Intractable Seizures and Limbic Encephalitis, Unaccounted Complications of Type 1 Diabetes Autoimmunity

Glutamic acid decarboxylase 65kD autoantibody (GAD65Ab) is frequently detected in patients with refractory epilepsy and stiff person syndrome (SPS). In contrast to T1D, the pathological role of GAD65Ab in neurological disorders is still debatable. As a result, the implementation of possible immunotherapy is usually delayed. This report presents two cases of GAD65Ab associated brain autoimmunity and their different management. We present clinical data and discuss management based on available evidence in the reviewed literature. Both cases presented with acute on chronic neurological symptoms and were GAD65Ab positive. Case 1, a 30-year-old man with a history of early-onset T1D at 14 months, followed by cryptogenic temporal epilepsy at 11 years of age, presented with intractable seizures. Case 2, a 48-year-old woman, presented with a history of recurrent severe headaches, cognitive impairment, decreased memory, and behavioral symptoms. GAD65Ab was detected in both patients’ sera. CSF GAD65Ab was only checked and positive in case 1. Case 2 was diagnosed with limbic encephalitis, treated with immunotherapy, and showed a remarkable clinical improvement. Case 1 with refractory epilepsy failed multiple AEDs and Responsive-Stimulator System (RNS) treatments. He was finally diagnosed with autoimmune epilepsy. The delay in diagnosis resulted in a lost opportunity for early immunotherapy. In conclusion, autoantibody screening and early initiation of immunotherapy should be considered to manage GAD65Ab associated neurological disorders.

Temporal Lobe Epilepsy and Psychiatric Comorbidity

Most focal seizures originate in the temporal lobe and are commonly divided into mesial and lateral temporal epilepsy, depending upon the neuronal circuitry involved. The hallmark features of the mesial temporal epilepsy are aura, unconsciousness, and automatisms. Symptoms often overlap with the lateral temporal epilepsy. However, the latter present a less evident psychomotor arrest, frequent clones and dystonic postures, and common focal to bilateral tonic–clonic seizures. Sclerosis of the hippocampus is the most frequent cause of temporal lobe epilepsy (TLE). TLE is among all epilepsies the most frequently associated with psychiatric comorbidity. Anxiety, depression, and interictal dysphoria are recurrent psychiatric disorders in pediatric patients with TLE. In addition, these alterations are often combined with cognitive, learning, and behavioral impairment. These comorbidities occur more frequently in TLE with hippocampal sclerosis and with pharmacoresistance. According to the bidirectional hypothesis, the close relationship between TLE and psychiatric features should lead to considering common pathophysiology underlying these disorders. Psychiatric comorbidities considerably reduce the quality of life of these children and their families. Thus, early detection and appropriate management and therapeutic strategies could improve the prognosis of these patients. The aim of this review is to analyze TLE correlation with psychiatric disorders and its underlying conditions.

Functional Connectivity as a Potential Mechanism for Language Plasticity

Background and Objectives:Task-fMRI is a clinical tool for language lateralization, but has limitations, and cannot provide information about network-level plasticity. Additional methods are needed to improve the precision of presurgical language mapping. We investigate language resting-state functional connectivity(RS fMRI;FC) in typically developing children and children with epilepsy. Our objectives were to: 1)Understand how FC components differ between typically developing (TD) children and those with epilepsy. 2)Elucidate how the location of disease (frontal/temporal epilepsy foci) effects FC. 3)Investigate the relationship between age and FC.Methods:Sample includes 55 TD children (mean age 12 years, range 7-18, and 31 patients with focal epilepsy (mean age 13) with same range. All subjects underwent RS fMRI. Using a bilateral canonical language map as target, vertex wise intra-hemispheric FC map and inter-hemispheric FC map for each subject were computed and thresholded at top 10% to compute an FC laterality index (FCLI;((L-R)/(L+R)) of the frontal and temporal regions for both integration (intra-hemispheric FC; FCLIi) and segregation (Inter-hemispheric FC; FCLIs) maps.Results:We found FC differences in the developing language network based on disease, seizure foci location, and age. Frontal and Temporal FCLIi was different between groups (t(84)=2.82, p<.01; t(84)=4.68, p<.01, respectively). Frontal epilepsy foci had the largest differences from TD (Cohen’s D Frontal FCLIi=0.84, FCLIs=0.51; Temporal FCLIi=1.29). Development and disease have opposing influences on the laterality of FC based on groups. In the frontal foci group, FCLIi decreased with age (r=-0.42), whereas in the temporal foci group FCLIi increased with age (r=0.40). Within the epilepsy group, increases in right frontal integration FCLI relates to increased right frontal task activation in our mostly left language dominant group (r=.52, p<.01). Language network connectivity is associated with higher verbal intelligence in children with epilepsy (r=.45, p<.05).Discussion:These findings lend preliminary evidence that FC reflects network plasticity in the form of adaptation and compensation, or the ability to recruit support and reallocate resources within and outside of the traditional network to compensate for disease. FC expands on task-based fMRI and provides complementary and potentially useful information about the language network that is not captured using task-based fMRI alone.

P.125 Discriminating sharp-wave ripples and interictal epileptiform discharges in patients with mesial temporal epilepsy using intracranial EEG recordings

Background: Interictal epileptiform discharges (IEDs) are known as epilepsy biomarkers for seizure detection, and It is essential for clinicians to detect them from from physiological events with similar temporal frequency characteristics. Methods: We analyzed the SEEG recordings obtained from patients with medically-resistant epilepsy (MRE) implanted with DE at the Western University Hospital Epilepsy Unit. The data were cleaned, denoised, montaged and segmented based on the clinical annotations, such as sleep intervals and observed Ictals. For event detection, the signal waveform and its power were extracted symmetrically in non-overlapping intervals of 500 ms. Each waveform’s power across all detected spikes was computed and clustered based on their energy distributions. Results: The recordings included thirteen sessions of 24 hours of extracellular recordings from two patients, with 312 hours extracted from four hippocampus electrodes anterior and posterior hippocampus. Our results indicate IEDs carrying the most different characteristics in the bands [25-75] Hz; SWR, on the other hand, are distributed between [80-170] Hz. Conclusions: Our algorithm detected and successfully distinguished IED from SWRs based on their carrying energy during non-sleep periods. Also, the most powerful spectral features that they were distinguished from occur in [15-30] Hz and [75-90] Hz.

Ictal Syncope or Isolated Syncope? A case report highlighting the overlap

Background Ictal bradyarrhythmia is a rare condition defined by temporal lobe epilepsy resulting in bradycardia or asystole and can result in syncope. This needs to be differentiated from isolated syncope in patients with seizure disorder, as treatment strategies differ. Case Summary A 50-year-old female with well-controlled temporal epilepsy and a 20-year seizure-free period presented to her neurologist with abrupt onset of sudden drop attacks, thought to be ictal events with potential underlying ictal bradyarrhythmia and was initially treated with escalation of anti-convulsant therapy. However, her workup was consistent with a diagnosis of cardiac syncope. She subsequently underwent successful insertion of a pacemaker, with no recurrence of her presenting episodes at a 13-month Follow-up. Discussion Ictal syncope and isolated syncope may share a common terminal pathway and may have similar presenting symptoms. In patients with known seizure disorder, loss of consciousness may be attributable to epileptic events, ictal syncope, or isolated syncope—which can be difficult to differentiate. This case highlights the ambiguous nature of such episodes and the importance of simultaneous EEG/ECG monitoring, as this can have implications on treatment.

QT INTERVAL IN TEMPORAL LOBE EPILEPSY VERSUS NON TEMPORAL LOBE EPILEPSY

Introduction Background SUDEP is leading cause of mortality in patients with chronic refractory epilepsy. Despite several epidemiological studies, case series , monitored and witnessed SUDEP the exact mechanism is not proposed Objective This work was carried out to assess QT interval prolongation in epilepsy and whether there’s a difference in QT interval prolongation between temporal epilepsy and non-temporal epilepsy. Patients and methods This study was conducted on 100 patients, 50 aged and sex matched healthy controls who underwent a prolonged (6 to 24 hours) 22 channel computerized EEG monitor with 10-20 system electrode placement and 12 lead electrocardiogram (25 millisecond speed). QT, QTd and QTc using Bazzet’s formulae were calculated. Results The results showed statistically significant difference prolongation of QT interval in epilepsy particularly temporal lobe epilepsy. Conclusion Significant prolongation of QT interval in epilepsy patients (11% suffered pathological prolonged QT). Marked prolongation of QTc and QTd in temporal lobe epilepsy over non temporal group.