Seizure Clusters Research Articles

Seizures in alcohol withdrawal syndrome

Alcohol withdrawal syndrome develops in individuals with alcohol dependence who discontinue or reduce alcohol intake after long-term or binge drinking. Withdrawal symptoms usually occur 6–8 hours after the last alcohol consumption and peak between 24–72 hours. Typical manifestations include tremor, nausea, vomiting, insomnia, agitation, and excess sweating. Complicated withdrawal syndrome may manifest with seizures (including cluster seizures), status epilepticus, acute psychosis and delirium, when hallucinations are accompanied by disorientation in time, place and situation. About 10–15% of patients develop complicated withdrawal syndrome. The seizures in alcohol withdrawal syndrome are triggered in the brain stem and have a mechanism other than that of classic epileptic seizures. Benzodiazepines, which are more effective than other classes of anticonvulsants (they primarily reduce the frequency of convulsions in the first two days after alcohol discontinuation and significantly reduce the risk of death), are the gold standard for the treatment of alcohol withdrawal syndrome. The Clinical Institute of Withdrawal Assessment for Alcohol Scale (CIWA-Ar) is a helpful tool for making decisions on treatment initiation or discontinuation. It should be noted that chronic use of benzodiazepines in the secondary prevention of alcohol withdrawal seizures is not recommended due to the addictive potential of these agents and a more severe course of alcohol withdrawal seizures with benzodiazepine co-dependence.

Identification of seizure clusters using free text notes in an electronic seizure diary

SignificanceOnline seizure diaries offer a wealth of information regarding real world experience of patients living with epilepsy. Free text notes (FTN) written by patients reflect concerns and priorities of patients and provide supplemental information to structured diary data. ObjectiveThis project evaluated feasibility using an automated lexical analysis to identify FTN relevant to seizure clusters (SCs). MethodsData were extracted from EpiDiary™, a free electronic epilepsy diary with 42,799 unique users, generating 1,096,168 entries and 247,232 FTN. Both structured data as well as FTN were analyzed for presence of SC. A pilot study was conducted to validate an automated lexical analysis algorithm to identify SC in FTN in a sample of 98 diaries. The lexical analysis was then applied to the entire dataset. Outcomes included cluster prevalence and frequency, as well as the types of triggers commonly reported. ResultsAt least one FTN was found among 13,987 (32.68%) individual diaries. An automated lexical analysis algorithm identified 5797 of FTN as SC. There were 2423 unique patients with SC that were not identified by structured data alone and were identified using lexical analysis of FTN only. Seizure clusters were identified in n = 10,331 (24.1%) of diary users through both structured data and FTN. The median number of SCs days per year was 13.7, (interquartile rank (IQR): 3.2–54.7). The median number of seizures in a cluster day was 3 (IQR 2–4). The most common missed medication linked to patients with SC was levetiracetam (n = 576, 29%) followed by lamotrigine (n = 495, 24%), topiramate (n = 208, 10.5%), carbamazepine (n = 190, 9.6%), and lacosamide (n = 170, 8.6%). These percentages generally reflected prevalence of medication use in this population. The use of rescue medications was documented in 3306 of structured entries and 4305 in FTN. ConclusionThis exploratory study demonstrates a novel approach applying lexical analysis to previously untapped FTN in a large electronic seizure diary database. Free text notes captured information about SC not available from the structured diary data. Diary FTN contain information of high importance to people with epilepsy, written in their own words.

Variante patogénica en el gen PCDH19 en una paciente con epilepsia y discapacidad cognitiva

La asociación de casos familiares de epilepsia y discapacidad intelectual (DI) en mujeres fue reportada en 1971. El año 2008, se identificó el rol de variantes patogénicas del gen PCDH19 en algunas familias. La enfermedad se presenta con crisis febriles en cluster, DI y rasgos autistas. La mayoría se debe a variantes de novo, pero hay algunos casos heredados por un modo peculiar de transmisión ligada X.Objetivo: Comunicar el caso de una paciente con epilepsia portadora de una variante patogénica en el gen PCDH19, revisando la historia natural de la enfermedad y la evidencia disponible para su manejo.Caso Clínico: Paciente femenina, con antecedentes de embarazo y período perinatal normal. A los 6 meses, estando febril, presentó crisis focales motoras en cluster que repitieron a los 14, 18, 21 meses y 3 años siempre asociadas a fiebre, presentando incluso estatus epiléptico. Mantiene biterapia con topiramato y ácido valproico, completando 13 años sin crisis. El estudio del gen SCN1A no mostró anomalías y el estudio del gen PCDH19 reveló una variante patogénica en heterocigosis, “de novo”. La paciente ha evolucionado con DI y alteraciones conductuales severas que requieren atención de salud mental.Conclusiones: Las variantes patogénicas PCDH19 tienen expresión fenotípica variada. El diagnóstico genético debe sospecharse con la clínica. La morbilidad psiquiátrica a largo plazo puede ser incapacitante.

Variante patogénica en el gen PCDH19 en una paciente con epilepsia y discapacidad cognitiva

The association of family cases of epilepsy and intellectual disability in women was reported in 1971. In 2008, the role of pathogenic variants of the PCDH19 gene in some families were identified. The disease presents with febrile seizure clusters, intellectual disability, and autistic features. Most cases are due to de novo variants, however, there are some inherited cases, with an atypical way of X-linked transmission. To report the case of a patient with epilepsy carrier of a pathogenic variant of the PCDH19 gene, reviewing the natural history of this condition and the available evidence for its management. Female patient, with normal history of pregnancy and perinatal period. At 6 months, while febrile, she presented focal motor seizure clusters that repeated at 14, 18, 21 months and 3 years old, always associated with fever, even presenting status epilepticus. She is on therapy with topiramate and valproic acid, achieving 13 seizure-free years. The analysis of the SCN1A gene showed no abnormalities and the study of the PCDH19 gene revealed a de novo heterozygous pathogenic variant. The patient evolved with intellectual disability and severe behavioral disorders that require mental health team support. PCDH19 pathogenic variants have varied phenotypic expression. The genetic diagnosis should be guided with the clinical features. Long-term psychiatric morbidity can be disabling.

Analysis of Early Assessable Risk Factors for Poor Outcome in Dogs With Cluster Seizures and Status Epilepticus.

Status epileptics (SE) and cluster seizures (CS) are serious neurological emergencies associated with poor outcome in epileptic patients. Data on risk factors associated with outcome in epileptic patients affected by CS and SE have not been studied extensively to date. In the present retrospective study potential risk factors predictive of negative outcome in a population of dogs affected by CS and SE were analyzed. Ninety-three dogs were included in the study: 21/93 patients (23%) presented with SE and 72/93 (77%) with CS. Based on multivariate statistical analysis, factors statistically associated with a poor outcome were the occurrence of the first epileptic seizure outside the defined idiopathic interval (6 months−6 years), a condition of hyperthermia at presentation and the absence of previous antiepileptic drugs (AEDs) in case of previous history of seizures. The results of the present study implement data on risk factors associated with poor outcome in dogs affected by CS or SE and can aid in the creation of an ad hoc scoring system, similar to systems currently applied in human medicine upon hospital admission to benchmark performances and establish protocols for triage and therapeutic management.

Repetitive transcranial magnetic stimulation in drug-resistant idiopathic epilepsy of dogs: A noninvasive neurostimulation technique.

BackgroundAlthough repetitive transcranial magnetic stimulation (rTMS) has been assessed in epileptic humans, clinical trials in epileptic dogs can provide additional insight.ObjectivesEvaluate the potential antiepileptic effect of rTMS in dogs.AnimalsTwelve client‐owned dogs with drug‐resistant idiopathic epilepsy (IE).MethodsSingle‐blinded randomized sham‐controlled clinical trial (dogs allocated to active or sham rTMS) (I) and open‐labeled uncontrolled clinical trial (dogs received active rTMS after sham rTMS) (II). Monthly seizure frequency (MSF), monthly seizure day frequency (MSDF), and number of cluster seizures (CS) were evaluated for a 3‐month pre‐TMS and post‐rTMS period and safety was assessed. The lasting effect period of rTMS was assessed in each dog treated by active stimulation using the MSF ratio (proportion of post‐TMS to pre‐rTMS MSF) and treatment was considered effective if the ratio was <1.ResultsNo adverse effects were reported. In trial I, MSF and MSDF decreased significantly (P = .04) in the active group (n = 7). In the sham group (n = 5), no significant changes were found (P = .84 and .29, respectively). Cluster seizures did not change significantly in either group. No significant differences were detected between the groups. In trial II, previously sham‐treated dogs (n = 5) received active rTMS and significant decreases in MSF and MSDF were noted (P = .03 and .008, respectively). The overall effect of rTMS lasted for 4 months; thereafter, the MSF ratio was >1.Conclusions and Clinical ImportanceRepetitive transcranial magnetic stimulation may be a safe adjunctive treatment option for dogs with drug‐resistant IE, but large‐scale studies are needed to establish firm conclusions.

Seizure burden fluctuates with the female reproductive cycle in a mouse model of chronic temporal lobe epilepsy

Women with catamenial epilepsy often experience increased seizure burden near the time of ovulation (periovulatory) or menstruation (perimenstrual). To date, a rodent model of chronic temporal lobe epilepsy (TLE) that exhibits similar endogenous fluctuations in seizures has not been identified. Here, we investigated whether seizure burden changes with the estrous cycle in the intrahippocampal kainic acid (IHKA) mouse model of TLE. Adult female IHKA mice and saline-injected controls were implanted with EEG electrodes in the ipsilateral hippocampus. At one and two months post-injection, 24/7 video-EEG recordings were collected and estrous cycle stage was assessed daily. Seizures were detected using a custom convolutional neural network machine learning process. Seizure burden was compared within each mouse between diestrus and combined proestrus and estrus days (pro/estrus) at two months post-injection. IHKA mice showed higher seizure burden on pro/estrus compared with diestrus, characterized by increased time in seizures and longer seizure duration. When all IHKA mice were included, no group differences were observed in seizure frequency or EEG power. However, increased baseline seizure burden on diestrus was correlated with larger cycle-associated differences, and when analyses were restricted to mice that showed the severe epilepsy typical of the IHKA model, increased seizure frequency on pro/estrus was also revealed. Controls showed no differences in EEG parameters with cycle stage. These results suggest that the stages of proestrus and estrus are associated with higher seizure burden in IHKA mice. The IHKA model may thus recapitulate at least some aspects of reproductive cycle-associated seizure clustering.

Influence of the COVID-19 outbreak in people with epilepsy: Analysis of a Spanish population (EPICOVID registry)

BackgroundThe aim of this study was to have a better understanding of the influence of the coronavirus disease 2019 (COVID-19) pandemic in people with epilepsy (PWE) and to assess whether there have been changes in seizure control during the current COVID-19 outbreak, exploring the possible causes thereof. MethodsThis is an observational, retrospective study based on prospective data collection of 100 successive patients who attended an epilepsy outpatient clinic either face-to-face or telephonically during the months of the COVID-19 outbreak and national state of emergency. ResultsOne hundred patients were included, 52% women, mean age 42.4 years. During the COVID-19 period, 27% of the patients presented an increase of >50% of seizure frequency. An increase of stress/anxiety (odds ratios (OR): 5.78; p = 0.008) and a prior higher seizure frequency (OR: 12.4; p = 0.001) were associated with worsening of seizures. Other risk factors were exacerbation of depression, sleep deprivation, less physical activity, and history of epilepsy surgery. Three patients had status epilepticus (SE) and one a cluster of seizures. Likewise, 9% of patients improved their seizure control. Reduction in stress/anxiety (OR: 0.05; p = 0.03) and recent adjustment of antiepileptics (OR: 0.07; p = 0.01) acted as protecting factors. ConclusionsA high proportion of PWE suffered a significant worsening of their seizure control during the months of the COVID-19 pandemic. Emotional distress due to home confinement was the main factor for the change in seizure control. Promoting physical activity and adequate sleep may minimize the potential impact of the pandemic in PWE. Ensuring correct follow-up can prevent decompensation in those PWE at high risk.

Treatment of Low Cerebrospinal Fluid 5-Methyltetrahydrofolate With Leucovorin Improves Seizure Control and Development in PCDH19-Related Epilepsy

This six-year-old girl presented to the Neurometabolic Clinic for evaluation of medically intractable seizures, global developmental delay, and behavioral concerns. Since developing clusters of seizures at age two years, she had tried multiple medications. She had multiple seizure types, consisting primarily of focal seizures with secondary generalization, which were exacerbated by fever. Prior electroencephalographs were normal or were consistent with a right frontal seizure onset. At the time of her initial assessment, her medications were oxcarbamazepine, topiramate, valproic acid, and lacosamide.

Idiopathic epilepsy in dogs: insights into factors that may predict upcoming seizure activity

Idiopathic epilepsy (IE) is the most common chronic neurological disorder in dogs. Most dogs with IE first experience seizures when they are under six years old, and they usually require...

Disseminated phaeohyphomycosis in a dog with seizures and suspected hyperadrenocorticism in the United Kingdom

A twelve-year-old female entire Lurcher-cross dog presented for investigation of an acute onset of cluster seizures and elevation of the liver enzymes. Physical examination was unremarkable; neurological examination was suggestive...

Investigating the efficacy of medical management for canine structural epilepsy

BackgroundStructural epilepsy in dogs is often treated medically with a combination of antiseizure drugs (ASDs) and other concurrent therapies for the primary condition. Unlike idiopathic epilepsy, there have been few...

Can we accurately lateralize the epileptogenic zone in patients who have seizure clusters? A study using stereo-electroencephalography

ObjectiveTo determine if the ictal onset recorded with stereoelectroencephalography (SEEG) during clusters of seizures is reliable to identify the laterality of the epileptogenic zone. BackgroundIn the presurgical evaluation of patients with focal drug-resistant epilepsy, the presence of bilateral ictal onset is usually associated with a poor surgical outcome. It has been reported that the laterality of seizures can be influenced during seizure clusters, although this remains controversial. Most studies have addressed this issue using scalp EEG which could erroneously determine the laterality of the ictal onset. MethodsWe examined all consecutive patients who underwent SEEG with bilateral hemispheric coverage at our institution between January 2013 and September 2018. We assessed the presence of seizure clusters (clinical or subclinical), their laterality by SEEG and the surgical outcome of the patients. A descriptive clinical and electrographic analysis was performed. ResultsOf 143 patients who underwent SEEG recordings, we identified only six patients who had bilateral ictal onset that went on to resective surgery. In all six patients the discordant seizures occurred during a seizure cluster. Three of these patients were seizure free at last follow up. ConclusionDiscordant seizures obtained during a seizure cluster may not necessarily mean that the patient has bilateral epilepsy, and therefore a poor post-surgical outcome. Seizure clusters may not reliably lateralize the epileptogenic zone.

Lissencephaly in Shih Tzu dogs

BackgroundLissencephaly is a brain malformation characterized by smooth and thickened cerebral surface, which may result in structural epilepsy. Lissencephaly is not common in veterinary medicine. Here, we characterize the first cases of lissencephaly in four Shih Tzu dogs, including clinical presentations and findings of magnetic resonance imaging of lissencephaly and several concomitant brain malformations.Case presentationEarly-onset acute signs of forebrain abnormalities were observed in all dogs, which were mainly cluster seizures and behavioral alterations. Based on neurological examination, the findings were consistent with symmetrical and bilateral forebrain lesions. Metabolic disorders and inflammatory diseases were excluded. Magnetic resonance imaging for three dogs showed diffuse neocortical agyria and thickened gray matter while one dog had mixed agyria and pachygyria. Other features, such as internal hydrocephalus, supracollicular fluid accumulation, and corpus callosum hypoplasia, were detected concomitantly. Antiepileptic drugs effectively controlled cluster seizures, however, sporadic isolated seizures and signs of forebrain abnormalities, such as behavioral alterations, central blindness, and strabismus persisted.ConclusionsLissencephaly should be considered an important differential diagnosis in Shih Tzu dogs presenting with early-onset signs of forebrain abnormalities, including cluster seizures and behavioral alterations. Magnetic resonance imaging was appropriate for ante-mortem diagnosis of lissencephaly and associated cerebral anomalies.

Efficacy of medium chain triglyceride oil dietary supplementation in reducing seizure frequency in dogs with idiopathic epilepsy without cluster seizures: a non-blinded, prospective clinical trial

BackgroundDespite appropriate antiseizure drug (ASD) treatment, around two-thirds of dogs with idiopathic epilepsy (IE) have seizures long-term and 20–30per cent of affected dogs remain poorly controlled.MethodsThe current study aim is...

Antiepileptic drug withdrawal and seizure severity in the epilepsy monitoring unit

ObjectiveThe goal of this study was to identify a strategy for antiepileptic drug (AED) reduction to allow efficient recording of focal seizures (FS) in patients undergoing video-electroencephalography (EEG) in an epilepsy monitoring unit (EMU) while avoiding the risk of complications associated with more severe seizure types. MethodsWe retrospectively reviewed consecutive patients admitted to our institution's EMU from July 1, 2016 to December 31, 2017. We included 114 presurgical patients who had AEDs reduced and at least one seizure during the admission. We compared AED dosages at which FS versus focal to bilateral tonic–clonic seizures (f-BTCS), seizure clusters, and lorazepam administration occurred. We also examined rate of AED reduction and seizure types. We used a receiver-operating characteristic (ROC) curve to identify a dose maximizing FS and minimizing other seizure types. ResultsAntiepileptic drug withdrawal rates ranged from 0 to 100% in the first 24 h (mean: 20%, standard deviation: 20%). Focal to bilateral tonic–clonic seizures and lorazepam administration occurred at a lower median AED dose than did FS (0%, 7.2%, and 43.8%, respectively, expressed as a percentage of the patient's outpatient daily AED dose; p < 0.001). A daily EMU-administered dose of one-third of the patient's outpatient AED dose allowed 55.0% of FS to occur while avoiding 82.0% of more severe seizure types. The seizure types had no difference in rate of AED withdrawal in the first 24 h of EMU stay. ConclusionsFocal seizures occurred at a higher AED dose than did f-BTCS. This may imply that a low minimally effective dose of AED could allow FS to be recorded while providing protection against f-BTCS. This strategy could improve efficacy and safety in the EMU.

Randomized open-label trial of intravenous brivaracetam versus lorazepam for acute treatment of increased seizure activity

ObjectiveThe objective of the present trial was to assess efficacy and safety of intravenous (IV) brivaracetam (BRV) vs. lorazepam (LZP) in patients with epilepsy undergoing evaluation in an epilepsy monitoring unit (EMU) who experienced seizures requiring acute treatment. MethodsThis was a phase 2, open-label, randomized, active-control, proof-of-concept trial (EP0087; NCT03021018). Patients (18–70 years) admitted to EMU were randomized 1:1:1 to single-dose bolus IV LZP (dose per investigator's practice), IV BRV 100 mg, or IV BRV 200 mg. Trial medication had to be administered within 30 min of qualifying seizure. Primary efficacy outcome was time to next seizure (clinical observation with electroencephalogram [EEG] confirmation) or to rescue medication use within 12 h of trial medication administration. Secondary outcomes included seizure freedom and rescue medication use within 12 h of trial medication administration. Safety and tolerability outcomes included treatment-emergent adverse events (TEAEs). ResultsOverall, 46 patients were randomized, and 45 received trial medication for a qualifying seizure. Patients in the LZP arm had doses from 1 to 4 mg (median: 1 mg). Eleven of 45 patients had a seizure within 12 h of trial medication administration (LZP 5/15 [median time to next seizure: 5.55 h], BRV 100 mg 3/15 [5.97 h], BRV 200 mg 3/15 [3.60 h]). No patients received additional rescue medication to control their qualifying seizure. Most patients were seizure-free over 12 h (LZP 9/15 [60.0%], BRV 100 mg 12/15 [80.0%], BRV 200 mg 12/15 [80.0%]). Rescue medication use within 12 h was numerically higher for LZP (6/15 [40.0%]) vs. BRV 100 mg (1/15 [6.7%]) and vs. BRV 200 mg (2/15 [13.3%]). Treatment-emergent adverse events were reported by 5/16 (31.3%), 6/15 (40.0%), and 3/15 (20.0%) of LZP, BRV 100 mg, and BRV 200 mg patients; one LZP patient had a serious TEAE (seizure cluster). Most common TEAEs (≥10% of patients) were sedation and somnolence with LZP, and dizziness, headache, and nausea with BRV. SignificanceIntravenous LZP, IV BRV 100 mg, and IV BRV 200 mg showed similar efficacy in controlling acute seizure activity in the EMU. Treatment-emergent adverse events were as expected for each medication. Although this trial should be interpreted with caution because of small patient numbers, it suggests a possible role of BRV in the acute treatment of increased seizure activity.

Small Animal Review

Summary: Canine epilepsy can follow circadian and multiday seizure cycles, and seizure clusters can be characterised over months-long time scales with ambulatory iEEG devices.

Comparison of Clinical Characteristics Between Febrile and Afebrile Seizures Associated With Acute Gastroenteritis in Childhood.

Background: Acute gastroenteritis (AGE) accompanied by seizures is not a rare scenario in childhood. We investigated the clinical features of children with febrile or afebrile seizures during AGE and aimed to identify the impact of fever in this situation-related seizure.Methods: We retrospectively reviewed the medical charts of children admitted due to seizures associated with mild AGE between January 2008 and December 2017. These consecutive patients were divided into two groups: an “afebrile group” whose diagnosis was compatible with “benign convulsion with mild gastroenteritis (CwG)” and a “febrile group” who had a fever within 24 h of the onset of an AGE-related seizure. We compared the two groups' clinical and laboratory characteristics, electroencephalograms (EEG), neuroimaging, and outcomes.Results: Of the children suffering from AGE and seizures, 41 were afebrile and 30 were febrile, with a mean age of 32.2 ± 27.6 months. The gender, seizure semiology, frequency, duration of seizures, the time interval between AGE symptoms onset and first seizure, and levels of serum sodium, and hepatic enzymes were significantly different between the two groups. The most frequently identified enteropathogen was rotavirus (33%), especially in the male and febrile subjects. Afebrile patients had more EEG abnormalities initially, but all returned to normal later. All cases had an uneventful outcome. Of note, seizure clusters (≥2 episodes) occurred more frequently in the afebrile patients who had a duration of AGE symptoms lasting 2 days or more, or white blood cell counts ≥ 10,000/μL (p-values: 0.05 and 0.04, respectively). In comparison with seven similar studies, all showed more seizure clusters, partial seizures, and a shorter interval between AGE onset and seizures in afebrile patients than in febrile patients. Contrarily, afebrile patients had longer seizure duration and lower serum hepatic transaminases than febrile patients.Conclusion: Although fever partially influenced the clinical features of AGE-related seizures, febrile CwG might have pathophysiology distinctly different from that of febrile seizures. Comprehensive knowledge in discerning febrile and afebrile CwG can help to avoid unnecessary diagnostics tests, and anticonvulsants use.

Can We Accurately Lateralize the Epileptogenic Zone in Patients Who Have Seizure Clusters? A Study Using Stereoelectroencephalography (SEEG) (1710)

Can We Accurately Lateralize the Epileptogenic Zone in Patients Who Have Seizure Clusters? A Study Using Stereoelectroencephalography (SEEG) (1710)