Electroencephalography in encephalopathy and encephalitis.

Electroencephalography (EEG) is a useful adjunct to clinical neurological examination, particularly as it may detect subtle or subclinical disturbance of cerebral function and it allows monitoring of cerebral activity over time. Continuous EEG combined with quantitative analysis and machine learning may help identify changes in real time, before the emergence of clinical signs and response to interventions. EEG is rarely pathognomonic in encephalopathy/encephalitis but when interpreted correctly and within the clinical context, certain phenotypes may indicate a specific pathophysiology (eg, lateralised periodic discharges in HSV-1, generalised periodic discharges in sporadic Creutzfeldt-Jakob disease, and extreme delta brushes in anti-n-methyl-D-aspartate receptor autoimmune encephalitis). EEG is included in some specialist guidelines for disease assessment, monitoring and prognostication (ie, hepatic, cancer immunotherapy, viral, prion, autoimmune encephalitis and hypoxic ischaemic encephalopathy). EEG is invaluable for confirming or excluding non-convulsive seizures or status epilepticus, particularly in critically ill patients, and in understanding new concepts such as epileptic encephalopathy and the ictal-interictal continuum.

Somatosensory evoked potentials aid prediction after hypoxic-ischaemic brain injury.

Cardiopulmonary resuscitation, basic life support and early defibrillation are leading to more survivors of out-of-hospital cardiac arrest reaching hospital. Once stabilised on an intensive care unit, it can be difficult to predict the neurological outcome using clinical criteria alone, particularly with modern management using sedation, neuromuscular blockade and hypothermia. If we are to prevent ongoing futile life support, it is important to try to identify the majority of patients who, despite best efforts, will not make a meaningful recovery. Somatosensory evoked potentials are widely available electrophysiological tests that can provide an objective biomarker of a poor neurological outcome and assist in predicting the prognosis.

Repeat infusion of autologous bone marrow cells in progressive multiple sclerosis - A phase I extension study (SIAMMS II).

BACKGROUND: During the safety and feasibility 'Study of Intravenous Autologous Marrow in Multiple Sclerosis (SIAMMS)', intravenous infusion of autologous marrow was well tolerated. The efficacy of the approach is being explored in a placebo-controlled randomised controlled trial (ACTiMuS, NCT01815632) but it is not known whether repeated infusions will be required to optimise benefit. The objective of the current study was to explore the safety and feasibility of repeat treatment with intravenous autologous bone marrow for patients with progressive multiple sclerosis (MS). METHODS: 'SIAMMS II' was a prospective, single centre phase I extension study in which participants in the SIAMMS study were offered repeat bone marrow harvest and infusion of autologous, unfractionated bone marrow as a day-case procedure. The primary outcome measure was number of adverse events and secondary outcome measures included change in clinical rating scales of disability, global evoked potential and cranial magnetic resonance imaging (MRI). RESULTS: In total, 4 of the 6 participants in the SIAMMS study had repeat bone marrow harvest and infusion of filtered autologous marrow as a day case procedure which was well tolerated. There were no serious adverse effects. Additional outcome measures including clinical scales, global evoked potentials and cranial MRI were stable. CONCLUSION: SIAMMS II demonstrates the safety and feasibility of repeated, non-myeloablative autologous bone marrow-derived cell therapy in progressive MS.

Corrigendum to "A revised glossary of terms most commonly used by clinical electroencephalographers and updated proposal for the report format of the EEG findings. Revision 2017" [Clin. Neurophysiol. Practice 2 (2017) 170-185].

[This corrects the article DOI: 10.1016/j.cnp.2017.07.002.].

Neurophysiology contributes to outcome prediction after cardiac arrest.

This "Points of View" paper discusses the role of neurophysiology in predicting outcome in patients who have initially survived a cardiac arrest but remain in coma. The authors, from different clinical backgrounds, discuss their individual approaches to neuroprognostication.

Proposal for best practice in the use of video-EEG when psychogenic non-epileptic seizures are a possible diagnosis.

The gold-standard for the diagnosis of psychogenic non-epileptic seizures (PNES) is capturing an attack with typical semiology and lack of epileptic ictal discharges on video-EEG. Despite the importance of this diagnostic test, lack of standardisation has resulted in a wide variety of protocols and reporting practices. The goal of this review is to provide an overview of research findings on the diagnostic video-EEG procedure, in both the adult and paediatric literature. We discuss how uncertainties about the ethical use of suggestion can be resolved, and consider what constitutes best clinical practice. We stress the importance of ictal observation and assessment and consider how diagnostically useful information is best obtained. We also discuss the optimal format of video-EEG reports; and of highlighting features with high sensitivity and specificity to reduce the risk of miscommunication. We suggest that over-interpretation of the interictal EEG, and the failure to recognise differences between typical epileptic and nonepileptic seizure manifestations are the greatest pitfalls in neurophysiological assessment of patients with PNES. Meanwhile, under-recognition of semiological pointers towards frontal lobe seizures and of the absence of epileptiform ictal EEG patterns during some epileptic seizure types (especially some seizures not associated with loss of awareness), may lead to erroneous PNES diagnoses. We propose that a standardised approach to the video-EEG examination and the subsequent written report will facilitate a clear communication of its import, improving diagnostic certainty and thereby promoting appropriate patient management.

Consensus-based guidelines for Video EEG monitoring in the pre-surgical evaluation of children with epilepsy in the UK.

PURPOSE: Paediatric Epilepsy surgery in the UK has recently been centralised in order to improve expertise and quality of service available to children. Video EEG monitoring or telemetry is a highly specialised and a crucial component of the pre-surgical evaluation. Although many Epilepsy Monitoring Units work to certain standards, there is no national or international guideline for paediatric video telemetry. METHODS: Due to lack of evidence we used a modified Delphi process utilizing the clinical and academic expertise of the clinical neurophysiology sub-specialty group of Children's Epilepsy Surgical Service (CESS) centres in England and Wales. This process consisted of the following stages I: Identification of the consensus working group, II: Identification of key areas for guidelines, III: Consensus practice points and IV: Final review. Statements that gained consensus (median score of either 4 or 5 using a five-point Likerttype scale) were included in the guideline. RESULTS: Two rounds of feedback and amendments were undertaken. The consensus guidelines includes the following topics: referral pathways, neurophysiological equipment standards, standards of recording techniques, with specific emphasis on safety of video EEG monitoring both with and without drug withdrawal, a protocol for testing patient's behaviours, data storage and guidelines for writing factual reports and conclusions. All statements developed received a median score of 5 and were adopted by the group. CONCLUSION: Using a modified Delphi process we were able to develop universally-accepted video EEG guidelines for the UK CESS. Although these recommendations have been specifically developed for the pre-surgical evaluation of children with epilepsy, it is assumed that most components are transferable to any paediatric video EEG monitoring setting.

Repeat infusion of autologous bone marrow cells in multiple sclerosis: protocol for a phase I extension study (SIAMMS-II).

INTRODUCTION: The 'Study of Intravenous Autologous Marrow in Multiple Sclerosis (SIAMMS)' trial was a safety and feasibility study which examined the effect of intravenous infusion of autologous bone marrow without myeloablative therapy. This trial was well tolerated and improvement was noted in the global evoked potential (GEP)--a neurophysiological secondary outcome measure recording speed of conduction in central nervous system pathways. The efficacy of intravenous delivery of autologous marrow in progressive multiple sclerosis (MS) will be examined in the phase II study the 'Assessment of Bone Marrow-Derived Cellular Therapy in Progressive Multiple Sclerosis (ACTiMuS; NCT01815632)'. In parallel with the 'ACTiMuS' study, the current study 'SIAMMS-II' will explore the feasibility of repeated, non-myeloablative autologous bone marrow-derived cell therapy in progressive MS. Furthermore, information will be obtained regarding the persistence or otherwise of improvements in conduction in central nervous system pathways observed in the original 'SIAMMS' study and whether these can be reproduced or augmented by a second infusion of autologous bone marrow-derived cells. METHODS AND ANALYSIS: An open, prospective, single-centre phase I extension study. The six patients with progressive MS who participated in the 'SIAMMS' study will be invited to undergo repeat bone marrow harvest and receive an intravenous infusion of autologous, unfractionated bone marrow as a day-case procedure. The primary outcome measure is the number of adverse events, and secondary outcome measures will include change in clinical rating scales of disability, GEP and cranial MRI. ETHICS AND DISSEMINATION: The study has UK National Research Ethics Committee approval (13/SW/0255). Study results will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT01932593.

Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS): study protocol for a randomised controlled trial.

BACKGROUND: We have recently completed an evaluation of the safety and feasibility of intravenous delivery of autologous bone marrow in patients with progressive multiple sclerosis (MS). The possibility of repair was suggested by improvement in the neurophysiological secondary outcome measure seen in all participants. The current study will examine the efficacy of intravenous delivery of autologous marrow in progressive MS. Laboratory studies performed in parallel with the clinical trial will further investigate the biology of bone marrow-derived stem cell infusion in MS, including mechanisms underlying repair. METHODS/DESIGN: A prospective, randomised, double-blind, placebo-controlled, stepped wedge design will be employed at a single centre (Bristol, UK). Eighty patients with progressive MS will be recruited; 60 will have secondary progressive disease (SPMS) but a subset (n = 20) will have primary progressive disease (PPMS). Participants will be randomised to either early or late (1 year) intravenous infusion of autologous, unfractionated bone marrow. The placebo intervention is infusion of autologous blood. The primary outcome measure is global evoked potential derived from multimodal evoked potentials. Secondary outcome measures include adverse event reporting, clinical (EDSS and MSFC) and self-assessment (MSIS-29) rating scales, optical coherence tomography (OCT) as well as brain and spine MRI. Participants will be followed up for a further year following the final intervention. Outcomes will be analysed on an intention-to-treat basis. DISCUSSION: Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS) is the first randomised, placebo-controlled trial of non-myeloablative autologous bone marrow-derived stem cell therapy in MS. It will determine whether bone marrow cell therapy can, as was suggested by the phase I safety study, improve conduction in multiple central nervous system pathways affected in progressive MS. Furthermore, laboratory studies performed in parallel with the clinical trial will inform our understanding of the cellular pharmacodynamics of bone marrow infusion in MS patients and the mechanisms underlying cell therapy. TRIAL REGISTRATION: ISRCTN27232902 Registration date 11/09/2012. NCT01815632 Registration date 19/03/2013.

Hyperventilation during electroencephalography: safety and efficacy.

PURPOSE: To determine safety and efficacy of hyperventilation (HV) during electroencephalography (EEG). METHODS: We report the findings of a prospective multicentre National Service Evaluation of the occurrence of adverse events, seizures and interictal epileptiform discharges seen in association with HV during EEG, in a relatively unselected, largely out patient population of 3475 being investigated predominantly for possible epileptic seizures. RESULTS: Adverse events occurred rarely, and there were no reported significant cerebrovascular, cardiovascular or respiratory events. Of the 3170 patients suspected of 'epilepsy or possible epilepsy' 69 patients (2.2%) had seizures provoked by HV, but only one (0.03%) had a generalised tonic clonic seizure. The elicitation or increase of interictal epileptiform discharges (IEDs) was seen in 387 (12.2%) of the total 3170 patients with suspected epilepsy who hyperventilated. Furthermore 31 patients (0.9%) had psychogenic non-epileptic seizures. CONCLUSION: HV is rarely associated with adverse events, but contributes to the diagnosis and classification of seizure disorders in an appreciable proportion of patients with epilepsy and non-epileptic attacks. These findings confirm that HV in selected patients is a valid activation technique in diagnostic EEG, where the potential benefits out weigh the risks, and also provide information that may assist the informed consent process.