Interictal and seizure-onset EEG patterns in malformations of cortical development: A systematic review.

OBJECTIVES: Malformations of cortical development (MCDs) are common causes of drug-resistant epilepsy. The mechanisms underlying the associated epileptogenesis and ictogenesis remain poorly elucidated. EEG can help in understanding these mechanisms. We systematically reviewed studies reporting scalp or intracranial EEG features of MCDs to characterise interictal and seizure-onset EEG patterns across different MCD types. METHODS: We conducted a systematic review in accordance with PRISMA guidelines. MEDLINE, PubMed, and Cochrane databases were searched for studies describing interictal and seizure-onset EEG patterns in MCD patients. A classification framework was implemented to group EEG features into 20 predefined patterns, comprising nine interictal (five, scalp EEG; four, intracranial EEG) and 11 seizure-onset (five, scalp EEG; six, intracranial EEG) patterns. Logistic regression was used to estimate the odds ratios (OR) of each seizure-onset pattern being associated with specific MCD types. RESULTS: Our search yielded 1682 studies, of which 27 comprising 936 MCD patients were included. Of the nine interictal EEG patterns, five (three, scalp EEG; two, intracranial EEG) were detected in ≥2 MCD types, while four (rhythmic epileptiform discharges type 1 and type 2 on scalp EEG; repetitive bursting spikes and sporadic spikes on intracranial EEG) were seen only in focal cortical dysplasia (FCD). Of the 11 seizure-onset patterns, eight (three, scalp EEG; five, intracranial EEG) were found in ≥2 MCD types, whereas three were observed only in FCD (suppression on scalp EEG; delta brush on intracranial EEG) or tuberous sclerosis complex (TSC; focal fast wave on scalp EEG). Among scalp EEG seizure-onset patterns, paroxysmal fast activity (OR = 0.13; 95% CI: 0.03-0.53; p = 0.024) and repetitive epileptiform discharges (OR = 0.18; 95% CI: 0.05-0.61; p = 0.036) were less likely to occur in TSC than FCD. Among intracranial EEG seizure-onset patterns, low-voltage fast activity was more likely to be detected in heterotopia (OR = 19.3; 95% CI: 6.22-60.1; p < 0.001), polymicrogyria (OR = 6.70; 95% CI: 2.25-20.0; p = 0.004) and TSC (OR = 4.27; 95% CI: 1.88-9.70; p = 0.005) than FCD. SIGNIFICANCE: Different MCD types can share similar interictal or seizure-onset EEG patterns, reflecting common underlying biological mechanisms. However, selected EEG patterns appear to point to distinct MCD types, suggesting certain differences in their neuronal networks.

Interpretable surface-based detection of focal cortical dysplasias: a Multi-centre Epilepsy Lesion Detection study.

One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted 'gold-standard' subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.

Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia: A MELD study.

OBJECTIVE: Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome. METHODS: The MELD (Multi-centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging-based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom. RESULTS: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%. SIGNIFICANCE: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counseling in epilepsy.

Seizure Outcome After Surgery for MRI-Diagnosed Focal Cortical Dysplasia: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Focal cortical dysplasia (FCD) has been associated with poorer postsurgical seizure outcomes compared to other pathologies. FCD surgical series have been assembled on the basis of a histologic diagnosis, including patients with abnormal and normal preoperative MRI. However, in clinical workflow, patient selection for surgery is based on preoperative findings, including MRI. We performed a systematic review and meta-analysis of the literature to determine the rate and predictors of favorable seizure outcome after surgery for MRI-detected FCD. METHODS: We devised our study protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered the protocol with PROSPERO. We searched MEDLINE, EMBASE, and Web of Science for studies of patients followed up for ≥12 months after resective surgery for drug-resistant epilepsy with MRI-detected FCD. Random-effects meta-analysis was used to calculate the proportion of patients attaining a favorable outcome, defined as Engel class I, International League Against Epilepsy class 1 to 2, or seizure-free status. Meta-regression was performed to investigate sources of heterogeneity. RESULTS: Our search identified 3,745 references. Of these, 35 studies (total of 1,353 patients) were included. Most studies (89%) followed up patients for ≥24 months after surgery. The overall postsurgical favorable outcome rate was 70% (95% confidence interval [CI] 64-75). There was high interstudy heterogeneity. Favorable outcome was associated with complete resection of the FCD lesion (risk ratio [RR] 2.42 [95% confidence interval (CI) 1.55-3.76], p < 0.001) and location of the FCD lesion in the temporal lobe (RR 1.38 [95% CI 1.07-1.79], p = 0.013) but not lesion extent, intracranial EEG use, or FCD histologic type. The number of FCD histologic types included in the same study accounted for 7.6% of the observed heterogeneity. DISCUSSION: Seventy percent of patients with drug-resistant epilepsy and MRI features of FCD attain a favorable seizure outcome after resective surgery. Our findings can be incorporated into routine preoperative counseling and reinforce the importance of completely resecting the MRI-detected FCD when safe and feasible.

Ocular motor disorders.

PURPOSE OF REVIEW: Studying eye movements can provide insight into how the normal brain works, how diseases affect eye movements, and how eye movement abnormalities can be used to study diseases and/or their treatments. In this review, we concentrate on recent studies looking at abnormalities of saccades in various diseases. RECENT FINDINGS: Various saccadic abnormalities have been found in Parkinson's disease, Huntington's disease, dementia, cerebellar disease, schizophrenia, and several other conditions. In some of these, saccadic abnormalities appear to be capable of distinguishing different subtypes (e.g., progressive supranuclear palsy from idiopathic Parkinson's disease, Alzheimer's disease from frontotemporal dementia, or one type of spinocerebellar ataxia from another). Several studies have looked at functional associations of saccadic abnormalities (e.g., reading in spinocerebellar ataxia or recovery from stroke), which may prove clinically useful. Studies on microsaccades have revealed abnormalities in various diseases, and suggest that they may provide a useful marker of fatigue. SUMMARY: Saccadic eye movements provide an excellent way of studying the human motor system in health and disease, as well as providing insight into various aspects of cognitive function. Assessment of saccades in the laboratory and at the bedside is likely to become increasingly useful clinically.

Intravenous vasodilator therapy in congestive heart failure.

The prevalence of congestive heart failure (CHF) is increasing in the US and worldwide, partly because patients are living longer. Treatment of CHF is mostly on an outpatient basis, but inpatient care is required for decompensated CHF, acute CHF or poor response to outpatient treatment. Control of symptoms is usually achieved by diuresis. Intravenous (IV) vasodilators are an important adjunct to the inpatient treatment of CHF. They work mainly by reducing the afterload on the myocardium although preload reduction also occurs. After clinical stabilisation, the goal is to switch to a maintenance oral regimen to be continued as outpatient therapy. The range of IV vasodilators available for inpatient treatment of CHF includes nitrates, phosphodiesterase inhibitors, dobutamine, morphine, ACE inhibitors, B-type natriuretic peptides and endothelin receptor antagonists. As each agent may have a different mechanism or site of action, each agent may affect preload, contractility or afterload to a different extent and it may be desirable to choose one over the other in a particular clinical setting. Examples of standard therapy include dobutamine, milrinone and nitroglycerin. Nesiritide, a B-type natriuretic peptide, is a newer vasodilator and US FDA approved for use in acute CHF. However, most studies with this agent have been in small numbers of patients with anecdotal findings. Larger studies are warranted to pinpoint the efficacy and adverse effects of this agent. It is primarily used to reduce the acuity of decompensated CHF on admission to hospital.Endothelin receptor antagonists show promise in the management of acute CHF, but continue to be investigational. Long-term data on their efficacy and safety are limited. None of the endothelin receptor antagonists are FDA approved for use in patients with CHF.