Mild Seizures Research Articles

Neuropsychiatric comorbidities in adult patients with new-onset epilepsy

BackgroundNeuropsychiatric comorbidities in adult patients with new-onset epilepsy in our university hospitals has not been assessed, so the purpose of this study was to identify the neuropsychiatric comorbidities in adult patients with new onset epilepsy in our university hospitals. We recruited one hundred patients, assessed them clinically, radiologically, electrophysiologically, and we performed Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV), Liverpool Seizure Severity Scale (LSSS), Generalized Anxiety Disorder 7-item (GAD-7) scale, Beck’s Depression Inventory II (BDI II) and Quality of Life In Epilepsy-10 Questionnaire (QOLIE-10) to assess cognitive function, seizure severity, anxiety, depression, and quality of life of the patients, respectively.ResultsOlder adult age group had higher LSSS than other groups. Middle-aged adults’ group had higher WAIS-IV full scale Intelligence Quotient (IQ) score and lower GAD-7 scale scores than other age groups. Patients regularly on more than one anti-seizure medication had lower IQ results, more seizure severity, depression, anxiety and worse quality of life than those on monotherapy. Males had slightly higher IQ scores. Patients with moderate and severe BDI-II score had significantly higher rate of uncontrolled seizures, higher seizures’ frequency, more abnormal EEG and were regularly on valproate at significantly higher rates as compared to those with minimal BDI-II score. Patients with moderate anxiety were significantly older than those with normal and severe anxiety. Patients with severe anxiety had higher rate of family history of epilepsy, higher rates of uncontrolled seizures and higher seizures’ frequency as compared to those with mild and moderate anxiety. Patients with mild, moderate, and severe score on GAD-7 had more abnormal EEG as compared to those with normal GAD-7 score. Patients with severe and very severe seizures had significantly higher levels of anxiety, depression and impaired quality of life than those with mild and moderate seizure severity.ConclusionsMost patients with epilepsy had psychiatric comorbidities such as depression and anxiety which strongly reduce their quality of life and interfere with their compliance to anti-seizure medication. Males had slightly higher Intelligence Quotient (IQ) scores on WAIS-IV. Moreover, patients regularly taking more than one anti-seizure medication had a statistically significantly lower IQ score, more seizure severity, higher Beckʼs depression inventory II score, higher generalized anxiety disorder 7-item scale score, and worse quality of life than those on monotherapy.

Norwegian population-based study of effectiveness of vagus nerve stimulation in patients with developmental and epileptic encephalopathies.

Evaluate the long-term efficacy of vagus nerve stimulation (VNS) in patients with developmental and epileptic encephalopathies (DEE) compared with epilepsy patients without intellectual disability (ID). Long-term outcomes from a Norwegian VNS quality registry are reported in 105 patients with DEEs (Lennox-Gastaut syndrome [LGS] n = 62; Dravet n = 16; Rett n = 9; other syndromes n = 18) were compared with 212 epilepsy patients without ID, with median follow-up of 88 and 72 months, respectively. Total seizure reduction was evaluated at 6, 12, 24, 36, and 60 months. Effect on different seizure types was evaluated at baseline and last observation carried forward (LOCF). Median monthly seizure frequency at LOCF was reduced by 42.2% (p < 0.001) in patients with DEE and by 55.8% (p < 0.001) in patients without ID. In DEE patients, ≥50% seizure reduction at 6 and 24 months were 17.1% and 37.1%, respectively, and 33.5% and 48.6% for patients without ID. Seizure reduction ≥75% at 60 months occurred in 14.3% of DEE patients and 23.1% of patients without ID. Highest median reduction was for atonic seizures, most notably 64.6% for LGS patients. A better effect was seen at 2 years among DEE patients with unchanged medication compared with those with changed medication (54.5% vs. 35.6% responders, p = 0.078). More DEE patients were reported to have greater improvement in ictal or postictal severity (43.8% vs. 28.3%, p = 0.006) and alertness (62.9% vs. 31.6%, p < 0.001) than patients without ID. For both groups, use of the magnet reduced seizure severity. Hoarseness was the most common adverse effect in both groups. In addition, DEE patients were frequently reported to have sleep disturbance, general discomfort, or abdominal problems. Our data indicate that VNS is very effective for atonic seizures. Patients without ID had best overall seizure reduction, however, patients with DEE had higher retention rates probably due to other positive effects. DEE refers to a group of patients with severe epilepsy and intellectual disability. Many of these patients have restricted lifestyles with frequent seizures. VNS is a treatment option for patients who do not respond well to medicines, either because of insufficient effect or serious adverse effects. Our study shows that VNS is well tolerated in this patient group and leads to a reduction in all seizure types, most notably for seizures leading to fall. Many patients experience other positive effects like shorter and milder seizures, as well as improvement in alertness.

Corpus Callosotomy for Drug Resistant Epilepsy. Long Term Outcome in Adult Population. (S44.005)

<h3>Objective:</h3> Favorable outcome of corpus callosotomy is reported in pediatric population with intractable epilepsy and it is considered standard of care for patients with drop attacks. Our objective is to compare the long term outcome of corpus callosotomy for drug resistant epilepsy in adult population. <h3>Background:</h3> Corpus callosotomy is a palliative neurosurgical procedure for patients with medically drug-resistant epilepsy who are not candidates for resective epilepsy surgery. Corpus callosotomy is most commonly performed in children with epilepsy, either as an anterior two-thirds disconnection of corpus callosum or as a complete disconnection. Good long-term outcomes against drop attacks have been reported in a population-based prospective study and the risk of a persistent complication is low. <h3>Design/Methods:</h3> 17 adults with idiopathic generalized epilepsy, frontal lobe epilepsy and Lennox Gastaut Syndrome (LGS) were followed for the outcome measures of seizure and antiepileptic drug (AED) burden and quality of life (QoL). Data was extracted from patients registered in our RedCap database. <h3>Results:</h3> 17 patients fulfill the inclusion criteria. 4 underwent conventional corpus callsotomy and 14 had laser interstitial thermal therapy (LITT). 7 had failed prior Vagal Nerve Stimulator and 10 did not have VNS. All patients who had conventional procedure had complications and none from the LITT group reported complications. 11 patients reported presence of seizures and 6 were seizure free. None of the patients had persistent drop attacks, while 4 had convulsive seizures and 11 had mild focal impaired awareness seizures. More than 70 % of the patients reported improvement in speech, social abilities and activities of daily living. <h3>Conclusions:</h3> Corpus callosotomy for drug resistant epilepsy in adults provide significant improvement when observed for decreasing in seizure burden, reduction in medication and improvement of quality of life. LITT carries a low risk for complication and similar efficacy when compared with conventional one and should be utilize more frequently. <b>Disclosure:</b> Miss Proteasa has nothing to disclose. Dr. Proteasa has nothing to disclose. Dr. Lado has a non-compensated relationship as a Board Member with American Epilepsy Society that is relevant to AAN interests or activities. Dr. Lado has a non-compensated relationship as a Officer with National Association of Epilepsy Centers that is relevant to AAN interests or activities.

Hippocampal glucocorticoid receptors modulate status epilepticus severity

Status epilepticus (SE) is a life-threatening medical emergency with significant morbidity and mortality. SE is associated with a robust and sustained increase in serum glucocorticoids, reaching concentrations sufficient to activate the dense population of glucocorticoid receptors (GRs) expressed among hippocampal excitatory neurons. Glucocorticoid exposure can increase hippocampal neuron excitability; however, whether activation of hippocampal GRs during SE exacerbates seizure severity remains unknown. To test this, a viral strategy was used to delete GRs from a subset of hippocampal excitatory neurons in adult male and female mice, producing hippocampal GR knockdown mice. Two weeks after GR knockdown, mice were challenged with the convulsant drug pilocarpine to induce SE. GR knockdown had opposing effects on early vs late seizure behaviors, with sex influencing responses. For both male and female mice, the onset of mild behavioral seizures was accelerated by GR knockdown. In contrast, GR knockdown delayed the onset of more severe convulsive seizures and death in male mice. Concordantly, GR knockdown also blunted the SE-induced rise in serum corticosterone in male mice. GR knockdown did not alter survival times or serum corticosterone in females. To assess whether loss of GR affected susceptibility to SE-induced cell death, within-animal analyses were conducted comparing local GR knockdown rates to local cell loss. GR knockdown did not affect the degree of localized neuronal loss, suggesting cell-intrinsic GR signaling neither protects nor sensitizes neurons to acute SE-induced death. Overall, the findings reveal that hippocampal GRs exert an anti-convulsant role in both males and females in the early stages of SE, followed by a switch to a pro-convulsive role for males only. Findings reveal an unexpected complexity in the interaction between hippocampal GR activation and the progression of SE.

Protocol paper: kainic acid excitotoxicity-induced spinal cord injury paraplegia in Sprague-Dawley rats.

Excitotoxicity-induced in vivo injury models are vital to reflect the pathophysiological features of acute spinal cord injury (SCI) in humans. The duration and concentration of chemical treatment controls the extent of neuronal cell damage. The extent of injury is explained in relation to locomotor and behavioural activity. Several SCI in vivo methods have been reported and studied extensively, particularly contusion, compression, and transection models. These models depict similar pathophysiology to that in humans but are extremely expensive (contusion) and require expertise (compression). Chemical excitotoxicity-induced SCI models are simple and easy while producing similar clinical manifestations. The kainic acid (KA) excitotoxicity model is a convenient, low-cost, and highly reproducible animal model of SCI in the laboratory. The basic impactor approximately cost between 10,000 and 20,000 USD, while the kainic acid only cost between 300 and 500 USD, which is quite cheap as compared to traditional SCI method. In this study, 0.05mM KA was administered at dose of 10µL/100g body weight, at a rate of 10µL/min, to induce spinal injury by intra-spinal injection between the T12 and T13 thoracic vertebrae. In this protocol, detailed description of a dorsal laminectomy was explained to expose the spinal cord, following intra-spinal kainic acid administration at desired location. The dose, rate and technique to administer kainic acid were explained extensively to reflect a successful paraplegia and spinal cord injury in rats. The postoperative care and complication post injury of paraplegic laboratory animals were also explained, and necessary requirements to overcome these complications were also described to help researcher. This injury model produced impaired hind limb locomotor function with mild seizure. Hence this protocol will help researchers to induce spinal cord injury in laboratories at extremely low cost and also will help to determine the necessary supplies, methods for producing SCI in rats and treatments designed to mitigate post-injury impairment. Kainic acid intra-spinal injection at the concentration of 0.05mM, and rate 10µL/min, is an effective method create spinal injury in rats, however more potent concentrations of kainic acid need to be studied in order to create severe spinal injuries.

A novel de novo KCNB1 variant altering channel characteristics in a patient with periventricular heterotopia, abnormal corpus callosum, and mild seizure outcome.

KCNB1 encodes the α-subunit of Kv2.1, the main contributor to neuronal delayed rectifier potassium currents. The subunit consists of six transmembrane α helices (S1-S6), comprising the voltage-sensing domain (S1-S4) and the pore domain (S5-P-S6). Heterozygous KCNB1 pathogenic variants are associated with developmental and epileptic encephalopathy. Here we report an individual who shows the milder phenotype compared to the previously reported cases, including delayed language development, mild intellectual disability, attention deficit hyperactivity disorder, late-onset epilepsy responsive to an antiepileptic drug, elevation of serum creatine kinase, and peripheral axonal neuropathy. On the other hand, his brain MRI showed characteristic findings including periventricular heterotopia, polymicrogyria, and abnormal corpus callosum. Exome sequencing identified a novel de novo KCNB1 variant c.574G>A, p.(Ala192Thr) located in the S1 segment of the voltage-sensing domain. Functional analysis using the whole-cell patch-clamp technique in Neuro2a cells showed that the Ala192Thr mutant reduces both activation and inactivation of the channel at membrane voltages in the range of -50 to -30 mV. Our case could expand the phenotypic spectrum of patients with KCNB1 variants, and suggested that variants located in the S1 segment might be associated with a milder outcome of seizures.

A recurrent homozygous missense DPM3 variant leads to muscle and brain disease.

Biallelic pathogenic variants in the genes encoding the dolichol-phosphate mannose synthase subunits (DPM) which produce mannosyl donors for glycosylphosphatidylinositols, N-glycan and protein O- and C-mannosylation, are rare causes of congenital disorders of glycosylation. Pathogenic variants in DPM1 and DPM2 are associated with muscle-eye-brain (MEB) disease, whereas DPM3 variants have mostly been reported in patients with isolated muscle disease-dystroglycanopathy. Thus far, only one affected individual with compound heterozygous DPM3 variants presenting with myopathy, mild intellectual disability, seizures, and nonspecific white matter abnormalities (WMA) around the lateral ventricles has been described. Here we present five affected individuals from four unrelated families with global developmental delay/intellectual disability ranging from mild to severe, microcephaly, seizures, WMA, muscle weakness and variable cardiomyopathy. Exome sequencing of the probands revealed an ultra-rare homozygous pathogenic missense DPM3 variant NM_018973.4:c.221A&gt;G, p.(Tyr74Cys) which segregated with the phenotype in all families. Haplotype analysis indicated that the variant arose independently in three families. Functional analysis did not reveal any alteration in the N-glycosylation pathway caused by the variant; however, this does not exclude its pathogenicity in the function of the DPM complex and related cellular pathways. This report provides supporting evidence that, besides DPM1 and DPM2, defects in DPM3 can also lead to a muscle and brain phenotype.

Fine mapping and candidate gene analysis of a dravet syndrome modifier locus on mouse chromosome 11

Pathogenic variants in SCN1A result in a spectrum of phenotypes ranging from mild febrile seizures to Dravet syndrome, a severe infant-onset epileptic encephalopathy. Individuals with Dravet syndrome have developmental delays, elevated risk for sudden unexpected death in epilepsy (SUDEP), and have multiple seizure types that are often refractory to treatment. Although most Dravet syndrome variants arise de novo, there are cases where an SCN1A variant was inherited from mildly affected parents, as well as some individuals with de novo loss-of-function or truncation mutations that presented with milder phenotypes. This suggests that disease severity is influenced by other factors that modify expressivity of the primary mutation, which likely includes genetic modifiers. Consistent with this, the Scn1a+/− mouse model of Dravet syndrome exhibits strain-dependent variable phenotype severity. Scn1a+/− mice on the 129S6/SvEvTac (129) strain have no overt phenotype and a normal lifespan, while [C57BL/6Jx129]F1.Scn1a+/− mice have severe epilepsy with high rates of premature death. Low resolution genetic mapping identified several Dravet syndrome modifier (Dsm) loci responsible for the strain-dependent difference in survival of Scn1a+/− mice. To confirm the Dsm5 locus and refine its position, we generated interval-specific congenic strains carrying 129-derived chromosome 11 alleles on the C57BL/6J strain and localized Dsm5 to a 5.9 Mb minimal region. We then performed candidate gene analysis in the modifier region. Consideration of brain-expressed genes with expression or coding sequence differences between strains along with gene function suggested numerous strong candidates, including several protein coding genes and two miRNAs that may regulate Scn1a transcript.

Newborn with Microcephaly.

Newborn with Microcephaly.

Phenotypic Spectrum and Prognosis of Epilepsy Patients With GABRG2 Variants.

ObjectiveThis study aimed to obtain a comprehensive understanding of the genetic and phenotypic aspects of GABRG2-related epilepsy and its prognosis and to explore the potential prospects for personalized medicine.MethodsThrough a multicenter collaboration in China, we analyzed the genotype-phenotype correlation and antiseizure medication (ASM) of patients with GABRG2-related epilepsy. The three-dimensional protein structure of the GABRG2 variant was modeled to predict the effect of GABRG2 missense variants using PyMOL 2.3 software.ResultsIn 35 patients with GABRG2 variants, 22 variants were de novo, and 18 variants were novel. The seizure onset age was ranged from 2 days after birth to 34 months (median age: 9 months). The seizure onset age was less than 1 year old in 22 patients (22/35, 62.9%). Seizure types included focal seizures (68.6%), generalized tonic-clonic seizures (60%), myoclonic seizures (14.3%), and absence seizures (11.4%). Other clinical features included fever-sensitive seizures (91.4%), cluster seizures (57.1%), and developmental delay (45.7%). Neuroimaging was abnormal in 2 patients, including dysplasia of the frontotemporal cortex and delayed myelination of white matter. Twelve patients were diagnosed with febrile seizures plus, eleven with epilepsy and developmental delay, two with Dravet syndrome, two with developmental and epileptic encephalopathy, two with focal epilepsy, two with febrile seizures, and four with unclassified epilepsy. The proportions of patients with missense variants in the extracellular region and the transmembrane region exhibiting developmental delay were 40% and 63.2%, respectively. The last follow-up age ranged from 11 months to 17 years. Seizures were controlled in 71.4% of patients, and 92% of their seizures were controlled by valproate and/or levetiracetam.ConclusionThe clinical features of GABRG2-related epilepsy included seizure onset, usually in infancy, and seizures were fever-sensitive. More than half of the patients had cluster seizures. Phenotypes of GABRG2-related epilepsy were ranged from mild febrile seizures to severe epileptic encephalopathies. Most patients with GABRG2 variants who experienced seizures had a good prognosis. Valproate and levetiracetam were effective treatments for most patients.

DISCONTINUATION (СANCELLATION) OF TREATMENT OF EPILEPTIC SEIZURES

Currently, special attention is paid to the quality of life of patients with epilepsy. Therefore, great importance is given to the possibility of canceling antiepileptic therapy with prolonged remission. Before discontinuation of therapy, it is necessary to conduct electroencephalography (EEG) and determine the level of antiepileptic drugs (AED) in blood plasma. The presence of signs of typical epileptic activity on the EEG is a likely question of the correctness of the chosen tactics and the need to identify possible symptomatic mild seizures has no clearly defined standards for reducing the dosage of AED. On the recommendation of some experts, benzodiazepines and barbiturates are canceled within 4-8 weeks, with a combination therapy with a break for each drug of 1 month for 4-8 weeks for each.

Frameshift Mutation in Polar Rich Domain (PRD) of PQBP1 Gene Associated with Asymmetric Cerebellar Hemispheres: A Case Report of Renpenning Syndrome

Introduction: In 1962, Renpenning et al. published an article with 20 male patients from three generations with mental retardation. Scientists suggested that the syndrome with mutation mapped to the locus Xp11.2-p11.4 should be called Renpenning syndrome. The deletion/duplication of an AG dinucleotide on proximal Xp in the polyglutamine tract-binding protein 1 (PQBP1) gene causing frameshift in the fourth coding exon was identified as the most frequent mutation in this syndrome. Renpenning syndrome with asymmetric cerebellar hemispheres has not been reported previously. Case Presentation: In this case report, we presented an 11-year-old male with mild developmental delay and mild intellectual disability, microcephaly, dysmorphic face, short stature, and seizures. The following morphological abnormalities were detected: a wide nasal bridge, midfacial hypoplasia, short philtrum, low-set ears, low hanging columella, high palate, and narrow face. Neurological examination showed upper and lower extremities hypotonia with joint hypermobility. The patient had his first seizure at the age of seven, and he experienced a total of 10 seizures by the age 11. A systolic murmur of intensity 2/6 was present, and echocardiography showed chordae tendineae abnormalities in the left ventricle. Brain magnetic resonance imaging (MRI) showed asymmetric cerebellar hemispheres (mild right cerebellar hemisphere hypoplasia). A frameshift mutation in the polar reach domain (PRD) of the PQBP1 gene (c.459-462 delAGAG) was detected by exome sequencing. Conclusions: We showed the first case of genetically confirmed Renpenning syndrome in Serbia. Our patient had classical clinical manifestations for Renpenning syndrome as a consequence of frameshift mutation in the PRD of the PQBP1 gene. To the best of our knowledge, according to the literature, this is the first patient with Renpenning syndrome with asymmetric cerebellar hemispheres (mild right cerebellar hemisphere hypoplasia).

Clinical Characteristics of H1N1 Influenza A-Associated Mild Encephalopathy with Reversible Splenial Lesion: 4 Pediatric Cases.

Mild encephalopathy with reversible splenial lesion (MERS) is associated with a variety of infections and anti-epileptic drug withdrawal. Here we report the clinical characteristics of H1N1 influenza A-associated MERS based on our experience of four pediatric cases. A detailed retrospective analysis of four patients with H1N1 influenza A-associated MERS was performed at Guangzhou Women and Children's Medical Center. All patients exhibited mild influenza-like illness and seizures. Three patients presented with a new-onset seizure with fever after 5 years of age. 75% patients had altered mental status. For all four patients, influenza A (H1N1) viral RNA was detected in throat swab specimens at least twice. Brain magnetic resonance images revealed similar ovoid lesions in the corpus callosum, mainly in the splenium and for one patient in the splenium and genu of the corpus callosum. Only one patient had an abnormal electroencephalogram tracing. Cells and protein in the cerebrospinal fluid were normal in all patients. All patients received oseltamivir and one patient received intravenous immunoglobulin. As a result, all patients fully recovered after 2 months and showed no neurologic sequelae at discharge. This case series provides insight towards clinical features of H1N1 influenza A-associated MERS.

ASH1L mutation caused seizures and intellectual disability in twin sisters

ASH1L mutations have been identified with variable phenotypes, including intellectual disability, autism spectrum disorder (ASD), and multiple congenital anomalies (MCA). However, the mechanisms underlying this phenotypic variation remain unknown. Here, we present twin sisters exhibiting mild intellectual disability and seizures. Whole-exome sequencing of the family revealed a novel de novo heterozygous sequence variant, NM_018489.2: c.2678dup (p.Lys894*) in exon 3 of ASH1L which was estimated to be pathogenic. Furthermore, we reviewed previously reported ASH1L mutations in order to evaluate genotype-phenotype correlations for ASH1L variants. We found that patients with missense mutations in ASH1L appeared to present with more severe phenotypes and a higher likelihood of ASD than those with truncating mutations. The relationship between phenotype and genotype reported across several patients may help to explain the mechanisms underlying the phenotypic variation commonly observed between ASH1L mutations.

Ictal Occurrence of High-Frequency Oscillations Correlates With Seizure Severity in a Rat Model of Temporal Lobe Epilepsy.

High-frequency oscillations (HFOs, ripples 80–250 Hz, fast ripples 250–500 Hz) are biomarkers of epileptic tissue. They are most commonly observed over areas generating seizures and increase in occurrence during the ictal compared to the interictal period. It has been hypothesized that their rate correlates with the severity of epilepsy and seizure in affected individuals. In the present study, it was aimed to investigate whether the HFO count mirrors the observed behavioral seizure severity using a kainate rat model for temporal lobe epilepsy. Seizures were selected during the chronic epilepsy phase of this model and classified by behavioral severity according to the Racine scale. Seizures with Racine scale 5&6 were considered generalized and severe. HFOs were marked in 24 seizures during a preictal, ictal, and postictal EEG segment. The duration covered by the HFO during these different segments was analyzed and compared between mild and severe seizures. HFOs were significantly increased during ictal periods (p < 0.001) and significantly decreased during postictal periods (p < 0.03) compared to the ictal segment. Ictal ripples (p = 0.04) as well as fast ripples (p = 0.02) were significantly higher in severe seizures compared to mild seizures. The present study demonstrates that ictal HFO occurrence mirrors seizure severity in a chronic focal epilepsy model in rats. This is similar to recent observations in patients with refractory mesio-temporal lobe epilepsy. Moreover, postictal HFO decrease might reflect postictal inhibition of epileptic activity. Overall results provide additional evidence that HFOs can be used as biomarkers for measuring seizure severity in epilepsy.

The effects of naloxone, diazepam, and quercetin on seizure and sedation in acute on chronic tramadol administration: an experimental study

BackgroundTramadol is a widely used synthetic opioid. Substantial research has previously focused on the neurological effects of this drug, while the efficacy of various treatments to reduce the associated side effects has not been well studied. This study aimed to evaluate the protective effects of naloxone, diazepam, and quercetin on tramadol overdose-induced seizure and sedation level in male rats.MethodsThe project was performed with 72 male Wistar rats with an average weight of 200–250 g. The rats were randomly assigned to eight groups. Tramadol was administered intraperitoneally at an initial dose of 25 mg/kg/day. On the 14th day, tramadol was injected at 75 mg/kg, either alone or together with naloxone, diazepam, and quercetin (acute and chronic) individually or in combination. The rats were monitored for 6 h on the last day, and the number, the duration, and the severity of seizures (using the criteria of Racine) were measured over a 6-h observation period. The sedation level was also assessed based on a 4-point criterion, ranging from 0 to 3. Data were analyzed in SPSS software using Kruskal–Wallis, Chi-square, regression analysis, and generalized estimating equation (GEE) tests. The significance level was set at P < 0.05.ResultsThe naloxone-diazepam combination reduced the number, severity, and cumulative duration of seizures compared to tramadol use alone and reduced the number of higher-intensity seizures (level 3, 4) to a greater extent than other treatments. Naloxone alone reduced the number and duration of seizures but increased the number of mild seizures (level 2). Diazepam decreased the severity and duration of seizures. However, it increased the number of mild seizures (level 2). In comparison with the tramadol alone group, the acute quercetin group exhibited higher numbers of mild (level 2) and moderate (level 3) seizures. Chronic quercetin administration significantly increased the number of mild seizures. In the GEE model, all groups had higher sedation levels than the saline only group (P < 0.001). None of the protocols had a significant effect on sedation levels compared to the tramadol group.ConclusionThe combined administration of naloxone and diazepam in acute-on-chronic tramadol poisoning can effectively reduce most seizure variables compared to tramadol use alone. However, none of the treatments improved sedation levels.

Epilepsy surgery: Late seizure recurrence after initial complete seizure freedom.

This study was undertaken to improve understanding of late relapse following epilepsy surgery in pharmacoresistant epilepsy. Retrospective comparison was made of 99 of 1278 patients undergoing surgery during 1999-2015 with seizure relapses after at least 2years of complete seizure freedom with matched controls experiencing continued long-term seizure freedom. Univariate and multivariate analyses were performed. With a mean follow-up of 9.7years, mean time to seizure relapse was 56.6months. In multivariate analysis, incomplete resection based on magnetic resonance imaging (MRI), bilateral lesions on preoperative MRI, and epilepsy onset in the first year of life carried a significantly higher risk of late relapse. In patients with late relapse, additional functional imaging with positron emission tomography had been performed significantly more often. Although the differences were not significant in multivariate analysis, doses of antiepileptic drugs were higher in the relapse group preoperatively and in the first 24months and complete withdrawal was more frequent in the control group (68% vs. 51%). Regarding seizure frequency, most patients had mild seizure relapse (single relapse seizure or <1/month). In our predominantly lesional cohort, complete resection of the MRI lesion is the most important factor to maintain long-term seizure freedom. Two patterns of recurrence were identified: (1) incomplete resected lesions with seizure generation in proximity to the initial resection and (2) epileptogenic networks not detected preoperatively or evolving in the postoperative interval and manifesting with new clinical and diagnostic features.

Self-limited epilepsy of childhood with affective seizures: A well-defined epileptic syndrome?

ObjectiveHere we present cases of focal epilepsy with affective symptoms analyzing seizure characteristics, EEG pattern, treatment, and outcome. MethodsA multicenter, descriptive, retrospective study was conducted evaluating 18 patients with self-limited epilepsy who presented with seizures with affective symptoms seen between April 2000 and April 2018 at eight Argentinian centers. ResultsEighteen patients had focal seizures with affective symptoms; all of them had affective symptoms characterized by sudden fright or terror and screaming. Seizures started with manifestations of sudden fright or terror manifested by a facial expression of fear; consciousness was mildly impaired in 15/18 patients.Eleven of the patients also had autonomic manifestations, such as pallor, sweating, and abdominal pain. In addition, four of these 11 patients had ictus emeticus and one also presented with unilateral deviation of the eyes and head.Speech arrest, salivation, glottal noises, and chewing or swallowing movements were observed in 2/18 patients at the onset of the affective seizures. Two others also had mild asymmetric dystonic seizures involving both hands and arms. Three patients had tonic deviation of the mouth involving the lips and tongue as well pharyngeal and laryngeal muscles, resulting in anarthria and drooling. Two patients had brief hemifacial focal clonic seizures. ConclusionAffective manifestations associated or not with motor and/or autonomic manifestations and associated with typical EEG features of the idiopathic focal epilepsies of childhood is a particular presentation of self-limited focal epilepsy in childhood.

Classification and Severity Measurement of Epileptic Seizure using Intracranial Electroencephalogram (iEEG)

The Epileptic seizure is one of major neurological brain disorders and about 50 million of world’s population is affected by it. Electroencephalography is medical test which records brain signal by mounting electrodes on scalp or brain cortex to diagnosis seizure. Scalp Electroencephalography has low spatial resolution and presence of external artifact as compared to Intracranial Electroencephalography. In Intracranial Electroencephalography strip, grid and depth type of electrodes are implanted on cortex of brain by surgery to measure brain signal. Analysis of brain signal was carried out in past in diagnosis of Epileptic seizure. Seizure classification and Severity measurement of Epileptic Seizure are still challenging areas of research. Seizures are classified as focal seizure, generalized and secondary generalized seizure depending upon the area of brain which it generates and how it spreads. Classification of seizure helps in treatment of seizure and during brain surgery to operate on brain part which is responsible for continuous seizures generation. Developed seizure classification algorithm classifies seizures as focal Seizure, generalized Seizure and secondary generalized seizure depending on the percentage of iEEG electrodes detecting seizure activity. Seizure severity measurement scale is developed by modification in National Hospital Seizure Severity Scale. Seizures are graded as Mild seizure, Moderate seizure and severe seizure depending on its severity. Seizure Classification and Seizure Severity Measurement improves life quality of Epileptic patients by proper drug management.

Detection and diagnostic value of serum NSE and S100B protein levels in patients with seizures associated with mild gastroenteritis: A retrospective observational study.

Benign convulsions with mild gastroenteritis (CwG) and febrile seizures (FS) associated with mild gastroenteritis are 2 different diseases in the spectrum of seizures associated with mild gastroenteritis. However, specific and useful indicators for the identification of the 2 diseases are lacking. A retrospective analysis was performed to compare the serum neuronal-specific enolase (NSE) and S100B protein levels between patients with these 2 diseases to evaluate the value of NSE and S100B for differential diagnosis between these 2 diseases.The clinical data and NSE and S100B protein levels of 81 children with seizure-associated mild gastroenteritis were collected. According to the axillary temperature at the time of convulsions, all patients were classified into an afebrile seizure (AFS) group, hereafter called the CwG group (n = 46), and a febrile seizure group (FS group, n = 35).The serum NSE level was higher in the CwG group than in the FS group (14.046 (11.095, 19.266) pg/ml and 9.034 (7.158, 12.165) pg/ml, respectively, P < .001); however, the serum S100B protein levels in the CwG and the FS group were not significantly different (P > .05). Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) for NSE was 0.806, P = .000, which was statistically significant. The Youden index was largest (0.605) for a serum NSE cut-off value of 10.460 pg/ml, which yielded a sensitivity and specificity of 89% and 71%, respectively, for prediction of a CwG diagnosis.NSE may contribute to the differential diagnosis of CwG and FS associated with mild gastroenteritis.