Feyissa, Anteneh M.

Background: The diagnostic issue of paroxysmal spells, including epileptic seizure (ES) mimics, is one that neurologists frequently encounter. This review provides an up-to-date overview of the most common causes of ES mimics encountered in the outpatient setting. Review Summary: Paroxysmal spells are characterized by changes in awareness, attention, perception, or abnormal movements. These can be broadly classified as ES and nonepileptic spells (NES). NES mimics ES but are distinguished by their symptomatology and lack of epileptiform activity on electroencephalography. NES may have psychological or physiological underpinnings. Psychogenic non-ES are the most common mimics of ES. Physiological causes of NES include syncope, cerebrovascular, movement, and sleep-related disorders. Conclusions: Distinguishing NES from ES at times may be challenging even to the most experienced clinicians. However, detailed history with an emphasis on the clinical clues, including taking a moment-by-moment history of the event from the patient and observers and physical examination, helps create an appropriate differential diagnosis to guide further diagnostic testing. An accurate diagnosis of NES prevents iatrogenic harm, including unnecessary exposure to antiseizure medications and overuse of health care resources. It also allows for the correct specialist referral and appropriate treatment.

While abnormalities of the hippocampus have been well characterized in temporal lobe epilepsy, various additional temporal lobe abnormalities have also been described. One poorly understood entity, the so-called temporal pole blurring (TPB), is one of the more frequently described neocortical abnormalities in TLE and is thought to represent dysmyelination and axonal loss due to chronic electrical perturbations in early age-onset temporal lobe epilepsy. In this study, we describe the first reported cases of TPB diagnosed by a recently described MRI sequence known as 3D Edge-Enhancing Gradient Echo (3D-EDGE), which has an effective “myelin weighting” making it exquisitely sensitive to this temporal pole dysmyelination. The value of detection of TPB lies in lateralizing seizure onset, as well as predicting a lower baseline neuropsychological performance compared to temporal lobe epilepsy without TPB. Additionally, it is critical to not mistake TPB for alternative diagnoses, such as focal cortical dysplasia or neoplasm.

ABSTRACTDespite advancements in the neurophysiology of language and presurgical evaluation for epilepsy surgery, there is a paucity of information in the literature regarding presurgical evaluation of multilingual patients. We present a case of a 52‐year‐old right‐handed woman with refractory epilepsy who was fluent in six languages and underwent subsequent trilingual presurgical evaluation which included neuropsychological testing, Wada testing, functional magnetic resonance imaging (fMRI), and electrocortical stimulation. These studies suggested a seizure focus in the left temporal lobe and language localization that was predominantly right‐hemispheric; she subsequently underwent left temporal laser interstitial thermal therapy without clinical disturbance in language function while remaining seizure‐free. A multidisciplinary effort was integral in providing an optimal outcome for this patient.

AbstractGlutamic acid decarboxylase 65‐kilodalton isoform (GAD65) antibodies have been associated with multiple nonneurological and neurological syndromes including autoimmune epilepsy (AE). Although immunotherapy remains the cornerstone for the treatment of AE, those with GAD65 Ab‐associated AE (GAD65‐AE) remain refractory to immunotherapy and antiseizure medication (ASM). Outcomes of epilepsy surgery in this patient population have also been unsatisfactory. The role of neuromodulation therapy, particularly direct brain‐responsive neurostimulation therapy, has not been previously examined in GAD65‐AE. Here, we describe four consecutive patients with refractory GAD‐65‐associated temporal lobe epilepsy (GAD65‐TLE) receiving bilateral hippocampal RNS System treatment. The RNS System treatment was well tolerated and effective in this study cohort. Three patients had a >50% clinical seizure reduction, and one patient became clinically seizure‐free following resective surgery informed by the RNS System data with continued RNS System treatment. In all four of our patients, the long‐term ambulatory data provided by the RNS System allowed us to gain objective insights on electrographic seizure lateralization, patterns, and burden as well as guided immunotherapy and ASM optimization. Our results suggest the potential utility of the RNS System in the management of ASM intractable GAD65‐AE.

Abstract OBJECTIVE Our goal is to identify new pathways perturbed in and which may lead to GRS. METHODS We collected brain transcriptome levels from healthy controls (n=5), patients with GRS (n=9), glioma without seizures (non-GRS, n=8), and idiopathic temporal lobe epilepsy (iTLE, n=7) using Illumina-based poly-A capture high-throughput RNA sequencing approach. Differential gene expression analysis was conducted to ascertain expression differences between the four groups. We identified molecular pathways enriched for differentially expressed genes (DEG) using Ingenuity Pathway Analysis. DEGs were defined as those with log2 fold change ≥ 2 and q-value < 0.01 when compared to GRS. RESULTS Principal component analysis revealed that diagnostic grouping was the main determinant of the transcriptome variance. We identified 212 DEGs in the GRS vs. non-GRS analysis. Among these, 108 genes were up-regulated and 104 genes were down-regulated. Among the genes that were down‐regulated, there was significant enrichment for those involved in acute phase response signaling and immune cell trafficking (e.g. H19, BMP5, CXCL8). Compared to iTLE samples, there were 1015 DEGs in the GRS samples. Among these 877 genes were up-regulated and 138 genes were down-regulated. There was significant enrichment for genes involved in cell-to-cell signaling among those that were either uniquely up‐regulated (e.g. NRK, RGS10, SLC4A4, and SELPLG) or down‐regulated in the GRS samples (e.g. SLC9A3 –Na+/H+ exchanger; SLC5A5-sodium-glucose co-transporter family). Further, two of the most down-regulated genes in samples with GRS, SCLC17A6- vesicular glutamate transporter 2 and FOSB, have previously been shown to be involved in glutamatergic transmission. CONCLUSIONS Our findings suggest that inflammation-related processes and alterations in cell-to cell signaling may underlie the pathogenesis of GRS. Our results also provide support for perturbations in glutamatergic transmission in GRS. Our findings require replication in larger human cohorts and functional experiments to explore the function of the genes perturbed in GRS.