Seizures In Association Research Articles

Convulsive behaviors of spontaneous recurrent seizures in a mouse model of extended hippocampal kindling.

Growing studies indicate that vigilance states and circadian rhythms can influence seizure occurrence in patients with epilepsy and rodent models of epilepsy. Electrical kindling, referred to brief, repeated stimulations of a limbic structure, is a commonly used model of temporal lobe epilepsy. Kindling via the classic protocol lasting a few weeks does not generally induce spontaneous recurrent seizures (SRS), but extended kindling that applies over the course of a few months has shown to induce SRS in several animal species. Kindling-induced SRS in monkeys and cats were observed mainly during resting wakefulness or sleep, but the behavioral activities associated with SRS in rodent models of extended kindling remain unknown. We aimed to add information in this area using a mouse model of extended hippocampal kindling. Middle-aged C57 black mice experienced ≥80 hippocampal stimulations (delivered twice daily) and then underwent continuous 24 h electroencephalography (EEG)-video monitoring for SRS detection. SRS were recognized by EEG discharges and associated motor seizures. The five stages of the modified Racine scale for mice were used to score motor seizure severities. Seizure-preceding behaviors were assessed in a 3 min period prior to seizure onset and categorized as active and inactive. Three main observations emerged from the present analysis. (1) SRS were found to predominantly manifest as generalized (stage 3-5) motor seizures in association with tail erection or Straub tail. (2) SRS occurrences were not significantly altered by the light on/off cycle. (3) Generalized (stage 3-5) motor seizures were mainly preceded by inactive behaviors such as immobility, standing still, or apparent sleep without evident volitional movement. Considering deeper subcortical structures implicated in genesis of tail erection in other seizure models, we postulate that genesis of generalized motor seizures in extended kindled mice may involve deeper subcortical structures. Our present data together with previous findings from post-status epilepticus models support the notion that ambient cage behaviors are strong influencing factors of SRS occurrence in rodent models of temporal lobe epilepsy.

Epilepsy in adults with neurodevelopmental disability - what every neurologist should know.

This seminar in epileptology addresses Learning Objective 6.1.4 of the International League against Epilepsy Curriculum: Demonstrate the ability to recognize and manage the special needs of persons with epilepsy (and Neurodevelopmental Disorders [NDDs]). The review identifies the essential competencies for neurologists working with people with epilepsy and NDDs, and these competencies are discussed alongside clinical examples. Furthermore, the seminar explores the opportunities offered by integrated service provision between neurology and services for NDD. The epileptic encephalopathies are not a subject of this seminar paper as they are circumscribed by other ILAE learning objectives. This seminar frames the complexity of seizures in association with NDD with a focus on major NDDs; intellectual disability, autism spectrum disorder, and attention deficit hyperactivity disorder. The evidence presented considers epidemiology, co-morbidities, risk factors, mortality, and the diagnostic and treatment challenges. People with NDDs and epilepsy have higher rates of physical and psychiatric co-morbidity, polypharmacy, neuropsychiatric side effects of drugs, and premature mortality including sudden unexpected death in epilepsy. There is a limited Level 1 evidence base to guide assessment and treatment for seizures in adults with NDDs. Therefore, throughout this seminar, the evidence presented for associations and treatment should be observed in context along with its limitations. The evidence for pharmacological treatment of seizures in association with NDDs is presented alongside expert commentary and guidance. There is Level 2 evidence to support treatment with some of the newer anti-seizure medications including brivaracetam, lacosamide, eslicarbazepine acetate, and perampanel as second-line choices. Seizures with a co-morbid NDD should be considered as a collective complex clinical presentation and not discrete conditions. This seminar was co-designed, co-produced and co-authored by an expert by experience and includes case studies and a video to highlight what can go wrong and how it can be avoided.

Clinical spectrum of pediatric drug refractory epilepsy secondary to parieto-occipital gliosis

BackgroundParieto-occipital (PO) gliosis secondary to perinatal insult, is often associated with neurologic sequelae such as epilepsy, which can be drug resistant. ObjectiveTo evaluate the spectrum of epilepsy among patients presenting with seizures in association with PO gliosis and to determine factors that influence the development of epileptic encephalopathy (EE) in these patients. MethodsWe retrospectively evaluated patients aged < 16 years with drug refractory epilepsy and PO gliosis who underwent video electroencephalography (Video EEG). We evaluated the clinical, electrophysiological and radiological profile including treatment responsiveness of subjects with EE. ResultsOne hundred one patients (M: F=3:1) with mean age of onset of epilepsy at 28.9 ± 33.1 months were recruited into the study. Based on video EEG findings, Based on video EEG findings, the commonest type of focal onset ictus was tonic seizures with impaired awareness (n = 26, 29.9%). Myoclonic jerks (n = 20, 23%) were the commonest type of generalised onset seizures. Ictal onset from parieto occipital region were observed in 28 patients. Ictal onset from frontal, temporal and fronto temporal region were observed in 6 (6.8%), 7(7.9%) and 9 (8.9%) patients, respectively. Comparison of the seizure types and ictal onset among subgroups of patients with occipital gliosis, parieto-occipital gliosis and parieto-occipital with frontal gliosis revealed that the extent of gliosis did not significantly affect seizure semiology or ictal onset. EE was significantly associated with presence of neonatal seizures (p = 0.04), hypoglycaemia (p = 0.005), longer duration of ICU stay (Z score = −3.55, p < 0.001) and younger age of onset of seizures (Z score = - 2.97, p = 0.03). Eleven out of eighteen (64.7%) subjects with EE showed greater than 50% improvement in seizure frequency following three months of pulse intravenous methylprednisolone therapy. ConclusionsAmong subjects with PO gliosis on MRI, the seizure semiology is unaffected by laterality, radiologic extension beyond the occipital cortex or presence of ulegyria. Patients with PO gliosis can have florid interictal epileptiform discharges anteriorly and can have seizures with ictal onset from frontal and temporal region. Development of EE is strongly related to the age of onset of seizures, neonatal seizures, prolonged NICU admission, rather than the radiological findings. Subjects with EE and PO gliosis show good response to intravenous pulse methylprednisolone.

Seizures after Posterior Fossa Surgery: Exploring the Unknown: A Systematic Review

Background: Seizures due to posterior fossa lesions is an uncommon phenomenon. In this study, a systemic literature review was done to (i) study the incidence of seizures in posterior fossa lesions, (ii) determine factors associated with high risk for seizures, and (iii) ascertain the role of prophylactic antiepileptic drugs (AEDs) in such cases. Methods: Systemic literature review was done, for the MeSH terms “posterior cranial fossa” AND “seizures” AND “anticonvulsants.” All original research articles, case reports, and systematic reviews pertaining to seizures or the use of anticonvulsants in posterior fossa lesions were considered for inclusion. Results: A total of 79 cases of posterior fossa lesions, identified from 8 studies, were included for analysis. The incidence of seizures in posterior fossa lesions ranged from 1.8% to 5% in various studies. The highest incidence for seizures was reported with medulloblastoma, cerebellar hemorrhage, and during microvascular decompression for cases of neurovascular conflict. The most significant risk factor for seizures in the postoperative period was the use of ventricular shunt or ventriculostomy. AEDs were administered symptomatically after the occurrence of seizures in 78 cases except for the use of prophylactic AEDs in a single case of posterior cranial fossa lipoma. Conclusion: Seizures in association with posterior fossa lesions are rare and associated with a poor prognosis. Clinical detection can often be difficult and electroencephalogram helps in early diagnosis and treatment. Further studies are needed to confirm the role of prophylactic AEDs in high-risk cases.

Exploring quality of life in individuals with a severe developmental and epileptic encephalopathy, CDKL5 Deficiency Disorder

BackgroundCDKL5 Deficiency Disorder (CDD) is a rare genetic disorder caused by a mutation in the cyclin-dependent kinase-like 5 (CDKL5) gene. It is now considered to be a developmental and epileptic encephalopathy because of the early onset of seizures in association with severe global delay. Other features include cortical visual impairment, sleep and gastro-intestinal problems. Progress in clinical understanding, especially regarding the spectrum of functional ability, seizure patterns, and other comorbidities was initially slow but accelerated in 2012 with the establishment of the International CDKL5 Database (ICDD). Our aim was to use this data source to investigate quality of life (QOL) and associated factors in this disorder. MethodA follow-up questionnaire was administered in 2018 to parents of children registered with the ICDD who had a pathogenic CDKL5 variant. QOL was assessed using QI Disability, an instrument, specifically developed to measure total and specific domains of QOL (physical health, positive emotions, negative emotions, social interaction, leisure and the outdoors (leisure) and independence) in children with intellectual disability. Associations with functional abilities, physical health, mental health and family factors were investigated, initially using univariate analyses followed by multivariate analyses for each of these groups with a final composite model which included the important variables identified from previous models. ResultsQuestionnaires were returned by 129/160 families with a child aged >3 years. Functional impairment, including lack of ability to sit, use hands and communicate had the greatest adverse impact on QOL. There were also some relationships with major genotype groupings. Individuals using three or more anti-epileptic medications had poorer QOL than those on one or no medication, particularly in the physical health domain. There was also variation by geographical region with those living in North America typically having the best QOL and those living in middle or lower income countries poorer QOL. ConclusionAlthough lower functional abilities were associated with poorer quality of life further research is needed to understand how environmental supports might mitigate this deficit. Comprehensive care and support for both the child and family have important roles to play in helping families to thrive despite the severity of CDD.

Prevalence of seizures in dogs and cats with idiopathic internal hydrocephalus and seizure prevalence after implantation of a ventriculo-peritoneal shunt.

BackgroundSeizures are considered a clinical sign in dogs with internal hydrocephalus but are not found in recent studies. Seizure prevalence due to ventricular enlargement and the prevalence of postoperative seizures in animals is not known.ObjectivesTo determine seizure prevalence in dogs and cats with idiopathic internal hydrocephalus, to identify risk factors for seizure development, and to determine seizure prevalence in a 2‐year period after ventriculo‐peritoneal shunting (VPS).AnimalsRecords and MRIs of 197 animals from 2001 to December 2019 were investigated. A total of 121 animals (98 dogs and 23 cats) were included in the study.MethodsA retrospective multicenter case cohort study was conducted. Databases were searched for dogs and cats with internal hydrocephalus. MRI and CSF examinations were evaluated for signs of additional underlying disorders. Prevalence of seizures was estimated for animals showing only hydrocephalus internus. Risk factors were evaluated according to age, morphometric and morphological findings in the brain. All animals that underwent surgery were reexamined 2 years after surgery.ResultsOne hundred twenty‐one animals (98 dogs and 23 cats) with internal hydrocephalus met the inclusion criteria. Seizure prevalence in dogs and cats with internal hydrocephalus was low (1.7%; <5.8% CI 95%). Seizures were not observed in the 2‐year period after surgery.Conclusion and Clinical ImportanceSeizure prevalence in dogs and cats diagnosed with hydrocephalus internus is low. Seizures in association with VPS do not seem to be a complication of the procedure.

Impaired EIF2S3 function associated with a novel phenotype of X-linked hypopituitarism with glucose dysregulation.

BackgroundThe heterotrimeric GTP-binding protein eIF2 forms a ternary complex with initiator methionyl-tRNA and recruits it to the 40S ribosomal subunit for start codon selection and thereby initiates protein synthesis. Mutations in EIF2S3, encoding the eIF2γ subunit, are associated with severe intellectual disability and microcephaly, usually as part of MEHMO syndrome.MethodsExome sequencing of the X chromosome was performed on three related males with normal head circumferences and mild learning difficulties, hypopituitarism (GH and TSH deficiencies), and an unusual form of glucose dysregulation. In situ hybridisation on human embryonic tissue, EIF2S3-knockdown studies in a human pancreatic cell line, and yeast assays on the mutated corresponding eIF2γ protein, were performed in this study.FindingsWe report a novel hemizygous EIF2S3 variant, p.Pro432Ser, in the three boys (heterozygous in their mothers). EIF2S3 expression was detectable in the developing pituitary gland and pancreatic islets of Langerhans. Cells lacking EIF2S3 had increased caspase activity/cell death. Impaired protein synthesis and relaxed start codon selection stringency was observed in mutated yeast.InterpretationOur data suggest that the p.Pro432Ser mutation impairs eIF2γ function leading to a relatively mild novel phenotype compared with previous EIF2S3 mutations. Our studies support a critical role for EIF2S3 in human hypothalamo-pituitary development and function, and glucose regulation, expanding the range of phenotypes associated with EIF2S3 mutations beyond classical MEHMO syndrome. Untreated hypoglycaemia in previous cases may have contributed to their more severe neurological impairment and seizures in association with impaired EIF2S3.FundGOSH, MRF, BRC, MRC/Wellcome Trust and NIGMS funded this study.

Chewing induced reflex seizures (“eating epilepsy”) and eye closure sensitivity as a common feature in pediatric patients with SYNGAP1 mutations: Review of literature and report of 8 cases

PurposeHeterozygous SYNGAP1 gene mutations have been associated with several forms of idiopathic generalized epilepsy, autism spectrum disorders and delay of psychomotor development. We report eight patients with a SYNGAP1 mutation and chewing/eating induced reflex seizures as new phenotype and compare them to other patients with eating epilepsy and genetic mutations. MethodsPresentation of clinical and anamnestic features and retrospective analysis of Video-EEG data of a 4 year old index patient with SYNGAP1 mutation and chewing /eating induced seizures. Clinical and anamnestic features and home videos of seven additional patients (4 female; age: 4–14 years) with SYNGAP1 mutation and eating induced reflex seizures were compared. ResultsAll reflex seizures of the index patient showed similar focal EEG pattern with 1–5 seconds high amplitude, irregular 3/sec spike-wave complexes with initiation from left temporo-occipital, right temporo-occipital or bi- occipital / temporo-occipital regions. Eyelid myoclonia, the most common seizure type in all 8 patients, were typically initiated by eating or other simple orofacial stimuli. In the index patient eye closure preceded eating induced-eyelid myoclonia in 30/38 seizures. ConclusionThe main clinical features of our patient (i.e. intellectual disability, epilepsy, autistic features) are compatible with previous reports on patients with SYNGAP1 mutations. This is the first complete description of eating induced seizures in association with SYNGAP1 mutations. Whether eye closure sensitivity (ECS) represents an independent reflex epileptic trait, as seen in other patients with idiopathic “generalized” epilepsies (IGE), or eye closure is part of a complex trigger mechanism in SYNGAP1 patients’ remains to be elucidated.

Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome

ADP-ribosylation, the addition of poly-ADP ribose (PAR) onto proteins, is a response signal to cellular challenges, such as excitotoxicity or oxidative stress. This process is catalyzed by a group of enzymes referred to as poly(ADP-ribose) polymerases (PARPs). Because the accumulation of proteins with this modification results in cell death, its negative regulation restores cellular homeostasis: a process mediated by poly-ADP ribose glycohydrolases (PARGs) and ADP-ribosylhydrolase proteins (ARHs). Using linkage analysis and exome or genome sequencing, we identified recessive inactivating mutations in ADPRHL2 in six families. Affected individuals exhibited a pediatric-onset neurodegenerative disorder with progressive brain atrophy, developmental regression, and seizures in association with periods of stress, such as infections. Loss of the Drosophila paralog Parg showed lethality in response to oxidative challenge that was rescued by human ADPRHL2, suggesting functional conservation. Pharmacological inhibition of PARP also rescued the phenotype, suggesting the possibility of postnatal treatment for this genetic condition.

Relationship between serum zinc levels and simple febrile seizures: hospital based case control study

Background: Owing to the excessive susceptibility of the immature brain to temperature, febrile seizures remain one of the common neurological conditions of childhood. Although simple febrile seizures do not pose any increased neurological problems in adult life, but the anxiety, hospitalization and prophylaxis for the episode do call for a genuine concern. A correlation between zinc deficiency and febrile seizures has been proposed and a few studies undertaken have shown mixed conclusions. This case control study was undertaken to compare the serum Zinc levels in patients with simple febrile seizures against the controlled patients with short febrile illness without seizures and to find the correlation if any between simple febrile seizures and serum zinc levels.Methods: The hospital based, observational case control study was done in Batra Hospital and Medical research Centre, New Delhi. A total of 200 children aged 6 months to 6 years admitted in the hospital with history of short pyrexia (fever for 2 days or less) and fulfilling our inclusion criteria were enrolled for the study after taking an informed consent from their attendants and classified into 2 groups of 100 each as cases and controls. Patients with history of simple febrile seizures as cases and those with fever without seizures as controls. A detailed history was taken, and complete physical examination was done on the patients and recorded on a precoded and pretested proforma. The data was analysed on SPSS 17.Results: Our results showed a mean of serum zinc levels in cases as 61.53±15.87 mcg/dl which was found to be lower compared to controls as 71.90+18.50 mcg /dl. Further the difference was found to be statistically significant (P&lt;0.05).Conclusions: Low serum zinc levels in the patients of simple febrile seizures in association with other risk factors may enhance the occurrence of seizures triggered by fever. Thus, a possible correlation exists between the mean serum zinc level and simple febrile seizures.

P.005 Painful epileptic seizures involving the insula

Background: We have previously described painful epileptic seizures involving the primary and second somatosensory cortices. A recently encountered 24 year old man described left hemicorporial, painful seizures in association with a tumor involving the right insula. Methods: Case description with imaging and EEG. Results: The patient described frequent, sharp pains simultaneously involving the left face, upper and lower limbs and trunk that lasted from several seconds to a minute and were 10/10 in intensity. These markedly lessened in frequency but the severity of the pain persisted with a maintenance dose of 600 mg/day of carbamazepine. Neurological examination, including cortical sensation, was normal. MRI revealed a 3 cm rounded lesion deep to but immediately against the entire right insula but not extending cortically beyond the confines of the insula. EEGs have been unremarkable. The lesion has been stable for over 1 year. Conclusions: Insular seizures can produce brief, sharp, intense pain that involves the whole of the contralateral body simultaneously. This is in keeping with the insula as part of the pain matrix with connections with the thalamus. Stimulation of the posterior insula can produce hemicorporial pain without a march similar to that experienced by our patient.

Risk of Seizures Associated with Antidepressant Use in Patients with Depressive Disorder: Follow-up Study with a Nested Case-Control Analysis Using the Clinical Practice Research Datalink.

Antidepressant use has been associated with an increased risk of seizures. Evidence on the association between antidepressant use at therapeutic doses and seizures mainly comes from clinical trials that were not designed to investigate this potential relationship. The objective of this study was to assess the risk of first-time seizures in association with exposure to antidepressants in patients with depressive disorders. We conducted a retrospective follow-up study with a nested case-control analysis between 1998 and 2012, using data from the UK-based Clinical Practice Research Datalink (CPRD). We estimated crude incidence rates with 95 % confidence intervals (CIs) of seizures in depressed patients who used selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), 'other antidepressants', no antidepressants, or who had used antidepressants in the past. To adjust for potential confounding, we estimated odds ratios of antidepressant drug use among cases with seizures and matched controls in a nested case-control analysis. Of 151,005 depressed patients, 619 had an incident seizure during follow-up. Incidence rates per 10,000 person-years were 12.44 (95 % CI 10.67-14.21) in SSRI users, 15.44 (95 % CI 8.99-21.89) in SNRI users, 8.33 (95 % CI 4.68-11.98) in TCA users, 9.33 (95 % CI 6.19-12.46) in non-users of antidepressants, and 5.05 (95 % CI 4.49-5.62) in past users of antidepressants. In the case-control analysis, relative risk estimates for seizures were increased in current users of SSRIs (adjusted odds ratio 1.98, 95 % CI 1.48-2.66) and SNRIs (adjusted odds ratio 1.99, 95 % CI 1.20-3.29), but not TCAs (adjusted odds ratio 0.99, 95 % CI 0.63-1.53), compared with non-users. Current use of SSRIs or SNRIs was associated with a twofold increased risk of first-time seizures compared with non-use, while current use of TCAs (mostly low dose) was not associated with seizures. Treatment initiation in SSRI and SNRI users was associated with a higher risk of seizures than longer-term treatment.

Serious complications associated with regadenoson administration for myocardial perfusion imaging

To the Editor, The Editorial by Hage and Iskandrian1 regarding “Serious complications associated with regadenoson administration for myocardial perfusion imaging: A commentary” (September/October 2014 issue) includes a table as a guide for serious complications associated with regadenoson administration. In the table, the authors reported whether or not each listed event occurs with exercise and/or adenosine and that seizures have not been reported with adenosine. Astellas has received spontaneous post-marketing reports of seizures in patients administered adenosine, and the package insert for Adenoscan® was updated in 2005 to reflect these reports. The current package insert includes “seizure” in the Warnings section.2 In addition, there is one published case report of bradyasystole and seizures associated with the use of adenosine to terminate supraventricular tachycardia.3 Astellas would like to clarify that seizures can occur following the administration of adenosine, and prescribers should be aware of this risk and prepared to treat if necessary.2 The use of methylxanthines (e.g., caffeine, aminophylline, and theophylline) is not recommended in patients who experience seizures in association with adenosine and regadenoson.2

Risk of Seizures Associated with Antidepressant Use in Patients with Depressive Disorder – a Nested Case-control Analysis

Objective To assess the risk of first-time seizures in association with exposure to antidepressants in patients with depressive disorders. Methods We conducted a retrospective follow-up study with a nested case-control analysis using data from the U.K.-based Clinical Practice Research Datalink. We estimated incidence rates (IRs) with 95% confidence intervals (CIs) of seizures in depressed patients who used no antidepressant treatment or who used selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), or ‘other antidepressants’. To better adjust for potential confounding, we estimated odds ratios (ORs) of antidepressant drug use among cases with seizures and matched controls in a nested case-control analysis. Results Of 151,005 depressed patients, 619 had an incident seizure during follow-up. IRs per 10,000 person-years were 9.33 (95% CI, 6.19-12.46) in non-users of antidepressants, 12.44 (95% CI, 10.67-14.21) in SSRI users, 15.44 (95% CI, 8.99-21.89) in SNRI users, 8.33 (95% CI, 4.68-11.98) in TCA users, and 5.05 (95% CI, 4.49-5.62) in past users of antidepressants. Across single antidepressants, the highest IR per 10,000 person-years (17.06 [95% CI, 7.41-26.72]) was observed in mirtazapine users. In the case-control analysis we observed the highest risks of seizure in male users of other antidepressants (OR 3.90, 95% CI 1.85-8.26), and in female users of SNRIs (2.70, 95% CI 1.33-5.48) compared with non-use. Conclusion With the exception of TCAs, antidepressant use in depressed patients was associated with an increased risk of seizures compared to non-use. Risk estimates differed across antidepressants and depended on timing of therapy, dose, and sex.

Commentary: ILAE Definition of Epilepsy.

Dr. Steven C. Schachter, is Professor of Neurology at Harvard Medical School in Boston, Massachusetts The practical clinical definition of epilepsy proposed by Fisher et al.1 is an important step forward. It reflects current science and clinical practice, particularly among many epileptologists who start therapy after a first seizure in patients at substantial risk for recurrence to spare them the potentially life-limiting medical and psychosocial consequences of additional seizures. This definition also emphasizes the need to identify the underlying cause of a first seizure and, just as significantly, provides a basis for determining when epilepsy has resolved. Broadly implementing this revised definition will enhance the care of patients, facilitate communication among clinicians and scientists, and set the stage for further progress. By working with the International League Against Epilepsy (ILAE), epilepsy-related organizations can expedite the new definition's utilization and amplify its impact through education of the clinical and patient communities; and by supporting additional research to expand knowledge in risks of seizure recurrence for specific brain pathologies, to develop new methods for diagnosing the underlying causes of first seizures when not apparent with available techniques, and to establish best practices for treatments after first seizures when recurrence is likely. Educating clinicians, patients and their families, the public, agents of licensing authorities (such as registries of motor vehicles), public officials, and others about the revised definition will increase awareness of epilepsy and counter any increase in stigma as an unintended consequence. The full spectrum of clinicians who encounter patients after a first seizure need to be familiar with the varied clinical presentations of seizures, especially those that are nonconvulsive, as well as the appropriate investigations to determine the underlying cause. Otherwise, unnecessary delays in diagnosing epilepsy and initiating therapy as well as inappropriate diagnosis and treatment will continue to occur. Early referral to a neurologist or epileptologist, prior to a patient's second seizure, should be encouraged to confirm the diagnosis when the underlying cause is not obvious or to assist in the selection of therapy, if needed. The risks of recurrence following a first seizure in association with many underlying pathologies will need to be studied further to establish whether these risks over time reach the threshold specified by the revised definition. Similarly, the evidence base for selecting particular therapies after a first seizure due to specific underlying etiologies, which at present is relatively thin and in many cases nonexistent, must be expanded. Concerted efforts in partnership with other subspecialties that represent specific etiologies of epilepsy are needed to design and conduct appropriate treatment trials for first seizures in addition to longitudinal observational studies to establish risk of seizure recurrence and the likelihood that epilepsy will resolve. Epidemiologic studies will need to be updated so that the demographics of epilepsy and incidence and prevalence values reflect the revised definition. Undoubtedly the revised definition will raise scientific and pragmatic concerns and issues that will be discussed, debated, and ultimately answered through research. Indeed, epileptology has been and will continue to be a vibrant and dynamically evolving field. Our definitions will therefore continue to change in order to represent the best current science, facilitate communication, enhance patient care, and stimulate further progress. The revised definition proposed by Fisher et al.1 is an important step forward in this long journey. I have no conflicts of interest to disclose. I confirm that I have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

A 67‐Year‐Old Woman Receiving Tumor Necrosis Factor α Inhibitor Therapy Presenting With Neurologic Dysfunction

A 67‐Year‐Old Woman Receiving Tumor Necrosis Factor α Inhibitor Therapy Presenting With Neurologic Dysfunction

Seizures Associated with Zoledronic Acid for Osteoporosis

Bisphosphonates represent potent antiresorptive drugs that are established for therapy of patients with benign and malignant bone diseases. Zoledronic acid is an iv aminobisphosphonate that is administered annually against osteoporosis. Because of its potency and the parenteral route of administration, zoledronic acid is an alternative to oral bisphosphonates, in particular in elderly patients with multiple comorbidities. The most common side effects include an acute-phase reaction and mild and transient hypocalcemia. Here, we report three cases of seizures that developed after the administration of zoledronic acid. We review case histories and laboratory results of three patients with seizures associated with the administration of zoledronic acid. We discuss their course and comorbidities in the context of the published literature. All three patients were elderly persons with multiple comorbidities, including neurological diseases, that required parenteral bisphosphonates for severe osteoporosis with concurrent contraindications for oral bisphosphonates. We analyze potential mechanisms underlying these seizures in association with zoledronic acid exposure and discuss potential strategies to minimize this risk.

Reversible posterior leukoencephalopathy induced by carboplatin and etoposide

Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare neurologic condition characterised by specific clinical and radiologic findings. It usually manifests subacutely as insidious onset of headache, visual disturbance, altered consciousness and seizures in association with MRI findings of posterior white matter vasogenic oedema. RPLS has been reported in a wide variety of clinical settings. Hypertension, eclampsia, pre-eclampsia, renal impairment, autoimmune conditions and cytotoxic drugs are all cited as aetiologic variables. RPLS, albeit rare, is an important entity for physicians to be aware of as early recognition, and prompt intervention is critical to ensure resolution of the neurological deficit. We describe the case of a 69-year-old lady who collapsed with seizure activity after receiving carboplatin and etoposide chemotherapy for small cell lung cancer. In our opinion, the clinical and radiological courses are typical of RPLS. RPLS has rarely been reported secondary to this chemotherapy regimen, and the purpose of this report is to add to the literature and highlight the association between RPLS and cytotoxic chemotherapy.

Magnesium sulphate versus diazepam for eclampsia.

Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains a rare but serious complication of pregnancy. A number of different anticonvulsants are used to control eclamptic fits and to prevent further fits. The objective of this review was to assess the effects of magnesium sulphate compared with diazepam when used for the care of women with eclampsia. Magnesium sulphate is compared with phenytoin and with lytic cocktail in other Cochrane reviews. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2010) and CENTRAL (2010, Issue 3). Randomised trials comparing magnesium sulphate (intravenous or intramuscular administration) with diazepam for women with a clinical diagnosis of eclampsia. Two authors assessed and extracted data independently. We have included seven trials, involving 1396 women. Three trials (1030 women) were good quality. Magnesium sulphate was associated with a reduction in maternal death (seven trials;1396 women; risk ratio (RR) 0.59, 95% confidence interval (CI) 0.38 to 0.92) and recurrence of seizures (seven trials;1390 women; RR 0.43, 95% CI 0.33 to 0.55) compared to diazepam. There were no clear differences in other measures of maternal morbidity.There was no clear difference in perinatal mortality (four trials; 788 infants; RR 1.04, 95% CI 0.81 to 1.34) or neonatal mortality (four trials; 759 infants; RR 1.18, 95% CI 0.75 to 1.84). In the magnesium sulphate group, fewer liveborn babies had an Apgar score less than seven at one minute (two trials; 597 babies; RR 0.75, 95% CI 0.65 to 0.87) or at five minutes (RR 0.70, 95% CI 0.54 to 0.90), and fewer appeared to need intubation at the place of birth (two trials; 591 infants; RR 0.67, 95% CI 0.45 to 1.00). There was no difference in admission to a special care nursery (four trials; 834 infants; RR 0.91, 95% CI 0.79 to 1.05), but fewer babies in the magnesium sulphate group had a length of stay more than seven days (three trials 631 babies; RR 0.66, 95% CI 0.46 to 0.96). Magnesium sulphate for women with eclampsia reduces the risk ratio of maternal death and of recurrence of seizures, compared with diazepam.

Magnesium sulphate versus phenytoin for eclampsia.

Eclampsia, the occurrence of a seizure in association with pre-eclampsia, remains a rare but serious complication of pregnancy. A number of different anticonvulsants have been used to control eclamptic fits and to prevent further seizures. The objective of this review was to assess the effects of magnesium sulphate compared with phenytoin when used for the care of women with eclampsia. Magnesium sulphate is compared with diazepam and with lytic cocktail in other Cochrane reviews. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2010). Randomised trials comparing magnesium sulphate (intravenous or intramuscular administration) with phenytoin for women with a clinical diagnosis of eclampsia. Two review authors assessed trial quality and extracted data. We have included data from seven trials, involving 972 women. One large trial (775 women) was of good quality. Magnesium sulphate was associated with a substantial reduction in the recurrence of seizures, when compared to phenytoin (six trials, 972 women; risk ratio (RR) 0.34, 95% confidence interval (CI) 0.24 to 0.49). The trend in maternal mortality favours magnesium sulphate, but the difference does not reach statistical significance (three trials, 847 women; RR 0.50, 95% CI 0.24 to 1.05). There were reductions in the risk of pneumonia (one trial, RR 0.44, 95% CI 0.24 to 0.79), ventilation (one trial, RR 0.68, 95% CI 0.50 to 0.91) and admission to an intensive care unit (one trial, RR 0.67, 95% CI 0.50 to 0.89) associated with the use of magnesium sulphate rather than phenytoin.For the baby, magnesium sulphate was associated with fewer admissions to a special care baby unit (SCBU) (one trial, 518 babies; RR 0.73, 95% CI 0.58 to 0.91) and fewer babies who died or were in SCBU for more than seven days (one trial, 643 babies; RR 0.77, 95% CI 0.63 to 0.95) than phenytoin. There was no clear difference in perinatal deaths (two trials, 665 babies; (RR 0.85, 95% CI 0.67 to 1.09). Magnesium sulphate, rather than phenytoin, for women with eclampsia reduces the risk ratio of recurrence of seizures, probably reduces the risk of maternal death, and improves outcome for the baby. Magnesium sulphate is the drug of choice for women with eclampsia. The use of phenytoin should be abandoned.