bluuebunny/crossref_metadata_2025_split huggingface dataset:
006  Secondary amenorrhea related to natalizumab
Authors: Obeng Laurenda , Brown Heather , Wheately Trevor , Good Catriona , Fisniku Leonora 
Published: May 2022

BackgroundAdverse events are inevitable for many pharmacological interventions, including disease modifying treatment (DMT) in Multiple Sclerosis (MS). Amenorrhoea was reported in less than 2% in phase 3 trials of Natalizumab. Isolated cases have also been reported post marketing.We present a patient who developed secondary amenorrhoea linked to Natalizumab treatment for her relapsing-remitting MS (RRMS).CaseA 36 year old female with highly-active RRMS was started on Natalizumab in June 2014. She developed secondary amenorrhoea by July 2014. Her blood results show low LH, normal FSH and low oestrogen and progesterone and normal thyroid function tests. She remained on Natalizumab for a year and her MS was stable. Due to continuing amenorrhoea Natalizumab was stopped and 3 months later she started menstruating regularly. Her hormonal changes were also normalised. Review of all her imaging from July 2014 – September 2016 revealed no evidence of a pituitary or hypothalamic abnormality or patho- logical enhancement. Patient was subsequently treated with Alemtuzumab and has remained stable.ConclusionWhereas a simple temporal association between a drug use and a particular event does not necessarily indicate a direct causal relationship, the occurrence of amenorrhoea in our patient linked to the start of Natalizumab and its resolution 3 months post treatment cessation, is too good of a coincidence to be fully dismissed.leonora.fisniku@nhs.net
125  Towards an optimal multiple sclerosis patient case-load for a full-time MSologist
Authors: Giovannoni Gavin , Hobart Jeremy , Mazibrada Gordon , Bateman Karen , Marta Monica 
Published: May 2022

IntroductionStrategy, evidence and anticipation should underpin workforce-planning.AimTo estimate a sustainable patient-caseload (PCL) for a full-time equivalent MS specialist neurologist (FTE-MSologist).MethodsHypothetically, an FTE-MSologist refers to 10-MSology-related programmed activities per week. We considered three service models (core, aspirational, alternative/DGH) with differing frequency, duration and content of patient consultations and monitoring. We computed the ideal number of new patients and existing patients, for each scenario, from detailed qualitative interviews with 4 MSologists at different NHS Trusts. Computations assumed all 3 scenarios had common support from MS nurses (@315 PLwMS/FTE MS nurse), MS coordinators, neuroradiology, neuropharmacist and administration.ResultsEstimates for 1-FTE-MSologist/year/service model were: Core: new-PCL=81 (range=46–115); existing- PCL=798 (range=672–923). Aspirational: new-PCL=21 (range=28–69); existing-PCL=481 (range=401–561). Alternative/DGH: new-PCL=89 (range=51–126); existing-PCL=874 (range=733–1015).ConclusionsThese MS PCL/FTE-MSologist estimates enable future NHS manpower planning to optimally staff specialist MS services. It is notable that few (if any) UK MS services have the support considered pre- requisite. Much of the direct clinical care work undertaken is “unseen” and not formally job-planned. These results have significant implications formal time and motion studies may be required to improve estimates’ accuracy.Support.Karen Bateman was supported by Novartis. Disclosures: See poster g.giovannoni@qmul.ac.uk
127  ACTA1 associated myopathy with neurogenic EMG changes
Authors: Doherty Carolynne , Blake Julian , Manzur Adnan , Wakeling Emma , Shah Sachit , Muntoni Francesco , Reilly Mary 
Published: May 2022

BackgroundWe describe a proband and her son who have proximal limb and facial weakness and marked hand involvement. A congenital myopathy panel demonstrated two RYR1 variants and the p.Ile289Phe novel variant in ACTA1.Cases: The proband had initially been diagnosed with SMA following premature birth, late milestones, scoliosis and proximal and distal weakness which was relatively static until age 40. EMG as a child was neurogenic. Her son had poor feeding after birth, delayed motor milestones, intellectual delay, and by his teens, severe facial weakness and distal upper limb wasting particularly the finger flexors and extensors, with hip flexion of grade 3. Repeat neurophysiological evaluation of the proband at age 60, demonstrated a neurogenic pattern but also brief polyphasic motor units, raising suspicion of an addi- tional myopathic process.DiscussionZukosky and colleagues1also described a family with a different missense mutation in the ACTA1 gene who had been diagnosed with SMA on the basis of neurogenic EMG findings. Our additional family confirms that myopathy can be accompanied by neurogenic EMG changes in ACTA1 associated myopathy.Reference1. Zukosky K, Meilleur K, Traynor BJ, Dastgir J, Medne L, Devoto M, et al. Association of a Novel ACTA1 Mutation With a Dominant Progressive Scapuloperoneal Myopathy in an Extended Family. JAMA Neurol. 2015 Jun 1;72(6):689–98.carolynnedoherty@doctors.org.uk|NIHR Bursary
129  Limb girdle muscular dystrophy R12 (LGMD 2L, anoctaminopathy) presenting as refractory myositis: a case series
Authors: Marago Italo , Chinoy Hector , Roberts Mark , Roncaroli Federico , Duplessis Daniel , Marini-Bettolo Chiara , Lilleker James 
Published: May 2022

The idiopathic inflammatory myopathy (IIMs) are a rare heterogenous group of immune-mediated diseases leading to muscle inflammation. Prompt and accurate diagnosis is important so that immunosuppressive treatment can commence and irreversible tissue damage be avoided. Other rare conditions may mimic IIM, making confirmation of diagnosis sometimes difficult.Limb girdle muscular dystrophy type R12 (LGMD 2L, anoctaminopathy) is a recessive genetic myopathy which may present in adulthood and is caused by pathogenic variants in the ANO5 gene. Clinical pres- entation can vary from asymptomatic hyper-CK-aemia to exertional myalgia and/or progressive muscle weakness.Here we present four cases of genetically confirmed LGMD R12 who were initially misdiagnosed with IIM. In each case treatment with immunosuppressants, >15 years in one case, was observed without a clear therapeutic response. All patients were negative for anti-nuclear antibodies and all myositis-associated/specific autoantibodies for which testing is available. Prominent fatty infiltration and selective pattern of muscle involvement on muscle magnetic resonance imaging was also observed.The diagnosis of IIM must be carefully considered in autoantibody-negative patients. Adult-onset genetic myopathies, particularly LGMD R12, are differential diagnoses. Avoidance of potentially harmful immu- nosuppressive therapies, genetic counselling, and involvement in research are key benefits of accurate diagnosis in such cases.italo.marago@nhs.net
131  Pooled safety data from the risdiplam clinical trial development programme
Authors: Servais Laurent , Baranello Giovanni , Chiriboga Claudia , Darras Basil , Bader-Weder Silvia , Gorni Ksenija , Jaber Birgit , McIver Tammy , Scalco Renata ,   et al
Published: May 2022

Risdiplam is a centrally and peripherally distributed oral survival of motor neuron 2 (SMN2) pre mRNA splicing modifier that increases the levels of functional SMN protein. Risdiplam (EVRYSDI™) has been approved by the US Food and Drug Administration for the treatment of patients with spinal muscular atrophy (SMA), aged 2 months and older. The risdiplam clinical development programme consists of four studies in a broad population of individuals with SMA.FIREFISH (NCT02913482) and SUNFISH (NCT02908685) are two-part studies assessing safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy in infants with Type 1 SMA and patients with Type 2/3 SMA, respectively. JEWELFISH (NCT0302172) assesses safety, tolerability, PK and PD in patients with SMA who previously received RG7800 (R06885247), nusinersen (SPINRAZA®), olesoxime or onasemno- gene abeparvovec-xioi (ZOLGENSMA®). RAINBOWFISH (NCT03779334) assesses efficacy, safety, PK and PD in infants with genetically diagnosed and presymptomatic SMA.Pooled analyses of FIREFISH and SUNFISH Parts 1 and 2 and JEWELFISH were conducted to determine the long-term safety profile of risdiplam. At the data-cut (15th January 2020) no treatment-related safety findings led to withdrawal from up to 39 months’ risdiplam treatment in 465 patients. Here we will present updated pooled safety analyses for the risdiplam studies.g.baranello@ucl.ac.uk
132  Thymectomy for myasthenia gravis in the West of Scotland: a retrospective study
Authors: Fenech Valentina , Kirk Alan , Carmichael Caroline , Farrugia Maria Elena 
Published: May 2022

The international thymectomy trial (MGTX) demonstrated benefits in myasthenia gravis (MG) patients without thymoma and up to the age of 65 years. This data and the increased availability of minimally invasive thymectomy surgery has resulted in an increasing number of patients being referred for thymec- tomy. We evaluated the clinical outcomes after thymectomy in 61 MG patients with or without thymic epithelial tumours (TET) from the West of Scotland Myasthenia database over a 10-year period.All patients had positive acetylcholine receptor antibodies. Twenty-five (41%) patients were male. Fifty-five (90.2%) had generalised MG (27 patients with TET [TET-MG], all thymoma except for one with squamous cell thymic carcinoma; 28 patients without TET [non-TET-MG]) and 6 (9.8%) had ocular MG (including 3 TET-MG patients with thymoma). Overall, age at onset and diagnosis were comparable, with a lower median age at onset for female MG patients without TET. More severe symptoms at onset and at nadir were noted in TET-MG patients.MGFA-post intervention status was similar in both groups, although more MG relapses were observed in the TET-MG group. TET-MG patients had slightly worse disease severity and outcomes. However, the two groups were largely comparable in their MG status and the therapies they received.vallyfenech@gmail.com91
134  A qualitative study of patient perceptions of immunoglobulin treatment regimens for inflammatory neuropathy
Authors: Callanan E , Levee V , Compton L , Ramdharry G , Lunn M , Carr A 
Published: May 2022

IntroductionWith RCT evidence of equivalency between intravenous (IVIg) and subcutaneous (SCIg) immunoglobulin in the management of CIDP, we sought to optimise uptake of homecare SCIg in our inflammatory neuropathy cohort. This is of particular importance in the context of the COVID pandemic.AimTo explore patient perception of IVIg and SCIg and understand treatment preferences.MethodsWe performed a non-hypothesis driven qualitative study of patient perception. Data was collected from adult patients with CIDP via an open-ended telephone interview and a focus group facilitated by medics independent members of the treating team. The data was coded using Braun and Clarke’s reflexive thematic analysis.Results11 patients were interviewed (mean age=51.55; S.D. 8.70, mean time on immunoglobulin treatment 61 months, S.D. 35.64). Patients found the treatment effective but highlighted perceived side-effects. The hospital environment (IVIg treatment) was reassuring but brought with it a range of difficulties, both logisti- cal and financial. Knowledge and direct experience of SCIg was lacking.ConclusionWe will develop a structured questionnaire based on these themes for broader application across the cohort. From this qualitative data we will continue to adapt our service in a patient focused manner and identify measures of quality improvement.emmacallanan1@nhs.net92
137  Outcome measures in CMT: case examples from the muscle MRI in CMT study
Authors: Doherty Carolynne , Zuccarino Riccardo , Howard Pagie , McDowell Amy , Wastling Stephen , Laura Matidle , Thedens Daniel , Thornton John , Shy Micheal , Reilly Mary 
Published: May 2022

BackgroundTwelve month increase in muscle fat fraction(FF) at calf has been demonstrated in patients with CMT1A.(1,2) Our MDA funded study builds on our previous work by investigating this method in patients with the three next most common subtypes of CMT: due to mutations in GJ1B, MPZ, and MFN2.MethodsSixty participants and 30 controls have been recruited. In select examples, baseline and follow-up FF were calculated at mid-calf and mid-thigh.ResultsA 45-year-old male with a MPZ mutation had imaging age 35 (CMTES 17), with FF at calf 20.9%. At age 45, CMTES was 20 and calf FF 35.6%. In a 32-year-old male with GJB1, CMTES rose from 9 to 10 at 12 months, with all muscle mid-calf FF rising from 9.5% to 11.8%. In the left peroneus longus, FF increased from 26% to 55% correlating with reduced ankle plantarflexion power. In a MFN2 patient, baseline CMTES was 16 and at 12-months 17. FF increased at thigh level from 10.5% to 15%.DiscussionWe present three cases illustrating key points from the study and demonstrate an increase in FF at 12 months in one patient each with CMT1X and CMT2A, and over 10 years in a patient with CMT1B.carolynnedoherty@doctors.org.uk|NIHR Bursary
138  Frey’s syndrome: a review of the aetiology and possible role of neurotrophic factors
Authors: Hignett Sarah , Judd Owen 
Published: May 2022

Frey’s syndrome describes the phenomenon of gustatory sweating and is a cause of significant social embarrassment for sufferers. It has been attributed to aberrant growth of parasympathetic salivatory fibres in the auriculotemporal nerve towards overlying sweat glands. However, the exact mechanism behind this growth is unknown.Frey’s syndrome is a common sequela of parotidectomy and is usually preceded by trauma to the auricu- lotemporal nerve. In some neonates, however, Frey’s syndrome presents with no history of nerve injury. In these patients, the underlying trigger for Frey’s syndrome is unclear.A review of the recent literature on nerve regeneration after injury and on nervous development in utero was conducted with the aim of developing further insights into the aetiology of both adult onset and paediatric Frey’s syndrome.Neurturin, a neurotrophic factor released by both salivary and sweat glands, was identified as a possible key player in the aetiology of Frey’s syndrome. This factor is released both in utero and after nerve damage, so could connect the two presentations of gustatory sweating.Further research into the role of neurturin could help to elucidate the pathogenic mechanisms underly- ing the condition and might reveal neurturin to be a potential target for pharmacological intervention um16sh@leeds.ac.uk94
140  Baseline variation in commonly used inflammatory neuropathy clinical outcome measures
Authors: Keh Ryan , Lilleker James , Lavin Tim , Gosal David , Compton Laura , Kapoor Mahima , Carr Aisling , Lunn Michael 
Published: May 2022

BackgroundReliable outcome measures are vital for guiding immunoglobulin therapy in inflammatory neuropathy. Disease-specific outcome measures exist with statistically sound minimal clinically important difference (MCID) to detect change (I-RODS:+/-4; grip strength:+/-8kPa). Scores generally remain stable in well-treated disease but variation occurs.AimsTo appreciate random variability of serially assessed grip strength, RODS and MRC-SS in clinically stable CIDP/MMN patients and explore early identification of non-random trends.MethodsWe performed a longitudinal study of serial outcome measures from Manchester neurosciences immunoglobulin database (June 2009 - September 2012). We used first score on maintenance dosing as baseline, and increase in dose (g/kg/month) as indicative of meaningful clinical deterioration. We cal- culated mean/SD actual and percentage change(Δ) for grip(kPa), I-RODS(logit scale) and MRC-SS(/70) over periods of clinical stability.Results54/152 patients had sufficient stability: 39CIDP (9F), 15MMN (2F). Median age:66 years(mean:64.8, range:28–89). ΔRODS: 313 timepoints over 0.4–83.9months (median:27.4). Median change:0(0%), mean:- 0.08(0.17%), SD:4.3(8.9%). Δgrip: 569 timepoints over 0.9–98.1months (median:29.7). Δright grip median:- 1kPa(-0.11%), mean:-0.87(-0.96%), SD:5.34(5.9%). Δleft median:0kPa(0%), mean:-0.82(-0.91%), SD:5.70(6.3%).ΔMRC-SS: 75 timepoints over 1.9–52.7 months (median:10.7). Median change:0(0%), mean:0.59(0.83%), SD:4.73(6.8%). Analysis on trend identification and randomness is underway.ConclusionAppreciation of magnitude of normal variation is clinically important. Early identification of trends will influence dosing decisions.ryankeh@srft.nhs.uk|ABN Bursary95
143  Is it ‘CLIPPERS’? Is it CNS Hemophagocytic Lymphohistiocytosis (HLH)?
Authors: Parida Amitav , Hemingway Cheryl , Eleftheriou Despina , Wassmer Evangeline 
Published: May 2022

ObjectiveWe aim to share our experiences with an Adult Neurology audience of five children (3F, 2M) with Hemophagocytic Lymphohistiocytosis (HLH), who presented with an atypical neuroinflammatory disorder.MethodsSingle institution retrospective case seriesResultsMean age of presentation was 6 years (3–11). Presenting features were headache (N=1), optic neuritis (N=1), diplopia (N=2) and hemiplegia (N=1).4 children had MRI imaging suggestive of demyelination. One child had an isolated area of restricted diffusion in the brainstem. An initial working diagnosis of ‘CLIPPERS’ (Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) was made in three cases. Only two children ever met the criteria for systemic HLH. Pathogenic variants of RAB27A, STXBP2, UNC13 and PRF1 were separately identified in four children which are all associated with familial Hemophagocytic Lymphohis- tiocytosis (fHLH). Four children in this series have already undergone successful Haemopoietic Stem Cell Transplantation (HSCT).ConclusionsWe propose that adult neurologists consider genetic panel and immunological (Natural Killer Cell function, perforin expression and granulocyte release assay) testing for HLH in cases of atypical recurrent CNS inflammation and presentations consistent with ‘CLIPPERS’. Clinical management may be changed as HSCT is considered the gold standard treatment for familial HLH. Nonetheless, the long term history of these cases and risk of recurrent CNS inflammation post HSCT remains unclear.a.parida@nhs.net
Ten years of monoclonals in MS have not made an obvious dent in disability progression
Authors: Allen Christopher Martin , Almulaifi Mariam , Balaska Effrosyni , Fleck Catherine , Halsey Lloyd , Tallantyre Emma , Evangelou Nikos 
Published: May 2022

We audited the clinical characteristics of 327 patients with MS and clinical onset with either a transverse myelitis (TM) or optic neuritis (ON) at our two MS specialist centres. We compared those diagnosed in 2000–2010 and 2010–2020 to determine if MS disability progression is being altered by the use of mono- clonal disease modifying treatments. Our hypothesis was that TM onset disease might no longer carry a worse clinical prognosis.More patients are being treated with monoclonals first line in the last decade (TM 12% to 27%, ON 7% to 11%). The time to MS diagnosis is shorter (5 months for TM and 25 months for ON), as was the time to treatment (4 years for both TM and ON). Contrary to our expectations, patients presenting with ON or TM during 2010–20 did not have a reduced risk of reaching EDSS 4.0. In fact, those with TM onset MS diagnosed in the last decade performed the worst overall, with 50% of the cohort reaching EDSS 4.0 within four years. Our study suggests that the effect of monoclonals is not as positive as widely assumed and pragmatic randomised trials are needed to test their real value in clinical practice.christopher.allen@nottingham.ac.uk
011  UK variance in DMT advice and prescribing in MS and pregnancy
Authors: Dobson Ruth , Hughes Stella , Ford Helen , Murray Katy , Pearson Owen , Brex Peter , Rog David 
Published: May 2022

BackgroundThere is limited evidence to guide DMT prescribing prior to and during pregnancy, leading to wide variation in practice. In 2019, ABN consensus guidelines were published to address this. We set out to establish what impact these have had.MethodsAn online questionnaire was cascaded to UK MS neurologists. Individuals completed the ques- tionnaire anonymously.Results85 responses were obtained; 76 from DMT prescribers in a variety of settings. 74/76 (97%) were aware of the ABN guidelines. 74% reported a recent change in prescribing IFN-B and 70% in prescribing natalizumab around pregnancy, compared to 5% for alemtuzumab and 1% for teriflunomide and fingoli- mod. The ABN guidelines were the most commonly cited reason for change (58 individuals), followed by SmPC changes and influence from peers.There was significant variation in natalizumab prescribing - 51% ‘normally continue to prescribe’ until 34/40, 12% stop when pregnancy confirmed and 11% stop prior to conception. 58% encourage breastfeeding on natalizumab whilst 34% discourage this.ConclusionsThere remains significant variation in advice given to women with MS considering pregnancy. This is most marked with higher efficacy DMT, where risk-benefit decision making is complex. Additional data and resources for women with MS, including a UK MS Pregnancy register, are urgently needed.ruth.dobson@qmul.ac.uk
019  Autologous stem cell transplantation versus alemtuzumab or ocrelizumab in relapsing remitting multiple sclerosis (StarMS)
Authors: Sharrack Basil , Snowden John , Muraro Paolo 
Published: May 2022

In recent years, autologous haematopoietic stem cell transplantation (aHSCT) has been increasingly used to treat patients with highly-active relapsing remitting multiple sclerosis (RRMS). Observational and limited clinical trial data suggest that aHSCT reduces relapse rates, improves disability and enhances quality of life to a greater degree than most disease modifying therapies (DMTs). There is now a need to compare aHSCT with the two most efficacious DMTs: Alemtuzumab and Ocrelizumab.StarMS aims to determine whether aHSCT has superior clinical efficacy to Alemtuzumab and Ocreli- zumab with an acceptable safety profile. Mechanistic studies will assess immune re-constitution which will enhance understanding of the biological mechanisms of these treatments. Other sub-studies will assess their effect on cognitive recovery, neurofilament light and retinal nerve fibre layer measurements as markers of neuronal damage, and the safety of re-vaccination post-aHSCT.This EME funded parallel-group rater-blinded RCT will randomise 198 patients (1:1) to aHSCT versus DMT (Alemtuzumab or Ocrelizumab) from 19 centres across the UK. The primary endpoint, NEDA rate, will be assessed throughout the 2-year follow-up period.The StarMS trial has the potential to provide definitive data on the comparative efficacy of aHSCT vs highly efficacious DMTs, help improve patient outcomes, and impact national and international guidelines.basil.sharrack@nhs.net
029  The evaluation of pain and pain management in patients with multiple sclerosis
Authors: Wallace Victoria , Cotterell Sophia , Nicholas Zara , Blain Camilla 
Published: May 2022

Pain has been reported in 50–75% of people with MS. Pain is poorly understood and poorly managed impacting greatly on quality of life. Further information is required to aid better clinical recognition and management. The goal of this study was to explore the incidence, nature and management of pain in patients attending specialist MS clinic.Methods/ResultsData was obtained using The Brief Pain Inventory and Pain Detect questionnaires and clinic letters were reviewed. 63% of MS patients reported pain. Pain was on average 6/10 at worst and 2/10 at best. 30% used simple analgesia, 43% used prescription analgesia with 56% pain relief at best. Pain interfered with activity levels, mood, sleep, relationships, and enjoyment of life. 26% had neuropathic pain and 35% had non-neuropathic pain. Pain was mentioned in 56% of clinic letters for those reporting pain. 36% had a pain management plan documented.ConclusionPain is a prevalent symptom associated with MS that interferes significantly with quality of life. Pain was not always adequately or accurately addressed in MS clinic. To improve management, we suggest pain questionnaires &/or Apps are used to provide ongoing objective pain measures.vcjwallace@gmail.com