Secondary Generalization Research Articles

Not Part of the Temporal Lobe, but Still of Importance? Substantia Nigra and Subthalamic Nucleus in Epilepsy.

The most researched brain region in epilepsy research is the temporal lobe, and more specifically, the hippocampus. However, numerous other brain regions play a pivotal role in seizure circuitry and secondary generalization of epileptic activity: The substantia nigra pars reticulata (SNr) and its direct input structure, the subthalamic nucleus (STN), are considered seizure gating nuclei. There is ample evidence that direct inhibition of the SNr is capable of suppressing various seizure types in experimental models. Similarly, inhibition via its monosynaptic glutamatergic input, the STN, can decrease seizure susceptibility as well. This review will focus on therapeutic interventions such as electrical stimulation and targeted drug delivery to SNr and STN in human patients and experimental animal models of epilepsy, highlighting the opportunities for overcoming pharmacoresistance in epilepsy by investigating these promising target structures.

Controversies in Ocular Myasthenia Gravis.

Myasthenia gravis (MG) with symptoms limited to eye muscles [ocular MG (OMG)] is a rare disease. OMG incidence varies according to ethnicity and age of onset. In recent years, both an increase in incidence rate, particularly in the elderly, and a lower risk for secondary generalization may have contributed to the growing disease prevalence in Western countries. OMG should be considered in patients with painless ptosis and extrinsic ophthalmoparesis. Though asymmetric muscle involvement and symptom fluctuations are typical, in some cases, OMG can mimic isolated cranial nerve paresis, internuclear ophthalmoplegia, and conjugate gaze palsy. Diagnostic confirmation can be challenging in patients negative for anti-acetylcholine receptor and anti-muscle-specific tyrosine kinase antibodies on standard radioimmunoassay. Early treatment is aimed at relieving symptoms and at preventing disease progression to generalized MG. Despite the absence of high-level evidence, there is general agreement on the efficacy of steroids at low to moderate dosage; immunosuppressants are considered when steroid high maintenance doses are required. The role of thymectomy in non-thymoma patients is controversial. Prolonged exposure to immunosuppressive therapy has a negative impact on the health-related quality of life in a proportion of these patients. OMG is currently excluded from most of the treatments recently developed in generalized MG.

Miastenia gravis ocular y factores asociados al desarrollo de una generalización secundaria: descripción de una serie española

IntroductionOcular myasthenia gravis (MG) is the most common phenotype of MG at onset. A variable percentage of these patients develop secondary generalisation; the risk factors for conversion and the protective effect of immunosuppressive treatment are currently controversial. Patients and methodsWe designed a retrospective single-centre study with the aim of describing the demographic, clinical, and laboratory characteristics of a Spanish cohort of patients with ocular MG from Hospital Universitario de Albacete from January 2008 to February 2020. ResultsWe selected 62 patients with ocular MG from a cohort of 91 patients with MG (68.1%). Median age at diagnosis was 68 (IQR, 52-75.3), and men accounted for 61.3% of the sample (n = 38). Most patients presented very late-onset ocular MG (n = 34, 54.8%). Binocular diplopia was the most frequent initial symptom (51.7%). The rate of progression to generalised MG was 50% (n = 31), with a median time of 6 months (IQR, 2-12.8). Female sex (OR: 5.46; 95% CI, 1.16-25-74; p = .03) and anti–acetylcholine receptor antibodies (OR: 8.86; 95% CI, 1.15-68.41; p = .04) were significantly associated with the risk of developing generalised MG. ConclusionsThe conversion rate observed in our series is relatively high. Generalisation of MG mainly occurs during the first 2 years of progression, and is strongly associated with female sex and especially with the presence of anti–acetylcholine receptor antibodies.

LEVETIRACETAM INDUCED URTICARIA IN PATIENT OF FOCAL SEIZURES; A CASE REPORT

Drug rash due to medications are common and can be serious leading to increase in morbidity and mortality. Drug rash can be caused by antiepileptic medications also. We are reporting a case of cutaneous reaction secondary to levetiracetam. A 22 years old female presented to the hospital with history of three episodes of seizures. She was diagnosed with focal seizures with secondary generalization and was prescribed tablet levetiracetam 500 mg twice a day for seizure prophylaxis. After 3rd dose, the patient developed diffuse, erythematous and itchy rashes over whole body without any breathing difculties. Levetiracetam was discontinued, and tablet lacosamide 200 mg twice daily was substituted. After 1 day, the rash dissipated. Our case was classied as drug-induced urticaria with red itchy hives. The world health organization Uppsala monitoring Centre (WHO-UMC) causality assessment system suggested a probable/likely cause for levetiracetam-induced skin reaction. Levetiracetam seemingly have fewer side effects than the traditional antiepileptic medications but it is important for the healthcare providers to continuously monitor the medication for adverse effects, so that necessary modications and required labeling may be reformed in-time.

Coffin-Siris syndrome and epilepsy.

Coffin-Siris syndrome is a rare genetic disorder defined by the presence of particular facial traits, congenital malformations, intellectual disability, and speech impairment. Epilepsy in Coffin-Siris syndrome has only occasionally been reported, and its features are poorly defined. We provide a detailed description of the clinical and instrumental findings of three patients with Coffin-Siris syndrome and epilepsy. The clinical diagnosis in our patients was confirmed by molecular analysis, which identified the presence of de novo mutations of ARID1B and SMARCB1 genes, in two patients and one patient, respectively. All the patients presented with epilepsy, with a mean age of seizure onset of 5.5years. Seizures were brief and had a focal onset with secondary generalization. Electroencephalographic recording documented a unilateral, and less commonly bilateral, paroxysmal activity in the temporal, parietal, and occipital regions. Clinical response to anticonvulsive therapy was satisfactory, with a low rate of seizure recurrence. Our case series contributes to delineate the phenotype of Coffin-Siris syndrome. We wish this report could pave the way for further studies that will better define the prevalence and clinical manifestations of epilepsy in this rare syndrome.

Allergic contact dermatitis due to the liquid skin adhesive Dermabond® predominantly occurs after the first exposure.

The clinical characteristics of patients with allergic contact dermatitis (ACD) due to a skin adhesive containing 2-octyl cyanoacrylate, Dermabond®, have not yet been elucidated. To investigate the clinical characteristics of patients with ACD caused by Dermabond® application. In this retrospective study, 577 patch tested patients were included. We identified patients with positive patch test results for Dermabond® and evaluated their results concerning (meth)acrylates and ethyl cyanoacrylate adhesive. Nine patients had positive patch test results to Dermabond®; six had developed secondary generalization.The mean time between Dermabond® application and ACD onset was 34 days (range, 27-44) in six patients with ACD after the first use, whereas, in the other three patients, it was 5.6 days (range, 4-8) after the second use. The time was significantly different between the two groups (P < .01). Positive reactions to ethyl cyanoacrylate adhesive (Aron Alpha) occurred in seven of nine patients, to ethyl cyanoacrylate 10% pet. in four of eight patients tested, and to 2-hydroxyethyl methacrylate in one of eight patients tested. Dermabond®-induced ACD is apparently characterized by a high prevalence of primary sensitization at first exposure to Dermabond®, secondary generalization is frequent, and most patients show cross-reactivity to ethyl cyanoacrylate.

Brivaracetam for the treatment of focal-onset seizures: pharmacokinetic and pharmacodynamic evaluations

ABSTRACT Introduction The goal of pharmacologic therapy with antiseizure medications (ASMs) is to achieve a seizure-free state with minimal side effects. About one third of patients treated with available ASMs continue to experience uncontrolled seizures. There is still need for new ASMs with enhanced effectiveness and tolerability. Areas covered The present manuscript is based on an extensive Internet and PubMed search from 1999 to 2020. It is focused on the clinical and pharmacological properties of brivaracetam (BRV) in the treatment of epilepsy. Expert opinion BRV is approved as add-on or monotherapy (in US) for the treatment of focal-onset seizures with or without secondary generalization. BRV is a high affinity synaptic vesicle glycoprotein 2A ligand, with 15–30-fold higher affinity than levetiracetam. The selectivity of BRV may be associated with fewer clinical adverse effects. BRV shares many of the pharmacokinetic characteristics of an ideal ASMs. Additionally, BRV has a low potential for clinically relevant drug–drug interactions. Its pharmacokinetic profile makes BRV a promising agent for the treatment of status epilepticus (SE). Although BRV is not approved for the treatment of SE, it has demonstrated promising preliminary results. Further studies are needed to explore the efficacy and tolerability of BRV in SE.

Juberg-Hayward syndrome and Roberts syndrome are allelic, caused by mutations in ESCO2

ObjectiveJuberg-Hayward syndrome (JHS; MIM 216100) is a rare autosomal recessive malformation syndrome, characterized by cleft lip/palate, microcephaly, ptosis, hypoplasia or aplasia of thumbs, short stature, dislocation of radial head, and fusion of humerus and radius leading to elbow restriction. A homozygous mutation in ESCO2 has recently been reported to cause Juberg-Hayward syndrome. Our objective was to investigate the molecular etiology of Juberg-Hayward syndrome in two affected Lisu tribe brothers. Materials and MethodsTwo patients, the unaffected parents, and two unaffected siblings were studied. Clinical and radiographic examination, whole exome sequencing, Sanger sequencing, Western blot analysis, and chromosome testing were performed. ResultsTwo affected brothers had characteristic features of Juberg-Hayward syndrome, except for the absence of microcephaly. The elder brother had bilateral cleft lip and palate, short stature, humeroradial synostosis, and simple partial seizure with secondary generalization. The younger brother had unilateral cleft lip and palate, short stature, and dislocation of radial heads. The homozygous (c.1654C > T; p.Arg552Ter) mutation in ESCO2 was identified in both patients. The other unaffected members of the family were heterozygous for the mutation. The presence of humeroradial synostosis and radial head dislocation in the same family is consistent with both being in the same spectrum of forearm malformations. Chromosome testing of the affected patients showed premature centromere separation. Western blot analysis showed reduced amount of truncated protein. ConclusionOur findings confirm that a homozygous mutation in ESCO2 is the underlying cause of Juberg-Hayward syndrome. Microcephaly does not appear to be a consistent feature of the syndrome.

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.

Thalamus and focal to bilateral seizures: A multiscale cognitive imaging study.

ObjectiveTo investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE) using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. Because the thalamus modulates propagation of temporal lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized seizures, i.e., focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity, and whole-brain network centrality.MethodsFBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 left/58 right), who performed a verbal fluency fMRI task that elicited robust thalamic activation. Thirty-three patients (29%) had experienced at least one FBTCS in the year preceding the investigation. We compared patients with TLE-FBTCS to those without FBTCS via a multiscale approach, entailing analysis of statistical parametric mapping (SPM) 12–derived measures of activation, task-modulated thalamic functional connectivity (psychophysiologic interaction), and graph-theoretical metrics of centrality.ResultsIndividuals with TLE-FBTCS had less task-related activation of bilateral thalamus, with left-sided emphasis, and left hippocampus than those without FBTCS. In TLE-FBTCS, we also found greater task-related thalamotemporal and thalamomotor connectivity, and higher thalamic degree and betweenness centrality. Receiver operating characteristic curves, based on a combined thalamic functional marker, accurately discriminated individuals with and without FBTCS.ConclusionsIn TLE-FBTCS, impaired task-related thalamic recruitment coexists with enhanced thalamotemporal connectivity and whole-brain thalamic network embedding. Altered thalamic functional profiles are proposed as imaging biomarkers of active secondary generalization.

Evaluation of the Neonate with Seizures.

Neonatal seizures are common, occurring in 2 to 5 of 1,000 live births in the United States. The neonatal brain is thought to be predisposed toward seizures due to a combination of excessive excitatory and deficient inhibitory neuronal activity. The seizures tend to be focal or multifocal without secondary generalization, resulting in subtle seizure appearance. There are five main categories of neonatal seizures: focal clonic, focal tonic, myoclonic, subtle, and generalized tonic. An electroencephalogram is recommended to diagnose and treat neonatal seizures due to poor reliability of the clinical examination. Causes of neonatal seizures are broad, including trauma, structural brain anomalies, infections, metabolic disorders, drug withdrawal or intoxication, and neonatal epilepsy syndromes. Treatment of neonatal seizures involves management of cardiorespiratory status, correction of metabolic derangements, and antiepileptics as needed. The most common antiepileptics used in neonates are phenobarbital, levetiracetam, and fosphenytoin. The long-term risk of neurodevelopmental disability varies depending upon the etiology of neonatal seizures. Close attention to developmental milestones and neurology follow-up is recommended for all neonates with seizures. [Pediatr Ann. 2020;49(7):e292-e298.].

Incontinentia Pigmenti with Extensive Brain Infarction in a Newborn

Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal multisystemic disorder with characteristic skin lesions. In addition to skin lesions, the teeth, nails, hair, eyes, and central nervous system are involved. Central nervous system involvement in the neonatal period may cause intellectual disabilities, severe neurologic impairment, or death. IP is associated with mutations in the NF-kappa B essential modulator gene located on chromosome Xq28 and is most commonly seen in female patients. We experienced one case of a newborn with multiple vesiculobullous skin lesions over the entire body after birth and partial seizures with secondary generalization. The brain magnetic resonance imaging showed extensive cerebral infarction, and retinal hemorrhage was observed in the fundus examination. The patient was clinically diagnosed with incontinentia pigmenti. Key words: Incontinentia pigmenti; Cerebral infarction; Retinal hemorrhage; NEMO gene

A systematic review and indirect treatment comparison of perampanel versus brivaracetam as adjunctive therapy in patients with focal-onset seizures with or without secondary generalization

PurposeTo date, there has not been a single randomized controlled trial (RCT) conducted to directly compare the efficacy and safety of perampanel to brivaracetam in the adjunctive treatment of focal-onset seizures. This study makes these comparisons through the use of indirect treatment comparison (ITC) methods. MethodsA systematic review was conducted to identify RCTs that evaluated either one of perampanel or brivaracetam in the treatment of patients with focal-onset seizures. The Bucher ITC method was then used to compare efficacy and safety outcomes between perampanel and brivaracetam. Additional subgroup analyses, by levetiracetam usage (prior or concomitant), were conducted. ResultsEight RCTs (four comparing perampanel to placebo, four comparing brivaracetam to placebo) were included in the ITC. For patients taking concomitant levetiracetam, perampanel showed a significantly better responder rate compared to brivaracetam [relative risk (RR) and 95 % confidence interval (CI): 2.62 (1.15, 5.99)]. For patients who had previously, or never, taken levetiracetam, there was no difference in the responder rate. In the overall population, both perampanel and brivaracetam were more effective than placebo in terms of responder rate, seizure freedom, and secondarily generalized tonic-clonic seizure responder rate; however, for these outcomes, no evidence of a difference between perampanel and brivaracetam was found. Patients taking brivaracetam showed significantly less dizziness compared to patients taking perampanel. No differences for any other safety outcome were found. ConclusionPerampanel and brivaracetam are effective for the adjunctive treatment of focal-onset seizures and display similar adverse event profiles. Perampanel demonstrated an improved focal-onset seizure responder rate compared to brivaracetam in patients taking concomitant levetiracetam. This may be due to the similarity in the mechanism of action between brivaracetam and levetiracetam.

Who seizes longest? Impact of clinical and demographic factors.

To investigate the impact of clinical and demographic parameters on the duration of focal onset seizures with and without secondary generalization using precise duration measurements from intracranial electroencephalographic (iEEG) recordings. Patients with unifocal epilepsy syndromes and iEEG recording were retrospectively identified from the database of the local epilepsy center (2006-2016). Seizure duration was defined as time difference of iEEG seizure pattern onset and cessation. The seizure semiology was classified based on video recordings. Clinical and demographic data were extracted from patient reports. In total, 69 adults were included, and 654 focal onset seizures were analyzed. Focal to bilateral tonic-clonic seizures (FBTCSs; 98/654) were significantly longer than focal seizures (FSs) without generalization (FS-BTCs; 556/654, P<.001), and most FSs (545/654, 83.3%) terminated within 2 minutes. The duration of FSs was prolonged with increasing age of the patients (P=.003) and was significantly shortened (P<.001) by evolution into an FBTCS. FBTCSs with lateralizing semiologies like version (P=.015) and sign of four (P=.043) were associated with longer bilateral tonic-clonic manifestations. Furthermore, FBTCSs with preceding aura, frontal origin, or onset during sleep were by trend shorter. Age (P<.001) and disease duration (P=.028) were essential for prediction of FS-BTC duration, whereas the vigilance state (P=.085) was the main prediction factor for the duration of FBTCSs. The identified modifiers of seizure duration are of great relevance for clinical risk evaluation, especially in the aging epilepsy patient suffering from temporal lobe epilepsy with secondary generalized seizures.

Noninvasive detection of focal seizures in ambulatory patients.

Reliably detecting focal seizures without secondary generalization during daily life activities, chronically, using convenient portable or wearable devices, would offer patients with active epilepsy a number of potential benefits, such as providing more reliable seizure count to optimize treatment and seizure forecasting, and triggering alarms to promote safeguarding interventions. However, no generic solution is currently available to reach these objectives. A number of biosignals are sensitive to specific forms of focal seizures, in particular heart rate and its variability for seizures affecting the neurovegetative system, and accelerometry for those responsible for prominent motor activity. However, most studies demonstrate high rates of false detection or poor sensitivity, with only a minority of patients benefiting from acceptable levels of accuracy. To tackle this challenging issue, several lines of technological progress are envisioned, including multimodal biosensing with cross‐modal analytics, a combination of embedded and distributed self‐aware machine learning, and ultra–low‐power design to enable appropriate autonomy of such sophisticated portable solutions.

Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats.

Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

Clinical signs, aetiology and outcome in 30 cats with recurrent seizures (2002-2018)

The purpose of the current study was to describe seizure types, aetiology, treatment response and outcome in 30cats with recurrent seizures. This retrospective case series study included the medical records of client-owned cats, admitted to the Clinic of Companion Animals for seizure disorders, from 2002 to 2018. Recorded data included history, seizure type, physical and neurological examination findings, blood pressure measurements, complete blood counts, serum biochemistry profile and urinalysis, tentative/final diagnosis, treatment, hospitalization and longterm outcome. A total of 298 feline neurology cases were examined during the study period. Of those, 38 cases were admitted for seizure disorders and 30 met the inclusion criteria. Median age on admission was 38,2 months (3,1 years) (range 2 months- 14 years old).Seizure types, as per owner description, were generalized (26 cats), focal with secondary generalization (3 cats), focal (2 cats) and complex (1 cat). Cluster seizures appeared at least once in 18/30 and status epilepticus in 7/30. Different seizure types were also recorded in individual cases. Fifteen cats (15/30) were hospitalized at least once and the duration of hospitalization ranged from 1-10 days. In most cases, in which diagnosis was established, epilepsy wassecondary (25/30), due to previous head trauma(11/30),metabolic (1/30), or inflammatory (4/30) disease, arterial hypertension (3/30), toxicosis (3/30) and intracranial neoplasia (2/30).Congenital hydrocephalus was detected in 1 cat. Tentative diagnosis could not be established in 5cats; however differential diagnosis included inflammatory or neoplastic encephalopathies.Antiepileptic drug monotherapy (phenobarbital or levetiracetam) was sufficient to control the seizures in 14 cases, while administration of combination therapy with 2 or more antiepileptic drugs was required in 5 cases (phenobarbital, levetiracetam, gabapentin). Successful control was achieved in 11/30 animals for 1-5 years. Seven cats required intensive care at least once due to status epilepticus. Until today, eighteen (18/30) cats are still alive and 11 died or were euthanized.Although in most cases epilepsy was secondary, seizure control was adequate and quality of life (QoL) was improved with antiepileptic drugs when metabolic, inflammatory and neoplastic encephalopathies were excluded.

Effectiveness and tolerability of adjunctive brivaracetam in patients with focal seizures: Second interim analysis of 6-month data from a prospective observational study in Europe

Brivaracetam (BRV) is indicated for adjunctive treatment of focal (partial-onset) seizures with or without secondary generalisation in patients 4 years of age and older in the European Union (EU). An ongoing 12-month, prospective, non-interventional post-marketing study (EP0077; NCT02687711) is collecting real-world information on patients receiving treatment with adjunctive BRV in Europe. In this study, BRV is prescribed according to routine clinical practice and the EU Summary of Product Characteristics. This second interim analysis assessed effectiveness, tolerability and health-related quality of life outcomes for up to 6 months of treatment.At the cut-off date (13 April 2018), 266 patients from five countries had attended Visit 1, 24.1 % (64/266) had completed the study, 37.6 % (100/266) were ongoing, and 38.3 % (102/266) had discontinued. In total, 261 patients had at least one dose of BRV and were included in the analyses. Patients had a mean time since epilepsy diagnosis of 23.2 years, a mean of eight lifetime AEDs (sum of AEDs discontinued prior to study entry and concomitant at study entry), and a median of five focal seizures per 28 days during the 3-month retrospective Baseline. 66.3 % of patients initiated BRV at a dose within the recommended starting range (50–100 mg/day) and 87.1 % of patients received BRV modal doses within the recommended dose range (50–200 mg/day) during the study. Retention rates were 79.1 % (N = 239) at 3 months and 62.1 % (N = 211) at 6 months. The 50 % responder rates for focal seizures were 46.8 % (N = 139) at 3 months and 53.6 % (N = 97) at 6 months. The proportions of patients who were seizure-free were 10.7 % (21/196) and 7.5 % (15/199) at 3 and 6 months of treatment, respectively. Median percent reductions in focal seizure frequency per 28 days from Baseline to 3 and 6 months were 34.6 % (N = 139) and 53.3 % (N = 97), respectively. Overall, 44.2 % of patients had an improvement and 15.4 % had a worsening in Patient Weighted Quality of Life in Epilepsy Inventory-Form 31 total score from Baseline to 6 months (N = 52). At least one treatment-emergent adverse event (TEAE) was reported in 51.0 % (133/261) of patients, and 34.5 % (90/261) of patients had drug-related TEAEs. The most common drug-related TEAEs (≥5% of patients) were drug ineffective (7.7 %), seizure (6.5 %), and fatigue (6.1 %).In this 6-month interim analysis, BRV showed effectiveness when used in clinical practice in five European countries. BRV was well tolerated, and no new safety signals were observed.

Efficacy and tolerability of brivaracetam in patients with intellectual disability and epilepsy.

Patients with intellectual disability (ID) are often excluded from clinical trials, and little is known about the best approach to treat their epilepsy. Brivaracetam (BRV) is a new antiepileptic drug (AED) for adjunctive treatment in patients with focal-onset seizures with or without secondary generalization. We analyzed the efficacy and tolerability of BRV in patients with ID and epilepsy who either had or had not previously received treatment with levetiracetam (LEV). Data on efficacy and tolerability were retrospectively collected. After the initial start of BRV in our tertiary epilepsy center, we analyzed medical records at 0, 3, 6 and 12months of follow-up. 116 patients were included (mean age = 34.9years, 44% female). All had complete data of 3-month follow-up, 76 of 6-month follow-up, and 39 patients of 1-year follow-up. Median starting dose of BRV was 50.0mg/day and the mean number of concomitant AEDs was 2.6. Seizure reduction and no side effects were reported in more than half of all patients. The most reported side effects were somnolence, dizziness and aggression. Retention rates for BRV were 84.4%, 75.5% and 58.1% after 3, 6 and 12months, respectively. Seizure reduction and side effects did not differ significantly between the groups with or without previous LEV treatment. We demonstrate that BRV is effective and well tolerated in patients with epilepsy and ID, even in those where previous LEV treatment failed.

Subdural hematomas in young children: clinical and electrophysiological features

Subdural hematoma is a sufficiently rare, but serious pathology of the brain in infants, which can lead to severe neurological deficit or result in death. Subdural hematomas are detected in 2025 per 100,000 children under 1 year. A retrospective analysis of autopsy material revealed that subdural hematomas were diagnosed in 72% of children who died before the age of 5 months from intracranial hemorrhage. According to localization, subdural hematomas are divided into supra- and subtentorial, mainly associated localization, which are located along the tent of cerebellum and sickle of the brain, mainly. The main mechanism of development of subdural hematomas is associated with the rupture of the bridge veins of the subdural space as a result of their tension, both traumatic etiology and nontraumatic brain damage, accompanied by progressive cerebral atrophy. It is believed that perinatal hypoxic-ischemic brain damage is one of the leading etiological factors of developed subdural hematomas in young children. In addition, the formation of subdural hematomas in young children can be observed with intraamniotic infections, congenital fermentopathies, and above all, in children with aciduria. In some infants, subdural hematomas occur without clinical manifestation, but in most cases are accompanied by the development of neurological disorders, both in acute and in distant periods. In the main, subdural hematomas in the acute period manifest with focal convulsions with secondary generalization of seizures, behavioral disturbances, respiration, and symptoms of intracranial hypertension. During the formation of chronic subdural hematoma, development of structural epilepsy (up to 20%), microcephaly, impaired psychomotor development is observed. In 55% of young children with acute subdural hematomas, the formation of chronic subdural hematomas is observed.