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IntroductionObjective algorithms (OA; Ramanujam, 2020) identify SPMS in those with clinically assigned (CA) RRMS, suggesting SPMS is under-diagnosed in practice. It’s unclear if clinicians are aware of this evolution and escalate therapy in response to clinical worsening with highly active (HA) disease modifying treatments (DMT).ObjectiveAssess whether treatment intensity escalates as the disease advances from RRMS to OA-SPMS and from RRMS to CA-SPMS.MethodsMS registries in Czech Republic, Denmark, Germany, Sweden and UK were used. Active DMTs at the date of last visit were classified as highly active (HA) or not, and DMT usage prior to CA-SPMS or OA-SPMS classification.Results3740 SPMS and 9542 OA-SPMS patients were on DMTs. HADMT use was 21.3% prior to OA-SPMS clas- sification in RRMS and 27.9% (p<0.0001) once classified. HADMT use was 23.5% prior to CA-SPMS diagnosis and 36.9% (p<0.0001) once diagnosed. HADMT use in the UK was lower than in other registries for all groups.ConclusionAcross Europe the evolution to clinical SPMS via OA-SPMS is eliciting a response from clini- cians that is not initially reflected in a change of diagnosis. Country variations in HADMT use in transitioning patients should be explored further.r.m.middleton@swansea.ac.uk74

Pre and post-herpetic SUNCT syndrome is a rare but previously reported complication of herpes zoster reactivation. We report a case of a zoster associated SUNCT syndrome developing at the same time as reactivation.A 79-year-old gentleman was referred to Neurology for refractory right sided facial pain. 7 months prior to presentation he had developed shingles in the right upper face around his forehead area, which was managed by his GP. At the same time, he developed daily attacks of sharp stabbing pain behind his eye, up to 5 a day, lasting up to 5 minutes each. This was associated with injection and lacrimation of the affected eye. The attacks can be triggered by touch, such as a shower. Neurological examination was unremarkable except for allodynia in the right V1 distribution. Plain MRI scan showed cortical atrophy only.He had a good response to lamotrigine. nchlasim@doctors.org.uk

Andersen-Tawil Syndrome (ATS) is a rare channelopathy caused by mutations in the KCNJ2 gene that encodes the ubiquitously expressed Kir2.1 potassium channel. We describe key findings in a large UK cohort of 52 patients, pertinent to the diagnosis and management of ATS. We report a new point prevalence of0.105 per 100 000 (increased from 0.08 per 100 000).While ATS has historically been considered a triad of episodic weakness, cardiac arrhythmias and dys- morphic features, we show that there is considerable variability to this phenotype. Pure cardiac or muscle phenotypes may exist. The absence of dysmorphic features does not exclude the diagnosis. Similarly, a normal long exercise test was seen in five patients.Importantly, we identify that the phenotype includes a significant risk of cardiac morbidity and mortality with 13% of our cohort requiring cardiac defibrillator or pacemaker insertion and an additional 23% reporting syncope. Syncope has been recently associated with an increased risk of life threatening arhythmic events in this cohort. Severe fixed myopathy was seen in a quarter of our cohort with 14% requiring a wheelchair or gait aid.We additionally describe novel neurological features and report eight new KCNJ2 variants with in vitro functional data. We provide key clinical insights and management recommendations. We also identify new features which are interesting areas for future research and collaboration.v.vivekanandam@ucl.ac.uk

Objectives(1) To evaluate adherence to local status epilepticus (SE) guidelines. (2) To characterise patients with SE and identify causes and predisposing factors.MethodsWe reviewed notes of patients presenting to Morriston Hospital with SE in 2019/20. The cause of SE and compliance with local guidelines were evaluated, and it was documented whether SE patients with previous epilepsy (SEPE) had been reviewed in the 12 months prior to admission.Preliminary Results 57 cases were identified. Of the 13 reviewed so far, 11 correctly received an initial ben- zodiazepine. 5 of the 9 patients who did not respond to two doses of benzodiazepines correctly received levetiracetam. Those who failed to respond to medication were intubated. 4 of the 9 patients requiring a second intervention were intubated where guidelines recommend levetiracetam. Of the SEPE cases, 50% were reviewed in the 12 months pre-admission. The commonest causes of SE were cerebrovascular disease, background epilepsy, and alcohol withdrawal.ConclusionPreliminary findings suggest that 61.5% of patients received treatment in compliance with local guidelines, and further work will evaluate whether deviations have impacted outcomes. After iden- tifying common causes of SE and evaluating how patients are reviewed, we can consider implementing improvements in its management.950448@swansea.ac.uk

Anterior temporal lobe resection (ATLR) for temporal lobe epilepsy (TLE) has remission rates up to 80%, however is underutilised, in part because of the risk of language decline following surgery. Language decline occurs in up to 50% of ATLR in the language dominant side. This can occur despite careful planning with functional MRI (fMRI) language mapping. Several white matter bundles are close to the resection area which could contribute to language decline. Diffusion MRI-based fibre tracking to map the arcuate, uncinate, inferior fronto-occipital, inferior, and middle longitudinal fasciculus was performed on 43 patients. We extracted the left-sided bundles in those temporal lobe epilepsy patients who had left-dominant language based on verbal fluency functional MRI (fMRI) and a left-sided resection. Resection masks were manually drawn and used as exclusion regions. Changes from pre- to post-operative tractography and language ability were measured as percentages. Linear regression revealed that the McKenna Graded Naming test decline was predicted by the arcuate and middle longitudinal fasciculus resection (F(2,41)=5.562, p=0.007) with an adjusted R2 of 0.175. These findings demonstrate that damage to anterior arcuate extensions and the middle longitudinal fasciculus affects picture naming ability.lawrence.binding.19@ucl.ac.uk

IntroductionSORD is a newly described autosomal recessive gene that is emerging as the commonest cause of autosomal recessive CMT (Charcot-Marie-Tooth disease) and hereditary motor neuropathy (HMN).MethodsWe present nine cases of SORD-related neuropathy.ResultsNine unrelated patients were found to have biallelic mutations in SORD. Eight were male (89%) and median age of assessment was 34 years (range 18–55 years). Median age of symptom onset was 15 years (range 12–18 years) and all patients initially presented with difficulty walking and/or problems involving distal lower limbs. Only one patient (11%) had sensory symptoms. 5/9 (56%) had distal upper limb weakness and all had distal lower limb weakness. Sensory examination was abnormal to at least one modality in 7/9 cases (78%). The median CMT Examination and CMT Neuropathy Scores were 6 (range 2–12) and 7.5 (range 3–14) respectively. Neurophysiology showed conduction velocities in the axonal or intermediate ranges in all cases. Clinical diagnosis was distal HMN in 5/9 (56%), CMT2 in 2/9 (22%) and CMT intermediate in 2/9 (22%).ConclusionsThe SORD phenotype is typically a slowly progressive, length-dependent motor neuropathy of onset during the second decade. Sensory symptoms are rare and sensory signs minimal.chris.record@ucl.ac.uk

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

BackgroundSensory ganglionopathies classically present with subacute onset of marked sensory loss with ataxia and preserved strength. These clinical findings are complemented by nerve conduction studies (NCS) demonstrating absent or markedly reduced amplitudes of the sensory nerve action potentials (SNAPs) with normal motor nerve conduction studies.CaseWe present two cases in their 6th and 7th decade of life who present with a 5-year history of gradual onset of unsteadiness and ‘burning’ sensory symptoms, worst in the lower limbs. Clinically, they had mild ataxia and preserved deep tendon reflexes.Results of Investigations: NCS demonstrated marked reduction in the amplitudes of the SNAPs in upper and lower limbs. The motor nerve conduction studies were normal. Unexpectedly, H-reflexes were per- sistently retained. There was no significant change in interval neurophysiological studies. These findings indicate a marked peripheral sensory axonopathy with sparing of the Ia afferents. Extensive investigations for underlying infectious, autoimmune or paraneoplastic cause all returned negative.DiscussionWe describe a distinctive neurophysiological pattern with preserved H-reflexes without severe clinical ataxia. We hypothesise that this is a unique type of ganglionopathy due to the selective sparing of the Ia afferents.mary.mc-kenna.1@ucdconnect.ie

BackgroundIn the EXPAND study, patients with active SPMS (aSPMS) demonstrated a reduced risk of 3/6-month confirmed disability progression (3m/6m CDP) and risk of decline in cognitive processing speed (CPS, 6-month confirmed cognition worsening of ≥4-point on Symbol Digit Modalities Test [6mCCW]) versus placebo.ObjectivesAssess long-term efficacy and safety of siponimod in patients with aSPMS.MethodsIn aSPMS patients who entered the EXPAND Extension, time to 3m/6mCDP, 6mCCW, and annu- alized relapse rate (ARR) were assessed for the Continuous (siponimod in Core and Extension) and Switch (placebo in Core and open-label siponimod in Core/Extension) groups.ResultsRisk of 6mCDP was reduced by 29% (0.71 [0.57–0.90]; p=0.0044) for Continuous versus Switch group, corresponding to approximately 70% delay in time to 6mCDP. The risk of 6mCCW for Continuous versus Switch group was reduced by 33% (0.67 [0.53–0.86]); p=0.0018), corresponding to approximately 70% delay in time to 6mCCW. A significant reduction in ARR for the Continuous versus Switch groups was observed in patients with or without active disease.ConclusionsLong-term data analyses showed that siponimod effects on disability, cognitive processing speed, and relapse outcomes in patients with active SPMS are sustained up to 5 years, and highlight the value of early treatment initiation.teresa.sawtell@novartis.com

A man, currently aged 72, developed a spastic paraparesis without sensory abnormalities progressing to wheel-chair dependence and late urinary incontinence over 14 years. Apart from a history of type 2 diabetes mellitus, he was otherwise well. Extensive blood and CSF investigations including screening for HIV, HTLV1, syphilis, and Lyme disease were normal or negative. There was no evidence of neuropathy or denervation on EMG. MRI showed mild non-specific white matter signal change in both cerebral hemi- spheres. A provisional diagnosis of primary lateral sclerosis (PLS) was revised with the finding of elevated Very Long Chain Fatty Acids (VLCFAs). Genetic testing revealed a novel missense variant c.1771C>Gp. (Arg591Gly) in exon 7 of the ABCD1 gene. Mutation in ABCD1 transporter leads to accumulation of VLCFAs in the peroxisomes and cytosol which is toxic, causing oxidative stress and demyelination in the CNS and PNS. Literature review did not reveal reports of AMN mimicking PLS. Our patient highlights the importance of screening VLCFAs (abnormal in ~99% of men with AMN) in suspected PLS, a diagnosis of exclusion. Diagnosis of ALD/AMN allows genetic counselling, screening for adrenal failure, and access to stem cell therapy for children with asymptomatic cerebral onset ALD.sara.leddy1@nhs.net