bluuebunny/crossref_metadata_2025 huggingface dataset:
Non‐paraneoplastic limbic encephalitis associated with antibodies to potassium channels leading to bilateral hippocampal sclerosis in a pre‐pubertal girl
Authors: Kröll‐Seger Judith , Bien Christian G. , Huppertz Hans‐Jürgen
Published: August 2019

Limbic encephalitis (LE) is increasingly recognized as a precipitating factor of adult onset temporal lobe epilepsy frequently associated with bilateral hippocampal damage. So far, clinical data in children are rare and only comprise paraneoplastic forms of LE. We describe a 13‐year‐old pre‐pubertal girl in whom non‐paraneoplastic LE was diagnosed according to diagnostic criteria proposed by Bien and Elger (2007). The girl presented with a subacute syndrome comprising memory impairment, affective disturbances, and refractory temporal lobe seizures. Serial MRI scans demonstrated an initial temporomedial swelling with T2/FLAIR signal increase progressing to bilateral hippocampal atrophy within seven months. Two years after onset of symptoms, antibodies to potassium channels were found to be slightly elevated. Immunosuppressive therapy with steroid‐pulses was followed by a transient reduction of seizure frequency, even though this was started more than two years after onset of first symptoms. However, extended immunotherapy was refused by the patient's parents, so no full assessment of the treatment response was possible. In conclusion, this case shows that non‐paraneoplastic LE leading to mesial temporal lobe epilepsy is not restricted to adult patients. The proposed diagnostic criteria therefore should be adapted for paediatric patients. Patients may profit from immunosuppressive therapy even when it is started at a late stage with already overt hippocampal sclerosis.
Efficacy and tolerability of zonisamide in idiopathic generalized epilepsy
Authors: Marinas Ainhoa , Villanueva Vicente , Giráldez Beatriz G. , Molins Albert , Salas‐Puig Javier , Serratosa Jose M.
Published: August 2019

Objective

The objective of this study is to evaluate the efficacy and safety of zonisamide (ZNS) for the treatment of idiopathic generalized epilepsies (IGEs).

Methods

Thirteen patients with different types of IGEs who were treated with ZNS between the years 2006 and 2008 were identified. Efficacy and tolerability were assessed at months 6 and 12 post‐treatment. Response was defined as a 50% or greater reduction in seizure frequency.

Results

Twelve patients (92.3%) continued with ZNS at month 6, and 11 (84.6%) at month 12. Mean daily dose was 319 mg (range 100‐500 mg/d). Response was achieved at month 6 in eight of the 12 patients that continued with ZNS (66.6%), of which 7 were seizure‐free (58.3%). At month 12, eight of the 11 patients that continued with ZNS were responders (72.7%) and 6 were seizurefree (63.6%). For different types of seizures, better responses were observed for absences and generalized tonic‐clonic seizures. Four out of 13 patients (30.7%) experienced adverse events and in two (15.3%), these led to withdrawal.

Conclusion

In this retrospective study, ZNS showed efficacy and tolerability for the treatment of different types of IGEs. Limitations include a small sample size and a relatively short period of follow‐up. Our results are promising and justify the need for prospective controlled trials in IGE.
Status epilepticus in Wilson's disease
Authors: Knight Elia M. Pestana , Gilman Sid , Selwa Linda
Published: August 2019

Rationale. Seizures occur in Wilson's disease (WD), with prevalence figures as high as 4‐6% in specialized academic centers, but status epilepticus is rare. We report a patient with WD who developed non‐convulsive status epilepticus (SE) during therapy with Tetrathiomolybdate (TTM) and review the last 20 years of the relevant literature. Case report. A 55 year‐old right handed man with WD who had parkinsonian features and hepatic cirrhosis was admitted for seizures. Seizures began on week 4 of treatment with TTM (Phase III Study of Tetrathiomolybdate Dose Regimen in Neurological Wilson's Disease). Seizures were characterized by forced clonic eye, head deviation to the right and right arm posturing followed by unresponsiveness, bilateral eye blinking and right hand automatisms. EEG confirmed frequent left frontal seizures. He developed non‐convulsive status epilepticus (NCSE) with electrographic seizures every 5‐10 minutes, lasting for 1‐2 minutes each. Seizures were controlled within 24 hours with fosphenytoin, midazolam and levetiracetam. Brain MRI showed diffuse atrophy, mineralization of the basal ganglia, and patchy FLAIR increase signal in the left frontal lobe. Literature review. We found reports of 6 WD patients with SE, two upon presentation of the disease and before copper removing treatment, and four after months to years of treatment with D‐penicillamine. Conclusion. SE occurs rarely in WD, and our case is the only one reported to develop SE during treatment with TTM. As the literature documented two patients with WD who developed SE prior to copper deposit treatment, our hypothesis is that seizures in WD can be the result of the progression of the disease or a combination of factors but not necessarily due to its treatment alone.
Impairment of the cortical GABAergic inhibitory system in catatonic stupor: a case report with neuroimaging
Authors: Iseki Kazumi , Ikeda Akio , Kihara Takeshi , Kawamoto Yasuhiro , Mezaki Takahiro , Hanakawa Takashi , Hashikawa Kazuo , Fukuyama Hidenao , Shibasaki Hiroshi
Published: August 2019

We report the case of a 32‐year‐old patient who presented with catatonic stupor during the course of acute aseptic encephalitis involving the right frontotemporal area. Flumazenil‐PET performed during the stupor indicated decreased benzodiazepine receptor binding in the right frontotemporal area where glucose metabolism was preserved as revealed by FDG‐PET. An injection of diazepam immediately ameliorated catatonic symptoms and reduced widespread high amplitude slow EEG activities with right frontotemporal predominance. Compared with a SPECT study performed a week earlier, there was no abnormal right‐sided anteriorly predominant cerebral hyperperfusion after injection of diazepam. While neither flumazenil‐ nor FDG‐PET could be repeated, and with the caveat that generalized convulsions occurred initially and epilepsia partialis continua was present for two weeks starting on the 23rd day after illness onset, these findings suggest that in our case the presentation with catatonic stupor may be related to impairment of the cortical GABAergic inhibitory system.
Everyday cognition in temporal lobe and frontal lobe epilepsy
Authors: Cahn‐Weiner Deborah A. , Wittenberg Dana , McDonald Carrie
Published: August 2019

The purpose of this pilot study was to compare the performance of patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) on cognitively‐based daily living tasks. The hypothesis was that patients with TLE would demonstrate relatively more impairment on a test of everyday memory, while patients with FLE would demonstrate relatively more impairment on a test of everyday executive function. The five Daily Living subtests of the Neuropsychological Assessment Battery (NAB) were administered to twenty‐five patients with TLE and nine patients with FLE. The two groups were matched on all demographic variables. The hypothesis was not confirmed: the TLE and FLE patient groups did not demonstrate a double dissociation in memory and executive daily functioning. Rather, both groups were significantly impaired in daily memory functioning, while their executive daily functioning test scores were within normal limits. Relative deficits were also noted in attention in the TLE group and in language in the FLE group, suggesting that despite having focal lesions, functional impairments may be seen in a broad range of daily activities in these patient groups. Generalizability of the findings is limited due to the small number of subjects and because the everyday cognition measures employed may not have been adequately sensitive. Future studies are needed with larger sample sizes to provide a better understanding of how cognitive impairment in epilepsy is associated with deficits in daily functioning.
Predictors and prognosis of status epilepticus treated with intravenous sodium valproate
Authors: Tiamkao Somsak , Sawanyawisuth Kittisak
Published: August 2019

Objective

To retrospectively review the efficacy of intravenous sodium valproate (VPAiv) treatment of status epilepticus (SE) and analyse predictive factors for seizure control and death.

Methods

Patients were included with a diagnosis of SE who had received intravenous sodium valproate (VPAiv) during 2005‐2007 at Srinagarind Hospital, Khon Kaen University, Thailand. Logistic regression analysis with a stepwise approach was used to evaluate the predictors of seizure control and death.

Results

Thirty‐two cases were diagnosed as SE with VPAiv treatment; 12 and 20 patients received VPAiv as the first‐ and second‐line therapy, respectively. SE ceased in nine out of 12 patients (75%) and in seven out of 20 (35%) patients with VPAiv as the first‐ and second‐line therapy, respectively. No serious cardiovascular compromise was recorded. The first‐line therapy of VPAiv was the only factor that was significantly related to seizure control with an adjusted odds ratio [OR] of 5.571; 95% confidence interval [CI] of 1.128‐27.523. Initial leukocytosis and hypotension were significantly associated with death (adjusted OR: 22.765, 95% CI: 1.176‐440.640 and adjusted OR: 37.591, 95% CI: 3.035‐465.571, respectively).

Conclusion

For SE patients who received VPAiv treatment, the first‐line VPAiv was effective. Initial leukocytosis and hypotension were factors that correlated with death.
Effect of methylphenidate on the quality of life in children with epilepsy and attention deficit hyperactivity disorder: an open‐label study using an osmotic‐controlled release oral delivery system
Authors: Yoo Hanik K. , Park Subin , Wang Hee‐Ryung , Lee Joong Sun , Kim Kunwoo , Paik Kyoung‐Won , Yum Mi Sun , Ko Tae‐Sung
Published: August 2019

This open study explored whether methylphenidate could be tolerated and effective in improving the quality of life (QOL) and attention deficit hyperactivity disorder (ADHD) symptoms of children with epilepsy and ADHD. Twenty‐five subjects (aged 10.1 ± 3.0 years) with ADHD and epilepsy were recruited at an outpatient clinic in Seoul, Korea. We used the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), ADHD rating scale (ARS) and clinical global impression (CGI) in this study. Osmotic‐controlled release oral delivery system (OROS) methylphenidate, 1.0 ± 0.4 mg/kg/day, was administered for 55.2 ± 7.5 days. The QOL subscales including physical restriction (p = 0.005), self‐esteem (p = 0.002), memory (p < 0.001), language (p = 0.005), other cognition (p < 0.001), social interaction (p = 0.002), behaviour (p < 0.001), general health (p = 0.002) and QOL (p < 0.001) were significantly increased and the ARS (p < 0.001) and CGI‐Severity of illness scores (p < 0.001) were significantly reduced after medication. Although 60% of subjects had experienced adverse effects, most were tolerable and only two subjects withdrew from the study owing to unbearable adverse effects (anorexia and insomnia). Two subjects had seizure attacks during the study period without having to discontinue the trial drug. Despite limitations related to the small sample size and the open design of the present pilot study, our results suggest that OROS methylphenidate may be well tolerated and effective in reducing ADHD symptoms and improving QOL in this patient population.
Significance of interictal occipital epileptiform discharges in children
Authors: Wang Chunyang , Khurana Divya S. , Kothare Sanjeev V. , Legido Agustin , Harrison Geoffrey , Carvalho Karen S. , Valencia Ignacio
Published: August 2019

Objective

Interictal occipital epileptiform abnormalities have not been well characterized. The objective of this pilot study was to assess their significance in children.

Methods

A search was performed on the EEG database for the keywords “occipital”, “spike”, “sharp wave” and “epileptiform”. Patients were divided into two groups based on the absence of all (group 1) or presence of any (group 2) of the following criteria: mental retardation, cerebral palsy, neurological deficits, abnormal MRI and/or intractable epilepsy. Special attention was given to the spike/sharp wave amplitude/duration and background slowing.

Results

A total of 44 children (eight months to 15 years) were studied. Groups 1 and 2 were each composed of 22 children. Background slowing was more frequent in group 2 (10/22, 45%) compared to group 1 (1/22, 4.5%; p = 0.002). In group 2, 8/22 (36%) had spikes or sharp waves with amplitudes below 50 μV or above 150 μV with a positive predictive value of 89%, and a negative predictive value of 39%. Only 1/22 (4.5%) in group 1 had epileptiform activity outside of the 50‐150 μV range.

Conclusions

The presence of very high or low‐amplitude occipital epileptiform abnormalities or background slowing may be indicative of encephalopathy.
Prevalence of epilepsy in northeast Turkey
Authors: Velioglu Sibel K. , Bakirdemir Metin , Can Gamze , Topbas Murat
Published: August 2019

The aim of this study was to determine the prevalence and clinical and socio‐demographic characteristics of active epilepsy in the population, aged 15 and over, in the province of Trabzon in northern Turkey. We surveyed households and identified 34 epileptic patients (prevalence of 6/1,000), 28 of whom had active epilepsy (prevalence of 5/1,000). Only one case of hot water epilepsy was established among the 5,254 participants. Of the various seizure types, the most common were partial seizures (63%), over half of which were secondary generalised seizures. The largest syndromic category was that of localisation‐related symptomatic cases (46%). Forty‐six percent of cases were of unknown cause, and 16% were resistant to medication. The prevalence rate of active epilepsy in Trabzon is low compared to other parts of Turkey and other developing countries. This may be attributable to several factors, and particularly to variations among socio‐economic factors. The population of Trabzon is regarded as relatively stable and homogenous, and socio‐demographic and health data for the province of Trabzon are much better than those for the rest of the country.
A distinct variant of focal cortical dysplasia type I characterised by magnetic resonance imaging and neuropathological examination in children with severe epilepsies
Authors: Blümcke Ingmar , Pieper Tom , Pauli Elisabeth , Hildebrandt Michelle , Kudernatsch Manfred , Winkler Peter , Karlmeier Anja , Holthausen Hans
Published: August 2019

Focal Cortical Dysplasias (FCDs) present with a large clinicopathological spectrum. FCDs are believed to relate directly to an epileptogenic condition, although seizure control by surgical resection is variable. This applies in particular to young children with multilobar FCDs, suffering from severe epilepsies and psychomotor retardation. Herein, we performed a comparative analysis of presurgically available data and microscopic inspection of resected cortical specimens to further characterise the pathomorphological spectrum of FCD. Multilobar resection procedures were performed in a consecutive series of 18 young children (mean 7.6 years) with severe pharmaco‐resistant epilepsies following extensive presurgical surface‐/invasive video‐EEG monitoring intraoperative electro‐corticography (iECoG), as well as high resolution MRI. In all cases, systematic neuropathological examination of surgical specimens was performed with respect to architectural abnormalities and cell density measurements. These histomorphological data were compared with volumetric MRI analysis. Histopathological examination revealed increased neuronal densities correlating with decreased cortical thickness and abundance of neuronal microcolumns in all cases. Intriguingly, the affected cerebral hemisphere was significantly smaller, relative to the non‐epileptogenic contralateral side, in 16 children of our patient series. In conclusion, hypoplastic neocortex and columnar architectural disorganisation point to compromised cortical development, and appear as distinct FCD subtype in children suffering from severe epilepsies and psychomotor retardation.
Epilepsia partialis continua as the presenting symptom in probable sporadic Creutzfeldt‐Jakob disease
Authors: Taskiran Aslihan , Tezer F. Irsel , Saygi Serap
Published: August 2019

Creutzfeldt‐Jakob disease (CJD) is a rare form of rapidly progressive neurodegenerative disorder. Literature survey reveals only four reported cases of CJD with epilepsia partialis continua. Here, we present a review and a case study, with video‐EEG sequences and characteristic MRI findings, of a fifth patient who presented with epilepsia partialis continua in the very early stage of the disease and followed a fatal course which was faster than expected.[Published with video sequences]
Propofol withdrawal seizures: non‐epileptic nature of seizures in a patient with recently controlled status epilepticus
Authors: Zubair Salman , Patton Thomas , Smithson Kenneth , Sonmezturk Hasan H. , Arain Amir , Abou‐Khalil Bassel
Published: August 2019

Seizures or seizure‐like phenomena which are mostly convulsive have been observed during the induction, maintenance and withdrawal phases of propofol administration. The nature and mechanism of this phenomenon are not well understood and several case reports on these phenomena have presented only indirect evidence. We report on a patient who was administered propofol in order to control status epilepticus with success. However, every attempt at propofol withdrawal was followed by convulsive seizure‐like activity. Continuous EEG monitoring showed muscle artefacts without any ictal discharges. Based on this finding, the propofol treatment was withdrawn and the seizure‐like activity eventually attenuated and resolved. We propose that seizure‐like phenomena associated with propofol withdrawal may not be ictal in nature and should not lead to unnecessary resumption of propofol infusion without documentation of an epileptic origin by EEG.
Impact of side of lesion, seizure outcome and interictal epileptiform discharges on attention and memory after surgery in temporal lobe epilepsy
Authors: Wisniewski Ilona , Wendling Anne‐Sophie , Steinhoff Bernhard J.
Published: August 2019

Purpose

To determine the impact of side of surgery, seizure outcome and interictal epileptiform discharges (IEDs) on attention and memory in a cohort of patients with temporal lobe epilepsy who had undergone unilateral mesial temporal lobe resection.

Material and methods. Ninety‐four patients were investigated pre‐ and postoperatively by means of a standardised neuropsychological battery measuring subcomponents of attention, as well as short‐term, working and long‐term memory. The side of epilepsy surgery, seizure outcome and the presence of postoperative IEDs, as well as their possible relationship to the neuropsychological changes, were assessed. Statistical data were analysed using a repeated‐measures MANOVA.

Results

The absence of seizures following surgery had a positive effect on short‐term memory and attentional control. The occurrence of IEDs was found in patients with impaired figural learning. In terms of attentional control and working memory, patients who continued to present IEDs had also scored lower in these domains prior to surgery.

Conclusion

IEDs had an effect independent of seizure presence, but were found to have a “supplementary negative effect” when the two variables were combined.
Asymmetric hemispheric representation of periictal heart rate modulation is individually lateralised
Authors: Panchani Jaina , Adjei Patrick , Henneberger Christian , Scott Catherine A. , Thompson Alan J. , Diehl Beate , Walker Matthew C. , Surges Rainer
Published: August 2019

Asymmetric cortical representation of cardiac function is a matter of debate and large inter‐individual variability of cortical autonomic networks and different study designs may contribute to this controversy. Lateralised seizure activity in individual patients may provide valuable insights into cortical regulation of cardiac function. We report two patients with focal epilepsy who had seizures arising from both hemispheres. In Patient 1, heart rate increased over two‐fold with seizures arising from the right hemisphere, whereas heart rate increased invariably less with seizures arising from the left hemisphere. In Patient 2, heart rate increased 1.3 fold or less with seizures arising from the left hemisphere, whereas a seizure with right‐sided onset was followed by bradycardia and asystole. Our findings support the notion that effects on autonomic function are lateralised, although lateralisation varies from patient to patient. This may partially explain the difficulty in determining cortical representation of cardiac autonomic function.
Transient parietal hand syndrome after cortical resection
Authors: Oster Joel M. , Apetauerova Diana , Thomas Christine , Cosgrove G. Rees
Published: August 2019

This case study with video recording describes a brief neurological examination of a rare post‐surgical finding in a patient with intractable seizures who had a right parietal topectomy in order to cure focal and disabling epilepsy. Contemporaneously during the resection and while awake intraoperatively, the patient developed features characterised by involuntary, purposeless, and almost ballistic movements of the contralateral left upper extremity. These involved the shoulder and, more distally, the arm with less involvement of the hand itself and some clonic movement at the elbow, persisting for approximately 24 hours after surgery. Although identified in only one case in our series, we have named the resulting clinical phenomenology “parietal hand syndrome”. A Medline search does not reveal any other such case in the English literature with the clinical elements and actual video documentation of neurological examination noted in our case report in the immediate post‐operative setting. In this regard, this is a unique clinical report. [Published with video sequences]
A case imitating Panayiotopoulos syndrome
Authors: Bolukbasi Feray , Hamamcioglu Irem , Demirbilek Veysi , Dogangun Burak , Dervent Aysin
Published: August 2019

Panayiotopoulos syndrome is one of the most common childhood‐specific epileptic disorders. It is characterized by autonomic‐symptoms; the most common being emesis. However, the presence of emetic symptoms may cause misdiagnosis, for example with some organic disorders which have similar autonomic features. On the other hand, since this syndrome has been recently well documented, the tendency for early recognition may lead to overdiagnosis. Here, we present a case which could be mistaken for Panayiotopoulos syndrome based on anamnesis, however, with the aid of ictal video‐EEG monitoring, the patient was shown to present with a non‐epileptic psychogenic seizure. This report is an example of careful evaluation in order to avoid over‐ or underdiagnosis of this benign disorder. [Published with video sequences]
Bilaterally independent epileptic spasms in a case of Aicardi syndrome
Authors: Kobayashi Katsuhiro , Watanabe Kiyoko , Yoshinaga Harumi , Ohtsuka Yoko
Published: August 2019

A girl with Aicardi syndrome was observed to have two distinct types of asymmetric epileptic spasms, as detected by ictal video‐EEG recording at three months of age. When the two types of spasm concurred, they showed no mutual interactions based on either clinical or EEG aspects. This observation does not support the hypothesis that the brainstem always plays an initiating role in generating spasms. [Published with video sequences]
Lamotrigine is favourable for startle‐induced seizures
Authors: Ikeda Hiroko , Imai Katsumi , Ikeda Hitoshi , Shigematsu Hideo , Shishido Takeo , Takayama Rumiko , Fujiwara Tateki , Takahashi Yukitoshi , Inoue Yushi
Published: August 2019

Falling due to startle‐induced seizures (SISs) often leads to injury. The triggers of SIS are mostly unexpected auditory stimuli, which are too common to avoid in daily life. As SISs are often refractory to conventional medications, effective therapeutic options have to be established. We report a small series of six patients treated with lamotrigine (LTG) as add‐on therapy. Seizure control was improved greatly in three of the six patients, resulting in less restricted daily life, but no effect was observed in two and a skin rash developed in one. Patient 1 was a 19‐year‐old man. His seizure comprised of a sudden tonic extension of the extremities induced by auditory or visual stimulus. He fell down due to SISs, five to ten times a day, with frequent injuries. After adding LTG to treatment with valproate (VPA) and clobazam (CLB), SISs were reduced to once a month. Patient 2 was a 51‐year‐old woman. Sudden tonic extension of all limbs induced by unexpected sounds frequently threw her down onto the floor. Addition of LTG to treatment with CLB, zonisamide and phenytoin reduced her SISs from several to less than once a day. Patient 3 was a seven‐year‐old girl with post‐encephalitic epilepsy. After adjunctive treatment of LTG to VPA, the severity of SISs became milder thus avoiding injury, although seizure frequency did not decrease. LTG is potentially effective for the treatment of SISs and may prevent falling. The addition of LTG treatment dramatically improved the lives of the patients presented here and should be considered as an option for startle‐induced seizures.
Early‐onset childhood absence epilepsy: is it a distinct entity?
Authors: Farooque Pue , Goraya Jatinder , Valencia Ignacio , Carvalho Karen S , Hardison H Huntley , Legido Agustin , Khurana Divya S
Published: August 2019

Childhood absence epilepsy (CAE) typically starts between four and seven years of age. Onset before three years is rare and has not been previously reported from North America. We retrospectively reviewed the electroencephalography laboratory database and paediatric neurology clinic records (from January 2000 to June 2009) at our institution in order to identify patients with absence seizures beginning before age three. Information was collected for age, gender, neurodevelopment, antiepileptic drugs (AEDs) used, seizure control, follow‐up, and side effects. Of 12 patients identified, mean age at onset was 20.5 months (range:11 months to two years; follow‐up: six months to 11 years). Seven of 12 patients had normal neurodevelopment and five had speech delay. Four patients were seizure‐free without AEDs, three were seizure‐free with a single AED, and five still had seizures with multiple AEDs. Three patients had recurrences after medication withdrawal. Other previously published series have identified better seizure control than that reported here, however, 16% of the 130 patients so far documented are reported to have poorly controlled epilepsy, indicating that early‐onset CAE is not a homogeneous condition. The debate as to whether early‐onset CAE is a distinct epilepsy syndrome therefore continues. We believe that early‐onset CAE may be a distinct epilepsy syndrome, with some features that overlap with those of typical CAE, as well as unique distinguishing features. Large prospective multicentric studies would be necessary to definitely resolve this matter.
Coexistence of two distinct benign EEG variants in the same subject
Authors: Brigo Francesco , Manganotti Paolo , Fiaschi Antonio , Bongiovanni Luigi Giuseppe
Published: August 2019

Rhythmic temporal theta bursts of drowsiness (RTTD), also known as “psychomotor variant”, and subclinical rhythmic EEG discharge of adults (SREDA) are two EEG patterns of uncertain significance that occur without any correlation with epilepsy. Each of these patterns has been described to occur alone and in the literature there are no previous reports of co‐occurrence of the two distinct benign EEG variants in the same patient. We describe the coexistence of RTTD and SREDA in EEG recordings from the same subject. Although the coexistence of two distinct EEG variants in the same patient is a rarity, these patterns are not so infrequently encountered when present alone and should thus be promptly recognised in order to avoid misdiagnosis of epilepsy due to an over‐interpretation of normal sharp patterns.
Analysis of acylcarnitine levels by tandem mass spectrometry in epileptic children receiving valproate and oxcarbazepine
Authors: Cansu Ali , Serdaroglu Ayse , Biberoglu Gursel , Tumer Leyla , Hirfanoglu Tugba Luleci , Ezgu Fatih Suheyl , Hasanoglu Alev
Published: August 2019

This prospective study was designed to investigate whether or not monotherapy with sodium valproate (VPA) or oxcarbazepine (OXC) affects plasma levels of fatty acylcarnitine esters in children with epilepsy. A total of 56 children with idiopathic partial or generalised epilepsy were included in the study. Patients were assigned to receive either VPA or OXC monotherapy. Free carnitine (C0) and acylcarnitine profiles of the patients were investigated using tandem mass spectrometry at baseline and at six and 18 months after commencement of therapy. For patients receiving VPA or OXC monotherapy, there were no significant differences in plasma levels of C0, compared with baseline, at six and 18 months (p>0.05). Treatment with VPA for six and 18 months correlated with a significant increase in 3‐hydroxy‐isovalerylcarnitine (C5‐OH) (six months: +23%; 18 months: +73%), and significant decreases in the following acylcarnitines: C6‐acylcarnitine (six months: ‐60%; 18 months: ‐66%), C14‐acylcarnitine (six months: ‐25%; 18 months: ‐38%), C16‐acylcarnitine (six months: ‐73%; 18 months:‐73%), and C18:1‐OH‐acylcarnitine (six months:‐60%; 18 months: ‐70%), compared with baseline (p<0.05). In patients receiving OXC monotherapy, on the other hand, plasma concentrations (μmol/L) of acylcarnitines (from C2 to C18:1‐OH) fell within the normal reference range. The results of this study indicate that there are significant biochemical changes in acylcarnitines in ambulatory children on VPA monotherapy but these are not clinically significant. OXC monotherapy had no effect on acylcarnitine metabolism in ambulatory children.
Starting at the beginning: the neuropsychological status of children with new‐onset epilepsies*
Authors: Hermann Bruce P , Jones Jana E , Jackson Daren C , Seidenberg Michael
Published: August 2019

This review examines the neurodevelopmental contribution to the cognitive and behavioural complications of epilepsy. Following a brief review of the lifespan complications of childhood epilepsies, attention turns to cognitive, psychiatric and social correlates of childhood epilepsies reported in population‐based and tertiary care studies. The focus then becomes the neurobehavioural status of children with new‐onset epilepsy; a point in time not confounded by the effects of years of recurrent seizures, medications, and social reactions to epilepsy. Recent research shows that abnormalities in cognition, brain structure and behaviour are present at or near the time of diagnosis. Further, careful history taking indicates that neurobehavioural problems may be present in advance of the first seizure suggesting the potential influence of epileptogenesis, antecedent neuro‐developmental abnormalities, genetic and environmental susceptibilities, and other risk factors. This becomes the substrate upon which to characterise the effects of epilepsy and its treatment on subsequent neurodevelopment. The review concludes with suggestions for future clinical care and research.
PET follow‐up in a case of anti‐NMDAR encephalitis: arguments for cingulate limbic encephalitis
Authors: Chanson Jean‐Baptiste , Diaconu Mihaela , Honnorat Jérôme , Martin Thierry , De Seze Jérôme , Namer Izzie‐Jacques , Hirsch Edouard
Published: August 2019

Background. The lack of specific MRI abnormalities in anti‐NMDA receptor encephalitis makes the identification of the most affected areas difficult. Functional neuroimaging could be useful to identify brain dysfunction associated with psychiatric symptoms, but few precise data are available up to now. Case study. A 27‐year‐old woman was referred for recent behavioural changes and jerks of the right foot. Serial left fronto‐temporal seizures were recorded. Identification of anti‐NMDA receptor antibodies in CSF indicated a diagnosis of anti‐NMDA receptor encephalitis. Two foci of hypermetabolism, in the left prefrontal cortex and the anterior cingulate cortex, were identified using 18‐fluorodeoxyglucose PET and both disappeared after treatment. Brain MRI was normal, except for a mild left prefrontal hypersignal. Conclusions. The increase in marker uptake in motor and premotor regions in our case probably corresponds to epileptic activity. Our data suggest that the anterior cingulate cortex could play an important role in psychiatric symptoms. Other studies are needed to better understand the pathophysiology of anti‐NMDA receptor encephalitis.
Ambulatory non‐convulsive status epilepticus evolving into a malignant form
Authors: Fernández‐Torre José L , Kaplan Peter W , Rebollo Mariano , Gutiérrez Agustín , Hernández‐Hernández Miguel A , Vázquez‐Higuera José L
Published: August 2019

We retrospectively analysed the clinical characteristics, electroencephalogram (EEG) records, brain magnetic resonance imaging (MRI) scans, antiepileptic therapy and prognosis of a case series with ambulatory non‐convulsive status epilepticus (NCSE) which evolved into a malignant form (mNCSE). mNCSE was defined as NCSE that continues or recurs five days or more after the onset of general anaesthesia, including those cases where NCSE recurs upon reduction or withdrawal of anaesthetic therapy. Four women and two men were studied. The mean age was 42.8 years (range: 19‐63 years). Two of six patients had a previous diagnosis of epilepsy. Four patients died. Two patients had a good outcome with return to consciousness and activities of daily life, and one of these subjects developed temporal lobe epilepsy. In four patients, the cause of mNCSE was encephalitis. Clinical presentation was complex partial status epilepticus (CPSE) in three patients and generalised NCSE (GNCSE) in the other three. Two of the latter had encephalitis and one was diagnosed with progressive myoclonus epilepsy (PME) of Lafora type. The mean duration of the NCSE episode was 47.5 days (range: 9‐139 days; SD: 53.1). In three patients, continuous or rhythmic focal epileptiform discharges were the EEG pattern at onset. In the other three, continuous rhythmic generalised spike‐wave, polyspike‐wave or sharp slow‐wave complexes were observed. Antiepileptic treatment was heterogeneous and patients were treated with an average of 6.0 AEDs (range: 3‐10; SD: 3.0). In summary, mNCSE is a severe epileptic condition that occurs often in the context of encephalitis or pre‐existing epilepsy. Both CPSE and GNCSE may occur. Although high mortality is associated with mNCSE, some patients may survive with normal or good recovery.
Possible induction of West syndrome by oxcarbazepine therapy in a patient with complex partial seizures
Authors: Veerapandiyan Aravindhan , Singh Piyush , Mikati Mohamad A
Published: August 2019

Oxcarbazepine has been reported to precipitate myoclonic, generalised tonic‐clonic, absence, and complex partial seizures, and carbamazepine to precipitate absences, myoclonic seizures and spasms. Here, we report a one‐year, six‐month‐old girl with complex partial seizures who developed infantile spasms, developmental regression, and hypsarrhythmia during the two weeks directly following initiation of oxcarbazepine (14 mg/kg/day). All of these resolved within a few days after discontinuation of this medication. Although we cannot rule out that the above association may have been coincidental, or that the improvement may have been due to concurrent therapy, this case raises the possibility that oxcarbazepine, like carbamazepine, may precipitate infantile spasms and West syndrome.
Frontal lobe epilepsy with atypical seizure semiology resembling shuddering attacks or wet dog shake seizures
Authors: Jahodova Alena , Krsek Pavel , Komarek Vladimir , Kudr Martin , Kyncl Martin , Zamecnik Josef , Tichy Michal
Published: August 2019

We report a girl with a drug‐resistant frontal lobe epilepsy caused by focal cortical dysplasia, who exhibited uncommon seizures. The seizures consisted of shoulder or whole body shuddering after a short psychic aura and face grimacing. Consciousness was fully preserved. The seizures resembled “wet dog shake” seizures described in rat models of epilepsy or shuddering attacks in infants. EEG findings were inconclusive, however, MRI showed a clear dysplastic lesion in the right frontal mesial and polar structures. The patient underwent an extended lesionectomy guided by neuronavigation and intraoperative electrocorticography. Focal cortical dysplasia type Ib was histologically confirmed and the patient has been seizure‐free for the three years following resection. [Published with video sequences]
Topiramate and temporal lobe epilepsy: an open‐label study
Authors: Labate Angelo , Siniscalchi Antonio , Mumoli Laura , Aguglia Umberto , Quattrone Aldo , Gambardella Antonio
Published: August 2019

Purpose. To evaluate the efficacy and tolerability of topiramate (TPM) as monotherapy for patients with temporal lobe epileptic seizures based on an observational study. Methods. We evaluated 41 patients (20 female, mean age 54+18 years) with temporal lobe epilepsy (TLE) referred to the Epilepsy Unit, University of Catanzaro, Italy. Patients received TPM as monotherapy directly or after having taken other antiepileptic drugs. Seizure frequency changes and adverse events were recorded. Follow‐up was conducted for a period of at least two years after treatment. Results. Patients received TPM, 50‐600 mg/day, de novo (n=29) or initially as add‐on therapy before the switch (n=12). In total, 28 of 41 patients achieved seizure freedom, whereas 10 showed a ≥50% reduction of seizure frequency. Two patients did not respond well and one patient discontinued TPM due to adverse effects. Conclusions. Our results confirm that TPM as either monotherapy or add‐on therapy at doses of 50‐600 mg/day effectively reduces seizure frequency in TLE. TPM is particular effective and very well tolerated in patients with mild TLE.
Psychogenic gelastic seizures in a patient with hypothalamic hamartoma
Authors: Scarella Timothy , Macken Michael P , Gerard Elizabeth , Schuele Stephan U
Published: August 2019

Gelastic seizures are classically associated with hypothalamic hamartoma. The most effective treatment for gelastic epilepsy is surgery, although confirming that a hypothalamic hamartoma is an epileptic lesion prior to surgical intervention is challenging. Here, we report the case of a patient with a hypothalamic hamartoma who was diagnosed with psychogenic non‐epileptic gelastic seizures using video‐EEG monitoring. [Published with video sequences]
Novel trial designs for monotherapy*
Authors: Brodie Martin J
Published: August 2019

Unlike many other areas of therapeutics, specific regulatory trial programmes are required to be undertaken in newly diagnosed epilepsy to support the licensing of novel antiepileptic drugs for use in drug‐naïve patients. To complicate matters further, American and European regulators have taken markedly different approaches to this issue, with the FDA requiring withdrawal to monotherapy data comparing more than one dose of newer agents with historical controls, whereas the EMA recommends undertaking randomised head‐to‐head studies versus an established comparator. The former studies are designed to show superiority compared to previously published data, whereas the latter will accept a non‐inferiority (equivalence) outcome. This paper discusses the positive and negative aspects of both designs and explores novel alternative options. Particular focus has been placed on placebo‐controlled studies following a single seizure with supportive electroencephalographic and/or brain imaging evidence, in the hope of identifying a realistic design that will satisfy licensing authorities on both sides of the Atlantic Ocean.
Use of simultaneous depth and MEG recording may provide complementary information regarding the epileptogenic region
Authors: Kakisaka Yosuke , Kubota Yuichi , Wang Zhong I. , Piao Zhe , Mosher John C. , Gonzalez‐Martinez Jorge , Jin Kazutaka , Alexopoulos Andreas V. , Burgess Richard C.
Published: August 2019

Simultaneous SEEG‐MEG recording has the potential to define the epileptic spike source accurately. We present a case of a 55‐year‐old female with intractable left temporal lobe epilepsy in whom we evaluated the relationship between the amplitude recorded from SEEG electrodes, inserted in the lateral temporal region, and their distance from the MEG‐modelled spike. We found a quadratic fall‐off relationship between the amplitude and distance. This result supports the concept that the MEG dipoles reflect the “centre” of spike locations and may provide comprehensive information for SEEG which records spike activities directly but is inherently limited in spatial sampling.
Pupillary hippus in nonconvulsive status epilepticus
Authors: Schnell David , Arnaud Laurent , Lemiale Virginie , Legriel Stephane
Published: August 2019

We report the video recording of a patient who experienced pupillary hippus during an episode of nonconvulsive status epilepticus. [Published with video sequences]
Extratemporal surface EEG features do not preclude successful surgical outcomes in drug‐resistant epilepsy patients with unitemporal MRI lesions
Authors: Garganis Kyriakos , Kokkinos Vasileios , Zountsas Basilios
Published: August 2019

Of 47 patients with onset of intractable partial seizures and temporal lobe MRI lesions, subjected to presurgical evaluation and temporal lobe surgery, we identified eight (mean age: 24 years; range: 7‐52 years) demonstrating surface interictal and/or ictal EEG features suggestive of an extratemporal localisation. All eight patients underwent surgery aiming to predominantly resect the lesion, without extending to the extra‐temporal region. The patients were prospectively followed (mean follow‐up duration: 38 months; range: 12‐66 months) and all achieved excellent postoperative seizure control. Extratemporal surface interictal/ictal EEG features were more often encountered in tumoural and focal cortical dysplasia cases, compared with medial temporal sclerosis cases, and were most frequently localised over frontopolar and suprasylvian‐pericentral locations. We postulate that propagation of interictal/ictal activity from the epileptogenic region of the temporal lobe to extratemporal neocortical areas, perhaps utilising the temporal pole and insula as intermediary nodes of a common epileptogenic network, accounts for the presence of our cohort's discordant lesion and EEG features.
Randomised controlled monotherapy trials: which comparators to use?*
Authors: Beghi Ettore
Published: August 2019

As approximately 50% of patients with newly diagnosed epilepsy achieve seizure remission after initial monotherapy, the selection of the first‐choice drug to be used as the gold standard in randomised clinical trials is critical. Several first and second generation drugs have been used in regulatory and pragmatic monotherapy trials with similar efficacy but differing pharmacokinetic, tolerability, and safety profiles. None of the available compounds has an ideal profile and second generation drugs do not appear to present unequivocal advantages in this regard. Compared to first generation drugs, some newer generation antiepileptic drugs may be preferred as they have similar efficacy but lower potential for idiosyncratic reactions and drug interactions. However, more recent antiepileptic drugs also have limitations, which include lack of superiority and, in some cases, unbearable adverse effects. In this light, there are no standard criteria as a reference for the selection of the best comparator for new mono‐therapy trials. However, according to the recommendations of evidence‐based guidelines, carbamazepine still represents the first‐choice drug for patients with partial epilepsy. Ethosuximide may be an option for absence epilepsy. In contrast, for the treatment of patients with other generalised epilepsies, there is no clear indication of preferred drug, as valproate, which has been found to prevail over other compounds, should be withheld in women of childbearing age due to its teratogenic potential, and there is insufficient evidence to choose an alternative drug.
Patient and physician preferences: impact on treatment effectiveness*
Authors: Rheims Sylvain , Ryvlin Philippe
Published: August 2019

The greater reliability of randomised controlled trials (RCTs) over non‐randomised studies to objectively assess efficacy and/or safety of new therapeutic interventions is one of the main paradigms which sustains the evidence‐based decision process in clinical practice. This assumption is primarily based on the hypothesis that randomisation, and particularly blinding procedure, drastically reduces the potential bias related to the preferences of patients and physicians. However, from non‐randomised studies to double‐blind, placebo‐controlled RCTs, the preferences of patients and physicians can impact the evaluation of treatment effectiveness. Both internal validity and external validity of RCTs are impacted by various biases related to patient and physician preferences. Thus, influence of patient and physician expectations on trial outcomes might be much less trivial than expected, both in open‐label and double‐blind, placebo‐controlled, randomised trials. Accordingly, it might be interesting to systematically collect information about patient preferences before randomisation, using dedicated questionnaires, in order to be able to evaluate the impact of non‐preferred allocation on trial results.
Increasing off‐time improves sleep‐disordered breathing induced by vagal nerve stimulation
Authors: Bhat Sushanth , Lysenko Liudmila , Neiman Eli S , Rao Gautami K , Chokroverty Sudhansu
Published: August 2019

Vagal nerve stimulation (VNS) has been reported to adversely impact breathing in sleep. While continuous positive airway pressure is often employed to treat these patients, little data exist on the effects of adjusting various settings on VNS‐induced sleep‐disordered breathing. We describe a patient in whom increasing off‐time caused resolution of VNS‐induced arterial oxygen desaturations in sleep, which we believe is a novel observation.
Discontinuation of antiepileptic drugs after successful surgery: who and when?
Authors: Tellez‐Zenteno Jose F , Hernandez‐Ronquillo Lizbeth , Moien‐Afshari Farzad
Published: August 2019

Surgery is a highly effective treatment for some specific types of refractory epilepsy and once seizure freedom is achieved many patients and clinicians have to ponder whether to taper or discontinue antiepileptic drugs (AEDs). However, there is no standard practice or guidelines and practices vary widely. The few studies that have addressed this question are retrospective and lack randomised, controlled comparisons, making it difficult to draw any solid inferences. This review examines this topic by analysing key data based on the following: controlled studies which compare outcomes in patients with either withdrawn or unmodified AEDs after epilepsy surgery, non‐controlled studies, information from meta‐analyses and systematic reviews, surveys of clinical practice, and other relevant reviews. Between 12 and 32% of patients had seizure relapse following tapering or discontinuation of AEDs, which was not significantly different from 7 to 45% in patients without AED modification. In the event of seizure relapse upon tapering of AEDs, 45‐92.3% restarted AED treatment and regained seizure freedom. The most consistent risk factors for seizure relapse were: age older than 30 years at the time of surgery, persistent auras, early drug tapering, seizure recurrence before a reduction of drugs, normal MRI, a longer period with epilepsy, absence of hippocampal sclerosis, and the presence of interictal discharges on EEG after surgery.