Managing the patient with epilepsy and renal impairment.

PURPOSE: Epilepsy affects more than 50 million people worldwide and its management can be complicated by comorbidities such as impaired renal function. To optimize epilepsy control in patients with kidney disease, clinicians need to be aware of how antiepileptic drugs (AEDs) are affected by impaired renal function and how the kidneys are affected by epilepsy management strategies. Herein we present a narrative review with systematic literature search to discuss the use of AEDs in patients with renal impairment, including those undergoing dialysis, as well as the nephrotoxic effects of some AEDs. We finally conclude the article by providing practical tips about our approach to using AEDs in the setting of renal disease. METHODS: A literature search targeting epilepsy management in patients with kidney disease was performed in MEDLINE database (1946 to 7th Jan 2019). RESULTS: A total of 1193 articles were found. After duplicate removal, title and abstract screening followed by full text screening, a total of 110 references were included in this review. Additional information was included from drug product monographs. CONCLUSION: The disposition of AEDs can be altered in patients with impaired renal function, leading to a higher risk of AED toxicity or therapy failure. Renal dosage adjustment and close monitoring is recommended. Although AED-induced nephrotoxicity is rare, it is unpredictable and clinicians need to vigilant about this possibility. In addition, AEDs renal adverse reactions and renal drug interactions should be considered when selecting an AED.

Automated detection of focal cortical dysplasia using a deep convolutional neural network.

Focal cortical dysplasia (FCD) is one of the commonest epileptogenic lesions, and is related to malformations of the cortical development. The findings on magnetic resonance (MR) images are important for the diagnosis and surgical planning of FCD. In this paper, an automated detection technique for FCD is proposed using MR images and deep learning. The input MR image is first preprocessed to correct the bias field, normalize intensities, align with a standard atlas, and strip the non-brain tissues. All cortical patches are then extracted on each axial slice, and these patches are classified into FCD and non-FCD using a deep convolutional neural network (CNN) with five convolutional layers, a max pooling layer, and two fully-connected layers. Finally, the false and missed classifications are corrected in the post-processing stage. The technique is evaluated using images of 10 patients with FCD and 20 controls. The proposed CNN shows a superior performance in classifying cortical image patches compared with multiple CNN architectures. For the system-level evaluation, nine of the ten FCD images are successfully detected, and 85% of the non-FCD images are correctly identified. Overall, this CNN based technique could learn optimal cortical (texture and symmetric) features automatically, and improve the FCD detection.

Critical Care Management of Status Epilepticus at a Tertiary Care University Hospital.

BACKGROUND: Status epilepticus (SE) is a neurological emergency associated with significant morbidity and mortality. The objective of this study was to review the critical care management of patients with SE focusing on antiepileptic drugs (AEDs) as well as to determine the optimal dosing strategies of phenytoin (PHT) and predictors of its effectiveness. METHODS: A retrospective chart review of adult patients with SE admitted to the University of Alberta Hospital, Canada, was conducted. RESULTS: Fifty-six admissions were included. Benzodiazepines (BDZs) were initially given in 89% of our patients. Following BDZs, PHT and levetiracetam were the most commonly initiated AEDs as first- and second-line agents and were deemed effective in 30/44 and 5/11 patients, respectively. Patients who received a PHT loading dose (LD) of 1000 mg were less likely to reach target levels compared with a weight-based LD ≥15 mg/kg (29% vs. 60%). Likewise, patients who received a maintenance dose (MD) of 300 mg/day were less likely to reach target compared with 400 mg/day or >5 mg/kg per day; however, this did not reach statistical significance. Three variables were found to be associated with PHT effectiveness: tonic-clonic SE (OR 5.01, 95% CI 1.02-24.7, p = 0.048), history of seizures and BMI <30 kg/m2 (OR 0.16, 95% CI 0.03-1.07, p = 0.059). CONCLUSIONS: Further studies of the predictors of PHT effectiveness, specifically obesity, are necessary to help individualize care. Finally, we suggest that PHT should be loaded according to the guidelines as 20 mg/kg followed by an MD of at least 400 mg/day or >5 mg/kg per day.

Gérer les soins intensifs prodigués à des patients atteints de l'état de mal épileptique qui ont été admis dans un hôpital universitaire de niveau tertiaire Contexte: L'état de mal épileptique (status epilepticus) constitue une urgence neurologique associée à des taux notablement élevés de morbidité et de mortalité. L'objectif de cette étude a été d'examiner la gestion des soins intensifs prodigués à des patients atteints de cette complication en mettant l'accent sur des médicaments antiépileptiques. Nous avons aussi cherché à déterminer des stratégies optimales de posologie pour la phénytoïne et des indicateurs de son efficacité. Méthodes: Nous avons effectué un examen rétrospectif des dossiers de patients adultes atteints de l'état de mal épileptique qui ont été admis au University of Alberta Hospital (Canada). Résultats: Au total, cinquante-six patients admis ont été inclus dans cette étude. Soulignons que des benzodiazépines (BZD) ont été donnés à 89 % de ces patients dès leur admission. Une fois ces médicaments administrés, la phénytoïne et le lévétiracétam se sont avérés les antiépileptiques les plus couramment utilisés comme traitements de première intention et de seconde intention. À cet égard, la phénytoïne a été jugée efficace chez 30 patients sur 44 tandis que le lévétiracétam l'a été chez 5 patients sur 11. Les patients à qui l'on avait administré une dose d'attaque (loading dose) de 1000 mg de phénytoïne étaient moins susceptibles d'atteindre des cibles de traitement en comparaison avec une dose d'attaque fondée sur le poids (≥ 15 mg/kg ; 29 % contre 60 %). De même, les patients ayant reçu une dose de maintien de 300 mg par jour étaient moins susceptibles d'atteindre des cibles de traitement en comparaison avec une dose de 400 mg par jour ou > 5 mg/kg par jour. Cela dit, ces résultats n'ont pas revêtu de signification statistique valable. Il a été constaté par ailleurs que trois variables pouvaient être associées à l'efficacité de la phénytoïne: une manifestation tonico-clonique de l'état de mal épileptique (rapport des cotes 5,01; IC 95 % 1,02­24,7; p = 0,048), des antécédents de crises convulsives et un IMC < 30 kg/m2 (rapport de cotes 0,16; IC 95 % 0,03­1,07; p = 0,059). Conclusions: Des études plus poussées portant sur les prédicteurs de l'efficacité de la phénytoïne, l'obésité en particulier, demeurent nécessaires pour contribuer à individualiser les soins prodigués. Enfin, nous suggérons aussi que les doses d'attaque de phénytoïne devraient respecter une ligne directrice de 20 mg/kg et être suivies par des doses de maintien d'au moins 400 mg par jour ou >5 mg/kg par jour.

Computer-aided diagnosis of cavernous malformations in brain MR images.

Cavernous malformation or cavernoma is one of the most common epileptogenic lesions. It is a type of brain vessel abnormality that can cause serious symptoms such as seizures, intracerebral hemorrhage, and various neurological disorders. Manual detection of cavernomas by physicians in a large set of brain MRI slices is a time-consuming and labor-intensive task and often delays diagnosis. In this paper, we propose a computer-aided diagnosis (CAD) system for cavernomas based on T2-weighted axial plane MRI image analysis. The proposed technique first extracts the brain area based on atlas registration and active contour model, and then performs template matching to obtain candidate cavernoma regions. Texture, the histogram of oriented gradients and local binary pattern features of each candidate region are calculated, and principal component analysis is applied to reduce the feature dimensionality. Support vector machines (SVMs) are finally used to classify each region into cavernoma or non-cavernoma so that most of the false positives (obtained by template matching) are eliminated. The performance of the proposed CAD system is evaluated and experimental results show that it provides superior performance in cavernoma detection compared to existing techniques.

No Further Yield of Ambulatory EEG for Epileptiform Discharges Beyond 13 Hours.

INTRODUCTION: This study aimed at evaluating the value added by 24-hour ambulatory EEG (AEEG) by comparing the presence of epileptiform discharges (EDs) between the first 30 minutes of recording versus the following 23.5 hours. MATERIALS AND METHODS: A retrospective review of AEEGs of subjects divided into two groups, epilepsy and undiagnosed episodes of loss of consciousness, was conducted. AEEGs were divided into early EEG (E-EEG) (first 30 minutes) and extended EEG (remaining 23.5 hours). Extended EEGs were further divided into segments (S): 31st minute to 8th hour (SI), 9th to 16th hours (SII) and 17th to 24th hours (SIII). Each consecutive segment was reviewed to identify new EDs not seen previously. RESULTS: Fifty-seven AEEGs were included, the median age being 36.3 years, the range being 18.7 to 78.6 years. There were 38 (66.6%) females. The collective yield of AEEG for detecting EDs was 19/57 (33.4%). The yield of E-EEG of new EDs was 5/57 (9%). During extended EEG, the distribution of EDs was as follows: SI, 12/55 (21.8%); SII, 2/43 (4.6%); and SIII 0/41 (0%). The yield, however, did not increase beyond the 13th hour. In undiagnosed episodes of loss of consciousness group (11), yield was 0/11 in all segments. CONCLUSIONS: (1) There was no value added for yield of EDs by extending the EEG recording beyond 13 hours in epilepsy group. (2) The probability of capturing EDs is negligible if the clinical history does not clearly support the diagnosis of seizure or epilepsy.

Fully automated segmentation of corpus callosum in midsagittal brain MRIs.

In the diagnosis of various brain disorders by analyzing the brain magnetic resonance images (MRI), the segmentation of corpus callosum (CC) is a crucial step. In this paper, we propose a fully automated technique for CC segmentation in the T1-weighted midsagittal brain MRIs. An adaptive mean shift clustering technique is first used to cluster homogenous regions in the image. In order to distinguish the CC from other brain tissues, area analysis, template matching, in conjunction with the shape and location analysis are proposed to identify the CC area. The boundary of detected CC area is then used as the initial contour in the Geometric Active Contour (GAC) model, and evolved to get the final segmentation result. Experimental results demonstrate that the proposed technique overcomes the problem of manual initialization in existing GAC technique, and provides a reliable segmentation performance.

Establishment of a comprehensive epilepsy center in pakistan: initial experiences, results, and reflections.

Background. Developing countries, home to 80% of epilepsy patients, do not have comprehensive epilepsy surgery programs. Considering these needs we set up first epilepsy surgery center in Pakistan. Methods. Seventeen teleconferences focused on setting up an epilepsy center at the Aga Khan University (AKU), Karachi, Pakistan were arranged with experts from the University of Alberta Hospital, Alberta, Canada and the University of West Virginia, USA over a two-year period. Subsequently, the experts visited the proposed center to provide hands on training. During this period several interactive teaching sessions, a nationwide workshop, and various public awareness events were organized. Results. Sixteen patients underwent surgery, functional hemispherectomy (HS) was done in six, anterior temporal lobectomy (ATL) in six, and neuronavigation-guided selective amygdalohippocampectomy (SAH) using keyhole technique in four patients. Minimal morbidity was observed in ATL and, SAH groups. All patients in SAH group (100%) had Grade 1 control, while only 5 patients (83%) in ATL group, and 4 patients (66%) in HS group had Grade 1 control according to Engel's classification, in average followups of 12 months, 24 months and 48 months for SAH, ATL, and HS, respectively. Conclusion. As we share our experience we hope to set a practical example for economically constrained countries that successful epilepsy surgery centers can be managed with limited resources.

Telemedicine and epilepsy care - a Canada wide survey.

BACKGROUND: Canadian provinces boast one of the most sophisticated telemedicine infrastructures in the world. Feasibility of epilepsy care through telemedicine is established, but its use by practicing neurologists is unknown. The Canadian League against Epilepsy's telemedicine task force conducted this study to understand the perceptions, barriers and usage of telemedicine in epilepsy care. METHODS: Using a 14 item questionnaire we prospectively surveyed all the epileptologists across Canada with regards to current use, perceived benefits and barriers to the use of telemedicine. The survey was mailed out to 76 neurologists who had a primary interest in epilepsy. RESULTS: We received 39 responses (54.1%) spanning seven provinces. Majority of the responders were 50 years and over (56.4%). Although 61.5% of the physicians acknowledged a need for tele-epilepsy services, the majority (64.1%) had not used telemedicine. The most common forms of technology were videoconferencing and telephone but some physicians had also used email. Telemedicine was mainly used for clinical and educational purposes. 79.5% of physicians had access to videoconferencing equipment and 61.5% assessed that there was a need/use for clinical telehealth. The main perceived obstacles in the use of telemedicine were: lack of infrastructure support and remuneration problems followed by limitations in clinical examination. CONCLUSIONS: Although widely available, telemedicine is under-utilized in epilepsy care. Most of the obstacles can be easily fixed and overcome through education and simple interventions. Partnering of epilepsy centers across Canada in the development of a comprehensive national telemedicine network would create an excellent opportunity to expand epilepsy care.

Acetaminophen toxicity with concomitant use of carbamazepine.

Acetaminophen is a widely used analgesic that can cause acute liver failure when consumed above a maximum daily dose. Certain patients may be at increased risk of hepatocellular damage even at conventional therapeutic doses. We report a case of a 34-year-old man on carbamazepine for complex partial seizures who developed acute liver and renal failure on less than 2.5 grams a day of acetaminophen. This raises caution that patients on carbamazepine should avoid chronic use of acetaminophen, and if required use at lower doses with vigilant monitoring for signs of liver damage.

Experiences from an international tele-epilepsy collaboration.

OBJECTIVE: Our main objective was to use videoconferencing as a primary means to: a) assist in launching an epilepsy surgery program in Pakistan; 2) participate in case conferences on complex epilepsy patients in each country. METHODS: Extensive testing using both point to point and bridged integrated service digital network (ISDN) and internet protocol (IP) connections was carried out using bandwidths of 384-768 kilobits per second (kbps). Videoconferences between sites were arranged two to three weeks in advance and connections were tested a day prior to the scheduled conference. Sharing of PowerPoint presentations, neuroimaging and video-EEG was available to all sites. Discussions centered on patients with medically refractory epilepsy. RESULTS: Between July 2006 and June 2008, 17 sessions were booked. Five of these conferences bridged in specialists from West Virginia University. Most successful connections occurred using IP point to point calls or a bridge connecting end points through IP at 512 kbps. We conducted three surgeries for medically refractory temporal lobe epilepsy in Pakistan. At follow-up in January 2009, two patients have been seizure free and one had two breakthrough seizures after sudden unsupervised discontinuation of Levetiracetam. CONCLUSION: Our international tele-epilepsy collaboration has proven feasible and valuable to all participants. Our experience suggests considerable thought and preparation are needed before a teleconference to ensure its success. We provide a recipe to set-up similar telemedicine collaborations. Considerations include time zone differences, equipment type, interoperability between endpoints, connection capabilities, bandwidth availability, and backup plans for unsuccessful connections. Telemedicine can facilitate epilepsy care around the world, identifying with the concept of a "Global Health Village".

Oculogyric crisis masquerading as ventriculoperitoneal shunt dysfunction.

Oculogyric crisis (OGC) is an underrecognized oculodystonic reaction associated with several medications including carbamazepine. The authors present a patient who had presented to the emergency department on multiple occasions with a questionable ventriculoperitoneal (VP) shunt dysfunction. Symptoms included nausea, vomiting, altered level of consciousness, ataxia, and vertical eye deviation. The patient underwent multiple revisions of the VP shunt with transient and questionable improvement. During her visit to the neurology clinic, OGC from carbamazepine was suspected, and the dose was reduced. The patient has been completely asymptomatic for the past 18 months. The authors report this case to increase the awareness of carbamazepine-induced OGC as one of the differential diagnoses for VP shunt dysfunction.

Pearls & Oy-sters: selective postictal aphasia: cerebral language organization in bilingual patients.

BACKGROUND: Ictal and postictal language dysfunction is common and strongly predictive of language laterality in monolingual patients. For bilingual patients, selective dysfunction has been reported for a single language with focal cerebral lesions, electrical brain stimulation, and intracarotid sodium amytal. METHODS: Two right-handed Ukrainian-English bilingual patients with left perisylvian structural lesions, late onset complex-partial seizures, and postictal aphasia for English are presented and discussed with regard to mechanisms of selective aphasia and factors contributory to language lateralization in bilingual patients. RESULTS: Ukrainian was the native language of both patients with English acquired after 7 years of age. Regular/video-EEG showed left temporal epileptogenesis. A 56-year-old man, who had a left hemorrhagic stroke at age 50 and had not spoken Ukrainian for 40 years, was unable to speak English for approximately 20 minutes postictally but had global preservation of Ukrainian. A 71-year-old woman, who had a left temporal epidermoid cyst and had not spoken Ukrainian since childhood, had 10- to 15-minute postictal expressive aphasia in English but not Ukrainian and preservation of comprehension in both languages. CONCLUSIONS: These cases are instructive and consistent with the literature on cerebral organization of language in bilingual individuals. For both patients, postictal aphasia with preservation of Ukrainian is consistent with findings from clinical and experimental studies indicating that later age of second language acquisition (>6 years) rather than language proficiency is a primary factor in language laterality. Second, global aphasia in the man with a late lesion vs expressive aphasia with preservation of comprehension of English in the woman with a prenatal/early lesion is consistent with the atypical language laterality described for individuals with left-sided lesions sustained prior to age 5. Although neither Wada test nor fMRI was done to assure left hemisphere laterality of spoken Ukrainian and English, this is probable, and the selective postictal aphasia observed for both patients is consistent with the differential intrahemispheric organization reported for the two languages of bilingual individuals. Possible mechanisms of selective postictal aphasia, e.g., active inhibition, and differences in language networks in bilingual patients are discussed.

Treatment adherence and outcomes in the management of convulsive status epilepticus in the emergency room.

PURPOSE: According to published literature status epilepticus (SE) is associated with 7-39% mortality. Timely management is one variable that potentially influences the outcome. We sought to review the process of acute management of SE at the University of Alberta Hospital and correlate outcome with adherence to a recommended treatment protocol. METHODS: We identified 86 patients 18 years of age or older who presented with convulsive SE to our emergency room between 2000 and 2004. We defined SE as continuous convulsive activity for 30 or more minutes or >or= 2 convulsions with incomplete recovery in the interim. Information was collected pertaining to etiology, epidemiology, and management. We then reviewed the relationship of the treatment protocol in terms of mortality and morbidity. RESULTS: Forty five patients were included. There were 18 males and 27 females with a mean age of 45 years; 80% were known to have epilepsy. Sub-therapeutic drug levels were found in the majority 60%; benzodiazepines (diazepam 81% and lorazepam 19%) were the first line agent in 93.3% mostly initiated by paramedics (EMS); 48.9% of patients required intubation and 26.7% required admission to intensive care. Four patients died. Control of convulsive SE was obtained sooner for patients in whom therapy was administered according to the recommended time frame (p