Motor Seizures Research Articles

Epilepsy Phenotypes of Vitamin B6-Dependent Diseases: An Updated Systematic Review

Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects). We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected. 497 published patients fulfilled the inclusion criteria. Seizure onset manifested at 59.8 ± 291.6 days (67.8% of cases in the first month of life). Clonic, tonic-clonic, and myoclonic seizures accounted for two-thirds of the cases, while epileptic spasms were observed in 7.6%. Burst-suppression/suppression-burst represented the most frequently reported specific EEG pattern (14.4%), mainly in PLPB, ALDH7A1, and PNPO deficiency. Pyridoxine was administered to 312 patients (18.5% intravenously, 76.9% orally, 4.6% not specified), and 180 also received antiseizure medications. Pyridoxine dosage ranged between 1 and 55 mg/kg/die. Complete seizure freedom was achieved in 160 patients, while a significant seizure reduction occurred in 38. PLP, lysine-restricted diet, and arginine supplementation were used in a small proportion of patients with variable efficacy. Global developmental delay was established in 30.5% of a few patients in whom neurocognitive tests were performed. Despite the wide variability, the most frequent hallmarks of the epilepsy phenotype in patients with vitamin B6-dependent seizures include generalized or focal motor seizure semiology and a burst suppression/suppression burst pattern in EEG.

PRRT2 benign familial infantile seizures (BFIS) with atypical evolution to encephalopathy related to status epilepticus during sleep (ESES).

Heterozygous variants in PRRT2 are mostly associated with benign phenotypes, being the major genetic cause of benign familial infantile seizures (BFIS), as well as in paroxysmal disorders. We report two children from unrelated families with BFIS that evolved to encephalopathy related to status epilepticus during sleep (ESES). Two probands presented with focal motor seizures at 3months of age, with a limited course. Both children presented, at around 5years of age, with centro-temporal interictal epileptiform discharges with a source in the frontal operculum, markedly activated by sleep, and associated with stagnation on neuropsychological development. Whole-exome sequencing and co-segregation analysis revealed a frameshift mutation c.649dupC in the proline-rich transmembrane protein 2 (PRRT2) in both probands and all affected family members. The mechanism leading to epilepsy and the phenotypic variability ofPRRT2variants remain poorly understood. However, its wide cortical and subcortical expression, in particular in the thalamus, could partially explain both the focal EEG pattern and the evolution to ESES. No variants in thePRRT2gene have been previously reported in patients with ESES. Due to the rarity of this phenotype, other possible causative cofactors are likely contributing to the more severe course of BFIS in our probands.

Neurological Manifestations of Hyperosmolar Hyperglycemic State: A Case Report and A Review of the Literature

Hyperosmolar hyperglycemic state (HHS), a life-threatening complication of diabetes mellitus, may initially manifest with a broad spectrum of neurological symptoms. These include encephalopathy, coma, chorea-hemiballismus and epileptic activity. Focal motor seizures are among the most common manifestations whilst aphasia has rarely been described so far. Based on a recent experience from our hospital, we herein report a rare case of a patient with nonketotic hyperglycemia-induced global aphasia, followed by focal motor seizures and attempt a comprehensive review of the literature with regards to the various neurological syndromes through which, undiagnosed diabetes and HHS may present. Neurological aspects of HHS are not so well-documented and are certainly under-represented in the literature.

Sentinel seizure heralding Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease

BackgroundIsolated seizure as a manifestation of myelin oligodendrocyte antibody-associated disease (MOGAD) has rarely been reported previously.Case presentationA 16-year-old-male presented with single episode of left focal onset motor seizure with secondary generalization and impaired awareness, without any other focal neurological deficits. There was a history of right focal onset motor seizure with secondary generalized tonic–clonic seizure and impaired awareness 4 years ago. Neurological examination showed bilateral gaze evoked nystagmus. Brain imaging revealed bilateral superficial and deep white matter lesions including the corpus callosum. Anti-MOG antibody was positive. The patient received steroids and Rituximab therapy without any further recurrence of seizure or any neuro-deficits and gradual improvement in lesion burden in brain imaging.ConclusionsThis case of an adolescent boy with sole manifestation of episodes of focal seizures 4 years apart, finally diagnosed to be a case of MOGAD, not only boosts the evidence of establishing the possibility of MOG antibody-associated autoimmune epilepsy but also reinforces the importance of unexplained seizure as a clinical phenotype in MOGAD.

Poor Seizure Control Among Children Attending a Tertiary Hospital in South Western Uganda - A Retrospective Study.

Seizure control among children with epilepsy (CWE) receiving anti-seizure medications (ASMs) remains a challenge in low-resource settings. Uncontrolled seizures are significantly associated with increased morbidity and mortality among CWE. This negatively impacts their quality of life and increases stigma. This study determined seizure control status and described the factors associated among CWE receiving ASMs at Mbarara Regional Referral Hospital (MRRH). In a retrospective chart review study, socio-demographic and clinical data were obtained from 112 medical records. CWE receiving ASMs for at least six months and regularly attending the clinic were included in the study. Physical or telephone interviews were conducted with the immediate caregivers of the CWE to establish the current seizure control status of the participants. A total of 112 participants were enrolled. Of these, three-quarters had generalized onset seizures, 23% had focal onset seizures, while 2% had unknown onset motor seizures. About 60.4% of the study participants had poor seizure control. Having a comorbidity (p-value 0.048, AOR 3.2 (95% CI 1.0-9.9)), history suggestive of birth asphyxia (p-value 0.014, AOR 17.8 (95% CI 1.8-176.8)), and being an adolescent (p-value 0.006, AOR 6.8 (95% CI 1.8-26.6)) were significantly associated with poor seizure control. Seizure control among CWE receiving ASMs at MRRH remains poor. Efforts geared to addressing seizure control and optimizing drugs are needed, especially among children with comorbidities, those with history of birth asphyxia, and adolescents.

Patient profile, management, and quality of life associated with Dravet syndrome: a cross-sectional, multicentre study of 80 patients in Spain

The aim of this study was to describe the profile of patients diagnosed with Dravet syndrome (DS), their clinical management, and the impact of DS on their quality of life (QoL) and family. Data of 80 patients from 11 centres in Spain was collected. Patients (47.5% female) were 12.7 (9.6) years on average (SD, standard deviation). Despite the first episode occurred when patients were a mean (SD) of 0.4 (0.2) years, DS was not diagnosed until they were 6.9 (10.1) years old. The majority (86.7%) had SCN1A gene mutations and 73.4% had seizures during the last year (mostly generalized motor seizures [47.8%]). The mean (SD) number of status epilepticus episodes was 3.6 (8.0) since diagnosis and 0.1 (0.5) in the last year. On the Health Utilities Index Mark (HUI) multi-attribute scale, the mean global score (SD) was 0.56 (0.24) in HUI2 and 0.32 (0.37) in HUI3. The impact of the disease was severe in most patients (HUI2, 81%; HUI3, 83.5%). In the Care-related QoL (CarerQol) the mean (SD) well-being score was 7.2 (2.1). Most caregivers (90%) were satisfied with their caregiving tasks, although 75% had difficulties combining these tasks with daily activities, 68.8% reported mental health problems and 61.2% physical problems.

Epilepsy with myoclonic absence presenting with unilateral jerks: A case of 2q13 microdeletion syndrome

Epilepsy with myoclonic absence (EMA), which was originally depicted by Tassinari in 1969 and 1971, is now classified by the International League Against Epilepsy (ILAE) as a genetic generalised epilepsy syndrome of childhood. EMA is characterised by rhythmic jerks and tonic contractions with impaired consciousness accompanied by synchronous and symmetric 3 Hz spike-and-wave discharges. It is generally bilateral, but it must be differentiated from focal impaired awareness motor seizures when it is unilateral [1].

Skeletal and Dental Fractures Associated With Electroconvulsive Therapy.

During the motor seizure associated with electroconvulsive therapy (ECT), the muscles of the trunk and limbs contract forcefully and repetitively, predisposing to injuries to muscles, joints, teeth, and bones. This motor seizure is irrelevant to the therapeutic action of the treatment. It is therefore modified by the administration of an intravenous muscle relaxant, such as succinylcholine, after the administration of the anesthesia in the ECT premedication. Well-modified ECT is associated with markedly diminished skeletal muscle contractions and hence with minimal skeletal and dental risks. In this context, anecdotal reports across a range of skeletal disorders testify to the safety of well-modified ECT in ultrahigh-risk patients. Population-based data suggest that the fracture risk with modified ECT is 2 events per 100,000 ECTs; if only recent data are examined, the risk may be as low as 0.36 events per 100,000 ECTs. Population-based data also suggest that the dental fracture risk with modified ECT is 0.02% per ECT and 0.17% per ECT course. The overall magnitude of skeletal and dental fracture risk depends on patient factors and on how well the ECT procedure is performed. Preexisting bone and dental disease increase the risk; good seizure modification, proper use of bite blocks, and effective jaw immobilization during ECT reduce the risk. Careful assessment of preexisting risk and good ECT practice can minimize the risk of skeletal and dental complications during ECT.

Semiology characteristics and location of epileptogenic zone in motor seizures of axial and shoulder girdle muscles assessed by video stereoelectroencephalography study in 65 patients.

To study the semiology characteristics of motor seizures of axial and shoulder girdle muscles (ASMs) by stereoelectroencephalography (SEEG) and its value in determining location of epileptogenic zone. A total of 598 patients underwent SEEG assessment in Sanbo Brain Hospital were reviewed; 65 patients with ASMs selected. Thirteen semiology feature items were extracted according to the location and symmetry of involved axial muscles, direction of movement, etc. Seizures were grouped with items, and the k-means was used to analyze association between ASMs semiology characteristics and seizure-onset zone (SOZ). The SOZs of ASMs involved 23 combinations of seven different brain regions: 31 patients (47.7%) had one brain region, 19 (29.2%) had two, 14 (21.5%) had three, and one patient (1.5%) had four. One hundred and fifteen brain regions were analyzed. Seven brain regions accounted for a significant difference in chi-square test, χ2 = 62.79, p < 0.0001, with the highest proportion of insular and perisylvian. The k-means method identified two clusters: cluster 1 had a high degree of agreement with temporal lobe epilepsy (12/15), characterized by less shrug-like movement, later involvement of axial shoulder girdle muscles, longer duration, and lower seizure frequency; cluster 2 had a high degree of agreement with posterior cortex epilepsy (14/18), characterized by earlier involvement of axial shoulder girdle muscles, shorter duration, and higher seizure frequency. In frontal lobe, insular and perisylvian, anterior and middle cingulate gyrus, are the two categories accounted for similar proportion. Seizure-onset lateralized at the contralateral of unilateral cervical tonic, with rate of seizure-free was 73.7%. The incidence of ASMs is high in insular and perisylvian. Unilateral cervical tonic seizures have good lateralizing value. Based on semiology characteristics, ASMs can be roughly clustered into two categories, which can only effectively distinguish the origins of temporal lobe and posterior cortex, with low discrimination for the seizure-onset of other lobes.

Development of a clinical model to predict vagus nerve stimulation response in pediatric patients with drug-resistant epilepsy.

Epilepsy impacts 470,000 children in the United States. For patients with drug-resistant epilepsy (DRE) and unresectable seizure foci, vagus nerve stimulation (VNS) is a treatment option. Predicting response to VNS has been historically challenging. The objective of this study was to create a clinical VNS prediction tool for use in an outpatient setting. The authors performed an 11-year retrospective cohort analysis with 1-year follow-up. Patients < 21 years of age with DRE who underwent VNS (n = 365) were included. Logistic regressions were performed to assess clinical factors associated with VNS response (≥ 50% seizure frequency reduction after 1 year); 70% and 30% of the sample were used to train and validate the multivariable model, respectively. A prediction score was subsequently developed. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. Variables associated with VNS response were < 4-year epilepsy duration before VNS (p = 0.008) and focal motor seizures (p = 0.037). The variables included in the clinical prediction score were epilepsy duration before VNS, age at seizure onset, number of pre-VNS antiseizure medications, if VNS was the patient's first therapeutic epilepsy surgery, and predominant seizure semiology. The final AUCs were 0.7013 for the "fitted" sample and 0.6159 for the "validation" sample. The authors developed a clinical model to predict VNS response in a large sample of pediatric patients treated with VNS. Despite the large sample size, clinical variables alone were not able to accurately predict VNS response. This score may be useful after further validation, although its predictive ability underscores the need for more robust biomarkers to predict treatment response.

Dyke-Davidoff-Masson Syndrome (DDMS) in Adult: A Rare Case in Rural Area

Highlight: Dyke-Davidoff-Masson syndrome (DDMS) is an uncommon neurological disease defined as cerebral hemiatrophy with a contralateral motor deficit, facial asymmetry, and seizures. The proper diagnosis and early causative treatment significantly improve the outcome of thee disease. ABSTRACT Introduction: Dyke-Davidoff-Masson syndrome (DDMS) could be a rare neurological disorder characterized by cerebral hemiatrophy and an engine shortfall on the contralateral side of the body. Furthermore, facial asymmetry and seizures are common symptoms. Classic imaging findings in individuals with DDMS are ventriculomegaly, cerebral hypoplasia, paranasal sinus hyperpneumatization, and compensatory osseous broadening. The relationship between symptoms and imaging findings is used to determine DDMS. Case: A 46-year-old female patient arrived at the hospital with an inability to speak three days before admission, refused to eat or drink, and had a fever. She also had a slanted mouth and right-sided hemiparesis with a history of seizures. A firm boundary consolidation on the right pericardium was found on the chest X-ray, suggesting pulmonary TB. On a non-contrast head CT scan, thickening of the left hemicalvaria was found, accompanied by a widening of the left frontal-ethmoidal sinus, hyperpneumatization of the left mastoid air cell, and left cerebral hemiatrophy, all accompanied by left lateral ventricular dilatation. Conclusion: The proper diagnosis and early causative treatment significantly improve the outcome of the disease.

Ganaxolone in seizures associated with cyclin-dependent kinase-like 5 deficiency disorder: a profile of its use in the USA

Ganaxolone (ZTALMY®), a synthetic neuroactive steroid that acts as a positive allosteric modulator of the synaptic and extrasynaptic gamma-aminobutyric acid (GABA)A receptor, is an effective and well tolerated, orally-administered adjunct to existing antiseizure treatments in patients 2 years of age or older with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD)-associated seizures. CDD (a rare X-linked genetic disorder) is a severe developmental epileptic encephalopathy with onset in early infancy. In the randomized, double-blind, phase 3 Marigold trial, adjunctive ganaxolone significantly reduced the 28-day major motor seizure frequency from baseline compared with placebo in patients with CDD-associated refractory epilepsy. Preliminary results from the Marigold open-label extension suggest that the clinical benefits of ganaxolone in patients with CDD are maintained longer term. Ganaxolone is generally well tolerated; somnolence is the most frequent adverse reaction.

Adaptive Remote Sensing Paradigm for Real-Time Alerting of Convulsive Epileptic Seizures

Epilepsy is a debilitating neurological condition characterized by intermittent paroxysmal states called fits or seizures. Especially, the major motor seizures of a convulsive nature, such as tonic-clonic seizures, can cause aggravating consequences. Timely alerting for these convulsive epileptic states can therefore prevent numerous complications, during, or following the fit. Based on our previous research, a non-contact method using automated video camera observation and optical flow analysis underwent field trials in clinical settings. Here, we propose a novel adaptive learning paradigm for optimization of the seizure detection algorithm in each individual application. The main objective of the study was to minimize the false detection rate while avoiding undetected seizures. The system continuously updated detection parameters retrospectively using the data from the generated alerts. The system can be used under supervision or, alternatively, through autonomous validation of the alerts. In the latter case, the system achieved self-adaptive, unsupervised learning functionality. The method showed improvement of the detector performance due to the learning algorithm. This functionality provided a personalized seizure alerting device that adapted to the specific patient and environment. The system can operate in a fully automated mode, still allowing human observer to monitor and override the decision process while the algorithm provides suggestions as an expert system.

Clinical characteristics and risk factors of cerebral cavernous malformation-related epilepsy

PurposeThis study aimed to summarize the clinical characteristics and explore the risk factors for cerebral cavernous malformation (CCM)-related epilepsy (CRE). MethodsWe retrospectively analyzed the clinical data of patients with CCM in our cerebral vascular malformations database. Descriptive statistics were used to present the clinical characteristics of CRE patients. Patients were divided into a CRE and a non-CRE group according to clinical presentation. Binary logistic regression analysis was used to analyze the risk factors of CRE. ResultsA total of 199 patients with CCM confirmed by postoperative pathological examination were enrolled, 93 of whom were diagnosed with CRE, and 34 patients had drug-resistant epilepsy. The most common seizure type of CRE patients was focal to bilateral tonic-clonic seizure (FBTCS), followed by focal impaired awareness motor seizure. All CCM lesions were supratentorial, 97.8% of which involved the cerebral cortex, 86.0% of lesions had hemosiderin rim, and 50.5% of lesions were located in the temporal lobe. Binary logistic regression analysis indicated that CCM diagnosis age ≤ 44 years (odds ratio [OR] 2.79, p = 0.010), temporal lobe lesion location (OR = 9.07, p = 0.042), medial temporal lobe lesion (OR = 14.09, p = 0.002), cortical involvement of the lesion (OR = 32.77, p = 0.010), and hemosiderin rim around the lesion (OR = 16.48, p = 0.001) significantly increased the risk of CRE. ConclusionsThe most common seizure type of CRE was FBTCS. Those whose CCM diagnosis age was ≤ 44 years, having a temporal lobe lesion location, especially the medial temporal lobe lesion, cortical involvement, and hemosiderin rim around the lesion had a higher risk of developing CRE.

Attitudes toward persons with epilepsy as friends: Results of a factorial survey.

Discrimination against persons with epilepsy (PWEs) may persist. The aim of this study was to examine whether epilepsy is an obstacle to desired friendship. A factorial survey (vignettes), which is less biased by social desirability, was applied to PWEs, their relatives, and lay persons. The vignettes described a person who was varied by the dimensions of age (younger, same age, older), gender (male, female), disease (healthy, mild epilepsy, severe epilepsy [generalized tonic-clonic seizures], diabetes), origin (German, non-German), contact (phone/internet, activities at home, activities outside), frequency of contacts (weekly, monthly), and distance (around the corner, 10km away). Respondents rated their willingness to befriend the person on a 10-point Likert scale. Multivariate regression determined the contribution of each dimension on the judgment. Participants were 64 PWEs (age=37.1± 14.0 years), 64 relatives of PWEs (age=45.1± 13.6 years), and 98 controls without contact with PWEs (age=24.4± 10.1 years). Controls were less interested in a friendship with a PWE with mild epilepsy (-3.4%) and even more avoided PWEs with severe epilepsy (-11.7%), whereas in PWEs with tonic-clonic seizures, a mild form of epilepsy was actually conducive to friendship (+7.0%). Controls preferred females (+5.0%) and disliked younger people (-12.3%) and contacts via the internet or telephone (-7.3%). PWEs were also less interested in younger people (-5.8%), and relatives of PWEs had a lower preference for friendships with longer distance (-2.3%). PWEs still suffer from a risk of social avoidance, and this becomes more evident with generalized motor seizures.

Neuroinflammation in Bilirubin Neurotoxicity.

Bilirubin neurotoxicity is a serious consequence of hyperbilirubinemia, which is the most common disease of the neonatal period. Clinically, bilirubin neurotoxicity can result in motor deficit, auditory dysfunction, cerebral palsy, seizure and neurodevelopmental diseases, amongst others. Bilirubin neurotoxicity is one of the major worldwide causes of neonatal brain injury, especially in poorer developing countries. However, the mechanisms of bilirubin neurotoxicity are still unclear. After the failure of attempts targeting neurons in many neurodegenerative disorders, neuroinflammation has become a significant target of research. Here, recent advances concerning neuroinflammation in bilirubin neurotoxicity are reported with a focus on the clinical characteristics of bilirubin neurotoxicity, including age-dependency, region-specificity and its yin-yang properties. Effects of neuroinflammation on blood brain interfaces and treatments targeting neuroinflammation in bilirubin neurotoxicity are also reviewed, which may promote the precision of future treatment of bilirubin neurotoxicity.

Clinical Practice Guidelines for the Use of Electroconvulsive Therapy.

Clinical Practice Guidelines for the Use of Electroconvulsive Therapy.

Chapter 15 - Motor seizure semiology

Motor semiology is a major component of epilepsy evaluation, which provides essential information on seizure classification and helps in seizure localization. The typical motor seizures include tonic, clonic, tonic-clonic, myoclonic, atonic, epileptic spasms, automatisms, and hyperkinetic seizures. Compared to the "positive" motor signs, negative motor phenomena, for example, atonic seizures and Todd's paralysis are also crucial in seizure analysis. Several motor signs, for example, version, unilateral dystonia, figure 4 sign, M2e sign, and asymmetric clonic ending, are commonly observed and have significant clinical value in seizure localization. The purpose of this chapter is to review the localization value and pathophysiology associated with the well-defined motor seizure semiology using updated knowledge from intracranial electroencephalographic recordings, particularly stereoelectroencephalography.

Clinical and Electrophysiological Characteristics of Patients with Juvenile Absence Epilepsy in a Turkish Cohort

Juvenile absence epilepsy is an epileptic syndrome that usually begins between the ages of 9-13 and is classified in the group of genetic generalized epilepsies, in which absence seizures are seen mainly but may also be accompanied by motor seizures in the follow-up. In our study, 33 patients who were followed up in our clinic with the diagnosis of juvenile absence epilepsy between 2010-2022 were evaluated retrospectively. Thirteen of them were excluded from the study due to insufficient clinical or electrophysiological knowledge, being diagnosed with another epileptic syndrome during follow-up. The mean age of the 20 patients included in the evaluation was 16.8 years; The mean age of seizure onset was 10.6 years. All patients had absence seizures, which were not seen more often than once a day, 40% had additional generalized tonic-clonic seizures, and 20% had focal electroencephalographic abnormalities in addition to generalized discharges on electroencephalography. Seizures recurred in 3 of 5 patients whose treatment was terminated. It was found that currently 85% of the patients continued treatment with valproic acid and monotherapy was sufficient. While there are generalized discharges at the time of diagnosis electrophysiologically, focal findings tend to occur in the follow-up; This was also found to be important in the evaluation of seizure recurrence and treatment options in patients with long-term follow-up.

Midventricular variant of Takotsubo syndrome in a patient with threatening status epilepticus from simple motor seizures

We present a clinical case of a 70-year-old woman who was urgently admitted to the Department of Neurology with threatening status epilepticus from simple motor seizures in the right half of the face and right hand. Computed tomography of the head visualized a calcified extra axial round formation in the left posterofrontal, possibly a meningioma. On admission and during the symptomatic attacks, dynamic ECG changes were recorded with negative T waves precordially, as well as a dynamic increase in serum troponin. Echocardiography revealed hypokinesia involving the middle segments of the left ventricle. Coronary angiography was performed with no evidence of coronary disease. From the ventriculography hypokinesia of middle segments was found and measured EF 47%. Complex therapy with valproate, dexamethasone, mannitol and clonazepam, levetiracetam, acetizal, a statin and a beta-blocker was initiated. After controlling the epileptic seizures and diagnostic work-up of the cardiovascular status, the patient was referred for neurosurgical treatment of the tumor formation.