bluuebunny/crossref_metadata_2025 huggingface dataset:
Management and monitoring of patients treated with zonisamide: the OZONE study
Authors: Dupont Sophie , Biraben Arnaud , Lavernhe Gilles , Marquet Thierry , Allaf Bashar
Published: August 2019

Aim

Tocharacterise patients treated with zonisamide in everyday practice and describe the effectiveness and tolerability of treatment.

Methods

This was an observational, longitudinal, naturalistic study, conducted by neurologists in France. Patients who had started zonisamide treatment at least three months prior to inclusion were eligible. Data were collected at routine consultations at inclusion (Visit 1) and three to six months later (Visit 2). At Visit 1, investigators documented epilepsy‐related variables based on patient records before initiation of zonisamide and at inclusion. At Visit 2, the investigators re‐evaluated seizure activity and rated effectiveness. Adverse events were also documented.

Results

A total of 428 patients were included in the study based on evaluation by 132 neurologists. Zonisamide was initiated at a daily dose of 50 mg and 25 mg in 61% and 31.8% of patients, respectively. The median maintenance dose was 300 mg/day. Prior to initiation of zonisamide, the mean seizure frequency was 16.0 seizures/month. This was reduced to 8.7 seizures/month at Visit 1 and to 7.1 seizures/month at Visit 2. The response rate and proportion of seizure‐free patients was 61.9 and 31.1% at Visit 1 and 65.9 and 25.6% at Visit 2, respectively. The frequency of seizures at Visit 2 decreased significantly (p<0.05) for all seizure type subgroups, except for simple partial seizures. Responder rates were >60% for all analysed subgroups. The proportion of seizure‐free patients was significantly higher in patients receiving bitherapy, compared to the others (p=0.007). The most frequently reported adverse event was somnolence (5.1%); three serious adverse events were reported.

Conclusion

In everyday practice, zonisamide is principally used in association with other antiepileptic drugs for the treatment of focal epilepsy in adults. It is effective in improving seizure control and quality of life, and is generally well‐tolerated.
Presentation, diagnosis and treatment of bilateral Rasmussen's encephalitis in a 12‐year‐old female
Authors: Peariso Katrina , Standridge Shannon M , Hallinan Barbara E , Leach James L , Miles Lili , Mangano Francesco T , Greiner Hansel M
Published: August 2019

Aim

To describe the clinical course and pathological diagnosis of a 12‐year‐old female who presented with an acute syndrome of right hemispheric epilepsy and cortical dysfunction and brain MRI demonstrating atrophy of the left cerebral and right cerebellar hemispheres.

Results

The patient presented with occasional partial seizures consisting of a left calf sensation followed by left leg clonic jerking. Initial brain MRI showed left cerebral and right cerebellar atrophy with T2 hyperintensity in the left parietal region. After six months, the seizure frequency increased and semiology evolved to include frequent clonic movements of the left side of the face, arm and leg and epilepsia partialis continua (EPC) of the left arm and leg. There was progressive weakness of the left leg and, to a lesser extent, her left arm. MRI at this time demonstrated an additional T2 hyperintensity in the right frontal lobe. An extensive evaluation for paraneoplastic, mitochondrial, and genetic epilepsy syndromes was unrevealing. On biopsy evaluation, chronic T‐cell mediated encephalitis was demonstrated within bilateral frontal lobes. Treatment with immunomodulatory therapy resulted in some improvement in her seizure frequency and motor function.

Conclusion

Rasmussen's encephalitis can be a challenging diagnosis. The patient's clinical history, including EPC, with bilateral frontal lobe biopsies confirming a T‐cell mediated encephalitis supports a diagnosis of bilateral Rasmussen encephalitis. This case highlights the diagnostic challenges and treatment dilemmas that arise in an adolescent presenting with bilateral inflammatory lesions of Rasmussen's encephalitis. [Published with video sequences]
Epileptic and electroencephalographic manifestations of guanidinoacetate‐methyltransferase deficiency
Authors: Mikati Abdul G. , Gheida Ibrahim Abu , Shamseddine Alhan , Mikati Mohamad A , Karam Pascale E
Published: August 2019

Aim. Describe the seizure‐related manifestations of guanidinoacetate methyltransferase (GAMT) deficiency in two new cases and compare these to the related literature. Methods. We reviewed the clinical and electroencephalographic manifestations of two siblings with GAMT deficiency. We also performed a thorough literature review of all cases of GAMT deficiency, using the PubMed database, and compared our findings to those previously reported. Results. One sibling presented with Lennox‐Gastaut syndrome while the second had manifestations of late‐onset West syndrome. Based on a literature search, we found that the clinical picture of GAMT deficiency has been described in a total of 58 cases, including our two patients, 45 of whom had at least some description of EEG and/or seizure manifestation. Epilepsy was present in 81%, with age at onset usually between 10 months and 3 years. Drug resistance was observed in approximately 45%. Initial seizures were febrile, tonic, or tonic‐clonic. Drop attacks and generalised seizures were the most frequent seizure type. Absence and febrile seizures also occurred. Less frequently, focal seizures and late‐onset infantile spasms (one prior case) were observed. Multifocal spikes and generalised <3‐Hz‐spike slow waves were common while only one prior single case report of hypsarrhythmia was described. Lennox‐Gastaut syndrome was common, while progressive myoclonic epilepsy was also, less frequently, reported. Conclusions. To our knowledge, this is the second report of the occurrence of West syndrome in GAMT deficiency. The majority of patients with GAMT deficiency have seizures and approximately half are drug‐resistant. Late‐onset of hypsarrhythmia and/or epileptic spasms could potentially prove to be a distinctive, albeit infrequent, feature of this treatable metabolic disorder.
Pyridoxine‐dependent epilepsy due to antiquitin deficiency: achieving a favourable outcome
Authors: Oliveira Renata , Pereira Cristina , Rodrigues Fidjy , Alfaite Claudia , Garcia Paula , Robalo Conceição , Fineza Isabel , Gonçalves Olavo , Struys Eduard , Salomons Gajja , Jakobs Cornelis , Diogo Luísa
Published: August 2019

We report 4 pyridoxine‐dependent epilepsy patients in which good outcome was determined in three. The 4 patients were male and aged from 7 to 24 years old (from three unrelated Caucasian families). A clinical diagnosis of neonatal pyridoxine‐dependent epilepsy was confirmed by biochemical and genetic studies. Clinical evaluation was performed and medical records were reviewed for therapy implementation and management, neurodevelopment outcome, magnetic resonance imaging, and electroencephalography. All were taking pyridoxine treatment and were seizure‐free. Elevated urinary alpha‐aminoadipic semialdehyde excretion was found in all patients. Antiquitin gene analysis identified a large homozygous deletion in one patient and two heterozygous mutations in the others. Treatment with pyridoxine should be attempted for all cases of infantile and childhood refractory epilepsy, as has been the case over the last 20 years. Currently, urinary alpha‐aminoadipic semialdehyde is a reliable biomarker of pyridoxine‐dependent epilepsy, even under pyridoxine treatment. Detection of mutations in the antiquitin gene, encoding alpha‐aminoadipic semialdehyde dehydrogenase, establishes the diagnosis and allows for adequate genetic counselling.
What are the predictors of major depression in adult patients with epilepsy?
Authors: Kui Chen , Yingfu Pan , Chenling Xu , Wenqing Wu , Xiuhua Li , Di Sun
Published: August 2019

Epilepsy is not only a chronic neurological disorder but also a condition associated with other comorbidities. The purpose of this study was to determine the prevalence of major depression in a cohort of adult patients with epilepsy (PWEs) living in north China, and investigate the predictors of major depression in PWEs. A total of 215 consecutive cases were enrolled and divided into two groups: PWEs with major depression and PWEs without major depression. Patients were assessed for demographic characteristics, epilepsy details, and social status. A total of 65 of 215 (30.23%) PWEs exhibited comorbid major depression. A binary logistic regression model revealed the strong predictor variables of major depression to be drug responsiveness (odds ratio [OR]=0.23; p=0<0.01; 95% CI [0.13–0.39]), presence of chronic medical illnesses (OR=0.19; p=0.015<0.05; 95% CI [0.05–0.72]), and employment status (OR=0.42; p=0.015<0.05; 95% CI [0.21–0.84]).
Side‐to‐side axial movements
Authors: Franca Sara , Gupta Deepak K. , Rao Shyam , Pestana Elia , Freitas Joel , Loplumlert Jakrin , Lhatoo Samden D.
Published: August 2019

Aim. To study new semiological signs which help distinguish between primary and secondarily generalised tonic‐clonic seizures (GTCS). Methods. We retrospectively studied 86 GTCS, 13 primary and 73 secondary, in 58 patients who underwent video‐EEG (vEEG) evaluation in our epilepsy monitoring unit. Eleven patients had generalised epilepsy and 47 focal epilepsy. Two expert epileptologists, blinded to diagnosis, examined the vEEGs independently for the presence of five semiological signs. Results. Asymmetry of limb movements in clonic phase, side‐to‐side axial movements, and asymmetric seizure termination occurred more frequently (p<0.05) in secondary GTCS compared to primary GTCS. Combining asymmetry of limb movements in clonic phase and side‐to‐side axial movements provided the greatest value in differentiating secondary GTCS from primary GTCS. Conclusion. Careful examination of GTCS seizure semiology can help differentiate primary from secondary GTCS. The semiological sign of side‐to‐side axial movements, which has not previously been studied in this context, may add to existing literature of semiological signs and be of value for the evaluation of surgical patients in the epilepsy monitoring unit. In the out‐patient setting, a clear history of these signs may help guide drug treatment choices. [Published with video sequences].
Confirming an expanded spectrum of SCN2A mutations: a case series
Authors: Matalon Dena , Goldberg Ethan , Medne Livija , Marsh Eric D.
Published: August 2019

Mutations in sodium channel genes are highly associated with epilepsy. Mutation of SCN1A, the gene encoding the voltage gated sodium channel (VGSC) alpha subunit type 1 (Nav1.1), causes Dravet syndrome spectrum disorders. Mutations in SCN2A have been identified in patients with benign familial neonatal‐infantile epilepsy (BFNIE), generalised epilepsy with febrile seizures plus (GEFS+), and a small number of reported cases of other infantile‐onset severe intractable epilepsy. Here, we report three patients with infantile‐onset severe intractable epilepsy found to have de novo mutations in SCN2A. While a causal role for these mutations cannot be directly established, these findings contribute to growing evidence that mutation of SCN2A is associated with a range of epilepsy phenotypes including severe infantile‐onset epilepsy.
A 15‐year follow‐up of first unprovoked seizures: a prospective study of 200 children
Authors: Pereira Cristina , Resende Cristina , Fineza Isabel , Robalo Conceição
Published: August 2019

Epilepsy is associated with an extended spectrum of behaviour, psychiatric problems, and learning difficulties. The aim of this study was to establish the natural history of children with first unprovoked seizures. We studied prospectively 200 children under the age of 11 years who attended hospital emergency with a first unprovoked seizure. Demographic variables, personal and family history, neurological examination, EEG, psychiatric, and cognitive and educational profiles were analysed. Patients who developed epilepsy were characterised with respect to: time to relapse, remission rate, duration of epilepsy, neuroimaging, aetiology, epileptic syndrome, and therapeutic regimen. These results were compared to data of patients who had a single seizure over a follow‐up period of 15 years. Thirty percent of children who had a first unprovoked seizure developed epilepsy. Partial seizure type was a statistically significant variable for the development of epilepsy. An EEG with epileptic abnormalities proved to be the main risk factor for recurrence. Fifteen years later, the group with epilepsy exhibited a 2.6 greater risk of psychiatric and academic comorbidities, compared to the group without epilepsy.
Predicting diurnal and sleep/wake seizure patterns in paediatric patients of different ages
Authors: Ramgopal Sriram , Powell Christine , Zarowski Marcin , Alexopoulos Andreas V. , Kothare Sanjeev V. , Loddenkemper Tobias
Published: August 2019

Aim. To identify factors that influence diurnal and sleep/wake seizure timing in children undergoing tapered drug withdrawal in an epilepsy monitoring unit. Methods. Medical charts of patients that underwent video‐EEG were reviewed. Seizures were evaluated based on their occurrence in three‐hour time intervals (bins) and between wakefulness and sleep. Patients were classified according to EEG localisation and age: infants (≤3 years), children (3–12 years), and adolescents (>12–21 years). Analysis utilising generalised estimating equations with a negative binomial distribution was performed. Results. A total of 390 patients (188 girls; mean age: 9.2 years; SD: 6.0) had 1,754 seizures. Generalised seizures (109 patients; 490 seizures) occurred more during wakefulness (p<0.001) and during the day (p<0.001). Modelling revealed a greater occurrence of seizures at night with increasing age (p=0.046). Temporal lobe seizures (62 patients; 271 seizures) occurred overall more frequently during wakefulness (p=0.03). Frontal lobe seizures (41 patients; 184 seizures) occurred more frequently during wakefulness in infants (p<0.05) and more frequently during sleep in adolescents (p<0.0001). Adolescents with frontal lobe seizures were 3.6 times more likely to have seizures during sleep compared to other children (95% CI: 1.8–7.2). Conclusion. These findings are suggestive of changes in circadian rhythmicity that may alter seizure susceptibility in different age groups. The results may assist in prediction of periods of greatest seizure propensity.
Infantile epileptic encephalopathy with a hyperkinetic movement disorder and hand stereotypies associated with a novel SCN1A mutation
Authors: Ohashi Tsukasa , Akasaka Noriyuki , Kobayashi Yu , Magara Shinichi , Kawashima Hideshi , Matsumoto Naomichi , Saitsu Hirotomo , Tohyama Jun
Published: August 2019

We report a female patient who presented with intractable epileptic seizures, profound developmental delay since early infancy, and hyperkinetic movements with hand stereotypies. The patient initially developed focal seizures with multiple foci at 3 months of age. Thereafter, the seizures evolved to frequent episodes of hyperthermia‐induced status epilepticus. A novel de novo SCN1A mutation was identified by whole‐exome sequence analysis. This case demonstrates that SCN1A mutations may cause movement disorders as an atypical phenotype and the case history of this patient may expand our understanding of the clinical spectrum of SCN1A‐associated epileptic encephalopathy. [Published with video sequences]
Lacosamide‐induced rash
Authors: Koubeissi Mohamad Z. , Vismer Marta , Ehrlich Alison
Published: August 2019

Cutaneous eruptions and hypersensitivity represent frequently reported side effects of anti‐seizure medications. However, these side‐effects have rarely been previously reported for lacosamide, a newer‐generation anti‐seizure medication with a novel mechanism of action. Here, we report a case of diffuse skin eruption in a patient with history of epilepsy soon after initiation of lacosamide. The rash resolved after discontinuation of lacosamide and use of antihistamines and steroids. We also review the information on drug hypersensitivity syndrome.
Mutational analysis of paediatric patients with tuberous sclerosis complex in Korea: genotype and epilepsy
Authors: Lee Jin Sook , Lim Byung Chan , Chae Jong‐Hee , Hwang Yong Seung , Seong Moon‐Woo , Park Sung Sup , Kim Ki Joong
Published: August 2019

To date, only a few studies have reported that, in tuberous sclerosis, TSC2 mutations are more frequently associated with infantile spasms and cognitive impairment compared to TSC1 mutations. We analyzed the mutational spectrum of patients with tuberous sclerosis in Korea and attempted to explore the associations between genotype and seizure type/outcome. We performed mutational analyses on 70 unrelated patients with clinically confirmed tuberous sclerosis by using direct DNA sequencing and/or multiplex ligation‐dependent probe amplification. The patients’ medical records, including epilepsy type and outcome, were reviewed retrospectively. We identified pathogenic mutations in 55 patients (79%), 25 of which were novel. There were 12 TSC1 mutations and 43 TSC2 mutations. TSC1 mutations included 8 frameshift and 4 nonsense mutations. TSC2 mutations included 12 frameshift, 10 nonsense, 6 splicing, and 6 missense mutations, as well as 4 in‐frame deletions and 5 large deletions. Fifty‐eight patients had epilepsy (83%), including 19 patients with a history of infantile spasms. Compared to patients with TSC1 mutations, individuals with TSC2 mutations had a significantly higher frequency of epilepsy (p<0.05) and tended to have a higher frequency of infantile spasms (37% vs 17%; p<0.3). Most of the patients with TSC2 mutations who developed infantile spasms exhibited subsequent epilepsy (13/14; 93%). However, the presence/absence of infantile spasms did not influence seizure remission or cognitive outcome.
Epileptic spasms without hypsarrhythmia in infancy and childhood: tonic spasms as a seizure type
Authors: De Marchi Luciana R , Seraphim Evelyn A , Corso Jeana T , Naves Pedro VF , de Carvalho Kelly Cristina , Ramirez Milton David H , Ferrari‐Marinho Taissa , Guaranha Mirian SB , Yacubian Elza Márcia T
Published: August 2019

Epileptic spasms were defined by the International League Against Epilepsy Task Force on Classification and Terminology in 2001 as a specific seizure type. Epileptic spasms without hypsarrhythmia have been described in some series of patients, occurring either in infancy or childhood. More prolonged epileptic spasms without hypsarrhythmia were previously defined as a different seizure type, and referred to as “tonic spasm seizures”. Here, we present a 5‐year‐old boy who started having epileptic spasms without hypsarrhythmia at 8 months of age, effectively treated with oxcarbazepine. With the withdrawal of medication, epileptic spasms returned. Video‐EEG monitoring revealed high‐voltage slow waves superimposed by low‐voltage fast activity, followed by an electrodecremental phase and a burst of asymmetric fast activity, time‐locked to clinical tonic spasm seizures. Brain MRI showed left temporal atrophy with temporal pole grey/white matter junction blurring and ictal PET‐CT showed left basal frontal hypermetabolism. Seizures were refractory to several AEDs and vigabatrin was introduced with seizure cessation. Despite efforts to classify epileptic spasms, these are still considered as part of the group of unknown seizure types. In some cases, a focal origin has been suggested, leading to the term “periodic spasms” and “focal spasms”. In this case, epileptic spasms without hypsarrhythmia, associated with tonic spasms, may be a variant of focal spasms and might be considered as an epileptic syndrome. [Published with video sequence]
Cognitive impairment in epilepsy: the role of network abnormalities
Authors: Holmes Gregory L
Published: August 2019

The challenges to individuals with epilepsy extend far beyond the seizures. Co‐morbidities in epilepsy are very common and are often more problematic to individuals than the seizures themselves. In this review, the pathophysiological mechanisms of cognitive impairment are discussed. While aetiology of the epilepsy has a significant influence on cognition, there is increasing evidence that prolonged or recurrent seizures can cause or exacerbate cognitive impairment. Alterations in signalling pathways and neuronal network function play a major role in both the pathophysiology of epilepsy and the epilepsy comorbidities. However, the biological underpinnings of cognitive impairment can be distinct from the pathophysiological processes that cause seizures.
The natural history and prognosis of epilepsy
Authors: Beghi Ettore , Giussani Giorgia , Sander Josemir W.
Published: August 2019

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Generally, prognosis refers to the probability of attaining seizure freedom on treatment and little is known about the natural history of the untreated condition. Here, we summarize aspects of the prognosis and prognostic predictors of treated and untreated epilepsy and of its different syndromes. Usually, epilepsy is a fairly benign condition. Most epilepsies have a good prognosis for full seizure control and eventual discontinuation of AEDs, but epilepsy syndromes have differing outcomes and responses to treatment. Prognostic factors include aetiology, EEG abnormalities, type of seizures and the number of seizures experienced before treatment onset, and poor early effects of drugs. Early response to treatment is an important positive predictor of long‐term prognosis, while the history of a high number of seizures at the time of diagnosis, intellectual disability, and symptomatic aetiology are negative predictors. Different prognostic patterns can be identified, suggesting that the epileptogenic process is not static. Epilepsy carries a greater than expected risk of premature death. Aetiology is the single most important risk factor for premature death.
Epilepsy classification and additional definitions in occipital lobe epilepsy
Authors: Yilmaz Kutluhan , Karatoprak Elif Yüksel
Published: August 2019

Aim. To evaluate epileptic children with occipital lobe epilepsy (OLE) in the light of the characteristics of Panayiotopoulos syndrome and late‐onset occipital lobe epilepsy of Gastaut (OLE‐G).

Methods. Patients were categorized into six groups: primary OLE with autonomic symptoms (Panayiotopoulos syndrome), primary OLE with visual symptoms (OLE‐G), secondary OLE with autonomic symptoms (P‐type sOLE), secondary OLE with visual symptoms (G‐type sOLE), and non‐categorized primary OLE and non‐categorized secondary OLE according to characteristic ictal symptoms of both Panayiotopoulos syndrome and OLE‐G, as well as aetiology (primary or secondary). Patients were compared with regards to seizure symptoms, aetiology, cranial imaging, EEG, treatment and outcome.

Results. Of 108 patients with OLE (6.4±3.9 years of age), 60 patients constituted primary groups (32 with Panayiotopoulos syndrome, 11 with OLE‐G, and 17 with non‐categorized primary OLE); the other 48 patients constituted secondary groups (eight with P‐type sOLE, three with G‐type sOLE, and 37 with non‐categorized sOLE). Epileptiform activity was restricted to the occipital area in half of the patients. Generalized epileptiform activity was observed in three patients, including a patient with Panayiotopoulos syndrome (PS). Only one patient had refractory epilepsy in the primary groups while such patients made up 29% in the secondary groups.

Conclusion. In OLE, typical autonomic or visual ictal symptoms of Panayiotopoulos syndrome and OLE‐G do not necessarily indicate primary (i.e. genetic or idiopathic) aetiology. Moreover, primary OLE may not present with these symptoms. Since there are many patients with OLE who do not exhibit the characteristics of Panayiotopoulos syndrome or OLE‐G, additional definitions and terminology appear to be necessary to differentiate between such patients in both clinical practice and studies.
Inflammatory markers associated with seizures
Authors: Sohn Hong Seok , Kim Sung Keun , Lee Seo‐Young
Published: August 2019

Aim. Seizures can produce systemic changes, including elevated body temperature, white blood cell count, and C‐reactive protein levels, which raises concern for potential infection. We describe seizure‐induced inflammation‐like responses and discuss how these changes may be distinguished from those associated with infection.

Methods. We prospectively investigated 140 consecutive visits to the emergency room, in which patients presented with seizures. We defined elevated body temperature, white blood cell count, or C‐reactive protein levels as inflammation‐like responses. We investigated the occurrence of inflammation‐like responses, characteristics of the seizures, neurological status at the initial visit, outcomes, and clinical findings to determine the presence of infection. We ascertained whether the patients had infection or not based on the overall information post‐discharge.

Results. An inflammation‐like response was observed in 56.3% of all visits and 19.3% were diagnosed with concurrent infection. Among the visits with inflammation‐like response, 34.7% were shown to have an infection. Increases in body temperature and C‐reactive protein levels were milder (<39°C and <6 mg/dl, respectively) in patients without infection compared to those with infection, whereas there was no difference in leukocytosis, with regard to the presence or absence of infection. Increased body temperature occurred only in cases of generalized tonic‐clonic seizures, whereas leukocytosis and elevated C‐reactive protein levels were reported in patients with any type of seizure. Body temperatures returned to normal within eight hours in uncomplicated cases.

Conclusion. Seizures frequently induce an increase in body temperature, white blood cell count, or C‐reactive protein levels, making it challenging to distinguish these changes from those associated with infection. Nonetheless, elevated body temperature in the absence of generalized tonic‐clonic seizures, above 39°C, or persisting for more than eight hours after recovery of consciousness, and C‐reactive protein levels above 6 mg/dl warrant close observation and consideration for concurrent infection.
Reflex operculoinsular seizures
Authors: Xiao Handsun , Tran Thi Phuoc Yen , Pétrin Myriam , Boucher Olivier , Mohamed Ismail , Bouthillier Alain , Nguyen Dang Khoa
Published: August 2019

Activation of specific cortical territories by certain stimuli is known to trigger focal seizures. We report three cases of well documented operculo‐insular reflex seizures, triggered by somatosensory stimuli in two and loud noises in the third. Limited operculoinsular resection resulted in an excellent outcome for all. We discuss these observations in regard to the literature on reflex epilepsy and known functions of the insula. [Published with video sequences online]
One‐year clinical experience of perampanel in Spain: a multicentre study of efficacy and tolerability
Authors: Garamendi‐Ruiz Iñigo , García‐García María Eugenia , Bertol‐Alegre Vicente , Mauri‐Llerda José Ángel , García‐Morales Irene , Garayoa‐Irigoyen Vanesa , Agúndez‐Sarasola Marta , De Toledo‐Heras María , García‐Morales Vanessa , García‐Gomara María José , Arcos‐Sánchez Carolina , Gago‐Veiga Ana , Escalza‐Cortina Inés , Rueda‐Mena Eliana , Muñoz‐Fargas Elena , Santos‐Lasaosa Sonia , Oliván‐Usieto José Antonio , de Cerio‐Julián Leyre Díaz , Gómez‐Esteban Juan Carlos , Marinas‐Alejo Ainhoa
Published: August 2019

Perampanel, a non‐competitive antagonist of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid receptors, is the most recent antiepileptic drug available in Spain, marketed in January 2014. It was initially approved by the European Medicines Agency as adjunctive treatment for partial‐onset seizures in patients 12 years and older, but recently also for primary generalized tonic‐clonic seizures. Although clinical trials provide essential information about the drug, they do not reflect daily clinical practice. This retrospective study shows the initial experience with perampanel in 11 Spanish hospitals during its first year post‐commercialisation. All patients who started perampanel treatment were included, but efficacy and tolerability were only assessed in those patients with a minimum follow‐up period of six months. In total, 256 patients were treated with perampanel before September 2014, and 253 had an observational period of one year. After six months, 216/256 patients (84%) continued on perampanel and 180/253 (71.1%) completed one year of treatment. The mean number of previous antiepileptic drugs used was 6.83 and the median number of concomitant antiepileptic drugs was 2. The mean perampanel dose was 7.06 mg and 8.26 mg at six and 12 months, respectively. The responder rate was 39.5% and 35.9% at both follow‐up points, respectively. Adverse events were experienced by 91/253 (35.5%) and resulted in withdrawal in 37 (14.6%). The most common adverse events were somnolence, dizziness, and irritability. We found no significant differences between concomitant use of enzyme‐inducing and non‐inducing antiepileptic drugs, regarding efficacy, adverse effects, or withdrawals. Irritability was not influenced by concomitant use of levetiracetam, relative to other drugs, but was more frequently observed in patients with a history of psychiatric problems or learning disabilities.
Progressive myoclonus epilepsy associated with neuroserpin inclusion bodies (neuroserpinosis)
Authors: Roussel Benoit D. , Lomas David A. , Crowther Damian C.
Published: August 2019

Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a conformational proteinopathy characterised by neuronal inclusion bodies composed of the serine protease inhibitor (SERPIN), neuroserpin. Presenting clinically as a familial dementia‐epilepsy syndrome, the molecular mechanism of the pathogenic abnormalities in neuroserpin has been characterised at atomic resolution. There is a remarkable genotype‐phenotype correlation between the degree of molecular destabilisation of the several variants of the neuroserpin protein, their propensity to self‐associate and the age of onset of the dementia‐epilepsy complex. As with other serpinopathies there appears to be a mix of cell‐autonomous toxicity, due to neuronal accumulation of neuroserpin, and non‐cell autonomous toxicity, caused by loss of protease inhibition, in this case the dysregulated protease is likely to be tissue plasminogen activator (tPA). FENIB should be considered in cases of progressive myoclonic epilepsy and dementia particularly where there is family history of neuropsychiatric disease.
Post‐modern therapeutic approaches for progressive myoclonus epilepsy
Authors: Minassian Berge A.
Published: August 2019

While the PME are arguably the severest epilepsies and neurological disorders, the vast majority are monogenic. Additionally, many affect straightforward biochemical pathways. Finally, by definition, they occur in previously healthy and well‐developed brains. As such, their therapies should be easier than in complex, albeit often less severe, neurological developmental disorders where the complex, poorly understood, and extremely difficult‐to‐correct, neural network of the brain is affected. This last article reviews the latest cutting edge technologies in monogenic disease therapy, with some examples provided applicable to a number of disease. It aims to give a sense of where we are and how much closer we are, to the goal of making an actual organic difference.
Might the olfactory bulb be an origin of olfactory auras in focal epilepsy?
Authors: Sarnat Harvey B. , Flores‐Sarnat Laura
Published: August 2019

Olfactory auras (phantosmia) are an infrequent phenomenon in complex focal seizures generated in the mesial temporal lobe. It is generally assumed that all such auras arise from epileptic foci in the entorhinal cortex, amygdala or rostral insula, all of which have major afferent projections from the olfactory bulb or mainly from its relay, the anterior olfactory nucleus. The histological morphology, synaptic circuitry, and foetal development of the olfactory bulb are unique. The olfactory system is the only special sensory system that does not project to the thalamus because its bulb and tract incorporate an intrinsic thalamic equivalent: axonless granular and periglomerular neurons and the anterior olfactory nucleus. The olfactory bulb exhibits continuous synaptic turnover throughout life. Other brain structures with synaptic plasticity (neocortex, hippocampus, and amygdala) are epileptogenic; synaptically stable structures (brainstem, cerebellum, and basal ganglia) are not epileptogenic. Electrophysiological and neuropathological data of the olfactory bulb in epilepsy are sparse. We propose an alternative hypothesis, first hinted in 1954 by Penfield and Jasper, that some epileptic olfactory auras are primarily generated by the olfactory bulb and secondarily mediated by the amygdala and entorhinal cortex.
Antiepileptic drug adherence and persistence in children with epilepsy attending a large tertiary care children's hospital
Authors: Lee Yon‐Kyong , Ah Young‐Mi , Choi Yun Jung , Cho Yoon Sook , Kim Ki Joong , Lee Ju‐Yeun
Published: August 2019

We aimed to evaluate antiepileptic drug treatment persistence and adherence in paediatric epilepsy patients and investigate the association between medication‐taking behaviours and clinical outcome.

Methods. Medical and prescription records of newly treated paediatric epilepsy patients, aged 1–18 years who initiated antiepileptic drug monotherapy in a tertiary teaching hospital, were retrospectively reviewed. The rates of overall treatment, non‐persistence, a treatment gap >60 days, and adherence, as measured by a medication possession ratio ≥0.8, were assessed. The relationship between non‐adherence and clinical outcome, defined as an emergency department visit or hospitalisation due to seizure‐related reasons, was analysed.

Results. A total of 1,172 patients met the inclusion criteria. The proportion of patients who were both persistent and adherent at one year was 70.14% and decreased to 56.83% at two years. Patients who started an antiepileptic drug at one year of age, took older generation antiepileptic drugs as the initial treatment, and those diagnosed with localized seizures were less likely to be adherent to and persistent with overall antiepileptic drug treatment. Patients who were non‐adherent to antiepileptic drug treatment were at an increased risk of hospitalisation or emergency department visits for seizure‐related reasons (adjusted HR 2.10, 95% CI 1.25–3.55).

Conclusions. This large population study shows that 70% of paediatric epilepsy patients were persistent with and adherent to antiepileptic drugs after one year of treatment and confirms that non‐adherence to antiepileptic drug treatment is an important factor in seizure‐related clinical outcome.
Amoxicillin, a potential epileptogenic drug
Authors: Raposo João , Teotónio Rute , Bento Conceição , Sales Francisco
Published: August 2019

Beta‐lactams are known to cause a wide spectrum of neurotoxic manifestations including epileptic seizures. The neurotoxicity of penicillin was first reported in 1945 by Johnson and Walker and is believed to exert an inhibitory effect on gamma‐aminobutyric acid transmission of cortical pyramidal cells, due to its beta‐lactam ring structure. Epileptogenicity is also a feature of the semisynthetic beta‐lactams including aminopenicillins. In this report, we present a patient with a recurrent history of discrete body twitching/jerks of epileptic nature in the context of amoxicillin exposure. The EEG revealed intermittent generalized short bursts of beta‐frequency polyspikes. This electro‐clinical picture was reversed by amoxicillin discontinuation.
Dosing strategies for antiepileptic drugs: from a standard dose for all to individualised treatment by implementation of therapeutic drug monitoring
Authors: Landmark Cecilie Johannessen , Johannessen Svein I. , Tomson Torbjörn
Published: August 2019

This review focuses on the evolution of approaches to dosing of antiepileptic drugs (AEDs) in clinical practice through history. There has been a shift in the view of treatment of epilepsy, from “one dose fits all patients” in the early days to individualisation of treatment. Over the past 50 years, our knowledge of pharmacological variability of AEDs has markedly increased through implementation of therapeutic drug monitoring (TDM). The use of TDM has demonstrated extensive pharmacokinetic variability for AEDs and a need to individualise the treatment for an optimal outcome. Factors that contribute to pharmacokinetic variability include external factors (including food and comedication), physiological factors (gender, age, and pregnancy), pathological conditions (organ dysfunction), and genetic factors (polymorphisms in metabolising enzymes). Patient groups of children, pregnant women, and the elderly, in whom the most extensive pharmacokinetic changes occur, need special attention and close follow‐up of treatment. Patients with complicated and changing combination treatments are also vulnerable. Therapeutic drug monitoring may be particularly helpful in such situations. There are also challenges regarding the use and misuse of therapeutic drug monitoring, such as the use of drug monitoring without a clear indication, misinterpretation of the reference range, and erroneous sampling times.
Epileptic spasms in congenital disorders of glycosylation
Authors: Pereira Andreia G. , Bahi‐Buisson Nadia , Barnerias Christine , Boddaert Nathalie , Nabbout Rima , de Lonlay Pascale , Kaminska Anna , Eisermann Monika
Published: August 2019

Aim. Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, characterized by impaired glycosylation. Multisystemic involvement is common and neurological impairment is notably severe and disabling, concerning the central and peripheral nervous system. Epilepsy is frequent, but detailed electroclinical description is rare.

Methods. We describe, retrospectively, the electroclinical features in five children with CDG and epileptic spasms.

Results. Epileptic spasms were observed in patients with ALG1‐, ALG6, ALG11‐CDG and CDG‐Ix, and occurred at an early age, before 6 months in all cases, except one who had spasms that started at 18 months. In this patient, spasms had an unusual aspect; they did not occur in clusters and were immediately preceded by a myoclonus. All but one child also presented rare myoclonias. On EEG, background activity was poorly organized with abundant posterior spike and fast rhythm activity, but without hypsarrhythmia. At the last evaluation (age range: 6–12 years), two patients still presented epileptic spasms and subcortical myoclonias, one showed rare generalized tonic‐clonic seizures, and two were seizure‐free.

Conclusion. CDG disorders can be associated with epileptic spasms showing particular features, such as absence of hypsarrhythmia, posterior EEG anomalies, and an unusual combination of epileptic spasms with myoclonus. These features, associated with pre‐existing developmental delay and subcortical myoclonias, may shift toward CDG screening. [Published with video sequence and supplemental EEG plates on www.epilepticdisorders.com]
ILAE survey of neuropsychology practice in pediatric epilepsy surgery evaluation
Authors: Berl Madison M. , Smith Mary Lou , Bulteau Christine ,   and the Task Force for Pediatric Epilepsy Surgery for the ILAE Commissions of Pediatrics, Surgical Therapies
Published: August 2019

Aims. To determine the extent to which specific neuropsychological measures are in common use around the world for the assessment of children who are candidates for epilepsy surgery.

Materials and methods. As part of the work of the International League Against Epilepsy Pediatric Surgical Task Force, a survey was developed and distributed online. The survey consisted of questions related to demographics, training experience, general practice, and specific measures used and at what frequency.

Results. Seventy‐eight clinicians with an average of 13.5 years of experience from 19 countries responded to the survey; 69% were English‐speaking. Pre‐ and post‐neuropsychological evaluations were conducted with a majority of children undergoing surgical resection for epilepsy. There was high consistency (>90%) among the domains evaluated, while consistency rate among specific measures was more variable (range: 0–100%). Consistency rates were also lower among respondents in non‐English‐speaking countries. For English‐speaking respondents, at least one measure within each domain was used by a majority (>75%) of clinicians; 19 specific measures met this criterion.

Conclusion. There is consensus of measures used in neuropsychological studies of pediatric epilepsy patients which provides a basis for determining which measures to include in establishing a collaborative data repository to study surgical outcomes of pediatric epilepsy. Challenges include selecting measures that promote collaboration with centers in non‐English‐speaking countries and providing data from children under age 5.
Ictal asystole in a patient with posterior reversible encephalopathy syndrome (PRES) and seizures
Authors: Suski Joanna , Ho Reginald , Nei Maromi
Published: August 2019

We describe a case of ictal asystole in a patient with posterior reversible encephalopathy syndrome (PRES), which has never been described previously. Ictal asystole is rare and has possible serious medical consequences, including syncope, and may be a potential mechanism for sudden unexpected death in epilepsy (SUDEP). Awareness that PRES may be observed with recurrent ictal asystole may aid in the recognition and treatment of seizures in this condition and the prevention of asystole‐associated complications.
Seizure semiology of anti‐LGI1 antibody encephalitis
Authors: Beimer Nicholas J. , Selwa Linda M.
Published: August 2019

Limbic encephalitis associated with anti‐LGI1 antibody (LGI1 encephalitis) presents with a variety of features, the most prominent of which include seizures and progressive disturbance of memory and behaviour. Although varied in semiology, recognition of the pattern of seizures in LGI1 encephalitis is important, as early diagnosis and definitive treatment may prevent subsequent development of cognitive impairment. We present a patient with LGI1 encephalitis and “faciobrachial dystonic seizures‐plus”, which began as classic faciobrachial dystonic seizures and progressed to focal seizures with impaired awareness, dacrystic/gelastic‐like outbursts, ictal speech, manual automatisms, and autonomic signs (tachycardia). Recognition of the broad range of seizure types associated with LGI1 encephalitis is crucial for early diagnosis and definitive treatment. [Published with video sequence on www.epilepticdisorders.com]
Crossing the lines between epilepsy syndromes: a myoclonic epilepsy variant with prominent eyelid myoclonia and atonic components
Authors: Pinelopi Dragoumi , Emery Jacqueline , Chivers Fiona , Brady Megan , Desurkar Archana , Cross J Helen , Das Krishna B
Published: August 2019

Accurate diagnosis of a distinct epilepsy syndrome is based on well‐defined electroclinical features that differentiate separate nosological entities. In clinical practice, however, syndromes may overlap and cases may present with unusual manifestations posing a diagnostic challenge. This heterogeneity has been documented in several cases presenting with eyelid myoclonia with or without absences (EMA) diagnosed either as Jeavons syndrome (JS) variants or as genetic generalised epilepsies defined by the presence of this unique clinical entity. The hallmark of JS is the triad: (1) eyelid myoclonia with or without absences, (2) eye closure‐induced paroxysms, and (3) photosensitivity. The presence of massive myoclonus, intellectual disability, or slowing of the EEG background are not typical features of the syndrome and may cause delay in making the correct diagnosis. Adding to the variability of clinical features, we describe two female paediatric patients with probable genetic epilepsy who presented with EMA but demonstrated clear atypical features, such as prominent myoclonic seizures, atonic components on video‐EEG, and cognitive impairment. We also note the presence of interictal and ictal posterior discharges during eyelid myoclonia in one, supporting similar previous observations leading to consideration of EMA as an occipital cortex‐initiated seizure activity. [Published with video sequences on www.epilepticdisorders.com].
Adult‐onset Rasmussen encephalitis associated with focal cortical dysplasia
Authors: Hohenbichler Katharina , Lelotte Julie , Lhommel Renaud , Tahry Riëm El , Vrielynck Pascal , Santos Susana Ferrao
Published: August 2019

Rasmussen encephalitis is a rare, devastating condition, typically presenting in childhood. Cases of adult‐onset Rasmussen have also been described, but the clinical picture is less defined, rendering final diagnosis difficult. We present a case of adult‐onset Rasmussen encephalitis with dual pathology, associated with focal cortical dysplasia and encephalitis. We interpreted the Rasmussen encephalitis to be caused by severe and continuous epileptic activity due to focal cortical dysplasia. The best therapeutic approach for such cases remains unclear.
Rufinamide for the treatment of Lennox‐Gastaut syndrome: evidence from clinical trials and clinical practice
Authors: Striano Pasquale , McMurray Rob , Santamarina Estevo , Falip Mercè
Published: August 2019

Rufinamide was granted orphan drug status in 2004 for the adjunctive treatment of seizures associated with Lennox‐Gastaut syndrome in patients aged ≥4 years, and was subsequently approved for this indication in several countries, including Europe and the United States. Structurally unrelated to other antiepileptic drugs, rufinamide is thought to act primarily by prolonging the inactivation phase of voltage‐gated sodium channels. Rufinamide was approved on the basis of an international, randomised, placebo‐controlled Phase III trial, conducted in 138 patients with Lennox‐Gastaut syndrome, which demonstrated its favourable tolerability profile and efficacy in significantly reducing the frequency of drop attacks and total seizures, compared with placebo. The effectiveness and safety/tolerability of rufinamide in treating seizures associated with Lennox‐Gastaut syndrome have subsequently been confirmed in several other clinical trials and long‐term extension studies. These findings are supported by ‘real‐world’ data from a series of clinical practice studies conducted in Europe, the United States, and Korea. Rufinamide has been shown to be effective and generally well tolerated in children as young as one year and in adults. It is particularly effective as treatment for drop attacks and generalised tonic‐clonic seizures, and it has been suggested that it might be preferred over other antiepileptic drugs as a second‐line treatment for Lennox‐Gastaut syndrome when drop attacks are frequent. The most common side effects of rufinamide treatment include somnolence, headache, dizziness, nausea, vomiting, and fatigue. No new or unexpected safety signals have emerged following long‐term treatment with rufinamide, either in clinical trials or in clinical practice.