Estimating the likelihood of epilepsy from clinically noncontributory electroencephalograms using computational analysis: A retrospective, multisite case-control study.

OBJECTIVE: This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite case-control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder). METHODS: The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (N = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [n = 2], network-based [n = 4], and model-based [n = 2]) were calculated within each recording. Ensemble-based classifiers were developed using a two-tier cross-validation approach. We used standard regression methods to assess whether potential confounding variables (e.g., age, gender, treatment status, comorbidity) impacted model performance. RESULTS: We found levels of balanced accuracy of 68% across the cohort with clinically noncontributory normal EEGs (sensitivity =61%, specificity =75%, positive predictive value =55%, negative predictive value =79%, diagnostic odds ratio =4.64, area under receiver operated characteristics curve =.72). Group level analysis found no evidence suggesting any of the potential confounding variables significantly impacted the overall performance. SIGNIFICANCE: These results provide evidence that the set of biomarkers could provide additional value to clinical decision-making, providing the foundation for a decision support tool that could reduce diagnostic delay and misdiagnosis rates. Future work should therefore assess the change in diagnostic yield and time to diagnosis when utilizing these biomarkers in carefully designed prospective studies.

Lesson of the month: Cytotoxic lesions of the corpus callosum (CLOCCs) in status epilepticus.

A 26-year-old man was diagnosed with epilepsy a few months previously and admitted with status epilepticus. Computed tomography (CT) of the brain and CT venography were unremarkable. Magnetic resonance imaging (MRI) of the brain showed evidence of possible acute focal infarction in the splenium of the corpus callosum that showed a true restricted diffusion. The patient had no vascular risk factors and no focal neurological deficit on examination to explain the occurrence of an acute infarction. MRI of the brain was repeated 1 month later to assess for progression of that lesion and showed resolution of it. This case highlights the association of cytotoxic lesions of the corpus callosum that show true restricted diffusion with status epilepticus. It also emphasises the importance of medical reasoning and not being solely dependent on diagnostic investigations without reasonably linking them to the history and examination.

Statin-induced autoimmune necrotizing myositis-A single-center case series highlighting this potentially life-threatening but treatable condition.

Statin-induced autoimmune necrotizing myositis is a rare but important cause muscle weakness. Withdrawal of the statin and steroid treatment alone may be insufficient treatment for SIANM. Targeted immunosuppression may be needed and can be effective.

Prevalence and clinical correlates of non-convulsive status epilepticus in elderly patients with acute confusional state: A systematic literature review.

Non-convulsive status epilepticus (NCSE) is a potentially treatable condition that poses considerable diagnostic challenges. NCSE is thought to be more common in the elderly than in the general population, however additional diagnostic challenges complicate its recognition in older patients, because of the wide differential diagnosis with common underlying causes of acute confusional state in this age group. We set out to review the existing evidence on the clinical correlates of NCSE in the elderly population. A systematic literature review was conducted according to the methodological standards outlined in the PRISMA statement to assess the clinical correlates of NCSE in patients aged 60 or older. Our literature search identified 11 relevant studies, which confirmed that the incidence of NCSE increases with age, in particular with regard to focal forms with impairment of consciousness. Female gender, history of epilepsy (or a recently witnessed seizure with motor features), and abnormal ocular movements appeared to correlate with the diagnosis of NCSE in the elderly, prompting prioritization of electroencephalography tests for diagnostic confirmation. Epidemiological data in the elderly vary widely because of the heterogeneity of definitions and diagnostic criteria applied across different studies. Based on our findings, it is recommended to keep a low threshold for requesting electroencephalography tests to confirm the diagnosis of NCSE in elderly patients with acute confusional state, even in the presence of a presumed symptomatic cause.

The role of electroencephalography in the early diagnosis of non-convulsive status epilepticus in elderly patients with acute confusional state: Two possible strategies?

Non-convulsive status epilepticus (NCSE) can pose considerable diagnostic challenges, especially in the elderly, because of the wide differential diagnosis with common underlying causes of acute confusional state in this age group. We reviewed the proposed electroencephalography (EEG) strategies to improve the diagnostic yield of non-convulsive status epilepticus in the elderly population. Specifically, a debated topic of clinical relevance is the exact role of the EEG in the early diagnosis of NCSE in the elderly. Two EEG strategies have been proposed to improve the diagnostic yield of NCSE: emergent abbreviated EEG (EAEEG) recordings with reduced montages, and continuous EEG (CEEG) monitoring. Both approaches appear to be potentially advantageous, but at the same time subject to intrinsic limitations. Our literature review found initial evidence that the diagnostic yield for NCSE of prolonged EEG recordings is superior to routine EEGs. Further research is needed to confirm these preliminary findings and to explore strategies to improve the feasibility of a more widespread use of prolonged recordings within acute clinical settings.

Impact of video-ambulatory electroencephalography on the medical management of epilepsy.

Video-ambulatory electroencephalography (video-AEEG) is increasingly being used in secondary care centres for the diagnostic work-up of new cases with suspected epilepsy and for the review of known cases with active seizures despite medical treatment. We reviewed how the outcome of video-AEEG influenced the medical management of patients who underwent this investigation at a neurophysiology department within a secondary care centre. Out of a total of 171 consecutive video-AEEG studies performed over a period of two years, 111 could be included in our retrospective analysis, based on availability and completeness of relevant clinical information pre- and post-investigation. In our sample, 55.9% of patients had typical clinical events captured on video-AEEG and diagnostic yield was higher in patients with a previously established diagnosis of epilepsy (n=62; diagnostic yield 62.9%). A total of 27 patients (24.3%) had changes in medical treatment following video-AEEG, most frequently antiepileptic drug introduction/increase when epileptic seizures were captured. This proportion was similar between patients with or without a previously established diagnosis of epilepsy. Our findings in a real-life setting confirm the usefulness of video-AEEG in influencing the clinical attitude towards complex patients with suspected or longstanding history of epilepsy.

Posterior interosseous neuropathy: the diagnostic benefits of a multimodal approach to investigation.

Posterior interosseous neuropathy should be considered in patients presenting with finger and wrist drop and no sensory deficit. Clinical and electrophysiological assessments are key to a diagnosis. MRI may disclose etiological information not available to clinical or neurophysiological assessment, and should be thought as a complementary diagnostic tool.

Video-ambulatory EEG in a secondary care center: A retrospective evaluation of utility in the diagnosis of epileptic and nonepileptic seizures.

The development and optimization of protocols using simultaneous video recording alongside long-term electroencephalography (EEG), such as ambulatory EEG (AEEG), expanded the range of available techniques for the investigation of paroxysmal clinical events. In particular, video-AEEG has received increasing attention over the last few years because of its potential to further improve diagnostic utility in the differential diagnosis between epileptic and nonepileptic seizures. We retrospectively evaluated 88 video-AEEG studies in order to assess the diagnostic utility of video-AEEG in 87 patients consecutively referred to a neurophysiology department. Typical clinical events occurred during 55 studies (62.5%). In 26 of these, at least one event was also clearly seen on video recording, contributing to a confident diagnosis. Clinical events were classified according to three diagnostic categories: epileptic seizures (6 studies, 6.8%), physiologic nonepileptic events (13 studies, 14.8%), or psychogenic nonepileptic seizures (36 studies, 40.9%). Of the studies with an event not recorded on video, a confident diagnosis could be reached in 55.2% of cases. The main reason for unsuccessful video recording was failure to activate the camcorder by the patient or carer. We found an overall diagnostic utility of 67.0%, which confirms the findings of previous reports evaluating the diagnostic yield of AEEG. Implementation of video-AEEG protocols in a secondary care center appears to have high diagnostic utility, particularly for patients with psychogenic nonepileptic seizures. Our findings prompt further research into the potential applications of video-AEEG, in consideration of important implications for successful patient management and healthcare resource allocation.

The role of outpatient ambulatory electroencephalography in the diagnosis and management of adults with epilepsy or nonepileptic attack disorder: A systematic literature review.

Electroencephalography (EEG) is an established diagnostic tool with important implications for the clinical management of patients with epilepsy or nonepileptic attack disorder. Different types of long-term EEG recording strategies have been developed over the last decades, including the widespread use of ambulatory electroencephalography (AEEG), which holds great potential in terms of both clinical usefulness and cost-effectiveness. In this paper, we present the results of a systematic review of the scientific literature on the use of AEEG in the diagnosis of epilepsy and nonepileptic attacks in adult patients. Taken together, our findings confirmed that AEEG is a useful diagnostic tool in patients with equivocal findings on routine EEG studies and influences management decisions in the majority of studies. There is evidence that AEEG is also more likely to capture events than sleep-deprived EEG; however, there are currently insufficient data available to compare the diagnostic utility of modern AEEG technology with inpatient video-telemetry. Further research on the combined use of AEEG and home-video recording is, therefore, warranted.

Further insight on A-wave in acute and chronic demyelinating neuropathies.

A-wave is a late motor response that maintains the same characteristics of latency, amplitude and shape with every electrical stimuli at a proper given intensity. The presence of A-waves was reported both in chronic (CIDP) and acute (AIDP) forms of inflammatory demyelinating polyradiculoneuropathy. It is attributed to the effect of either sprouting phenomena or ephaptic/ectopic discharge. In the first condition it could be a sign of functional recovery, while in the second it could represent an early indicator of demyelination. Aims of our research were to investigate retrospectively the presence of the A-waves, establishing whether its frequency is more common in CIDP or AIDP. Data from 77 patients, 57 male and 20 female, mean age 60.7 years (SD 15.4), were recovered from clinical records and their neurophysiological tests retrieved for reanalysis. Our results seem to indicate that A-waves can represent an early sign of acute pathology of peripheral nervous system.

Review of the clinical evidence for interferon beta 1a (Rebif) in the treatment of multiple sclerosis.

Interferon (INF) beta 1a 22 or 44 mug (Rebif((R))) administered s.c. 3 times a week (t.i.w) is a well established immunomodulating treatment for relapsing remitting multiple sclerosis (RRMS). This review focuses on its mechanisms of action, evidence of efficacy, safety, and tolerability. Several pharmacodynamic properties explain the immunomodulatory actions of INF beta 1a 22 or 44 mug s.c. t.i.w. Pivotal trials and post-marketing studies proved that the drug is effective in reducing disease activity and likely in slowing disease progression. Head-to-head comparative studies with other marketed INFs beta in RRMS suggested a better therapeutic response associated with higher doses and frequency of administration of Rebif((R)). Additional evidence indicated a beneficial effect of INF beta 1a in patients with clinically isolated syndromes (CIS) suggestive of MS, as treatment reduced time to conversion to clinically definite (CD) disease. Further, although the drug did not prove to slow time to progression there were benefits on relapse- and MRI-related secondary outcome measures in secondary progressive (SP) MS. Pivotal trials, their cross-over extensions, and post-marketing studies consistently showed that INF beta 1a 22 or 44 mug s.c. t.i.w. is safe and well tolerated, as adverse drug reactions are usually mild and manageable.

Predicting progression in primary progressive multiple sclerosis: a 10-year multicenter study.

Rates of progression vary widely in primary progressive multiple sclerosis. This multicenter study aimed to identify predictors of progression over 10 years. A total of 101 patients who had been imaged at baseline and 2 years were scored on the expanded disability status scale after 10 years. Ordinal logistic regression identified the following independent variables that predicted progression: male sex, shorter disease duration, and slower timed walk test at baseline (best overall predictor), and deterioration in expanded disability status scale score and reduction in brain volume over 2 years. These predictors of long-term disability provide some insight into disease progression.

Normal-appearing brain t1 relaxation time predicts disability in early primary progressive multiple sclerosis.

OBJECTIVE: To investigate whether patients with early primary progressive multiple sclerosis show changes in T1 relaxation time (T1-RT) in normal-appearing white matter (NAWM) and normal-appearing gray matter (NAGM) during 2 years and whether T1-RT at baseline predicts disability. METHODS: Twenty-one patients and 12 control subjects were studied at baseline and after 2 years. Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores were assessed. T1 relaxation time histograms of NAWM and NAGM were obtained in all subjects, and mean, peak height, and peak location of the histograms were measured. Paired t tests were used to compare baseline and 2-year histogram values in patients and control subjects. To investigate whether T1-RT predicted clinical changes, multiple linear regression analysis was used. RESULTS: Patients showed increases in NAWM and NAGM T1-RT mean and peak location during follow-up, and significant decreases in NAWM and NAGM peak height. Baseline NAWM T1-RT mean values and peak height predicted disability at 2 years, as measured with the Multiple Sclerosis Functional Composite score. CONCLUSION: T1 relaxometry is a good marker of disease progression and has prognostic potential in primary progressive multiple sclerosis.