bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracranial electrographic analysis of preictal spiking and ictal onset in uni‐ and bitemporal epilepsy
Authors: Wasade Vibhangini S , Gaddam Shailaja , Burdette David E , Schultz Lonni , Spanaki‐Varelas Marianna , Constantinou Jules EC , Elisevich Kost
Published: August 2019

Aim. Ictal onset patterns in bilateral mesial temporal lobe epilepsy have not been comprehensively studied. A retrospective review of intracranial electrographic data was undertaken to establish whether it is possible to distinguish between unilateral and bilateral mesial temporal lobe epilepsy based on ictal onset patterns, including periodic preictal spiking.

Methods. A total of 470 ictal onset patterns were analyzed by bitemporal extraoperative electrocorticography in 13 patients with medically intractable mesial temporal lobe epilepsy. Ictal onset patterns were categorized, by frequency, as type A (<12 Hz), type B (12–40 Hz) and type C (>40 Hz). Preictal rhythmic spiking, of at least five seconds duration, and time to contralateral propagation were also measured with each ictal event. We determined if the proportion of “ictal onset pattern frequencies” or “incidence of preictal spiking” differed between unilateral and bilateral mesial temporal lobe epilepsy.

Results. Seven patients with unilateral mesial temporal lobe epilepsy received surgery and achieved Engel class I outcomes, while the remaining six did not undergo resective surgery, due to the bilateral ictal onsets in extraoperative electrocorticography. The proportion of patients experiencing any preictal spikes was higher in unitemporal than in bitemporal cases (100%vs50%;p=0.069). Of the 470 ictal onset patterns analyzed (174 unitemporal and 296 bitemporal), a significant greater percentage of preictal spikes was found in unilateral cases (78% unitemporalvs14% bitemporal;p=0.002). Low‐frequency patterns were more evident in bitemporal cases (45%) than in unitemporal (10%), although the difference was not statistically significant (p=0.129). No differences were detected between the unitemporal and bitemporal groups regarding age at onset or at presentation.

Conclusion. A greater proportion of preictal spiking, based on extraoperative electrocorticography, was present in unilateral, compared to bilateral, mesial temporal lobe epilepsy. Further studies are warranted to determine the causal significance of preictal spiking in mesial temporal lobe epilepsy.
Ictal asystole mimicking seizure deterioration in temporal lobe epilepsy
Authors: Guldiken Baburhan , Hartl Elisabeth , Rémi Jan , Noachtar Soheyl
Published: August 2019

We report on a patient with temporal lobe epilepsy, secondary to a left lateral temporal cavernoma, in whom the change in seizure semiology suggested recurrence of secondary generalized seizures. Anticonvulsive medication previously controlled secondary generalized seizures over a period of years but focal seizures continued at a lower rate. Continuous video‐EEG monitoring revealed ictal asystole associated with myoclonic syncope and falls during focal seizures arising from the left temporal lobe. After implantation of a cardiac pacemaker, no more falls occurred during the focal seizures. In conclusion, recurrence of seizure‐associated falls is typically attributed to recurrence of secondary generalized seizures, however, ictal asystole should be considered in selected epilepsy patients as a differential diagnosis of falls. [Published with video sequence]
Brief rhythmic discharges in neonates: a marker for seizures
Authors: Alix James JP , Ponnusamy Athi , Hart Anthony R
Published: August 2019

Brief rhythmic discharges (BRDs) are paroxysms of rhythmic electrographic activity with an amplitude of >2 μV and a duration of <10 seconds. Although BRDs are reported in neonates, this electrographic activity contrasts the accepted definition of neonatal seizures (duration of >10 seconds). BRDs are associated with background EEG abnormalities as well as increased morbidity and mortality (Oliveira et al., 2000, Nagarajan et al., 2011), and appear to be more closely related to formal neonatal seizures than post‐neonatal epilepsy (Nagarajan et al., 2011). Most neonatal units are restricted to one‐hour recordings, and if BRDs are observed without any accompanying electrographic seizures, then the neonate should be regarded as being at high risk of seizures and repeat recordings should be considered.
Vagus nerve stimulation in children with drug‐resistant epilepsy: age at implantation and shorter duration of epilepsy as predictors of better efficacy?
Authors: Lagae Lieven , Verstrepen An , Nada Ayman , Van Loon Johan , Theys Tom , Ceulemans Berten , Jansen Katrien
Published: August 2019

Aim. To study the efficacy of vagus nerve stimulation (VNS) therapy in a highly drug‐resistant childhood epilepsy patient group and to investigate the effect of age at implantation on efficacy.

Methods. The efficacy of VNS treatment was analysed in a cohort of 70 patients with drug‐resistant epilepsy. Both children with focal (n=16) and generalized epilepsies (n=54) were included. Age at implantation varied between 19 months and 25 years.

Results. Overall, responder rate was 54% with 5.7% children becoming seizure‐free. The only factor in our analysis that could predict good outcome was age at implantation. In the youngest group (<5 years), the responder rate was 77% and this group also included three of the four seizure‐free children. These three seizure‐free children were known to have tuberous sclerosis. There were no outcome differences between generalized and focal epilepsies.

Conclusions. Our single centre study confirms previous studies on the efficacy of VNS in children. A larger study using multivariate analysis to disentangle the contribution of different factors (such as age at implantation, aetiology, and epilepsy duration) is necessary to confirm our preliminary finding that younger age at VNS implantation might result in a better outcome.
Paroxysmal eyelid movements in patients with visual‐sensitive reflex seizures
Authors: Brinciotti Mario , Matricardi Maria
Published: August 2019

Aim. Paroxysmal eyelid movements (PEM) are non‐epileptic episodes characterized by eyelid closure, upturning of the eyes, and rapid eyelid flutter. The aim of this study was to report clinical and EEG data of patients with PEM and its relationship with visual sensitivity.

Methods. We studied 26 patients with epilepsy (12 males and 14 females; mean age: 14.0±6.9 years) who presented PEM. The epilepsy was idiopathic generalized (eight cases), idiopathic focal (six cases), symptomatic focal (five cases), and reflex epilepsy (seven cases). PEM and blinking were analysed by video‐EEG recordings at rest and during intermittent photic stimulation, pattern stimulation, and TV watching. Blink rate was evaluated during three different conditions: at rest, during a TV‐viewing period, and at the occurrence of PEM. Analysis of variance (ANOVA) was used for statistical comparisons.

Results. Repeated episodes of PEM were recorded in all patients. The frequency of PEM ranged from 8 to 12.5 Hz (average: 9.6±1.5). PEM were accompanied by a significant increase in blinking compared to the rest condition and TV watching (blink rate: 56.5±21.1vs25.0±16.2vs11.3±11.8, respectively;p<0.0001). Photoparoxysmal EEG responses (measured as sensitivity to photic stimulation) were found in 25 cases, associated with pattern sensitivity in 22; only one patient was sensitive to pattern but not photic stimulation. Visually‐induced seizures were recorded in 20 cases, triggered by both stimuli (photic and pattern stimulation) in 11 patients; seizures were triggered by pattern stimulation (but not photic stimulation) in five, photic stimulation (but not pattern stimulation) in three, and TV watching (but not photic or pattern stimulation) in one. Epileptic eyelid myoclonia was noted in 17 patients.

Conclusion. The coexistence of PEM, photoparoxysmal EEG responses, increased blinking, and epileptic eyelid myoclonia suggests an underlying dysfunction involving cortical‐subcortical neural networks, according to the recent concept of system epilepsies. [Published with video sequences]
Electroclinical and cytogenetic features of epilepsy in cri‐du‐chat syndrome
Authors: Nakagami Yukako , Terada Kiyohito , Ikeda Hitoshi , Hiyoshi Toshio , Inoue Yushi
Published: August 2019

Cri‐du‐chat syndrome (CdCs) is caused by deletion in the short arm of chromosome 5, occurring in 1:15,000 to 1:50,000 live births. Recent genotype‐phenotype correlation studies show the importance of 5p15.2 for facial dysmorphism and intellectual disability, and 5p15.3 for cat‐like cry. Numerous reports have shown the relative rarity of epilepsy in this syndrome. We identified two cases with epilepsy in CdCs, and described their electroclinical and cytogenetic features. The first case was a 25‐year‐old female who had axial tonic seizures with flexion of the neck and shoulders. Interictal EEG was characterized by generalized spike‐and‐slow‐wave complexes. Her ictal EEG started with diffuse electrodecremental pattern, followed by alpha‐range activities. High‐resolution banding analysis of chromosomes revealed a terminal deletion of 5p14.1. The second case was a 30‐year‐old female who had startle epilepsy with falling. Interictal EEG demonstrated generalized spike and slow waves. High‐resolution banding analysis revealed a terminal deletion of 5p13.3 with additional chromosomal material of unknown origin. Based on the cases presented here, as well as those previously reported, the relationship between epilepsy and CdCs is discussed. The data suggests that although CdCs patients rarely suffer from epileptic seizures, the seizures may vary in type.
Relationship between tumour location and preoperative seizure incidence in patients with gliomas: a systematic review and meta‐analysis
Authors: Su Xing , Chen Hong‐Lin , Wang Zhong‐Yong , Lan Qing
Published: August 2019

Aim. The aim of this meta‐analysis was to assess the relationship between tumour location and preoperative seizure incidence in patients with gliomas.

Methods. Systematic computerised searches of PubMed and the Web of Knowledge were performed. The meta‐analysis of pooled odds ratio (OR) and 95% confidence interval (CI) for preoperative seizure risk, stratified by tumour location, were calculated.

Results. Eleven studies with 2,047 patients were included for meta‐analysis. For gliomas with or without frontal lobe involvement, the preoperative seizure incidence ranged from 31.7% (19/60) to 85.7% (156/182) and 19.7% (12/61) to 85.7% (12/14), respectively; the pooled OR was 1.560 (95% CI: 1.266–1.923; Z: 4.17; p=0.000). For gliomas with or without temporal lobe involvement, seizure incidence was 22.6% (7/31) to 91.7% (11/12) and 26.7% (24/90) to 78.7% (174/221), respectively; the pooled OR was 1.070 (95% CI: 0.794–1.443; Z: 0.45; p=0.656). For gliomas with or without parietal lobe involvement, seizure incidence was 18.1% (3/16) to 100.0% (3/3) and 26.7% (28/105) to 80.4% (226/281), respectively; the pooled OR was 0.770 (95% CI: 0.570–1.040; Z: 1.71; p=0.088). For gliomas with or without occipital lobe involvement, seizure incidence was 0.0% (0/2) to 100.0% (2/2) and 26.8% (30/112) to 75.7% (56/74), respectively; the pooled OR was 0.336 (95% CI: 0.164–0.686; Z: 2.99; p=0.003). For gliomas with or without insula lobe involvement, seizure incidence was 34.8% (8/23) to 72.0% (77/107) and 34.3% (60/175) to 81.3% (247/304), respectively; the pooled OR was 1.058 (95% CI: 0.765–1.463; Z: 0.34; p=0.732). No significant publication bias was found.

Conclusion. Our meta‐analysis indicates that frontal lobe gliomas are related to a higher preoperative seizure incidence, while occipital lobe gliomas are related to a lower incidence.
Response to immunotherapy in a patient with Landau‐Kleffner syndrome and GRIN2A mutation
Authors: Fainberg Nina , Harper Amy , Tchapyjnikov Dmitry , Mikati Mohamad A.
Published: August 2019

Landau‐Kleffner syndrome (LKS) has been demonstrated in the past to respond to immunotherapy. Recently, some cases of LKS have been shown to be secondary to glutamate receptor (GRIN2A) mutations. Whether such cases respond to immunotherapy is not known. Here, we present the case of a 3‐year‐old boy with LKS found to have a GRIN2A heterozygous missense mutation, whose clinical symptoms and EEG responded to a course of combination oral steroids and monthly infusions of intravenous immunoglobulin. He then relapsed after discontinuation of this therapy, and responded again after a second course of intravenous immunoglobulin. We conclude that immunotherapy should be considered as a therapeutic option in patients with LKS who are also found to harbour GRIN2A mutations.
Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes
Authors: Khawaja Ayaz M. , Vines Brannon L. , Miller David W. , Szaflarski Jerzy P. , Amara Amy W.
Published: August 2019

Aim. Glutamic acid decarboxylase antibodies (GAD‐Abs) have been implicated in refractory epilepsy. The association with refractory status epilepticus in adults has been rarely described. We discuss our experience in managing three adult patients who presented with refractory status epilepticus associated with GAD‐Abs.

Methods. Case series with retrospective chart and literature review.

Results. Three patients without pre‐existing epilepsy who presented to our institution with generalized seizures between 2013 and 2014 were identified. Seizures proved refractory to first and second‐line therapies and persisted beyond 24 hours. Patient 1 was a 22‐year‐old female who had elevated serum GAD‐Ab titres at 0.49 mmol/l (normal: <0.02) and was treated with multiple immuno‐ and chemotherapies, with eventual partial seizure control. Patient 2 was a 61‐year‐old black female whose serum GAD‐Ab titre was 0.08 mmol/l. EEG showed persistent generalized periodic discharges despite maximized therapy with anticonvulsants but no immunotherapy, resulting in withdrawal of care and discharge to nursing home. Patient 3 was a 50‐year‐old black female whose serum GAD‐Ab titre was 0.08 mmol/l, and was discovered to have pulmonary sarcoidosis. Treatment with steroids and intravenous immunoglobulin resulted in seizure resolution.

Conclusion. Due to the responsiveness to immunotherapy, there may be an association between GAD‐Abs and refractory seizures, including refractory status epilepticus. Causation cannot be established since GAD‐Abs may be elevated secondary to concurrent autoimmune diseases or formed de novo in response to GAD antigen exposure by neuronal injury. Based on this report and available literature, there may be a role for immuno‐ and chemotherapy in the management of refractory status epilepticus associated with GAD‐Abs.
Olanzapine‐related repetitive focal seizures with lingual dystonia
Authors: Anzellotti Francesca , Capasso Margherita , Frazzini Valerio , Onofrj Marco
Published: August 2019

Olanzapine‐related seizures have rarely been reported despite associated proconvulsant risk factors described in the literature: myoclonic status, increased frequency of seizures, tonic‐clonic seizures, as well as fatal status epilepticus. We present a psychiatric patient who developed repetitive focal motor seizures and lingual dystonia when olanzapine was added for psychomotor agitation and aggressiveness. Olanzapine was immediately suspended and the seizures progressively disappeared. A control EEG showed no paroxysmal discharges. Olanzapine shares some pharmacological similarities with clozapine, a neuroleptic with a high risk of dose‐dependent seizures. This adverse effect should be taken into account, and olanzapine should be used with caution if concomitant circumstances decrease the seizure threshold. [Published with video sequence online]
Benign adult familial myoclonus epilepsy is a progressive disorder: no longer idiopathic generalized epilepsy
Authors: Hitomi Takefumi , Kobayashi Katsuya , Sakurai Takeyo , Ueda Sakiho , Jingami Naoto , Kanazawa Kyoko , Matsumoto Riki , Takahashi Ryosuke , Ikeda Akio
Published: August 2019

Background. Brain dysfunction in Japanese benign adult familial myoclonus epilepsy (BAFME) has not been elucidated.

Aim. To clarify diffuse brain dysfunction as indicated by posterior dominant rhythm (PDR) slowing in patients with BAFME.

Methods. The frequency of PDR on EEG was studied in 19 BAFME patients (50.6±15.7 years) and 38 age‐matched control subjects (50.1±14.5 years). We investigated the relationship between age and PDR in both groups.

Results. PDR frequency in the patient group (9.1±0.7 Hz) was significantly slower than that of age‐matched control subjects (10.4±1.1 Hz; p<0.0001), regardless of the use of anticonvulsants. There was no significant difference in PDR slowing with age between groups.

Conclusion. These findings suggest that Japanese patients with BAFME have mild diffuse brain dysfunction with minimal progression.
How many adults with temporal epilepsy have a mild course and do not require epilepsy surgery?
Authors: Hernández‐Ronquillo Lizbeth , Buckley Samantha , Ladino Lady Diana , Wu Adam , Moien‐Afshari Farzad , Rizvi Syed AA , Téllez‐Zenteno Jose F.
Published: August 2019

Aims. Temporal lobe epilepsy (TLE) is the most common type of drug‐resistant epilepsy in adults and commonly requires surgical treatment. While an overwhelming preponderance of literature supports the notion that a large percentage of patients with TLE benefit from surgery, there is a paucity of outcome data on patients who demonstrate a sustained response to pharmacological treatment. In this study, we present an adult cohort of patients with TLE, with the purpose of identifying the proportion of patients with a mild course of the disease, as well as potential risk factors.

Methods. A prospective cohort study of all patients with TLE assessed and followed by the Saskatchewan Epilepsy Program, from 1 March 2007 to Jan 29th 2014. Patients were dichotomized as having a mild (seizure freedom without surgical intervention) or severe (surgical intervention required and/or failure to achieve seizure remission) course. Descriptive statistics, odds ratios and confidence intervals were calculated to identify predictors of seizure freedom.

Results. The cohort consisted of 159 patients. Mean patient age at last follow‐up visit was 46±14.4 (range: 19–88) years. Mean follow‐up period was 43.4±22.6 (6 to 84) months. Forty‐six patients (29%) demonstrated mild‐course TLE while 113 (71%) had a severe course of TLE. Patients with a mild course of TLE were more likely to be older (p = 0.002), have late‐onset epilepsy (p < 0.001) with shorter evolution (p < 0.001). A good response to the first antiepileptic drug (OR: 6.8; 95% CI: 2.5–19; p < 0.001) was associated with a mild course of TLE.

Conclusions. Although a majority of patients with TLE eventually require surgery, operative treatment is not necessary for all patients. This study identifies prognostic factors that may help patients and clinicians characterize long‐term outcome.
Neuronal autoantibodies in patients with Rasmussen's encephalitis
Authors: Samanci Bedia , Tektürk Pınar , Tüzün Erdem , Erdağ Ece , Kınay Demet , Yapıcı Zuhal , Baykan Betül
Published: August 2019

Aim. Rasmussen's encephalitis (RE) is a rare disease with unknown pathophysiology. To disclose whether anti‐neuronal autoimmunity participates in the aetiology of RE, various neuronal autoantibodies (NAAbs) were investigated in sera of patients with RE and controls.

Methods. The study included five patients who fulfilled the RE diagnostic criteria (clinical, EEG, and MRI findings) as the patient group, and 50 multiple sclerosis patients and 50 healthy subjects as the control groups. Sera were evaluated for various NAAbs by radioimmunoassay or cell‐based assays. All sera were also screened for uncharacterized antibodies to neuronal cell surface or synapse antigens by indirect immunofluorescence using hippocampal cell cultures.

Results. The mean age at onset of seizures was 8.3±3.4 years (range: 4–13.5) and mean follow‐up time was 11.2±5.4 years (range: 5–19). All patients had unihemispheric atrophy of the cerebral cortex and epilepsia partialis continua. Two of the patients had moderate cognitive impairment, while the others were severely affected, as shown by neuropsychological testing. NAAb positivity was not detected in any of the patients.

Conclusion. Immune aetiology is thought to have a role in RE, but the responsible players have not yet been elucidated. Our extensive antibody screening in a small number of patients does not support the presence of antigen‐specific anti‐neuronal autoimmunity in RE pathophysiology.
Epilepsy in KCNH1‐related syndromes
Authors: Mastrangelo Mario , Scheffer Ingrid E. , Bramswig Nuria C. , Nair Lal. D.V. , Myers Candace T. , Dentici Maria Lisa , Korenke Georg C. , Schoch Kelly , Campeau Philippe M. , White Susan M. , Shashi Vandana , Kansagra Sujay , Van Essen Anthonie J. , Leuzzi Vincenzo
Published: August 2019

Aim. KCNH1 mutations have been identified in patients with Zimmermann‐Laband syndrome and Temple‐Baraitser syndrome, as well as patients with uncharacterized syndromes with intellectual disability and overlapping features. These syndromes include dysmorphic facial features, nail hypo/aplasia, thumb and skeletal anomalies, intellectual disability, and seizures. We report the epilepsy phenotype in patients with KCNH1 mutations.

Methods. Demographic data, electroclinical features, response to antiepileptic drugs, and results of significant diagnostic investigations of nine patients carrying mutations in KCNH1 were obtained from referring centres.

Results. Epilepsy was present in 7/9 patients. Both generalized and focal tonic‐clonic seizures were observed. Complete seizure control was achieved with pharmacological treatment in 2/7 patients; polytherapy was required in 4/7 patients. Status epilepticus occurred in 4/7 patients. EEG showed a diffusely slow background in 7/7 patients with epilepsy, with variable epileptiform abnormalities. Cerebral folate deficiency and an increase in urinary hypoxanthine and uridine were observed in one patient.

Conclusions. Epilepsy is a key phenotypic feature in most individuals with KCNH1‐related syndromes, suggesting a direct role of KCNH1 in epileptogenesis, although the underlying mechanism is not understood.
Neurophysiology of myoclonus and progressive myoclonus epilepsies
Authors: Avanzini Giuliano , Shibasaki Hiroshi , Rubboli Guido , Canafoglia Laura , Panzica Ferruccio , Franceschetti Silvana , Hallett Mark
Published: August 2019

The high temporal resolution of neurophysiological recordings makes them particularly suited to faithfully describing the time course of rapid events such as myoclonus and to precisely measure its time relationship with other related activities. In progressive myoclonus epilepsies (PMEs) polygraphy with simultaneous EMG‐EEG recordings is a crucial tool for defining the characteristic of myoclonic jerks their topography over different muscles (namely antagonists), their time course and relationship with vigilance muscle activation and stimulations. Moreover on polygraphic recordings it is possible to detect EEG activities associated to myoclonic jerks and define their time relationship with myoclonus thus differentiating cortical types of myoclonus from subcorticallly generated ones. Tanks to the back averaging technique non obvious time‐locked EEG potentials can be detected on polygraphy, furthermore in stimulus sensitive myoclonus the analysis can include the potential evoked by the somatosensory stimulus (SEP). The polygraphic recording also gives information on muscle activity suppression occurring after jerk or as pure negative myoclonus. Besides the time domain analysis, techniques based on frequency analysis have been developed to evaluate EEG‐EMG coherence. The neurophysiological techniques provide investigators and clinicians with an invaluable information to define the type of myoclonus and its generating circuitry thus substantially contributing in the diagnosis and management of PMEs.
Propagation of seizures in a case of lesional mid‐cingulate gyrus epilepsy studied by stereo‐EEG
Authors: Alkawadri Rafeed , Gonzalez‐Martinez Jorge , Gaspard Nicolas , Alexopoulos Andreas V.
Published: August 2019

Little is known about the propagation of seizures arising from the cingulate gyrus, as cingulate coverage with interhemispheric subdural electrodes is usually challenging and incomplete due to inherent anatomical and vascular limitations. We present a case of lesional mid‐cingulate epilepsy confirmed by stereotactically implanted intracranial depth electrodes and subsequent surgical resection. Hypermotor symptomatology was seen during the first seven seconds of seizure onset while the seizure was still confined to the mid‐cingulate gyrus contacts. The patient had brief contralateral clonic movements as seizure propagated to the primary motor cortex. There was a high concordance between the primary propagation contacts, as delineated by intracranial EEG, and the contacts, with higher coherence values in the connectivity matrix. Interestingly, cingulate‐extra‐cingulate connectivity and spread to the primary motor, premotor, and prefrontal cortex was seen preceding spread to other cingulate contacts, of which one was less than 15 mm from the onset contact. This report is one of a few published, documenting propagation of seizures arising from the mid‐cingulate cortex. As illustrated by these data, hypermotor semiology correlated with direct activation of the cingulate cortex. Subsequent seizure propagation activated an extensive extra‐cingulate rather than an intra‐cingulate epileptogenic network. Interestingly, had the region of onset not sampled, the seizure onset would have appeared as non‐localizing widespread rhythms over the fronto‐parietal convexities. Further studies to explore the propagation of seizures arising from the cingulate gyrus and the physiological and pathological connectivity patterns within the cingulate gyrus in humans are needed, preferably using stereotactic implantation. Specific targets to be investigated are also discussed.
GNAO1‐associated epileptic encephalopathy and movement disorders: c.607G>A variant represents a probable mutation hotspot with a distinct phenotype
Authors: Arya Ravindra , Spaeth Christine , Gilbert Donald L. , Leach James L. , Holland Katherine D.
Published: August 2019

We describe a case of GNAO1‐associated epilepsy and chorea in a patient with a de novo pathogenic mutation. This patient is unique in being the first reported male with this phenotype, and we propose that this genetic variant may represent a mutation hotspot that characterizes a unique phenotype. This 5.2‐years‐old boy presented with seizures, chorea, and severe global developmental delay. Brain imaging showed progressive diffuse cerebral atrophy. EEG monitoring revealed multifocal and diffuse discharges, along with generalized‐onset seizures. Genetic testing found a de novo pathogenic variant in the GNAO1 gene (c.607G>A; p.Gly203Arg). A review of the literature showed two other patients with similar phenotype and the same genetic variant. In contrast, other patients with neurological involvement had private mutations in the GNAO1 gene. The neurological phenotypes associated with GNAO1 mutations appear to lie on a spectrum, and it is possible that the c.607G>A (p.Gly203Arg) variant characterizes a phenotype with both severe epilepsy and chorea. [Published with video sequence on www.epilepticdisorders.com]
Sudden unexpected death in epilepsy (SUDEP): what every neurologist should know
Authors: Shankar Rohit , Donner Elizabeth J. , McLean Brendan , Nashef Lina , Tomson Torbjörn
Published: August 2019

This review aims to empower general neurologists to provide better informed person‐centred advice on sudden unexpected death in epilepsy (SUDEP) to people with epilepsy in order to help keep them safe. Past and present evidence is consolidated in order to inform readers about SUDEP, and up‐to‐date insights into the epidemiology, diagnostic classification, pathophysiology, risk factors, influence of co‐morbidity, and importance of sensitive person‐centred communication are outlined. This review provides “fingertip” information to the practicing neurologist with regards to identifying and communicating risks for SUDEP and suggests practical measures for managing these risks in partnership with the patient.
Managing Lafora body disease with vagal nerve stimulation
Authors: Mikati Mohamad A. , Tabbara Faysal
Published: August 2019

A 17‐year‐old female, of consanguineous parents, presented with a history of seizures and cognitive decline since the age of 12 years. She had absence, focal dyscognitive, generalized myoclonic, and generalized tonic‐clonic seizures, all of which were drug resistant. The diagnosis of Lafora body disease was made based on a compatible clinical, EEG, seizure semiology picture and a disease‐causing homozygous mutation in the EPM2A gene. A vagus nerve stimulator (VNS) was inserted and well tolerated with a steady decrease and then stabilization in seizure frequency during the six months following insertion (months 1–6). At follow‐up, at 12 months after VNS insertion, there was a persistent improvement. Seizure frequency during months 7–12, compared to pre‐VNS, was documented as follows: the absence seizures observed by the family had decreased from four episodes per month to 0 per month, the focal dyscognitive seizures from 300 episodes per month to 90 per month, the generalized myoclonic seizures from 90 clusters per month to eight per month, and the generalized tonic‐clonic seizures from 30 episodes per month to 1.5 per month on average. To our knowledge, this is the second case reported in the literature showing efficacy of VNS in the management of seizures in Lafora body disease.
Hemispheric polymicrogyria and neonatal seizures: a potentially life‐threatening combination
Authors: Brna Paula M. , Harvey A. Simon , Leventer Richard J.
Published: August 2019

Polymicrogyria (PMG) is a heterogeneous malformation of cortical development characterized by excessive gyration and abnormal cortical lamination. Typically, bilateral forms have more severe developmental delay and early‐onset epilepsy, but the full spectrum of severity remains ill‐defined. We report two cases of right hemispheric PMG and neonatal‐onset, drug‐resistant seizures culminating in early death. Case 1 began having seizures on Day 1 of life that intensified in severity and proved resistant to numerous antiepileptic drugs. He underwent right functional hemispherectomy but died three weeks post‐operatively due to ongoing seizures. Case 2 presented with seizures on Day 3 of life and required respiratory support for prolonged ictal apnoeas. Seizures were resistant to antiepileptic drugs and eventually led to respiratory arrest, once aggressive resuscitative measures were withdrawn. In both cases, seizures seemingly originated independently in both hemispheres. These cases represent a severe phenotype of unilateral hemispheric PMG with bilateral seizures.
Epilepsy with myoclonic atonic seizures and chronic cerebellar symptoms associated with antibodies against glutamate receptors N2B and D2 in serum and cerebrospinal fluid
Authors: Matsuura Ryuki , Hamano Shin‐ichiro , Ikemoto Satoru , Hirata Yuko , Suzuki Kotoko , Kikuchi Kenjiro , Takahashi Yukitoshi
Published: August 2019

A 3‐year‐old boy with normal development presented with acute cerebellitis at one year and 10 months of age. His truncal ataxia resolved without treatment. He experienced a relapse of truncal ataxia and atonic seizures at 2 years and one month of age. Five months later, he experienced myoclonic atonic seizures. By 3 years of age, the truncal ataxia had become severe, and the frequency of myoclonic atonic seizures increased. Compared to controls, we found higher levels of anti‐C‐terminal GluN2B and anti‐N terminal GluD2 antibodies in the serum, and anti‐N terminal GluN2B and anti‐C terminal GluD2 antibodies in the cerebrospinal fluid (CSF). A cell‐based assay revealed the presence of anti‐NMDA‐type glutamate receptor antibody in the serum, but absence in the CSF. Ictal EEG of myoclonic atonic seizures showed generalized spike and wave complexes. The patient was diagnosed with myoclonic atonic epilepsy. Adrenocorticotrophic hormone therapy resolved the truncal ataxia and myoclonic atonic seizures, along with the decreased serum anti‐C‐terminal GluN2B and anti‐N‐terminal GluD2 antibodies, and CSF anti‐N‐terminal GluN2B and anti‐C‐terminal anti‐GluD2 antibodies. Our results suggest that the anti‐GluN2B and anti‐GluD2 antibodies may be associated with myoclonic atonic epileptic seizures and chronic cerebellitis.
Ictus emeticus presenting as an unusual seizure type in chromosome 22q11.2 deletion syndrome
Authors: Hung Pi‐Lien , Huang Li‐Tung , Kwan Shang‐Yeong , Chang Kai‐Ping , Chen Hsin‐Hung , Lee Yi‐Yen , Fan Hueng‐Chuen , Chen Chien
Published: August 2019

We present a case study of a patient with chromosome 22q11.2 deletion syndrome presenting with ictus emeticus, together with a review of the relevant literature. The patient developed generalized tonic‐clonic seizures at 3 months old, and seizures eventually remitted after calcium therapy. He then experienced vigorous vomiting that occurred during sleep, with glassy eyes and legs flexion. Video‐EEG recordings exhibited a switch in background activity from organized reactivity during normal sleep to left lateralized temporal delta activity, which was bilaterally synchronized during an emetic attack. The ictal vomiting ceased following management with oxcarbazepine, high‐dose phenobarbital, and a ketogenic diet. The unique seizure type and rare ictal EEG findings are the first reported in a child with chromosome 22q11.2 deletion syndrome. This case highlights that ictus emeticus without detectable epileptic discharge on EEG is one potential epileptic presentation in this genetic syndrome. [Published with video sequence on www.epilepticdisorders.com]
Intracranial investigation of a patient with nodular heterotopia and hippocampal sclerosis: dealing with a dual pathology
Authors: Ladino Lady Diana , Dash Chelsea , Wu Adam , Tellez‐Zenteno Jose Francisco
Published: August 2019

The pre‐operative assessment and surgical management of patients with dual pathology is challenging. We describe a patient with drug‐resistant focal epilepsy with hippocampal sclerosis and extensive periventricular nodular heterotopia in the same hemisphere. The semiology, scalp EEG, and imaging were divergent, but the presence of focal interictal and ictal epileptic discharges of the putative ictal onset zone resulted in successful localization of the epileptogenic zone. A less aggressive resection was performed based on intracranial EEG recording. The patient has been seizure‐free for three years since resection. Electroclinical hypotheses and challenges in defining the epileptogenic network are discussed.
Educational needs of epileptologists regarding psychiatric comorbidities of the epilepsies: a descriptive quantitative survey
Authors: Mula Marco , Cavalheiro Esper , Guekht Alla , Kanner Andres M. , Lee Hyang Woon , Özkara Çiğdem , Thomson Alfredo , Wilson Sarah J. ,   on behalf of the Task Force on Education of the ILAE Commission on Neuropsychiatry
Published: August 2019

Aim. Psychiatric disorders are relatively frequent comorbidities in epilepsy and they have an impact on morbidity, mortality, and quality of life. This is a report from the Task Force on Education of the ILAE Commission on Neuropsychiatry based on a survey about educational needs of epileptologists regarding management of the psychiatric comorbidities of epilepsy.

Methods. The Task Force designed a quantitative questionnaire to survey the self‐perceived confidence of child and adult epileptologists and psychiatrists in managing major psychiatric comorbidities of epilepsy to identify: (1) critical areas of improvement from a list of skills that are usually considered necessary for effective management of these conditions, and (2) the preferred educational format for improving these skills.

Results. A total of 211 respondents from 36 different countries participated in the survey. Confidence and usefulness scores suggest that responders would most value education and training in the management of specific clinical scenarios. Child neurologists identified major Axis I disorders, such as mood and anxiety disorders, while adult neurologists identified attention deficit hyperactivity disorder, intellectual disabilities, and autistic spectrum disorder as key areas. Both adult and child neurologists identified screening skills as the priority. Psychiatrists mainly valued specific training in the management of psychiatric complications of epilepsy surgery or psychiatric adverse events of antiepileptic drugs. Sessions during congresses and face‐to‐face meetings represent the preferred educational format, while e‐learning modules and review papers were chosen by a minority of respondents.

Conclusions. Results of this survey identify key areas for improvement in managing the psychiatric comorbidities of epilepsy and suggest specific strategies to develop better training for clinicians involved in epilepsy care.
Transient lesions of the splenium of the corpus callosum following rapid withdrawal of levetiracetam
Authors: Sawagashira Ryo , Narita Hisashi , Hashimoto Naoki , Kurita Tsugiko , Nakagawa Shin , Saitoh Takuya , Kusumi Ichiro
Published: August 2019

Transient lesions of the splenium of the corpus callosum are characterized by MRI findings. The lesions are very rare, but significant from a clinical standpoint as differential diagnoses include serious conditions such as encephalitis, meningitis, and neuroleptic malignant syndrome. In addition, it is reported that some are attributed to the withdrawal of antiepileptic drugs. Here, we present a case of transient lesions of the splenium of the corpus callosum following rapid withdrawal of levetiracetam alone. To the best of our knowledge, this is the first report of such a case. Moreover, it is reported that cases of incidental transient lesions of the splenium of the corpus callosum are detected in Japan more often than in other countries, and as a result are prone to over‐triage. Taking this into consideration, in the event of transient lesions of the splenium of the corpus callosum, the utmost attention must be paid to clinical symptoms and history relating to any of the aforementioned serious conditions.
Practical clues for diagnosing WWOX encephalopathy
Authors: Tarta‐Arsene Oana , Barca Diana , Craiu Dana , Iliescu Catrinel
Published: August 2019

The WW domain‐containing oxidoreductase gene is implicated in autosomal recessive disorders of the central nervous system, expressed either as spinocerebellar ataxia or as a severe form with early‐infantile epileptic encephalopathy. Here, we describe the electroclinical evolution of these disorders, adding new diagnostic clues based on a case study. The patient, a boy with early‐onset epilepsy, presented with profound global developmental delay, persistent hypsarrhythmia, and epileptic spasms, associated with progressive cerebral atrophy without microcephaly. Metabolic disease was excluded. Whole‐exome sequencing showed mutations in the WW domain‐containing oxidoreductase gene. Our findings extend the phenotypic traits of this aggressive epileptic encephalopathy, with persistent epileptic spasms and hypsarhythmia as a part of the electroclinical phenotype, demonstrating that microcephaly is not mandatory for diagnosis, even when associated with progressive cerebral atrophy. These mutations might be more frequent than expected among early‐onset epileptic encephalopathies. We present practical clues for the diagnosis of WWOX encephalopathy in order to avoid unnecessary investigations and ensure appropriate genetic counselling for the families.
Brain connectivity changes during ictal aggression (a strangulation attempt)
Authors: Bartolomei Fabrice , Lagarde Stanislas , Lambert Isabelle , Trébuchon Agnes , Villalon Samuel Médina , McGonigal Aileen , Benar Christian G
Published: August 2019

Ictal aggressive behaviour is a rare manifestation of focal seizures. We report an episode of ictal aggression occurring during an intracerebrally recorded seizure (using stereoelectroencephalography) in a patient with drug‐resistant temporal lobe epilepsy. Aggression occurred during the last part of the seizure and was coincident with marked EEG slowing of the frontal regions and persistent ictal activity in the medial temporal lobe. A functional connectivity study (h2estimation of interdependencies) showed a bilateral massive hypersynchronization between frontal and temporal regions. This case illustrates the occurrence of aggression during imbalance between the electrical activity in the temporal limbic cortex and prefrontal cortex, in agreement with the current neurobiological theories of aggression.
The use of single bipolar scalp derivation for the detection of ictal events during long‐term EEG monitoring
Authors: Bennis Frank C , Geertsema Evelien E , Velis Demetrios N , Reus Elise EM , Visser Gerhard H
Published: August 2019

Aim. Epilepsy is difficult to diagnose using routine EEG recordings of short duration in patients who have low seizure frequency. Long‐term EEG may be useful but is impractical in an out‐of‐hospital setting. We investigated whether single‐channel scalp EEG placed behind the earlobe is suitable for seizure identification during prolonged EEG monitoring.

Methods. Scalp EEG samples were selected from subjects over 15 years of age, and comprised two segments of either background followed by seizure or background followed by background. Bipolar EEG derivations in three directions (F8‐T8, C4‐T8 and T8‐P8) were evaluated for the presence of a seizure by two experienced reviewers. For each EEG segment containing a seizure, one pair of electrodes was oriented towards the suspected region of seizure onset, while two pairs of electrodes were oriented elsewhere.

Results. The EEG data contained five frontally localized seizures, five parietal, five temporal, two occipital, and four primary or secondary generalized seizures. The sensitivity and specificity for recognition of seizures was 86% and 95% for Reviewer 1, and 79% and 99% for Reviewer 2, respectively. When identifying a seizure with the lead orientation towards the region of seizure onset, both reviewers identified 20 out of 21 seizures (95%). When the lead was not oriented towards the region of seizure onset, the reviewers identified 34 and 30 out of 42 ictal records correctly, respectively.

Conclusions. These results suggest that it is possible to identify epileptic seizures by bipolar EEG derivation using only two scalp electrodes. Lead orientation towards the suspected region of seizure onset is important for optimal detection sensitivity.
De novoabsence status epilepticus of late onset (DNASLO) precipitated by oral treatment with cefuroxime: description of an ambulatory case
Authors: Fernández‐Torre José L , Paramio‐Paz Alicia , López‐Delgado Anjana , Martín-García María , González‐Aramburu Isabel , Hernández‐Hernández Miguel A
Published: August 2019

We describe the case of an elderly woman with an episode of ambulatoryde novoabsence status epilepticus of late onset (DNASLO) after oral treatment with cefuroxime. A high level of suspicion of DNASLO in cases of unexplained confusion in adults or elderly subjects taking cephalosporins is essential to prompt an emergency EEG and, in turn, rapidly achieve an appropriate diagnosis and enable optimal treatment.
Serial EEG findings in anti‐NMDA receptor encephalitis: correlation between clinical course and EEG
Authors: Ueda Jun , Kawamoto Michi , Hikiami Ryota , Ishii Junko , Yoshimura Hajime , Matsumoto Riki , Kohara Nobuo
Published: August 2019

Anti‐NMDA receptor encephalitis is a paraneoplastic encephalitis characterised by psychiatric features, involuntary movement, and autonomic instability. Various EEG findings in patients with anti‐NMDA receptor encephalitis have been reported, however, the correlation between the EEG findings and clinical course of anti‐NMDA receptor encephalitis remains unclear. We describe a patient with anti‐NMDA receptor encephalitis with a focus on EEG findings, which included: status epilepticus, generalised rhythmic delta activity, excess beta activity, extreme delta brush, and paroxysmal alpha activity upon arousal from sleep, which we term“arousal alpha pattern”. Initially, status epilepticus was observed on the EEG when the patient was comatose with conjugate deviation. The EEG then indicated excess beta activity, followed by the emergence of continuous slow activity, including generalised rhythmic delta activity and extreme delta brush, in the most severe phase. Slow activity gradually faded in parallel with clinical amelioration. Excess beta activity persisted, even after the patient became almost independent in daily activities, and finally disappeared with full recovery. In summary, our patient with anti‐NMDA receptor encephalitis demonstrated slow activity on the EEG, including extreme delta brush during the most severe phase, which gradually faded in parallel with clinical amelioration, with excess beta activity persisting into the recovery phase.
A case of anti‐NMDA receptor encephalitis revealed by insular epilepsy
Authors: De Maeseneire Charlotte , Tahry Riem El , Santos Susana Ferrao
Published: August 2019

Anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system that typically manifests predominantly as a psychiatric disorder. However, other manifestations such as epileptic seizures, abnormal movements, and memory or language complications are not unusual. Here, we report the case of a young man who presented with a new‐onset epilepsy, with ictal semiology suggestive of insular involvement; this hypothesis was supported by a PET‐CT study. Anti‐NMDAR antibodies were found in the CSF, confirming the diagnosis of anti‐NMDAR encephalitis. A review of the literature reveals that epilepsy can be the first manifestation of NMDAR encephalitis, with a clear male predominance. Despite its rarity, neurologists should consider this diagnosis for any young patient developing a new‐onset epilepsy with temporal or insular features, particularly if the patient is male. Other cognitive or behavioural signs, even very subtle, should also prompt diagnosis.
Refractory chronic epilepsy associated with neuronal auto‐antibodies: could perisylvian semiology be a clue?
Authors: Gillinder Lisa , Tjoa Linda , Mantzioris Basil , Blum Stefan , Dionisio Sasha
Published: August 2019

Aims. We report a case series of 10 patients with chronic medically refractory antibody‐positive autoimmune epilepsy and assess their common clinical features. Immune‐mediated seizures are most commonly reported in the context of encephalitis or encephalopathy, with few reports focusing on lone, chronic epilepsy in the outpatient setting. Our aim was to define the potential diagnostic clues that might be present in these cases, leading to consideration of an autoimmune cause of the epilepsy.

Methods. We performed a retrospective review of all patients presenting to the outpatient department of our unit who underwent autoimmune screening. All patients with chronic epilepsy and a positive result for an antibody known to be associated with epilepsy were included.

Results. Sixty‐three patients underwent testing. Thirteen returned a positive result, however, only 10 of these were patients which chronic epilepsy who did not present with an acute illness. Common features in these cases included: perisylvian semiology, EEG abnormalities in the mid temporal region, normal or non‐specific MRI findings, depression, and head injury.

Conclusion. In cases of medically refractory, lesion‐negative epilepsy, with predominantly perisylvian semiology, clinicians should have a high level of suspicion for the diagnosis of autoimmune aetiologies and a low threshold to perform autoantibody screening. This is especially true if there are atypical electrographic findings, a previous history of head injury, or co‐morbid depression.