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Paediatric epilepsy surgery in the posterior cortex: a study of 62 cases

Commented by Pr. Michael Duchowny, Associate Editor

Moving Forward By Moving Backward - Pediatric Epilepsy Surgery in the Posterior Cerebral Hemisphere
Intractable focal epilepsy that begins in early postnatal life is associated with long-term neuro-cognitive dysfunction. Recognition of this poor prognosis is a decisive factor in the early surgical referral with a goal of definitive cure. However, candidates for surgical therapy in the first decade of life have many different etiologies and multiple regions of involvement that are approached utilizing different anatomic procedures. Despite these challenges, temporal and extra-temporal pediatric epilepsy surgery data in very early life is now widely available and serves as a helpful guide; ... .

BOOK OF THE MONTH

Benjamin Cretin

A guide to diagnosing even the rarest types of consciousness loss in routine practice. Healthcare providers are frequently called upon to deal with patients who have experienced fainting with and without consciousness loss. The multitude of possible causes makes this very difficult to diagnose. This book lists all...

AHEAD OF PRINT

Are febrile seizures an indication for intermittent benzodiazepine treatment, and if so, in which cases?

Peter Camfield, Carol Camfield

∼40%, but excellent studies document that febrile seizures do not cause brain damage or deficits in cognition or behaviour. The risk of subsequent epilepsy is 2-4%. Prolonged febrile seizures are of concern because a child may later develop mesial temporal sclerosis and intractable epilepsy in rare cases. Most prolonged febrile seizures represent the first febrile seizure and cannot be anticipated. A first prolonged febrile seizure does not increase the risk of recurrence, but if there is a recurrence, it is more likely to be prolonged. Prevention of recurrent febrile seizures is difficult. Antipyretics are ineffective. Daily AED treatment is not often justified. Intermittent oral diazepam at the time of illness is not very successful and has significant side effects. The most optimistic study found that the number of subjects required to treat in order to prevent one recurrence was 14. Intermittent clobazam has fewer side effects than diazepam and may be somewhat effective. Rescue benzodiazepines given outside health care facilities may be effective in selected patients to prevent prolonged recurrences, although this has not been proven with rectal diazepam which has been more extensively studied than buccal or nasal midazolam. Currently, we suggest that, for children with febrile seizures, candidates for consideration for rescue benzodiazepines are those with a prolonged febrile seizure or poor access to medical care. It is possible that the use of a rescue benzodiazepine may alleviate severe parental anxiety, but this remains to be established.

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Outcome of status epilepticus. What do we learn from animal data?

Stéphane Auvin, Nina Dupuis

seizure. SE can represent an exacerbation of a preexisting seizure disorder, the initial manifestation of a seizure disorder, or an insult other than a seizure disorder. In humans, there are several differences between SE that occurs in adults and children. In adult patients, the mortality is high but the incidence is lower than in childhood. Experimental studies have been essential in helping clinicians describe SE, and since these early initial studies, further experimental studies have helped us to better understand the consequences of SE. Animal models of SE support the notion that SE induces brain damage and contribute to epileptogenesis. Laboratory models of SE in developing animals demonstrate age- and model-dependent propensity for brain injury and for epileptogenesis. The use of models with a double hit including a clinical relevant component to seizures provides data that allows us to further understand the contribution of early-life events in the future development of epilepsy. Using this approach, it has been shown that inflammation or a preexisting brain lesion enhance epileptogenesis in the developing brain. The use of models of SE also permits to establish that treatment to stop the seizure and/or the duration of the SE results in a decrease of SE induced cell injury. Preventing epileptogenesis remains an important goal to modify the development of comorbidities, and it still represents an area of research in need of much progress.

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Syndromes with very low risk of acute prolonged seizures

Thomas Bast

within five to ten minutes in the case of an acute prolonged seizure may preserve the patient from status epilepticus (SE). However, the risk of convulsive SE (CSE) differs markedly between patients depending on individual factors. This report summarizes the literature on risk factors for CSE in children with epilepsy and adolescents, and discusses the hypothesis that some electroclinical syndromes engender a very low risk of CSE. The most important risk factor for SE is the history of a previous event. The longer a patient lives without SE, the lower the risk will be. CSE occurs significantly less frequently in idiopathic epilepsies compared to epilepsies with symptomatic or unknown aetiology. It is very rarely observed in patients with (non-encephalopathic) idiopathic generalised epilepsies, i.e. childhood absence epilepsy or juvenile myoclonic epilepsy. However, non-compliance or inappropriate treatment may trigger CSE in these syndromes. A very low risk can be assumed for children with Rolandic epilepsy, while CSE occurs in a considerable percentage of patients with Panayiotopoulos syndrome. Although the risk of CSE in otherwise normal children with cryptogenic focal epilepsy is uncertain, it is presumably low under successful continuous medication. In conclusion, the choice for or against the prescription of rescue medication remains an individual decision. Consequently, for several electroclinical syndromes, a per se provision of rescue medication does not appear justified.

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What are the best ways to deliver benzodiazepines in children/patients with prolonged convulsive seizures?

Richard FM Chin

longer seizure durations may also increase risk of worse outcome. Thirty minutes of seizure activity is usually the time period used in longstanding definitions of CSE but it is not acceptable to wait for 30 minutes before treatment. Whilst intravenous therapy is best, pre-hospital treatment by a non-intravenous route is most practical in treating children. Benzodiazepines are the main class of first-line emergency antiepileptic drugs. This review will examine the available data on benzodiazepines according to: stability in the conditions of the emergency room services, drug absorption via non-intravenous route, clinical efficacy and safety, and ease of delivery and social acceptability.

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All Ahead Of Print

CURRENT ISSUE

Epileptic Disorders

Volume 16
Number 3,
September 2014

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Review article

Utility of electrocorticography in the surgical treatment of cavernomas presenting with pharmacoresistant epilepsy

Daniel San-Juan, Iván Cesár Díaz-Nuñez, Mónica Ojeda-Baldéz, Víctor Armando Barajas-Juárez, Iliana González-Hernández, Mario Alonso-Vanegas, David J. Anschel, Jesús Delgado de la Mora, Ned Merari Davila-Avila, Carlos Alfonso Romero-Gameros, Rafael Vázquez-Gregorio, Axel Hernández-Ruíz

literature on the utility of electrocorticography (ECoG) in cerebral cavernoma surgery. Methods. We searched studies in PubMed, MedLine, Scopus, Web of Science, and Google Scholar (from January 1969 to December 2013) using the keywords “electrocorticography” or “ECoG” or “prognosis” or “outcome” and “cavernomas”. Original articles that reported utility of ECoG in epilepsy surgery were included. Four review authors independently selected the studies, extracted data, and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines, and Jadad Scale. A meta-analysis was not possible due to methodological, clinical, and statistical heterogeneity of included studies. We analysed six articles with a total of 219 patients. Results. The most common surgical approach was lesionectomy using ECoG in the temporal lobe with Engel I outcome range from 72.7 to 100%. Conclusions. Small controlled studies suggest that ECoG-guided resection offers the best functional results in seizure control for subjects undergoing cavernoma surgery, especially in the temporal lobe.

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Seminars in Epileptology

History of epilepsy: nosological concepts and classification

Peter Wolf

are reflected by terminology and classification. Even the earliest written documents reveal awareness that there are multiple forms of epilepsy, and it is surprising that they should be included under the same disease concept, perhaps because the generalised tonic-clonic seizure served as a common denominator. The Hippocratic doctrine that the seat of epilepsy is in the brain may be rooted in earlier knowledge of traumatic seizures. Galenus differentiated cases where the brain was the primary site of origin from others where epilepsy was concomitant with illness in other parts of the body. This laid the fundament for the distinction between idiopathic and symptomatic epilepsies, the definition of which changed considerably over time. The description of the multiple seizure types as they are known at present started in the late 18th century. Attempts to classify seizure types began in the late 19th century, when Jackson formulated a comprehensive pathophysiological definition of epilepsy. Electroencephalography supported a second dichotomy, between seizures with localised onset and others with immediate involvement of both hemispheres which became known as “generalised”. In recent years, advanced methods of studying brain function in vivo, including the generation of both spontaneous and reflex epileptic seizures, have revolutionised our understanding of focal and “generalised” human ictogenesis. Both involve complex neuronal networks which are currently being investigated.

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Intraoperative ElectroCorticoGraphy (ECog): indications, techniques, and utility in epilepsy surgery

Tong Yang, Shahin Hakimian, Theodore H. Schwartz

Literature was reviewed to obtain published results on using intraoperative ECoG techniques for the surgical treatment of medically intractable epilepsy of various underlying aetiologies. Results. General intraoperative ECoG techniques were described, including effects of anaesthetic agents on intraoperative ECoG signals. Use of intraoperative ECoG in temporal lobe epilepsy with mesial temporal sclerosis (MTS) is generally considered not necessary, whereas intraoperative ECoG in temporal lobe epilepsy without mesial temporal sclerosis may provide useful information. Intraoperative ECoG in extra-temporal epilepsy with structural lesions may facilitate resection, whereas the use of intraoperative ECoG in extra-temporal epilepsy without a structural lesion is more controversial. Conclusions. Intraoperative ECoG is a useful technique to be employed in surgical treatment of medically intractable epilepsy. However, its effectiveness may vary depending on the underlying pathological causes of the seizures.

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Original article

Stereo-electroencephalography (SEEG) in 65 children: an effective and safe diagnostic method for pre-surgical diagnosis, independent of age

Delphine Taussig, Mathilde Chipaux, Axel Lebas, Martine Fohlen, Christine Bulteau, Jessica Ternier, Sarah Ferrand-Sorbets, Olivier Delalande, Georg Dorfmüller

Methods. We retrospectively studied all SEEG performed between 2009 and 2011 in our centre. As SEEG can have several indications, the patients were classified into three categories, according to the probability of surgery. The contribution of SEEG to the final decision regarding surgery was evaluated for each category separately. We also compared the main demographic and surgical data of children younger than 5 years of age (Group 1; 21 children) with those older than five years of age at the time of investigation (Group 2; 44 patients). Results. MRI was not contributory in 20% of patients (9.5% in group 1; 25% in group 2). Electrical stimulations localised the motor area in all patients when performed (49% of patients), even in group 1 (62% of patients). SEEG led to surgery in 78% of patients (90.5% in group 1; 73% in group 2), after a second invasive investigation in 9.2 % of patients. The resection involved more than one lobe in 25% of patients (37% in group 1; 19% in group 2). Ultimately, 78% of patients with a low probability of having surgery before SEEG received surgery (88% in group 1). The surgical outcome of Engel class 1 was reported for 67% of patients (79% of patients in group 1 and 59% in group 2). No complications occurred. Conclusion. SEEG in children is safe and useful, and the surgical outcome in younger children is as good as, or sometimes even better than, that in older children. As a result of lower rates of complication and morbidity, SEEG appears to be more appropriate, in comparison to subdural grids, in situations where it is unclear if patients will have surgery after an invasive investigation.

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Disconnective surgery in posterior quadrantic epilepsy: a series of 12 paediatric patients

Peng-Fan Yang, Zhen Mei, Qiao Lin, Jia-Sheng Pei, Hui-Jian Zhang, Zhong-Hui Zhong, Jun Tian, Yan-Zeng Jia, Zi-Qian Chen, Zhi-Yong Zheng

epilepsy and a unilateral posterior quadrant lesion based on MRI and functional imaging abnormality in the TPO region on one side. Methods. A retrospective review of data of 12 children who underwent TPO or PO disconnective surgery was carried out from September 2009 to September 2012. Three-dimensional surface reconstructions of MRI scans and intraoperative electrophysiological monitoring were used during surgery. Drugs were not discontinued after surgery in any patient. Results. The affected hemisphere was the left in seven patients and the right in five patients. The mean ages at seizure onset and at surgery were four years and 12.3 years, respectively. At the time of surgery, 3 children had atonic seizures, 4 had symptomatic epilepsy with focal seizures and alteration of conscioussness, 4 had secondarily generalised seizures, and 1 child had spasms and tonic seizures. All patients had developmental delay. A pure TPO disconnection was performed in 11 patients and a PO disconnection was performed in the remaining patient. On pathological examination, 3 patients were shown to have focal cortical dysplasia (FCD) Ib, 2 with FCD IIa, 5 with FCD IIb, 1 with gliosis, and 1 with gliosis plus FCD IIa. Following surgery, 2 patients had oedema; 1 required another operation to resect the occipital lobe. At a mean follow-up of 34.5 months, 9 patients (75%) were classified as Engel class I, 2 as Engel Class II, and 1 as Engel class III. All 12 children had contralateral hemianopia postoperatively and improvement in median IQ ( p=0.04) was reported three months postoperatively. Conclusions. With respect to the limits of a retrospective and relatively small sample size series TPO and PO disconnection are safe and effective motor-sparing epilepsy surgical procedures in selected patients with the epileptiform zone located in the posterior quadrant on one side.

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Time to relapse after epilepsy surgery in children: AED withdrawal policies are a contributing factor

Kim Boshuisen, Dieter Schmidt, Cuno S.P.M. Uiterwaal, Alexis Arzimanoglou, Kees P.J. Braun, TimeToStop Study Group

the persistence or re-emergence of epileptogenic pathology, and that early recurrences are associated with poor treatment response. Timing of antiepileptic drugs withdrawal policies, however, have never been taken into account when investigating time to relapse following epilepsy surgery. Methods. Of the European paediatric epilepsy surgery cohort from the “TimeToStop” study, all 95 children with postoperative seizure recurrence following antiepileptic drug (AED) withdrawal were selected. We investigated how time intervals from surgery to AED withdrawal, as well as other previously suggested determinants of (timing of) seizure recurrence, related to time to relapse and to relapse treatability. Uni- and multivariable linear and logistic regression models were used. Results. Based on multivariable analysis, a shorter interval to AED reduction was the only independent predictor of a shorter time to relapse. Based on univariable analysis, incomplete resection of the epileptogenic zone related to a shorter time to recurrence. Timing of recurrence was not related to the chance of regaining seizure freedom after reinstallation of medical treatment. Conclusion. For children in whom AED reduction is initiated following epilepsy surgery, the time to relapse is largely influenced by the timing of AED withdrawal, rather than by disease or surgery-specific factors. We could not confirm a relationship between time to recurrence and treatment response. Timing of AED withdrawal should be taken into account when studying time to relapse following epilepsy surgery, as early withdrawal reveals more rapidly whether surgery had the intended curative effect, independently of the other factors involved.

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Persistent frequent subclinical seizures and memory impairment after clinical remission in smoldering limbic encephalitis

Kyoko Kanazawa, Riki Matsumoto, Akihiro Shimotake, Masako Kinoshita, Akiko Otsuka, Osamu Watanabe, Keiko Tanaka, Ryosuke Takahashi, Akio Ikeda

clinical data, including video-EEG monitoring records, were analysed in two patients. Results. The two patients were positive for anti-voltage-gated potassium channel complex antibody and unspecified antineuronal antibody, respectively. The latter patient had small cell lung carcinoma. Both patients had memory impairment and clinical seizures. EEG showed frequent subclinical seizure patterns in the bilateral temporal regions. Subclinical seizure patterns and memory impairment persisted over one to two years after clinical seizure remission. Therapy (prednisolone and chemoradiation in the two patients, respectively) resulted in decreased occurrence of subclinical seizure patterns and memory improvement. Conclusions. EEG seizure patterns may persist years after clinical seizure remission in “smoldering” limbic encephalitis and lead to memory impairment.

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Quantitative MR and cognitive impairment in cryptogenic localisation-related epilepsy

Jacobus FA Jansen, Sylvie JM van der Kruijs, Mariëlle CG Vlooswijk, HJ Marian Majoie, Paul AM Hofman, Albert P Aldenkamp, Walter H Backes

We investigated, in a preliminary study, whether it is possible to detect cerebral biomarkers of cognitive impairment in patients with CLRE using sensitive quantitative MRI techniques. Neuropsychological assessment and quantitative 3.0 T MRI, comprising T2 relaxometry, diffusion tensor imaging, and spectroscopic imaging, were applied to 35 patients with CLRE and 21 healthy controls. Analysis included the left and right hippocampi, and frontal and temporal lobes. Differences between the groups and correlations with cognitive and clinical characteristics were assessed. Patients with epilepsy scored significantly worse on cognitive tasks compared to healthy controls. Significantly larger CSF fractions in the hippocampi and left temporal lobe, a longer T2 relaxation time in the left hippocampus, and a significantly higher concentration of glutamate/glutamine in the left frontal lobe were observed in patients with epilepsy. Moreover, poor memory performance was significantly correlated with larger CSF fractions in the right hippocampus and left temporal lobe in patients. In the temporal lobe, an association between subtle changes in morphology (indicative of atrophy) and memory performance was found, consistent with previous literature. These results may help to explain the alterations in brain functioning in patients with epilepsy.

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Multifocal dysembryoplastic neuroepithelial tumours associated with refractory epilepsy

Andrew I. Yang, Ayaz M. Khawaja, Leo Ballester-Fuentes, Svetlana D. Pack, Ziedulla Abdullaev, Nicholas J. Patronas, Sara K. Inati, William H. Theodore, Martha M. Quezado, Kareem A. Zaghloul

in both infra- and supra-tentorial locations, in a 23-year-old man with a coincident Type I Chiari malformation, presenting with medically refractory focal seizures. The extensive anatomical distribution of the lesions suggests a genetic component in their tumourigenesis.

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Osteoporosis is associated with antiepileptic drugs: a population-based study

Fang-Jen Wu, Shiow-Yunn Sheu, Herng-Ching Lin

study aimed to investigate the possible association between osteoporosis and epilepsy disease and AEDs therapy using a population-based dataset in Taiwan. We first identified 48,102 cases, ≥18 years of age, who received a first-time diagnosis of osteoporosis, and then randomly selected 144,306 controls. We used conditional logistic regression analyses to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) to compare a previous diagnosis of epilepsy between cases and controls. We found that of the 192,408 sampled subjects, epilepsy was found in 117 (0.24%) cases and 240 (0.17%) controls ( p<0.001). Cases were found to be more likely to have previously been diagnosed with epilepsy than controls (OR: 1.41, 95% CI: 1.11∼1.78, p<0.01), after taking confounders into consideration. Furthermore, we found that, compared to controls, the adjusted OR of cases in which enzyme-inducing AEDs had been prescribed was 2.06 (95% CI: 1.43∼2.95). A higher proportion of cases with prescribed NEIAED was also found (OR: 2.09, 95% CI: 1.49∼2.92) compared to controls. This study demonstrates that patients with osteoporosis were more likely to have epilepsy and receive EIAED or NEIAED treatment. For patients with epilepsy who take AEDs, attention should be paid to the adverse effects of osteoporosis.

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Obesity and its association with generalised epilepsy, idiopathic syndrome, and family history of epilepsy

Lady D Ladino, Lizbeth Hernández-Ronquillo, José F. Téllez-Zenteno

and data from a survey to assess physical activity in a sample of PWE from an epilepsy clinic. Methods. Between June of 2011 and January of 2013, 100 PWE from an adult epilepsy clinic were included. We obtained BMI, waist circumference, and information regarding physical activity using a standardised questionnaire. Clinical, demographic, electrographic, and imaging parameters were collected from charts. Results. Mean age of patients was 40±14 (18-77) years. The BMI distribution was as follows: 2 patients (2%) underweight, 26 (26%) normal weight, 34 (34%) overweight, 25 (25%) obese, and 13 (13%) with morbid obesity. In our study, obesity was defined as having a BMI ≥30. We found 38 (38%) patients in this range. There was no difference in the rate of drug-resistant epilepsy between obese and non-obese patients (55 vs. 55%; p=0.05). Leisure time habit was reported in 82% of obese patients and 79% of patients without obesity. Overall, the most frequent activity was walking (70%). Factors associated with obesity were generalised epilepsy (OR: 2.7, 1.1-6.6; p=0.012), idiopathic syndrome (OR: 2.7, 1.04-7; p=0.018), and family history of epilepsy (OR: 6.1, 1.5-24.2; p=0.002). Conclusion. Our study suggests an association between obesity, idiopathic generalised epilepsy, and family history of epilepsy. Our study shows that PWE are physically active and there is no clear relation between exercise and obesity. We could not identify any association between drug-resistant epilepsy and obesity. Absence of direct comparison with a control non-epileptic population; a cross-sectional design not allowing evaluation of a causal association among variables; and reliance on self-reported physical activity are to be considered as limitations of the present study.

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Clinical commentary

Neonatal hyperekplexia with homozygous p.R392H mutation in GLRA1

Fouzia Hmami, Sian-Elin Wood, Sana Chaouki, Abdellah Oulmaati, Mustapha Hida, Mark I. Rees, Seo-Kyung Chung, Abdelhak Bouharrou

admitted on the second day of life to the neonatal intensive care unit, due to tonic-clonic movements. Following clinical and paraclinical investigations, a final diagnosis of hyperekplexia was made. Genetic analysis revealed a homozygous mutation in GLRA1 resulting in a R392H amino acid substitution and altered receptor dynamics, as indicated from previous work. The infant showed a marked improvement of the startle response and muscle hypertonia with clonazepam which is a strong clinical feature of GLRA1-mediated hyperekplexia. [ Published with video sequences]

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PET-positive extralimbic presentation of anti-glutamic acid decarboxylase antibody-associated encephalitis

Gotaro Kojima, Michiko Inaba, Michiko K. Bruno

with limited investigation. Here, we report an extensive investigation with MRI, PET, and pathological examination. A 66-year-old Japanese female with a history of hypothyroidism, colon cancer, pheochromocytoma, and thymoma-associated myasthenia gravis presented with generalised tonic-clonic seizures. MRI showed multiple hyperintense lesions and PET showed hypermetabolic lesions in the brain. Biopsy showed non-specific gliosis, microglial proliferation, and perivascular lymphohistiocytic infiltrates. Various neuronal antibodies were negative, except for anti-GAD antibody. Anti-GAD antibody-associated encephalitis is an increasingly recognised CNS disease. Pathophysiology of this encephalitis is unclear. While PET showed hypermetabolic lesions, the biopsy showed non-specific changes. The treatments may include immunosuppressants, IVIg, and plasma exchange. One should consider to measure this antibody, in addition to others, when autoimmune encephalitis is suspected [ Published with video sequences] .

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Limbic encephalitis with anti-GAD antibodies and Thomsen myotonia: a casual or causal association?

Laura Licchetta, Francesca Bisulli, Ilaria Naldi, Greta Mainieri, Paolo Tinuper

case demonstrating an association between sporadic congenital myotonia and epilepsy was recently reported in a patient carrying a de novo mutation of the CLCN1 gene. Additional evidence for a role of CLCN1 in the pathogenesis of epilepsy is derived from large-scale exome analysis of ion channel variants and expression studies. Here, we describe the first case of association between familial Thomsen myotonia and epilepsy. All the affected members of a two-generation family presented myotonia and disclosed a pathogenic mutation in CLCN1. In addition, one individual experienced epileptic seizures due to limbic encephalitis (LE) with anti-GAD antibodies. The occurrence of the two diseases in this patient could be a chance association, however, CLCN1 mutation, as a susceptibility factor for epilepsy through dysfunction of GABA A inhibitory signalling, cannot be ruled out as a possible influence.

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Unusual presentation of hypothalamic hamartoma with hypersomnia in an adult patient

F. Irsel Tezer, Mehmet Yasir Pektezel, Rahsan Gocmen, Serap Saygi

resonance imaging revealed a hypothalamic hamartoma in the posterior region of the hypothalamus. The patient had no previous history of gelastic seizures. We suggest that patients who present with hypersomnia should be investigated for gelastic seizures in order to avoid misdiagnosis and receive appropriate treatment.

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Focal epilepsy recruiting a generalised network of juvenile myoclonic epilepsy: a case report

Myo Khaing, Kheng-Seang Lim, Chong-Tin Tan

seizures and temporal lobe seizures. The temporal lobe seizures were accompanied by a focal recruiting rhythm with rapid generalisation on EEG, in which the ictal EEG pattern during the secondary generalised phase was morphologically similar to the ictal pattern during myoclonic seizures. The secondary generalised seizures of the focal epilepsy responded to sodium valproate, similar to the myoclonic epilepsy. In this rare case of coexistent Juvenile Myoclonic Epilepsy and Temporal lobe epilepsy, the possibility of focal epilepsy recruiting a generalised epileptic network was proposed and discussed.

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Valproate-induced reversible sensorineural hearing loss: a case report with serial audiometry and pharmacokinetic modelling during a valproate rechallenge

Li-Ling Yeap, Kheng-Seang Lim, Yoke-Lin Lo, Mohd Zukiflee Abu Bakar, Chong-Tin Tan

by serial audiometry and pharmacokinetic modelling. A 39-year-old truck driver with temporal lobe epilepsy was treated with VPA at 400 mg, twice daily, and developed hearing loss after each dose, but recovered within three hours. Hearing loss fully resolved after VPA discontinuation. Audiometry performed five hours after VPA rechallenge showed significant improvement in hearing thresholds. Pharmacokinetic modelling during the VPA rechallenge showed that hearing loss occurred at a level below the therapeutic range. Brainstem auditory evoked potential at three months after VPA discontinuation showed bilateral conduction defect between the cochlear and superior olivary nucleus, supporting a pre-existing auditory deficit. VPA may cause temporary hearing threshold shift. Pre-existing auditory defect may be a risk factor for VPA-induced hearing loss. Caution should be taken while prescribing VPA to patients with pre-existing auditory deficit.

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Lacosamide-induced rash

Mohamad Z. Koubeissi, Marta Vismer, Alison Ehrlich

lacosamide, a newer-generation anti-seizure medication with a novel mechanism of action. Here, we report a case of diffuse skin eruption in a patient with history of epilepsy soon after initiation of lacosamide. The rash resolved after discontinuation of lacosamide and use of antihistamines and steroids. We also review the information on drug hypersensitivity syndrome.

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