AHEAD OF PRINT
Fouzia Hmami, Sian-Elin Wood, Sana Chaouki, Abdellah Oulmaati, Mustapha Hida, Mark I. Rees, Seo-Kyung Chung, Abdelhak Bouharrou
asphyxia, and sudden infant death. We present video sequences of a male newborn, 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]
Kyoko Kanazawa, Riki Matsumoto, Akihiro Shimotake, Masako Kinoshita, Akiko Otsuka, Osamu Watanabe, Keiko Tanaka, Ryosuke Takahashi, Akio Ikeda
in non-infectious “smoldering” limbic encephalitis.
Methods. Long-term 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.
Jacobus FA Jansen, Sylvie JM van der Kruijs, Mariëlle CG Vlooswijk, HJ Marian Majoie, Paul AM Hofman, Albert P Aldenkamp, Walter H Backes
provide measures to discern between patients with or without cognitive complaints. 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.
Gotaro Kojima, Michiko Inaba, Michiko K. Bruno
mostly as limbic encephalitis. Only few cases with extralimbic involvement are reported 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] .
Alexandra Liava, Roberto Mai, Laura Tassi, Massimo Cossu, Ivana Sartori, Lino Nobili, Giorgio Lo Russo, Stefano Francione
data are sparse, especially in children, and most published series report a high number of surgical failures and post-operative neurological deficits. In this article, we present a paediatric cohort of 62 children who underwent surgery for drug resistant posterior cortex epilepsy before the age of 16 years with a mean post-operative follow-up of 6.94 years (range: 2-16). Mean age at epilepsy onset was 3.2 years and 28 children (45%) had onset before 1 year of age. The mean age at surgery was 7.9 years (range: 1-16). Daily seizures were present in 63% of children. MRI was positive in 58 cases (93.5%) and invasive stereo-EEG was judged mandatory in 24/62 (39%) of patients.</p><p>Surgery was confined to the parietal lobe in 11 children, the occipital lobe in 8, the occipito-parietal region in four, the occipito-temporal region in 18, and involved both the temporal and parietal lobes in the remaining 21. Following surgery, 53 subjects (85.5%) remained seizure-free and among those who underwent a SEEG procedure, 75% achieved seizure freedom. Focal cortical dysplasia was the most frequent histopathological diagnosis (50%), followed by tumoural (24%) and gliotic lesions (14.5%).</p><p>An older age at epilepsy onset, the presence of a rather restricted epileptogenic area, and a complete resection of the epileptogenic zone were predictive of a favourable surgical outcome. These results demonstrate that a good surgical outcome is possible in children with drug resistant posterior cortex epilepsy. Accurate analysis of the chronology of ictal semiology and electrophysiological features, viewed in the context of the complete electroclinical pattern, provides a topographical orientation for posterior cortex epilepsy and, together with the presence of a lesion detectable on imaging, may improve the rate of surgical success of posterior cortex epilepsy at paediatric age.</p>
Franck Semah, Pierre Thomas, Safia Coulbaut, Philippe Derambure
prescribed antiepileptic drug (AED); alternative monotherapy vs early add-on treatment.</p><p>
Methods. We conducted an open, cluster-randomised, prospective, controlled trial in patients with persistent partial seizures, despite treatment with one AED, who were never administered any other AEDs. Neurologists were randomised to two strategies: in group A, an alternative monotherapy with a second AED was employed; in group B, add-on treatment with a second AED was employed. The primary outcome was the percentage of seizure-free patients during a two-month period after six months of treatment. The secondary outcomes were: (i) the percentage of patients achieving a 50% reduction in the number of seizures at six months; (ii) the quality of life based on the Quality Of Life In Epilepsy scale; and (iii) tolerability.</p><p>
Results. A total of 143 neurologists were included and randomised, and 264 patients were evaluated. At six months, the primary outcome was 51% in group A and 45% in group B (
p=0.34). The percentage of patients achieving a 50% reduction in the number of seizures at six months was 76% in group A and 84% in group B (
p=0.53). The quality of life and the tolerability did not significantly differ between the two groups.</p><p>
Conclusions. Alternative monotherapy or early treatment initiation with another AED drug resulted in similar efficacy, and the side effects associated with monotherapy and combined therapies were similar, which suggests that individual susceptibility is more important than the number and burden of AEDs used.</p>
Bo Qiu, Shaowu Ou, Teng Song, Jinqu Hu, Lingtong You, Yong Wang, Yunjie Wang
Method. Clinical data were obtained for 65 patients with supratentorial neoplasms who received surgery, with the aid of intraoperative electrocorticography to screen epileptogenic foci before and after removal of neoplasms, and depth electrodes when needed. According to electrocorticography findings, appropriate surgical procedures were performed to treat the epileptogenic foci. In the control group, 72 patients received simple lesionectomy. Postoperative seizure outcomes were documented and analysed retrospectively.
Results. In the case group, 33 patients received lesionectomy only, while the other 32 patients underwent intraoperative electrocorticography-guided tailored epilepsy surgery. In total, 57 patients (87.7%) in the case group and 38 patients (52.8%) in the control group were seizure-free (Engel Class I). Comparing outcomes of patients with temporal lesions between the two groups, 80.0% patients (12/15) in the case group and 20.0% (3/15) in the control group were seizure-free. Furthermore, comparing the seizure outcomes of patients who finally underwent tailored epilepsy surgery and simple lesionectomy (33 after electrocorticography and 72 without electrocorticography), intraoperative electrocorticography-guided tailored epilepsy surgery demonstrated superiority over lesionectomy (Engel Class I; 87.5%
vs. 63.8%, respectively).
Conclusions. Electrocorticography plays an important role in the localisation of epileptogenic foci and evaluation of the effects of microsurgical procedures intraoperatively. Isolated lesionectomy is not usually sufficient for better postoperative seizure outcome. In addition, for patients with temporal tumours, especially in the non-dominant hemisphere, a more aggressive strategy, such as an anterior temporal lobectomy, is recommended.
Giuseppe Gobbi, Giulia Loiacono, Antonella Boni, Lucia Marangio, Alberto Verrotti
forms of medically intractable epilepsy. We evaluated the short, medium, and long-term evolution of patients with frontal lobe epilepsy and secondary bilateral synchrony on the EEG, who received ACTH treatment. Patients were recruited for an add-on trial during clinical practice, and data was retrospectively analysed. The study group comprised 6 patients treated with ACTH. The effects of ACTH were assessed in the short term (at the end of a 6-week period of ACTH treatment), medium term (at 6 months after the end of treatment), and long term (at 12 months after the end of treatment). At short-term follow-up, ACTH treatment was effective for all types of seizures in 5 of 6 patients and ineffective in 1 patient. All patients who were seizure-free at the end of ACTH treatment maintained an excellent outcome, remaining seizure-free at the end of follow-up. Our study demonstrates that ACTH may represent an effective treatment for frontal lobe epilepsy with secondary bilateral synchrony. Further double-blind prospective studies are required to confirm our initial findings.
Reina Roivainen, Matti K. Karvonen, Tarja Puumala
or functional outcome in ULD patients remains obscure. We retrospectively identified all patients seen at Helsinki University Hospital due to Unverricht-Lundborg disease during 2003-2008 in order to determine which AED treatments had been retained for long-term use. The majority of the patients had severe functional disabilities. In the year preceding the last hospital visit, all patients (
n=20) were receiving polytherapy and 14 patients had been free of tonic-clonic seizures. During follow-up, improvement in myoclonia had been recorded for the majority of patients with either add-on piracetam, topiramate, or levetiracetam, but valproate was still in use by all patients. Treatment with lamotrigine had been started and retained less often relative to other AEDs. Add-on AED treatment was often associated with significant adverse effects. Unverricht-Lundborg disease patients may benefit from add-on treatment with levetiracetam or topiramate for seizure control. Treatment of eventual comorbidities with other than AEDs is also discussed.
Gulten Tata, Betul Tekin Guveli, Nimet Dortcan, Ozlem Cokar, Hatice Kurucu, Veysi Demirbilek, Aysin Dervent
ictal recordings obtained so far suggest an occipital origin, semiological and interictal EEG data appear to favour more extensive involvement. In this study, the characteristics (including those based on semiology and EEG) of children with Panayiotopoulos syndrome (
n=24) and those with lesion-related, symptomatic occipital lobe epilepsy (SOLE) (
n=23) were compared.</p><p>
Methods. Detailed semiological information and EEG parameters including the localisation, distribution, density (n/sec), reactivity, and morphological characteristics of spike-wave foci and their relationship with different states of vigilance were compared between the two groups.</p><p>
Results. The age at seizure onset was significantly younger in patients with symptomatic occipital lobe epilepsy than in those with PS (mean age at onset: 3.4
versus 5.6 years, respectively;
p=0.044). Autonomic seizures (
p=0.001) and ictal syncope (
p=0.055) were more frequent in PS than in symptomatic occipital lobe epilepsy (87.5% and 37.5%
versus 43.5% and 13%, respectively). The interictal spike-wave activity increased significantly during non-rapid eye movement (non-REM) sleep in both groups. The spike waves in non-REM seen in PS tended to spread mainly to central and centro-temporal regions.</p><p>
Conclusions. The results indicate that although common features do exist, Panayiotopoulos syndrome differs from symptomatic occipital lobe epilepsy and has a unique low epileptogenic threshold related to particular brain circuits.</p>
José Manuel Cimadevilla, Julio Ramos Lizana, Maria Dolores Roldán, Rosa Cánovas, Eva Rodríguez
are neuropsychological studies characterising the cognitive profile, there are no studies in this population focused on spatial orientation abilities. In this study, we compared children with genetic generalised epilepsy or epilepsy of unknown cause with a control group using a virtual spatial learning task. Children with epilepsy showed worse performance on the spatial orientation task, although their visuo-spatial memory, attention, and working memory were normal. These results confirm that genetic generalised epilepsy or epilepsy of unknown cause is associated with more cognitive deficits. Virtual reality technologies can complement clinical assessment.
Tsukasa Ohashi, Noriyuki Akasaka, Yu Kobayashi, Shinichi Magara, Hideshi Kawashima, Naomichi Matsumoto, Hirotomo Saitsu, Jun Tohyama
patient initially developed focal seizures with multiple foci at 3 months of age. Thereafter, the seizures evolved to frequent episodes of hyperthermia-induced status epilepticus. A novel
de novo SCN1A mutation was identified by whole-exome sequence analysis. This case demonstrates that
SCN1A mutations may cause movement disorders as an atypical phenotype and the case history of this patient may expand our understanding of the clinical spectrum of
SCN1A-associated epileptic encephalopathy. [
Published with video sequences]
Rosa Vydrova, Pavel Kršek, Martin Kyncl, Alena Jahodova, Josef Dvorak, Vladimir Komarek, Olivier Delalande, Michal Tichy
abundant epileptiform activity over the left (disconnected) hemisphere, including ictal patterns that neither generalised nor had clinical correlates. Antiepileptic medication was completely withdrawn four years following the surgery. One week after the withdrawal, she developed episodes of intense left-sided hemicranias (ipsilateral to the surgery) with vomiting and photophobia that did not resemble her habitual seizures and were unresponsive to non-steroidal anti-inflammatory drugs. Video-EEG showed association of the headache attacks with ictal patterns over the disconnected hemisphere. Brain MRI revealed increased signal changes in the left hemisphere. Attacks responded promptly to
i.v. midazolam and carbamazepine at a low dose. Mechanisms underlying peri-ictal headache originating in the disconnected hemisphere are discussed. [
Published with video sequences]
Eisuke Sakakibara, Yukitoshi Takahashi, Yoshiko Murata, Go Taniguchi, Daichi Sone, Masako Watanabe
for more than three months and are called “chronic” PLEDs, the pathophysiology of which is still debated. Herein, we report a man with right hemispheric PLEDs which lasted for more than 14 months and mild left hemispatial neglect after he experienced status epilepticus. Although MRI was normal, positron emission tomography revealed right temporo-parieto-occipital hypometabolism, which coincided with the source area of PLEDs estimated by magnetoencephalography. In addition, levels of anti-
N-methyl-D-aspartate (NMDA) receptor antibodies and granzyme B were found to be high in the cerebrospinal fluid. Following two courses of steroid pulse therapy, the patient's left spatial neglect improved and the PLEDs were partially resolved. These findings suggest that the chronic PLEDs present in this case were an interictal phenomenon and that their pathophysiology involved autoimmune processes.
Vittoria Cianci, Edoardo Ferlazzo, Giuseppe De Martino, Angela Vinci, Sara Gasparini, Giovanbattista Gaspare Tripodi, Umberto Aguglia
pattern suggestive of benign focal epilepsy with centro-temporal spikes has recently been described in four XYY patients. We report the first patient with XYY trisomy, rolandic spikes, and atypical evolution with continuous spikes and waves during slow sleep (CSWSS). The present report suggests that the association between an EEG pattern similar to that of BECTS and 47, XYY karyotype may not be coincidental. Moreover, we show that an atypical evolution with CSWSS may occur in this chromosomal disorder.
Naoto Jingami, Riki Matsumoto, Hirotaka Ito, Atsushi Ishii, Yukiko Ihara, Shinichi Hirose, Akio Ikeda, Ryosuke Takahashi
types, in addition to febrile seizures (FS) or febrile seizures plus (FS+), defined as either continued FS after 6 years of age or afebrile seizures following FS. A 27-year-old man with no history of FS/FS+ experienced intractable generalised convulsive seizures. The patient's father had a history of similar seizures during puberty and the patient's siblings had only FS. No individual in the family had both generalised seizures and FS/FS+, although GEFS+ might be considered to be present in the family. Analysis of
SCN1A, a sodium channel gene, revealed a novel mutation (c.3250A>T [S1084C]) in the cytoplasmic loop 2 of
SCN1A in both the patient and his father. Most previously reported
SCN1A mutations in GEFS+ patients are located in the conserved homologous domains of
SCN1A, whereas mutations in the cytoplasmic loops are very rare.
SCN1A gene analysis is not commonly performed in subjects with generalised seizures without FS.
SCN1A mutation may be a clinically-useful genetic marker in order to distinguish GEFS+ patients from those with classic idiopathic generalised epilepsy, even if they present an atypical clinical picture.
John Neilson, Tom Snyder, Jeff Pugh, Matt Wheatley, Richard Tang-Wai
Method. We present a 10-year-old patient with lesional epilepsy and ictal onset, localised to BA10 in the aPFC.
Results. Thirty-four seizures were recorded. All seizures involved a demonstration of elation with laughter that was associated with a variety of different patterns of complex motor behaviour that included performing specific celebratory movements and acting out a Michael Jackson dance move. Electrographically, the seizures were all stereotyped and arose from the right frontal region, followed by a distinct left temporal ictal rhythm that corresponded with the onset of the behaviours. The lesion in the right aPFC was identified as a mixed lesion with both dysembryoplastic neuroepithelial tumour cells and type II cortical dysplasia.
The electrographic analysis and unique seizure semiology suggest a connection between the aPFC and the contralateral temporal lobe. This neural pathway appears to be involved in the activation of previously formed procedural memories, creating an intensely positive emotional experience.
Dave F. Clarke, Kristi Tindall, Mark Lee, Bhairav Patel
safe way of reducing or aborting seizures. Most cases of MRI-guided thermal ablation have been performed in patients with isolated lesions. Placement of depth electrodes prior to laser ablation has been rarely performed. We present a case with bilateral independent lesions traversing eloquent cortex, which, after sampling for seizures and successful ablation, retained normal function. The patient is, to date, seizure-free.