Multimodal mapping of regional brain vulnerability to focal cortical dysplasia.

Focal cortical dysplasia (FCD) type II is a highly epileptogenic developmental malformation and a common cause of surgically treated drug-resistant epilepsy. While clinical observations suggest frequent occurrence in the frontal lobe, mechanisms for such propensity remain unexplored. Here, we hypothesized that cortex-wide spatial associations of FCD distribution with cortical cytoarchitecture, gene expression and organizational axes may offer complementary insights into processes that predispose given cortical regions to harbour FCD. We mapped the cortex-wide MRI distribution of FCDs in 337 patients collected from 13 sites worldwide. We then determined its associations with (i) cytoarchitectural features using histological atlases by Von Economo and Koskinas and BigBrain; (ii) whole-brain gene expression and spatiotemporal dynamics from prenatal to adulthood stages using the Allen Human Brain Atlas and PsychENCODE BrainSpan; and (iii) macroscale developmental axes of cortical organization. FCD lesions were preferentially located in the prefrontal and fronto-limbic cortices typified by low neuron density, large soma and thick grey matter. Transcriptomic associations with FCD distribution uncovered a prenatal component related to neuroglial proliferation and differentiation, likely accounting for the dysplastic makeup, and a postnatal component related to synaptogenesis and circuit organization, possibly contributing to circuit-level hyperexcitability. FCD distribution showed a strong association with the anterior region of the antero-posterior axis derived from heritability analysis of interregional structural covariance of cortical thickness, but not with structural and functional hierarchical axes. Reliability of all results was confirmed through resampling techniques. Multimodal associations with cytoarchitecture, gene expression and axes of cortical organization indicate that prenatal neurogenesis and postnatal synaptogenesis may be key points of developmental vulnerability of the frontal lobe to FCD. Concordant with a causal role of atypical neuroglial proliferation and growth, our results indicate that FCD-vulnerable cortices display properties indicative of earlier termination of neurogenesis and initiation of cell growth. They also suggest a potential contribution of aberrant postnatal synaptogenesis and circuit development to FCD epileptogenicity.

Prognostic significance and extra-hypothalamus dysfunction of hyponatremia in anti-leucine-rich glioma-inactivated protein 1 encephalitis.

This study aimed to investigate prognostic significance and brain metabolic mechanism of hyponatremia in anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis. After adjusting for confounders, patients with moderate and severe hyponatremia had significantly increased risk of poor functional outcome and sequelae of seizures. In addition, serum sodium was negatively correlated with normalized ratio of the standardized uptake value of medial temporal lobe (MTL), basal ganglia (BG), and hypothalamus on positron emission tomography (PET) and which was further validated using voxel-wise analysis, suggesting an extra-hypothalamus (BG and MTL) localization for hyponatremia.

Multicenter Validation of a Deep Learning Detection Algorithm for Focal Cortical Dysplasia.

BACKGROUND AND OBJECTIVE: To test the hypothesis that a multicenter-validated computer deep learning algorithm detects MRI-negative focal cortical dysplasia (FCD). METHODS: We used clinically acquired 3-dimensional (3D) T1-weighted and 3D fluid-attenuated inversion recovery MRI of 148 patients (median age 23 years [range 2-55 years]; 47% female) with histologically verified FCD at 9 centers to train a deep convolutional neural network (CNN) classifier. Images were initially deemed MRI-negative in 51% of patients, in whom intracranial EEG determined the focus. For risk stratification, the CNN incorporated bayesian uncertainty estimation as a measure of confidence. To evaluate performance, detection maps were compared to expert FCD manual labels. Sensitivity was tested in an independent cohort of 23 cases with FCD (13 ± 10 years). Applying the algorithm to 42 healthy controls and 89 controls with temporal lobe epilepsy disease tested specificity. RESULTS: Overall sensitivity was 93% (137 of 148 FCD detected) using a leave-one-site-out cross-validation, with an average of 6 false positives per patient. Sensitivity in MRI-negative FCD was 85%. In 73% of patients, the FCD was among the clusters with the highest confidence; in half, it ranked the highest. Sensitivity in the independent cohort was 83% (19 of 23; average of 5 false positives per patient). Specificity was 89% in healthy and disease controls. DISCUSSION: This first multicenter-validated deep learning detection algorithm yields the highest sensitivity to date in MRI-negative FCD. By pairing predictions with risk stratification, this classifier may assist clinicians in adjusting hypotheses relative to other tests, increasing diagnostic confidence. Moreover, generalizability across age and MRI hardware makes this approach ideal for presurgical evaluation of MRI-negative epilepsy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that deep learning on multimodal MRI accurately identifies FCD in patients with epilepsy initially diagnosed as MRI negative.

The Role of SPECT and PET in Epilepsy.

OBJECTIVE. The purpose of this article is to summarize the role of molecular imaging of the brain by use of SPECT, FDG PET, and non-FDG PET radiotracers in epilepsy. CONCLUSION. Quantitative image analysis with PET and SPECT has increased the diagnostic utility of these modalities in localizing epileptogenic onset zones. A multi-modal platform approach integrating the functional imaging of PET and SPECT with the morphologic information from MRI in presurgical evaluation of epilepsy can greatly improve outcomes.

A case study of voltage-gated potassium channel antibody-related limbic encephalitis with PET/MRI findings.

Preclinical and clinical studies have demonstrated the significance of inflammation and autoantibodies in epilepsy, and the use of immunotherapies in certain situations has become an established practice. Temporal lobe epilepsy can follow paraneoplastic or nonparaneoplastic limbic encephalitis associated with antibodies directed against brain antigens. Here, we focus on a patient with worsening confusion and temporal lobe seizures despite treatment with antiepileptic medications. Serial brain MRIs did not conclusively reveal structural abnormalities, so the patient underwent brain PET/MRI to simultaneously evaluate brain structure and function, revealing bitemporal abnormalities. The patient was diagnosed with voltage-gated potassium channel antibody-related limbic encephalitis based on clinical presentation, imaging findings, and antibody testing. Treatment included the addition of a second antiepileptic agent and oral steroids. His seizures and cognitive deficits improved and stabilized.

Laser ablation as treatment strategy for medically refractory dominant insular epilepsy: therapeutic and functional considerations.

Since its introduction to neurosurgery in 2008, laser ablative techniques have been largely confined to the management of unresectable tumors. Application of this technology for the management of focal epilepsy in the adult population has not been fully explored. Given that nearly 1,000,000 Americans live with medically refractory epilepsy and current surgical techniques only address a fraction of epileptic pathologies, additional therapeutic options are needed. We report the successful treatment of dominant insular epilepsy in a 53-year-old male with minimally invasive laser ablation complicated by mild verbal and memory deficits. We also report neuropsychological test data on this patient before surgery and at 8 months after the ablation procedure. This account represents the first reported successful patient outcome of laser ablation as an effective treatment option for medically refractory post-stroke epilepsy in an adult.

Heart rate analysis differentiates dialeptic complex partial temporal lobe seizures from auras and non-epileptic seizures

The distinction of non-epileptic from epileptic events is difficult even for experienced neurologists. We retrospectively evaluated 59 dialeptic events from 27 patients admitted for video EEG monitoring to check whether heart rate (HR) analysis could help in differentiating dialeptic complex partial temporal lobe seizures (TLS) from dialeptic simple partial TLS, and non-epileptic dialeptic events. Baseline HR was increased in the simple partial TLS in comparison to complex partial TLS and non-epileptic groups (p<0.05). HR increase accompanied each individual dialeptic complex partial TLS (100 percent of the events, p<0.05) bur HR returned to baseline in the post-ictal phase. Ictal HR was not altered in the non-epileptic or simple partial TLS groups. Our findings suggest that ictal centrally mediated tachycardia is characteristic of dialeptic TLS (both tachycardia and bradycardia have been reported during TLS). This finding may be used as a criterion to distinguish dialeptic complex partial TLS from simple partial and non-epileptic dialeptic events.

A distinção entre eventos não epilépticos de epilépticos é difícil mesmo para neurologistas experientes. Analisamos 59 eventos dialéticos de 27 pacientes internados para monitorização por video-EEG para checar se a análise da frequência cardíaca (FC) poderia auxiliar na diferenciação de crises dialépticas parciais complexas de crises dialépticas parciais simples e eventos dialépticos não epilépticos. A freqüência cardíaca basal estava aumentada nos pacientes com crises parciais simples em comparação com o período basal dos grupos parcial complexa e não epiléptico (p<0,05). Houve aumento da freqüência cardíaca em cada crise dialéptica parcial complexa (100 por cento dos eventos, p<0,05), mas a FC retornou aos níveis basais na fase pós-ictal. A FC ictal não foi alterada nos grupos de crises não epiléticas e nos pacientes com crises parciais simples. Nossos achados sugerem que a taquicardia ictal com mediação central é característica de crises parciais complexas dialépticas (tanto taquicardia quanto bradicardia têm sido relatados durante crises temporais parciais complexas). Tal achado poderá ser utilizado como critério para diferenciar crises dialépticas parciais complexas de crises dialépticas parciais simples e eventos dialépticos não epilépticos.