The negative impact of smoking in MS is well established, however, there is much less evidence as to whether smoking cessation is beneficial to progression in MS. Adults with MS registered on the United Kingdom MS Register (2011-2020) formed this retrospective and prospective cohort study. Primary outcomes were changes in 3 patient reported outcomes (PROs): normalised MS Physical Impact Scale (MSIS-29-Phys), normalised MS Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS-Anxiety and HADS-Depression). Time to event outcomes were clinically significant increases in the PROs. 7983 participants were included, 4130 (51.7%) of these had ever smoked; of whom 1315 (16.5%) were current smokers and 2815/4130 (68.2%) were former smokers. For all PROs, current smokers at the time of completing their first questionnaire had higher PRO scores indicating higher disability compared to those who had never smoked (∼10 points difference in MSIS-29-Phys and MSWS-12; 1.5-1.8 point for HADS-anxiety and HADS-depression). There was no improvement in PRO scores with increasing time since quitting in former smokers. 923 participants formed the prospective parallel group, which demonstrated that MSIS-29-phy 5.03, [3.71, 6.34], MSWS-12 5.28, [3.62, 6.94] and HADS-depression 0.71, [0.47, 0.96] worsened over a period of 4 years, whereas HADS-anxiety remained stable. Smoking status was significant at year 4; current smokers had higher MSIS-29-Phys and HADS-Anxiety scores (3.05 [0.22, 5.88], 1.14 [0.52,1.76]) while former smokers had a lower MSIS-29 score of -2.91[-5.03, -0.79]. 4642 participants comprised the time to event analysis. Still smoking was associated with a shorter time to worsening event in all PROs (MSIS-29-Phys: n = 4436, p = 0.0013; MSWS-12: n = 3902, p = 0.0061; HADS-anxiety: n = 4511, p = 0.0017; HADS-depression: n = 4511, p < 0.0001). Worsening in motor disability (MSIS-29-Phys and MSWS-12) was independent of baseline HADS-anxiety and HADS-depression scores. There was no statistically significant difference in the rate of worsening between never and former smokers. When smokers quit, there is a slowing in the rate of motor disability deterioration so that it matches the rate of motor decline in those who have never smoked. This suggests that smoking cessation is beneficial for people with MS.

Autosomal recessive disorders affecting pyridoxine (vitamin B6) metabolism are a rare but well-recognized cause of neonatal seizures. Antiquitin deficiency, caused by mutations in ALDH7A1, is a disorder of the lysine degradation pathway causing accumulation of an intermediate that complexes with pyridoxal phosphate. Reports of long-term followup of neonatal pyridoxine-dependent seizures (PDS) remain scarce and prognostic information is varied. We report a case of PDS in a 47-year-old lady who originally presented shortly after birth in 1964. Pyridoxine replacement was successful and diagnostic confirmation was obtained later in life, initially by biochemical analysis of serum pipecolic acid. Subsequently we organized genetic analysis of ALDH7A1, which revealed compound heterozygous mutations. To our knowledge, this represents the longest duration of follow-up published to date. Case Clinical HistoryOur patient was born full term weighing 3.6 kg; hours after delivery, generalized convulsions began. No cause was immediately apparent for the continuous seizures. Her sibling had died shortly after birth with uncontrollable seizures of unknown aetiology. After 24 h of unsuccessful treatment with anti-convulsants and sedatives, pyridoxine was prescribed. Convulsions ceased 5 min after administration of 75 mg IV. Maintenance therapy with oral pyridoxine, 20 mg 8 hourly, was commenced. EEG demonstrated excess generalized theta.Confirmatory testing of PDS was performed aged 8 months. After 48 h of pyridoxine withdrawal, there were frank convulsions and recurrence of encephalopathy. Recovery after reinstitution of pyridoxine was prompt. Oral replacement therapy was continued long term.Developmental assessment aged 6 years revealed mild developmental delay despite freedom from seizures. At 11 years, a further EEG was performed. An excess of theta and relative paucity of rhythmic alpha activity was noted. She attended a school for children with learning difficulties and has relatively poor literacy.Aged 20 years, she was reviewed in the adult neurology clinic, querying the necessity of continued pyridoxine therapy. Pyridoxine, then 50 mg three times daily, was withdrawn for 2 weeks. Seizure recurred and pyridoxine recommenced. A subsequent EEG revealed minimal epileptiform activity.

General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/userguides/explore-bristol-research/ebr-terms/ Alemtuzumab-related Eosinophilic CNS VasculitisOliver.leach@nhs.net @oliveraleach 01752 432028 fax: keywords: multiple sclerosis vasculitis autoimmune alemtuzumab eosinophilic Abstract A 36 year old woman with relapsing remitting MS presented with right sided spasms, focal seizures and neuropsychiatric symptoms 10 months after her first course of alemtuzumab. MRI brain imaging revealed multiple foci of T2 hyperintensity. Subsequent blood and CSF testing for PML, vasculitis and infective causes was negative. A brain biopsy was performed, revealing a prominent perivascular inflammatory infiltrate with multiple immune cells including eosinophils, suggesting eosinophilic vasculitis. The patient was treated successfully with cyclophosphamide. The potential sequelae of alemtuzumab treatment are discussed; this treatable complication should be considered when tests for JC virus are negative. Background to case A 36 year-old female presented in 2005 with right arm clumsiness, and was diagnosed with relapsing remitting multiple sclerosis after imaging and CSF analysis (fig 1A). Three relapses occurred over the next five years, including optic neuritis and right-sided weakness, which responded well to steroids. Surveillance MRI in 2011 revealed new lesions, and glatiramer acetate was commenced in 2012. Due to adverse effects treatment was stopped, but after further relapses dimethyl fumarate was commenced in July 2014. In December 2014 she experienced another relapse; MRI demonstrated new cervical lesions.After MDT discussion, treatment was escalated to alemtuzumab, and she

IntroductionPatients with low levels of knowledge, skills and confidence to manage their health and well-being (activation) are more likely to have unmet health needs, delay seeking healthcare and need emergency care. National Health Service England estimates that this may be applicable to 25%–40% of patients with long-term health conditions. Volunteer peer coaching may support people to increase their level of activation. This form of intervention may be particularly effective for people with low levels of activation.Methods and analysisThis single site, two-arm randomised controlled trial has been designed to assess the feasibility of conducting a definitive trial of volunteer peer health and well-being coaching for people with long-term health conditions (multiple sclerosis, rheumatic diseases or chronic pain) and low activation. Feasibility outcomes include recruitment and retention rates, and intervention adherence. We will measure patient activation, mental health and well-being as potential outcomes for a definitive trial. These outcomes will be summarised descriptively for each time point by allocated group and help to inform sample size calculation for the definitive trial. Criteria for progression to a full trial will be used.Ethics and disseminationEthical approval has been granted by the London - Surrey Research Ethics Committee, reference 21/LO/0715. Results from this feasibility trial will be shared directly with participants, presented at local, regional and national conferences and published in an open-access journal.Trial registration numberISRCTN12623577.

The negative impact of smoking in MS is well established, however, there is much less evidence as to whether smoking cessation is beneficial to progression in MS.Adults with MS registered on the United Kingdom MS Register (2011-2020) formed this retrospective and prospective cohort study. Primary outcomes were changes in 3 patient reported outcomes (PROs): normalised MS Physical Impact Scale (MSIS-29-Phys), normalised MS Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS-Anxiety and HADS-Depression). Time to event outcomes were clinically significant increases in the PROs. 7983 participants were included, 4130 (51.7%) of these had ever smoked; of whom 1315 (16.5%) were current smokers and 2815/4130 (68.2%) were former smokers. For all PROs, current smokers at the time of completing their first questionnaire had higher PRO scores indicating higher disability compared to those who had never smoked (~10 points difference in MSIS-29-Phys and MSWS-12; 1.5-1.8 point for HADS-anxiety and HADS-depression).There was no improvement in PRO scores with increasing time since quitting in former smokers.923 participants formed the prospective parallel group, which demonstrated that [3.71, 6.34], [3.62, [0.47, 0.96] worsened over a period of 4 years, whereas HADS-anxiety remained stable. Smoking status was significant at year 4; current smokers had higher MSIS-29-Phys and HADS-Anxiety scores