls. The longitudinal changes in disease severity and survival in com- parison to urinary p75ECD were examined using mixed-model analysis on SPSS.

Confirming previous findings, urinary p75ECD levels were significantly higher in patients with MND (median 6.78ng/mg) compared to controls (4.57ng/mg) at first study visit (p=0.013). There was a significant negative correlation between ALSFRS-R rating and p75ECD levels (p=<0.001), indicating that an increase in the severity of motor neuron injury correlated with an increase in p75ECD levels. There was a significant increase in p75ECD between first and second samples in the same participants, indicating an increase in the level of this biomarker longitudinally during the disease course (p=0.011).

Urinary p75ECD is a strong candidate as a biomarker which increases with disease progression, and which has potential as a pharmacodynamic biomarker.
172 Impact of age on interventions and survival in people with motor neuron disease in Scotland
Authors: Christides Alexander , Symonds Alexander , Johnson Micheala , Beswick Emily , Newton Judith , Chandran Siddharthan , Pal Suvankar , Consortium CARE-MND
Published: August 2022

Introduction

Motor neuron disease (MND) is rapidly progressive and largely fatal. The National Institute for Health and Care Excellence guidelines (2016) outline best practice for symptomatic interventions including riluzole, gastrostomy, and non-invasive ventilation (NIV). We aimed to investigate the impact of age on interventions and survival in MND using data from the Scottish MND register (CARE-MND), hypothesising these factors may be impacted by increasing age.

Methods

We interrogated the CARE-MND database for incident cases in Scotland diagnosed between 01-Jan-2015 to 31-Dec-2020. Survival was compared in different age cohorts using Kaplan-Meier curves and log-rank test. Management was compared in different age cohorts using Chi-squared test.

Results

828 individuals were included (median age at diagnosis 68.7 years (interquartile range 61.4-76.1)). We investigated age cohorts of <40, 40-60, 60-80, and >80 years. Median survival from diagnosis in each cohort was 24 months, 18 months, 11 months, and 4.5 months respectively (p<0.001). Riluzole, NIV and gastrostomy were implemented least in the oldest group (p<0.05).

Conclusions

Our data supports reduced survival of MND with increasing age, together with lower rates of riluzole prescribing, NIV use, and gastrostomy insertion, and offer insights into how care may be optimised in line with national guidelines.
176 Motor fatigability in motor neuron disease
Authors: Sassani Matilde , Alix James , Baster Kathleen , Cercignani Mara , Shaw Pamela , Jenkins Thomas
Published: August 2022

This study aimed to quantify, characterise and localise motor fatigue in people with motor neuron disease (MND) using a combination of clinical assessments, neurophysiology and muscle phosphorus-31 magnetic resonance spectroscopy (31P-MRS).

We quantified fatigability using the fatigue index (FI) in twenty patients and 10 healthy controls. F-wave amplitudes, motor unit number index (MUNIX) and 31P-MRS were acquired pre- and post-maximal voluntary contraction to investigate fatigability at different sites of the motor system (spinal cord, peripheral nerve and muscle, respectively). Between-group differences and associations were assessed using regression models.

There were no between-group differences in FI (p=0.115). MUNIX (p=0.008) and f-wave amplitude (p=0.024) declined significantly post-contraction in controls, but not in patients (MUNIX p=0.284, f-wave p=0.264). FI was associated with resting intracellular magnesium (R=0.869, p=0.001, FDR-corrected) in controls, but not patients. Resting magnesium and post-contraction MUNIX decrease were associated with greater fatigue in controls. A decrease in post-contraction f-wave amplitude was associated with greater fatigue in patients, after accounting for denervation (MUNIX) and magnesium.

There is a differential response to fatigue in MND compared to healthy controls. Fatigability appears related to spinal excitability (f-waves) in patients, whereas peripheral (MUNIX) and muscular (magnesium) components predominate in healthy controls.
184 ROADS to remote monitoring of ALS
Authors: Stephens Jessica , Proudfoot Malcolm
Published: August 2022

Monitoring disease progression in ALS is fundamental to both routine clinical care and outcome measure- ment in clinical trials. The ALS Functional Rating Scale (ALSFRS) has for decades provided a simple summary of disability progression but has well-recognised limitations. Rasch Overall ALS Disability Scale (ROADS) is a novel, mathematically designed, yet simple scale proposed to improve reporting of functional decline due to ALS. ROADS is, thus far, not widely validated or broadly applied in clinical practice. We describe the introduction of ROADS to patients attending an NHS trust, while gathering descriptive qualitative feedback on the questionnaire acceptability and utility. Remote data collection and self-completion was mandated by the Covid-19 pandemic. The results from the ROADS questionnaire are contrasted with ALSFRS scores, appraising the pattern of disability for each patient on both rating scales and highlighting additional information provided by ROADS to further inform clinical management. We encourage review of ROADS scores alongside objective respiratory measures and King’s staging.
185 JEWELFISH: Safety, pharmacodynamic and exploratory efficacy data in non-naïve patients with SMA receiving risdiplam
Authors: Scoto Mariacristina , Bruno Claudio , Fischer Dirk , Kirschner Janbernd , Mercuri Eugenio , Carruthers Imogen , Gerber Marianne , Kletzl Heidemarie , Warren Francis , Chiriboga Claudia ,   on behalf of the JEWELFISH Working Group
Published: August 2022

Risdiplam (EVRYSDI®) is an oral survival of motor neuron 2 (SMN2) pre-mRNA splicing modifier approved by the EMA and MHRA for the treatment of patients aged ≥2 months, with a clinical diagnosis of Type 1, 2 or 3 spinal muscular atrophy (SMA) or 1–4 SMN2 copies.

JEWELFISH (NCT03032172) is an open-label study of risdiplam in patients with SMA who previously received RG7800 (RO6885247), nusinersen (SPINRAZA®), olesoxime or onasemnogene abeparvovec (ZOLGENSMA®).

JEWELFISH assesses the safety, tolerability and pharmacokinetic/pharmacodynamic (PD) relationship of risdiplam in a broad range of ages (1–60 years), SMA types (1–3), SMN2 copy numbers (1–4) and motor function (nonsitters, sitters and walkers). We previously presented safety data from 173 patients (data cut-off: 31 July 2020): 13 previously received RG7800, 76 received nusinersen, 70 received olesoxime and 14 received onasemnogene abeparvovec. Risdiplam led to a rapid and sustained >2-fold increase in SMN protein (data cut-off: 1 June 2020), consistent with data from treatment-naïve patients with Types 2/3 SMA (SUNFISH;NCT02908685).

No drug-related safety findings leading to withdrawal were reported for any patients in JEWELFISH. The safety profile of risdiplam was consistent with observations in treatment-naïve patients. Here we present 12-month safety, PD and exploratory efficacy data.
189 Real world experience on use of rituximab at regional refractory myasthenia gravis clinic in Birmingham
Authors: San Pyae Phyo , Jacob Saiju , Sadalage Girija , Roe Alice
Published: August 2022

Myasthenia gravis (MG) is a T-cell dependent B-cell mediated autoimmune disease targeting neuro- muscular junction.

Rituximab is a chimeric CD20 monoclonal antibody which gives consistently high response rates in anti- Muscle Specific Kinase antibody positive MG. In contrast, the response rates were variable for anti-Ace- tylcholine Receptor antibody positive MG.

NHS approved use of rituximab in specific circumstances in Myasthenia patients since 2019. Our NHS regional refractory MG clinic reviewed 15 patients who received Rituximab from 2019 to 2021. 14 were anti-AchR positive and 1 was anti-LRP4 positive. 7 had severe disease (MGFA Class IV/V). 12 had had prednisolone and at least 2 other immunosuppressants.

9 received standard Rituximab regime of 2 doses of 1 Gram 2-weeks apart. 6 received more than 2 doses due to unsatisfactory clinical improvement or relapse. From an average of 10% before treatment, periph- eral CD19+ B cell depletion to 0% was achieved in all although 3 had reappearance with one needing retreatment due to an accompanying clinical relapse.

Outcome

Efficacy in MGFA Post-Intervention Status: 2 achieved Minimal Manifestations-3, 2 >50% Improved, 5 <50% Improved, 5 Unchanged and 1 Worse.

Safety

None experienced side effects.

Further analysis of steroid dose reduction and long-term outcome is currently being undertaken.
191 Real world treatment with risdiplam in adults with type-2 spinal muscular atrophy at St George’s Hospital, London
Authors: Ambawatte Sathyajith Buddhika , Weidner Derek , Chatfield Sherryl , Appleton Pamela , Matthews Emma , Nirmalananthan Niranjanan , Galtrey Clare
Published: August 2022

Risdiplam is a pre-mRNA splicing modifier designed to treat 5q-SMA. We describe our experience prescrib- ing Risdiplam to adults with type-2 SMA with a wider range of ages and comorbidities than in clinical trials.

Risdiplam was prescribed for nine people aged 20 to 56-years; six males. Eight patients had homozygous exon-7 and 8 deletions; one had isolated homozygous exon-7 deletions. Seven patients had three copies of the SMN-2-gene, two had four copies. Seven patients had spinal surgery and two had severe scoliosis. They had between 0-5 comorbidities and 1-12 other drugs already prescribed and were all assessed for known interactions. They had blood tests (month 1, 3, and 6), ECG, and visual function assessment. Females of childbearing age were offered long-acting contraception and males were offered sperm banking.

Seven patients required non-invasive ventilation while two had dysphagia (one with gastrostomy). Baseline forced-Vital-Capacity (19%-74%), RUL (score 0-19), CHOP-ATTEND (score 19-46), and 9-hole-peg-test and dynamometer were measured as appropriate.

One experienced abdominal pain and increased weakness (Risdiplam was stopped). One patient had transaminitis and treatment was withheld and restarted later at a lower dose and is being gradually increased.

We found Risdiplam is generally well tolerated, especially for those with greater disability and spinal surgery.
195 Management of optic disc swelling in atypical inflammatory neuropathy
Authors: Bellanti Roberto , Mukherjee Trisha , Coyle-Gilchrist Ian
Published: August 2022

An 18-year-old female presented with rapidly progressive ascending flaccid paralysis, respiratory failure and bilateral VI and VII cranial nerve palsies. She was diagnosed with Guillain-Barré syndrome (GBS) and, following intravenous immunoglobulin (IVIG) and plasma exchange (PLEX), made steady improvement. Seventy-four days after presentation and despite continued clear improvement in her other symptoms, she developed headaches, bilateral optic disc swelling and a dilated, tonic left pupil with light-near dissocia- tion. Her cerebrospinal fluid (CSF) protein was markedly elevated. She was managed with serial lumbar punctures and steroids and had an excellent response. Optic disc swelling is an unusual but described complication of GBS and may be caused by raised intracranial pressure, disorders of CSF protein (or its resorption) or direct inflammation of the optic nerve itself. Prompt recognition and appropriate manage- ment are essential to avoid permanent visual loss. We discuss differential diagnosis and management of this challenging clinical entity of delayed onset of optic disc swelling and very elevated CSF protein in the context of acute inflammatory neuropathy.
203 A case of post COVID-19 endotheliitis
Authors: Prossor Timothy , Christofi Gerolemos
Published: August 2022

A 49-year-old man presented with shortness of breath and fever. He was in diabetic ketoacidosis on admission and tested positive for COVID-19 on PCR. He became bacteraemic with streptococcus pneu- moniae secondary to a super-added left lower lobe pneumonia. He developed new heart failure felt to be secondary to myocarditis, evidenced by a resolving ejection fraction throughout his admission and an unremarkable cardiac MRI. After developing confusion on the ward, a CT head and MRI brain identified a spontaneous frontal haematoma and multiple micro-haemorrhages throughout the cerebral hemi- spheres, cerebellum and the pons. Repeat MRI brain with diffusion weighted imaging identified multiple silent infarcts in the small vessel territories. Bacterial endocarditis was excluded with Cardiology input and hypoperfusion also excluded based on normotension throughout admission. The case was discussed at the Encephalitis and Neurovascular MDT meetings where MRI vessel wall imaging was reviewed and felt to represent a post-infectious endotheliitis. He was treated with intravenous methylprednisolone for 3 days and a further 5 days, due to new silent infarcts on a subsequent MRI brain, before a 10 week oral steroid taper. Multi-system complications from COVID-19 are not limited to those in the intensive care unit or with severe respiratory illness.
Associations between antiepileptic use and hypogammaglobulinaemia: findings from a population-based case-control study using data linkage
Authors: Perrott Sarah , Macleod Angus
Published: August 2022

Background

Antiepileptic drugs (AEDs) have been previously associated with transient hypogammaglob- ulinaemia in small case series, which may predispose patients to infections. This study aimed to determine if an association exists between AEDs and hypogammaglobulinaemia.

Methods

A case-control study was conducted using data linkage of biochemistry, prescribing and morbidity data from 2009-2021. Cases were participants with immunoglobulin levels less than the normal range. Logistic regression was used to investigate associations between AED exposure and hypogamma- globulinaemia, adjusting for age and sex. Secondary analyses were conducted, investigating outcomes of low IgA, IgM and IgG separately. Cumulative exposure data were used to determine whether a exposure-response relationship exists.

Results

18,666 cases and 127,157 controls were identified. AEDs were associated with increased risk of hypogammaglobulinaemia (adjusted odds ratio (aOR) 1.26 (95% confidence interval 1.21-1.31), p<0.001). Individual AEDs (except topiramate) were also associated with significantly increased hypogammaglob- ulinaemia risk to varying degrees. There was evidence of an exposure-response relationship for those treated with any AED.

Conclusion

AEDs may increase hypogammaglobulinaemia risk. Specific classes of immunoglobulins are differentially affected, and risk may increase with AED exposure. Clinicians should test immunoglobulin levels if unusual or recurrent infections occur. Further research should assess whether AED-associated hypogammaglobulinaemia increases infection risk.
An astra-nomical headache
Authors: Mukherjee Trisha , Needham Edward , Crisp Sarah
Published: August 2022

Introduction

We present a case of myelin-oligodendrocyte glycoprotein antibody disease (MOGAD) requiring long-term immunosuppression triggered by a dose of the AstraZeneca COVID-19 vaccination. Relapsing MOGAD is thus far an unknown complication of COVID-19 vaccination.

Case Description: A 58-year-old lady developed headache, nausea, dizziness, facial numbness, ataxia and slurred speech 8 days after the COVID-19 AstraZeneca vaccination. Her imaging showed acute disseminated encephalomyelitis (ADEM) with a white matter lesion in the left cerebellum and bilateral smaller lesions. Her cerebrospinal fluid showed 38 white cells and elevated protein. She initially responded well to steroids, however relapsed with optic neuritis 7 months later, requiring long-term immunosuppres- sion with mycophenolate mofetil.

Discussion

Although there have been some case reports of MOGAD following COVID-19 infection, to our knowledge this is only the second reported case of MOGAD following vaccination against COVID-19, and the first such case to require long-term immunosuppression. The other reported case also occurred following the COVID-19 AstraZeneca vaccine, and also presented with ADEM. This is in contrast to reported cases of MOGAD following COVID-19 infection, where adults mostly presented with optic neuritis. We wanted to highlight the possibility of this vaccine-related neurological complication occurring, particularly in the context of potentially frequent ongoing COVID-19 booster vaccinations.
010 Trigeminal neuralgia in diffuse scleroderma – a rare but recognised association
Authors: Talbot Jamie , Patel Rachel , Gormley Joe
Published: August 2022

Trigeminal neuralgia is a common cause of facial pain, typically producing paroxysmal bursts of shooting pain in one or more divisions of the trigeminal nerve. Whilst it usually occurs as a primary phenomenon due to neurovascular conflict, secondary causes account for around 15% of cases, most commonly cerebellopontine angle tumours. Multiple sclerosis is another common secondary cause of presumed inflammatory aetiology.

We report a case of trigeminal neuralgia in association with diffuse scleroderma. A 43 year old carpenter presented with typical symptoms of unilateral facial pain around a year after receiving a diagnosis of systemic sclerosis with seropositivity to Scl-70 and centromere antibodies. MR imaging at the time revealed enhancement of the left trigeminal nerve, which resolved on subsequent imaging six months later.

The association of trigeminal neuralgia and diffuse scleroderma has previously been reported, with a recent case-control study providing novel evidence of a direct association between the two conditions. Nevertheless it represents a very rare cause in patients presenting to the neurology clinic. In this presen- tation we explore the subject of secondary trigeminal neuralgia and provide a précis of the up-to-date management for this painful condition.
015 Service evaluation: the role of same day emergency care in managing acute neurological presentations
Authors: Hsu Catherine , Elrhermoul Fatima-Zahra , Maduakor Chinedu , Everitt Alex , Gabriel Carolyn
Published: August 2022

Background and aim

During the COVID-19 pandemic, the neurology department at St Mary’s Hospital had to direct the bulk of its acute work to a newly expanded ‘hot clinic’ running Monday to Friday through Same Day Emergency Care (SDEC). Face to face clinic appointments were also halted and instead triaged to SDEC when examination of the patient was necessary. Patients were referred through a number of routes directly to the neurology consultants or on-call registrar, and subsequently seen on an urgent basis. We were interested in evaluating the types of referrals made to this service as well as their final outcomes.

Results

A total of 255 patients were seen between 3 March 2021 and 3 August 2021. Approximately a third were from the A&E department and just less than a third were from the Western Eye Hospital, our local ophthalmology A&E. Most referrals were for headache or visual change, and 61% of patients did not need to re-attend SDEC. Importantly, a quarter were discharged home after specialist review, and none required admission from clinic. Thus our emergency service was successful in avoiding admissions while ensuring patients received the care they required in a timely fashion.
020 The headache hub: a multidisciplinary diagnosis and management resource for GPs
Authors: Logan Anne-Marie , Lee Nicholas , Patel Bhavini , Dolling Rebecca , Pink Katharine , Nitkunan Arani , Mansour Nassif , Khan Usman , Wilkinson Thomas , Nirmalananthan Niranjanan
Published: August 2022

The need to improve care of patients with headache prompted development of a new model in South West London. The Headache Hub, piloted at St George’s University Hospitals NHS Foundation Trust, consisted of a multidisciplinary team; Consultant Neurologists, GP with Extended Role and Allied Health Professionals. The Hub triages new GP referrals and offers an online migraine group clinic (engaging patients through shared medical appointments in a group setting).

Between April-December 2021, 171 GP referred patients were seen, of which 96 (48%) had Chronic Migraine (CM), 36 (18%) High Frequency Episodic Migraine and 23 (12%) Low Frequency Episodic Migraine patients. CM patients reported 31 ED attendances in the prior year and 53% had the highest unmet needs, HURT 8 (Headache Under Response to Treatment) score 17-24. Real-time data on waiting times enabled clini- cians to make informed follow up choices.

Triage to “consultant only” occurred in 56% of referrals, enabling a subsequent reduction in consultant caseload to address tertiary headache waiting lists. Patient satisfaction was high (80%) and group clinic feedback highlighted beneficial shared experiences; “super productive and made me feel not so alone in a challenging time”.

This model is being considered at other secondary care hospitals in the region.