Abstract In this retrospective, multicentre, observational cohort study, we sought to determine the clinical, radiological, EEG, genetics and neuropathological characteristics of mitochondrial stroke-like episodes and to identify associated risk predictors. Between January 1998 and June 2018, we identified 111 patients with genetically determined mitochondrial disease who developed stroke-like episodes. Post-mortem cases of mitochondrial disease (n = 26) were identified from Newcastle Brain Tissue Resource. The primary outcome was to interrogate the clinico-radiopathological correlates and prognostic indicators of stroke-like episode in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (MELAS). The secondary objective was to develop a multivariable prediction model to forecast stroke-like episode risk. The most common genetic cause of stroke-like episodes was the m.3243A>G variant in MT-TL1 (n = 66), followed by recessive pathogenic POLG variants (n = 22), and 11 other rarer pathogenic mitochondrial DNA variants (n = 23). The age of first stroke-like episode was available for 105 patients [mean (SD) age: 31.8 (16.1)]; a total of 35 patients (32%) presented with their first stroke-like episode ≥40 years of age. The median interval (interquartile range) between first and second stroke-like episodes was 1.33 (2.86) years; 43% of patients developed recurrent stroke-like episodes within 12 months. Clinico-radiological, electrophysiological and neuropathological findings of stroke-like episodes were consistent with the hallmarks of medically refractory epilepsy. Patients with POLG-related stroke-like episodes demonstrated more fulminant disease trajectories than cases of m.3243A>G and other mitochondrial DNA pathogenic variants, in terms of the frequency of refractory status epilepticus, rapidity of progression and overall mortality. In multivariate analysis, baseline factors of body mass index, age-adjusted blood m.3243A>G heteroplasmy, sensorineural hearing loss and serum lactate were significantly associated with risk of stroke-like episodes in patients with the m.3243A>G variant. These factors informed the development of a prediction model to assess the risk of developing stroke-like episodes that demonstrated good overall discrimination (area under the curve = 0.87, 95% CI 0.82–0.93; c-statistic = 0.89). Significant radiological and pathological features of neurodegeneration were more evident in patients harbouring pathogenic mtDNA variants compared with POLG: brain atrophy on cranial MRI (90% versus 44%, P < 0.001) and reduced mean brain weight (SD) [1044 g (148) versus 1304 g (142), P = 0.005]. Our findings highlight the often idiosyncratic clinical, radiological and EEG characteristics of mitochondrial stroke-like episodes. Early recognition of seizures and aggressive instigation of treatment may help circumvent or slow neuronal loss and abate increasing disease burden. The risk-prediction model for the m.3243A>G variant can help inform more tailored genetic counselling and prognostication in routine clinical practice.

Objective To describe the clinical and genetic findings in a cohort of individuals with bathing epilepsy, a rare form of reflex epilepsy. Methods We investigated by Sanger and targeted resequencing the SYN1 gene in 12 individuals from 10 different families presenting with seizures triggered primarily by bathing or showering. An additional 12 individuals with hot-water epilepsy were also screened. Results In all families with bathing epilepsy, we identified 8 distinct pathogenic or likely pathogenic variants and 2 variants of unknown significance in SYN1, 9 of which are novel. Conversely, none of the individuals with hot-water epilepsy displayed SYN1 variants. In mutated individuals, seizures were typically triggered by showering or bathing regardless of the water temperature. Additional triggers included fingernail clipping, haircutting, or watching someone take a shower. Unprovoked seizures and a variable degree of developmental delay were also common. Conclusion Bathing epilepsy is genetically distinct reflex epilepsy caused mainly by SYN1 mutations.

Focal status epilepticus in POLG-related mitochondrial disease is highly refractory to pharmacological agents, including general anesthesia. We report the challenges in managing a previously healthy teenager who presented with de novo epilepsia partialis continua and metabolic stroke resulting from the homozygous p.Ala467Thr POLG mutation, the most common pathogenic variant identified in the Caucasian population. We applied transcranial direct current stimulation (tDCS; 2 mA; 20 min) daily as an adjunctive therapy because her focal seizures failed to respond to five antiepileptic drugs at maximal doses. The electrical and clinical seizures stopped after 3 days of tDCS. The second course of tDCS was administered for 14 days when the focal seizures re-emerged a month later. The patient tolerated the procedure well. Following 4 months of hospitalization and prolonged community rehabilitation, our patient has now returned to full-time education with support, and there is no report of cognitive deficit. We have demonstrated the safety and efficacy of tDCS in treating refractory focal motor seizures caused by mitochondrial disease.

Purpose: To produce an evidence base to formulate guidelines for optimal performance of EEG in patients referred with a possible diagnosis of non-epileptic attack disorder (NEAD). Methods: 51 UK EEG departments participated in the prospective study. A pro-forma was completed for all consecutive patients aged 5 years and over referred for EEG over a six month period. Information obtained included referral diagnosis, occurrence/type of attack during EEG, the use of suggestion, length of recording and who was present during the EEG. Results: 11,298 patients were entered into the study. 376 psychogenic non-epileptic seizures (PNES) occurred of which 337 were considered to be of the habitual type. In those patients suspected of having NEAD prior to referral, the use of verbal suggestion increased the yield of habitual attacks by a factor of three in both adults and children. Using suggestive techniques twice, improved the yield further. Non-habitual attacks occurred equally whether or not suggestion was used. At least 90% of habitual PNES occurred within the first 30 min of recording even in those patients having prolonged EEGs. In EEGs where additional professional personnel were present, PNES occurred more frequently. Conclusion: This large multicentre study provides evidence to inform recommendations for EEG to investigate NEAD. We recommend the use of verbal suggestion at least twice and where practical the presence of additional professional staff. A thirty minute recording is sufficient to record a habitual PNES in most instances. (C) 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

We describe the seizure phenotype of a 26 year old lady who presented with a probable photic-induced convulsion on a background of mild intellectual disability, facial dysmorphia, fused cervical vertebrae and ventricular septal defect. There was no prior history of seizures.Routine EEG was polyrhythmic with a prominent photoparoxysmal response at 14 Hz and 40 Hz. CT head was normal. A SNP array demonstrated a rare 51 kb deletion at 12 p12.1 which disrupts the SOX5 gene.SOX5 is a developmentally important gene encoding a transcription factor that plays a role in multiple developmental pathways including of the nervous system. Loss of function of this gene is associated with Lamb-Shaffer syndrome, first characterised in 2012 with global developmental delay, intellectual disability, mild dysmorphic facies, language impairment and variable skeletal abnormalities.3 of the original cohort of 16 patients described experienced seizures and the nature of their epilepsy was not further defined. Only a further 7 cases have been reported to date, none of whom experienced seizures. Our case helps to broaden the phenotype of Lamb-Shaffer syndrome, highlights the importance of looking for copy number variation and poses questions regarding the neurobiology of photo-sensitivity.

Objective: To establish the efficacy and tolerability of inhaled 5% carbon dioxide/95% oxygen as a treatment for paediatric non-convulsive status epilepticus (NCSE).Methods: In an open label clinical trial, children in NCSE were given high flow inhaled 5% carbon dioxide/95% oxygen by face mask for 120 s under EEG control.Results: Six children (five male; ages 3-13; all with severe underlying epilepsy and disability) were recruited. Inhalation was well tolerated in all cases. Capillary blood gasses showed no significant derangements at the end of the inhalation. Effects on EEG normalisation were limited and transient, and no clinical improvements were noted. No adverse effects occurred.Conclusion: Inhaled 5% carbon dioxide/95% oxygen has been suggested as a potent, well tolerated anticonvulsant. An anticonvulsant without sedating and respiration-depressing effects would be particularly welcome in the management of NCSE where the justification for aggressive anticonvulsant therapy is often uncertain, however it appears that 5% carbon dioxide is of limited efficacy in this context. (C) 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

The study was conducted to investigate the difference between Han Chinese and Caucasians on various parameters measured from responses to transcranial magnetic brain stimulation (TMS). Sixteen subjects were studied in each group. A circular coil at the vertex was used for stimulation, whilst recording surface electromyograms from right first dorsal interosseous. In the passive state, motor-evoked potential (MEP) threshold, MEP recruitment, short-interval intracortical inhibition (SICI) and intracortical facilitation were measured. The MEP threshold, recruitment and silent period were also measured in the active state. Chinese subjects showed significantly higher passive thresholds (P < 0.005), less inhibition of the motor response (SICI, P < 0.0005) and a shorter silent period (P < 0.05). Differences in SICI appeared to be a consequence of the differences in passive threshold and were not seen when active threshold was used to determine the conditioning stimulus intensity. Differences in silent period may also reflect differences in cortical excitability rather than inhibitory processes, as they were not seen when the silent-period duration was expressed as a function of MEP size, rather than TMS intensity. There appears to be a significant difference in some TMS parameters between Han Chinese and Caucasian subjects. This may reflect an underlying difference in cortical excitability.

PurposeTo assess patient safety during seizures occurring on UK video telemetry units and identify factors in unit infrastructure which may improve safety with the intention of producing national guidelines.MethodsA prospective multicentre national service evaluation of the occurrence of adverse events and level of nurse attendance during seizures occurring on video telemetry units was performed. Data from 272 seizures from 27 video telemetry units across the UK were analysed.ResultsAdverse events occurred in 12% of seizures: 7% were physical events such as falls or respiratory compromise and 5% were unnoticed seizures. Nursing staff did not attend the patients in 44% of seizures and attendance was delayed beyond 30 s in a further 29%. Only 27% of seizures were attended by a Healthcare Professional within half a minute. The most important factor shown to improve timely attendance of patients during seizures was the presence of a nurse dedicated to the telemetry bed(s). The site of the telemetry bed (bay or cubicle) and method of observation (direct or indirect) was less important. An optimal nurse-to-patient ratio was difficult to identify but the study suggests that a ratio of at least 1 nurse to 4 patients is appropriate.ConclusionThe results provide an evidence base for the production of national standards and guidelines for surveillance of patients during video telemetry to improve patient safety.

Background 82 Aims Primary biliary cirrhosis (PBC) is associated with fatigue memory impairment and sleep disturbances These symptoms suggest the possibility of underlying central nervous system (CNS) dysfunction During exercise fatigue develops due to muscular processes (peripheral fatigue) and decreased neurological activation of the muscle (central fatigue) In this study we objectively quantify central and peripheral fatigue in PBC and investigate the integrity of cortical inhibitory and excitatory circuits Finally we determine the relationship of these indices to the symptoms of PBCMethods 16 early-stage PBC patients 8 post-liver transplant PBC patients and 12 age-matched controls were studied at the Specialist PBC clinic and neuroscience research unit In these patients twitch interpolation was used to measure peripheral and central fatigue Paired-pulse trans-cranial magnetic stimulation was used to assess ultra-cortical inhibition (ICI) and facilitation (ICF)Results PBC patients had a significantly lower central activation before fatiguing exercise (mean 86 6 8% (+/- 12 75) vs 95 2% (+/- 74) p <0 05) and a greater response variability than controls The decline in central activation during exercise and peripheral fatigue were normal ICI was significantly reduced in PBC patients and daytime somnolence was greater in patients where net inhibition exceeded facilitation Transplanted and non-transplanted patients had similar central activation ICI and ICFConclusions PBC patients have impaired central activation and abnormal ICI suggesting CNS abnormalities beyond voluntary control Transplanted and non-transplanted patients show similar abnormalities raising interesting questions about the mechanisms underpinning these changes and the permanence of neurological dysfunction in PBC ICI and ICF and the balance between them are related to daytime somnolence (an important symptom in PBC) (C) 2010 European Association for the Study of the Liver Published by Elsevier B V All rights reserved

Objective: To investigate the efficacy of magnetic stimulation over the posterior fossa (PF) as a non-invasive assessment of cerebellar function in man.Methods: We replicated a previously reported conditioning-test paradigm in 11 healthy subjects. Transcranial magnetic stimulation (TMS) at varying intensities was applied to the PF and motor cortex with a 3, 5 or 7 ms interstimulus interval (ISI), chosen randomly for each trial. Surface electromyogram (EMG) activity was recorded from two intrinsic hand muscles and two forearm muscles. Responses were averaged and rectified, and MEP amplitudes were compared to assess whether suppression of the motor output occurred as a result of the PF conditioning pulse.Results: Cortical MEPs were suppressed following conditioning-test ISIs of 5 or 7 ms. No suppression occurred with an ISI of 3 ms. PF stimuli alone also produced EMG responses, suggesting direct activation of the corticospinal tract (CST).Conclusions: CST collaterals are known to contact cortical inhibitory interneurones; antidromic CST activation could therefore contribute to the observed suppression of cortical MEPs.Significance: PF stimulation probably activates multiple pathways; even at low intensities it should not be regarded as a selective assessment of cerebellar function unless stringent controls can confirm the absence of confounding activity in other pathways. (c) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Movement DisordersVolume 24, Issue 10 p. 1550-1553 Letter to the Editor Slow orthostatic tremor in multiple sclerosis† Mark Baker MA, PhD, MRCP, Corresponding Author Mark Baker MA, PhD, MRCP [email protected] Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, United KingdomInstitute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, United KingdomSearch for more papers by this authorKaren Fisher BSc, Karen Fisher BSc Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, United KingdomSearch for more papers by this authorMing Lai BSc, FRCP, Ming Lai BSc, FRCP Department of Clinical Neurophysiology, Royal Victoria Infirmary, Newcastle upon Tyne, United KingdomSearch for more papers by this authorMartin Duddy MD, FRCP, Martin Duddy MD, FRCP Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, United KingdomSearch for more papers by this authorStuart Baker MA, PhD, Stuart Baker MA, PhD Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, United KingdomSearch for more papers by this author Mark Baker MA, PhD, MRCP, Corresponding Author Mark Baker MA, PhD, MRCP [email protected] Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, United KingdomInstitute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, United KingdomSearch for more papers by this authorKaren Fisher BSc, Karen Fisher BSc Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, United KingdomSearch for more papers by this authorMing Lai BSc, FRCP, Ming Lai BSc, FRCP Department of Clinical Neurophysiology, Royal Victoria Infirmary, Newcastle upon Tyne, United KingdomSearch for more papers by this authorMartin Duddy MD, FRCP, Martin Duddy MD, FRCP Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, United KingdomSearch for more papers by this authorStuart Baker MA, PhD, Stuart Baker MA, PhD Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, United KingdomSearch for more papers by this author First published: 13 May 2009 https://doi.org/10.1002/mds.22630Citations: 13 † MRB is employed by the NHS and NIHR. MED and HML are NHS employees. SNB and KMF are employees of Newcastle University. Research activities of MRB, KMF and SNB are supported by grants from The Wellcome Trust, MRC, BBSRC, EPSRC and UCB Pharma held by SNB. SNB and KMF are engaged as consultants to Cambridge Pharmaceuticals on an unrelated project. MED has received honoraria from BiogenIdec, Bayer Schering, Merck Serono and Teva. HML, SNB, MRB, and KMF have received travel grants from UCB Pharma. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume24, Issue1030 July 2009Pages 1550-1553 RelatedInformation