International recommendation for a comprehensive neuropathologic workup of epilepsy surgery brain tissue: A consensus Task Force report from the ILAE Commission on Diagnostic Methods
Epilepsy surgery is an effective treatment in many patients with drug-resistant focal epilepsies. An early decision for surgical therapy is facilitated by a magnetic resonance imaging (MRI––visible brain lesion congruent with the electrophysiologically abnormal brain region. Recent advances in the pathologic diagnosis and classification of epileptogenic brain lesions are helpful for clinical correlation, outcome stratification, and patient management. However, application of international consensus classification systems to common epileptic pathologies (e.g., focal cortical dysplasia [FCD] and hippocampal sclerosis [HS]) necessitates standardized protocols for neuropathologic workup of epilepsy surgery specimens. To this end, the Task Force of Neuropathology from the International League Against Epilepsy (ILAE) Commission on Diagnostic Methods developed a consensus standard operational procedure for tissue inspection, distribution, and processing. The aims are to provide a systematic framework for histopathologic workup, meeting minimal standards and maximizing current and future opportunities for morphofunctional correlations and molecular studies for both clinical care and research. Whenever feasible, anatomically intact surgical specimens are desirable to enable systematic analysis in selective hippocampectomies, temporal lobe resections, and lesional or nonlesional neocortical samples. Correct orientation of sample and the sample's relation to neurophysiologically aberrant sites requires good communication between pathology and neurosurgical teams. Systematic tissue sampling of 5-mm slabs along a defined anatomic axis and application of a limited immunohistochemical panel will ensure a reliable differential diagnosis of main pathologies encountered in epilepsy surgery.
The sensitivity and significance of lateralized interictal slow activity on magnetoencephalography in focal epilepsy
Effects of selective serotonin and norepinephrine reuptake inhibitors on depressive- and impulsive-like behaviors and on monoamine transmission in experimental temporal lobe epilepsy
Examine therapeutic potential of a selective serotonin reuptake inhibitor (SSRI) and a norepinephrine reuptake inhibitor (NERI) in an animal model of comorbidity between epilepsy, depression-like, and impulsive-like impairments.Methods
Epilepsy was induced in male Wistar rats by LiCl and pilocarpine. An SSRI fluoxetine (FLX), and an NERI reboxetine (RBX) were administered either alone or as a combination over 1 week. Depressive-like and impulsive-like behaviors were examined using the forced swim test. Fast scan cyclic voltammetry was used to analyze serotonergic transmission in the raphe nucleus (RN)–prefrontal cortex (PFC) pathway, and noradrenergic transmission in locus coeruleus (LC)-PFC, and LC-RN projections. Monoamine levels in PFC were measured using high-performance liquid chromatography (HPLC). Functional capacities of 5-HT1A receptors and α2A adrenoreceptors in PFC were analyzed by autoradiography.Results
Epileptic rats showed behavioral signs of depression and hyperimpulsivity, suppressed serotonergic and noradrenergic tones, decreased levels of serotonin (5-HT), and norepinephrine (NE); 5-HT1A receptor and α2A adrenoreceptors functions remained intact. FLX failed to improve behavioral deficits, but effectively raised 5-HT level and marginally improved RN-PFC serotonergic transmission. RBX reversed impulsive-like behavior, normalized content of NE and noradrenergic tone in LC-PFC and LC-RN. FLX-RBX combination fully reversed depressive-like behavior, and normalized RN-PFC serotonergic transmission. None of the treatment modified the function of 5-HT and NE receptors.Significance
Depressive- and impulsive-like behaviors in the pilocarpine model of epilepsy stem respectively from dysfunctions of serotonergic and noradrenergic ascending pathways. At the same time, epilepsy-associated depression is SSRI resistant. The finding that an SSRI-NERI combination exerts antidepressant effect, along with RBX-induced improvement of LC-RN noradrenergic transmission point toward the involvement of LC-RN noradrenergic input in enabling therapeutic potential of FLX. Medications that improve serotonergic and noradrenergic transmission, such as serotonin–norepinephrine reuptake inhibitors may be effective in treating epilepsy-associated SSRI-resistant depression, as well as concurrent depression and attention-deficit/hyperactivity disorder (ADHD).
Seizures as presenting and prominent symptom in chorea-acanthocytosis with c.2343del VPS13A gene mutation
The aim of the study was to characterize the clinical features of nine patients in three families with chorea-acanthocytosis (ChAc) sharing the same rare c.2343del mutation in the VPS13A gene.Methods
Genetic test results, clinical description, magnetic resonance imaging (MRI), and electroencephalography (EEG), as well as laboratory results are summarized.Results
ChAc is a rare genetic disorder characterized by hyperkinetic movements, seizures, cognitive decline, neuropsychiatric symptoms, and acanthocytes on peripheral blood smear. This unique cohort of nine patients is characterized by seizures as a first and prominent symptom. In our patients, other features of ChAc appeared later, including tics, other movement disorders, dysarthria, and mild to moderate cognitive decline.Significance
Patients with chorea-acanthocytosis carrying the described rare mutation can present with focal, treatment-resistant seizures.
Heart rate variability in untreated newly diagnosed temporal lobe epilepsy: Evidence for ictal sympathetic dysregulation
To compare heart rate variability (HRV) parameters in newly diagnosed and untreated temporal lobe epilepsy (TLE) between the interictal, preictal, ictal, and postictal states.Methods
HRV parameters were extracted from single-lead electrocardiography data collected during video–electroencephalography (EEG) recordings from 14 patients with newly diagnosed TLE in a resting, awake, and supine state. HRV parameters in the time and frequency domains included low frequency (LF), high frequency (HF), standard deviation of all consecutive R wave intervals (SDNN), and square root of the mean of the sum of the squares of differences between adjacent R wave intervals (RMSSD). Cardiovagal index (CVI), cardiosympathetic index (CSI), and approximate entropy (ApEn) were also studied.Results
Frequency domain analysis showed significantly higher preictal, ictal, and postictal LF/HF ratio compared to the interictal state. Similarly, the LF component increased progressively and was significantly higher during the ictal state compared to interictal and preictal states. RR interval values were lower in the ictal state compared to basal and preictal states and in the postictal state compared to the preictal state. Interictal RMSSD was significantly higher compared to all other states, and ictal SDNN was significantly higher compared to all other states. Ictal CSI was significantly higher compared to preictal and interictal states, whereas preictal CVI was lower than in basal and ictal states. In addition, ictal ApEn was significantly lower than interictal and preictal ApEn. Interictal CVI was lower in left TLE compared to right TLE. In addition, in left TLE, ictal CVI was higher than interictal CVI, whereas in right TLE, CVI was lower in the preictal state compared to all other states.Significance
Our data suggest an ictal sympathetic overdrive with partial recovery in the postictal state. Higher sympathetic tone and vagal tone imbalance may induce early autonomic dysfunction and increase cardiovascular risk in patients affected by TLE.