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Cureus Jun 2024Malformations of cortical development (MCD) are a group of disorders affecting the normal development of the human cortex and are significant causes of delay in...
Malformations of cortical development (MCD) are a group of disorders affecting the normal development of the human cortex and are significant causes of delay in psychomotor development and epilepsy in children. Lissencephaly (smooth brain) forms a major group of brain malformations. Microtubules help in the migration of neuronal cells. Defect in tubulin gene alpha-tubulin (TUBA), beta-tubulin (TUBB), and gamma-tubulin (TUBG) leads to defective neuronal migration. This group of disorders is termed as "tubulinopathies." The important genes implicated in causing lissencephaly are LIS1, XLIS, and TUBA1A gene. Recently, a mutation in the TUBG1 gene is associated with it. Here, we report a one-and-a-half-year-old girl with global developmental delay, microcephaly, infantile-onset epilepsy, epileptic spasms, dysmorphism, and motor signs. There was no significant birth history. Neuroimaging (MRI) showed a broad thick gyri and a decreased number of sulci suggestive of lissencephaly/pachygyria spectrum. There was dilatation of the ventricles, and no grey matter heterotopia was noted. Sleep EEG showed multifocal epileptiform discharges. The child was treated with multiple anti-seizure medicines (ASMs). A genetic test, whole exome sequencing, was done to determine the etiology of MCD. A heterozygous missense variation in exon 6 of the TUBG1 gene was identified and reported as a "variant of unknown significance." Still, because the genotype matched with the clinical phenotype of the patient, it was considered clinically significant. Therefore, a complete diagnosis of TUBG1 mutation-associated cortical malformation (lissencephaly/pachygyria) with microcephaly and early-onset epilepsy was established. TUBG1 mutation is de novo in most cases, but parental testing is recommended. The parents of such patients need to be counseled about the need for prenatal testing and the risk of the disease to siblings. The overall prognosis in such cases is poor because of refractory seizures, physical limitations, and intellectual disability.
PubMed: 38912084
DOI: 10.7759/cureus.62749 -
ACS Omega Jun 2024Pentylenetetrazole (PTZ)-induced kindling is a broadly used experimental model to study the anticonvulsive potential of new and existing chemical moieties with the aim...
Pentylenetetrazole (PTZ)-induced kindling is a broadly used experimental model to study the anticonvulsive potential of new and existing chemical moieties with the aim of discovering drugs hindering seizure progression and associated neurological comorbidities. In the present study, the impact of brivaracetam (BRV) (10 and 20 mg/kg) as monotherapy as well as in combination with 0.25 mg/kg of perampanel (PRP) was investigated on seizure progression with simultaneous electroencephalographic changes in PTZ kindling mouse model. Subsequently, mice were experimentally analyzed for anxiety, cognition, and depression after which their brains were biochemically evaluated for oxidative stress. The outcomes demonstrated that BRV alone delayed the kindling process, but BRV + PRP combination significantly ( < 0.0001) protected the mice from seizures of higher severity and demonstrated an antikindling effect. The PTZ-kindled mice exhibited anxiety, memory impairment, and depression in behavioral tests, which were remarkably less ( < 0.001) in animals treated with drug combination (in a dose-dependent manner) as these mice explored central, illuminated, and exposed zones of open-field test, light/dark box, and elevated plus maze. Moreover, memory impairment was demonstrated by kindled mice, which was significantly ( < 0.001) protected by BRV + PRP as animal's spontaneous alteration, object discrimination, and step-through latencies were increased in various tests employed for the assessment of cognitive abilities. The brains of PTZ-kindled mice had increased malondialdehyde and reduced antioxidant enzymes while treatment with BRV + PRP combination prevented kindling-induced elevation in oxidative markers. The outcomes of this study demonstrate that combining the PRP at low dose augmented the antiseizure properties of BRV as both drugs when administered simultaneously hindered the process of kindling by reducing PTZ-induced excessive electrical activity and oxidative stress in the brain.
PubMed: 38911714
DOI: 10.1021/acsomega.4c00962 -
International Medical Case Reports... 2024Although rare, cerebral venous sinus thrombosis (CVT) can result in significant neurological complications, particularly after childbirth. Early diagnosis poses a...
BACKGROUND
Although rare, cerebral venous sinus thrombosis (CVT) can result in significant neurological complications, particularly after childbirth. Early diagnosis poses a challenge due to symptom overlap with other conditions. Limited publications and underdiagnosis of CVT are prevalent in developing nations, notably in Ethiopia.
CASE
A 29-year-old mother, having given birth four times, presented to the emergency department in her second month postpartum with complaints of persistent headaches and blurred vision over three weeks. Additionally, she reported sudden weakness on her right side for one day. Despite previous treatments for migraine headaches, she was diagnosed with CVT after magnetic resonance imaging/venography revealed blockage in the right anastomotic vein and the posterior segment of the superior sagittal sinus. Treatment commenced with the anticoagulant enoxaparin. During hospitalization, she experienced one episode of generalized seizures, leading to transfer to the intensive care unit where phenytoin was added. Subsequent diagnosis of papilledema occurred. After a 16-day hospital stay, she was discharged with warfarin, phenytoin, and acetazolamide. Oral anticoagulation and other medications ceased after six months of treatment, considering the postpartum period as a temporary risk factor for CVT. The patient currently maintains good health and has resumed normal activities.
CONCLUSION
Maintaining a high index of suspicion for CVT during the postpartum period and promptly conducting imaging scans are crucial for early diagnosis. This approach can halt neurological decline and facilitate immediate recovery through early therapeutic interventions.
PubMed: 38911608
DOI: 10.2147/IMCRJ.S457170 -
Frontiers in Neuroscience 2024An important challenge in epilepsy is to define biomarkers of response to treatment. Many electroencephalography (EEG) methods and indices have been developed mainly...
OBJECTIVES
An important challenge in epilepsy is to define biomarkers of response to treatment. Many electroencephalography (EEG) methods and indices have been developed mainly using linear methods, e.g., spectral power and individual alpha frequency peak (IAF). However, brain activity is complex and non-linear, hence there is a need to explore EEG neurodynamics using nonlinear approaches. Here, we use the Fractal Dimension (FD), a measure of whole brain signal complexity, to measure the response to anti-seizure therapy in patients with Focal Epilepsy (FE) and compare it with linear methods.
MATERIALS
Twenty-five drug-responder (DR) patients with focal epilepsy were studied before (t1, named DR-t1) and after (t2, named DR-t2) the introduction of the anti-seizure medications (ASMs). DR-t1 and DR-t2 EEG results were compared against 40 age-matched healthy controls (HC).
METHODS
EEG data were investigated from two different angles: frequency domain-spectral properties in δ, θ, α, β, and γ bands and the IAF peak, and time-domain-FD as a signature of the nonlinear complexity of the EEG signals. Those features were compared among the three groups.
RESULTS
The δ power differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, < 0.01 and DR-t2 vs. HC, < 0.01). The θ power differed between DR-t1 and DR-t2 ( = 0.015) and between DR-t1 and HC ( = 0.01). The α power, similar to the δ, differed between DR patients pre and post-ASM and HC (DR-t1 vs. HC, < 0.01 and DR-t2 vs. HC, < 0.01). The IAF value was lower for DR-t1 than DR-t2 ( = 0.048) and HC ( = 0.042). The FD value was lower in DR-t1 than in DR-t2 ( = 0.015) and HC ( = 0.011). Finally, Bayes Factor analysis showed that FD was 195 times more likely to separate DR-t1 from DR-t2 than IAF and 231 times than θ.
DISCUSSION
FD measured in baseline EEG signals is a non-linear brain measure of complexity more sensitive than EEG power or IAF in detecting a response to ASMs. This likely reflects the non-oscillatory nature of neural activity, which FD better describes.
CONCLUSION
Our work suggests that FD is a promising measure to monitor the response to ASMs in FE.
PubMed: 38911599
DOI: 10.3389/fnins.2024.1401068 -
SAGE Open Medical Case Reports 2024Valproate encephalopathy is one of the unusual and severe but treatable side effect. This research focuses on four female patients who had valproate medication for...
Valproate encephalopathy is one of the unusual and severe but treatable side effect. This research focuses on four female patients who had valproate medication for epilepsy and developed an increased frequency of seizures, exacerbated disruption of consciousness, gastrointestinal problems, cognitive dysfunction, ataxia, and psychobehavioral abnormalities. The patient's symptoms improved over time once sodium valproate was stopped. As a result, when using sodium valproate, one should be aware of the risk of sodium valproate encephalopathy and cease using the medication right once if any of the above symptoms of unknown etiology manifest clinically. We also go over the potential pathogenesis that lead to valproate encephalopathy and the heightened risk of encephalopathy from taking antiepileptic medications together. It was stressed how crucial it is to identify, diagnose, and treat sodium valproate encephalopathy as soon as possible.
PubMed: 38911175
DOI: 10.1177/2050313X241260152 -
Cureus May 2024Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been...
Glofitamab-Associated Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Presenting as Serial Seizures and Responding Positively to Antiseizure Drugs and Anakinra: A Case Report.
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been described with immune checkpoint inhibitors as well. Glofitamab-associated ICANS with a bispecific monoclonal antibody has rarely been reported. The patient is a 63-year-old male with a history of mantle cell lymphoma, diagnosed at age 37, and aggressive large-cell B-cell lymphoma, diagnosed at age 50. Despite adequate chemotherapy, immunotherapy, autologous stem cell transplantation, and CAR T-cell therapy, there were several relapses, including meningeal carcinomatosis at age 61 and intracerebral lymphoma at age 62. For this reason, glofitamab was started. One week after the ninth cycle, the patient developed drowsiness, behavioral changes, word-finding difficulties, aphasia, focal to bilateral tonic-clonic seizures, and focal onset seizures, which resolved after 16 days with levetiracetam, valproic acid, lorazepam, and midazolam. Since there was no infectious disease, electrolyte disturbance, metabolic disorder, cardiovascular disease, or relapse of lymphoma, glofitamab-associated ICANS was suspected, and anakinra was administered. The case shows that ICANS with drowsiness, behavioral changes, aphasia, and seizures can develop with glofitamab and that patients with structural brain abnormalities may be prone to this.
PubMed: 38910651
DOI: 10.7759/cureus.60833 -
Neuroscience Letters Jun 2024Brain somatic variants in SLC35A2, an intracellular UDP-galactose transporter, are commonly identified mutations associated with drug-resistant neocortical epilepsy and...
Brain somatic variants in SLC35A2, an intracellular UDP-galactose transporter, are commonly identified mutations associated with drug-resistant neocortical epilepsy and developmental brain malformations, including focal cortical dysplasia type I and mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). However, the causal effects of altered SLC35A2 function on cortical development remain untested. We hypothesized that focal Slc35a2 knockout (KO) or knockdown (KD) in the developing mouse cortex would disrupt cortical development and change network excitability. Through two independent studies, we used in utero electroporation (IUE) to introduce CRISPR/Cas9/targeted guide RNAs or short-hairpin RNAs into the embryonic mouse brain at day 14.5-15.5 to achieve Slc35a2 KO or KD, respectively, from neural precursor cells. Slc35a2 KO or KD caused disrupted radial migration of electroporated neurons evidenced by heterotopic cells located in lower cortical layers and in the sub-cortical white matter. Slc35a2 KO in neurons did not induce changes in oligodendrocyte number, importantly suggesting that the oligodendroglial hyperplasia observed in MOGHE originates from distinct cell autonomous effects of Slc35a2 mutations. Adult KO mice were implanted with EEG electrodes for 72-hour continuous recording. Spontaneous seizures were not observed in focal Slc35a2 KO mice, but there was reduced seizure threshold following pentylenetetrazol injection. Here we demonstrate that focal Slc35a2 KO or KD in vivo disrupts corticogenesis through altered neuronal migration and that KO leads to reduced seizure threshold. Together these results demonstrate a direct causal role for SLC35A2 in cortical development.
PubMed: 38909838
DOI: 10.1016/j.neulet.2024.137881 -
The Thoracic and Cardiovascular Surgeon Jan 2024Hypothermia is a neuroprotective strategy during cardiopulmonary bypass. Rewarming entailing a rapid rise in cerebral metabolism might lead to secondary neurological...
BACKGROUND
Hypothermia is a neuroprotective strategy during cardiopulmonary bypass. Rewarming entailing a rapid rise in cerebral metabolism might lead to secondary neurological sequelae. In this pilot study, we aimed to validate the hypothesis that a slower rewarming rate would lower the risk of cerebral hypoxia and seizures in infants.
METHODS
This is a prospective, clinical, single-center study. Infants undergoing cardiac surgery in hypothermia were rewarmed either according to the standard (+1°C in < 5 minutes) or a slow (+1°C in > 5-8 minutes) rewarming strategy. We monitored electrocortical activity via amplitude-integrated electroencephalography (aEEG) and cerebral oxygenation by near-infrared spectroscopy during and after surgery.
RESULTS
Fifteen children in the standard rewarming group (age: 13 days [5-251]) were cooled down to 26.6°C (17.2-29.8) and compared with 17 children in the slow-rewarming group (age: 9 days [4-365]) with a minimal temperature of 25.7°C (20.1-31.4). All neonates in both groups ( = 19) exhibited suppressed patterns compared with 28% of the infants > 28 days ( < 0.05). During rewarming, only 26% of the children in the slow-rewarming group revealed suppressed aEEG traces (vs. 41%; = 0.28). Cerebral oxygenation increased by a median of 3.5% in the slow-rewarming group versus 1.5% in the standard group ( = 0.9). Our slow-rewarming group revealed no aEEG evidence of any postoperative seizures (0 vs. 20%).
CONCLUSION
These results might indicate that a slower rewarming rate after hypothermia causes less suppression of electrocortical activity and higher cerebral oxygenation during rewarming, which may imply a reduced risk of postoperative seizures.
Topics: Humans; Rewarming; Infant; Prospective Studies; Pilot Projects; Electroencephalography; Male; Time Factors; Spectroscopy, Near-Infrared; Infant, Newborn; Female; Treatment Outcome; Hypothermia, Induced; Risk Factors; Seizures; Cardiopulmonary Bypass; Brain Waves; Hypoxia, Brain; Age Factors; Intraoperative Neurophysiological Monitoring; Brain; Cerebrovascular Circulation
PubMed: 38909608
DOI: 10.1055/s-0044-1787650 -
European Journal of Paediatric... May 2024Inflammation related to influenza virus infection can lead to multiple neurological presentations. Encephalitis is one of them, mostly accompanied by seizures, with...
INTRODUCTION
Inflammation related to influenza virus infection can lead to multiple neurological presentations. Encephalitis is one of them, mostly accompanied by seizures, with different profiles depending on the epidemics and previous medical conditions.
MATERIALS AND METHODS
All children presenting neurological symptoms and positive for influenza virus RNA detection in a respiratory sample between November 2018 and April 2023, hospitalized in the Department of Paediatric Neurology of Toulouse Children's Hospital, were retrospectively analysed.
RESULTS
Among the 1,277 children diagnosed with influenza in our centre, 131 (10.3 %) were hospitalized for neurological features. The year 2020-2021 was marked by zero incidence of positive influenza tests, associated with the COVID-19 pandemic. Among the 131 patients included, 71.6 % were under 5 years old. Most of them (80.9 %) were infected by influenza A virus. The first neurological symptoms were mainly seizures in 73.3 % of patients. Possible or confirmed encephalitis was observed in 29 % of cases, including one acute necrotizing encephalopathy. Few children (6.1 %) presented with acute myositis. Twenty-seven patients (20.6 %) had a personal history of significant previous neurological disorders. Most patients (88.5 %) displayed a rapid favourable outcome, marked by the disappearance of their neurological symptoms within the first 2 days. Anti-epileptic drugs were introduced in 1.5 % of cases, and adapted in 16.8 %, mainly in patients with febrile status epilepticus and an abnormal EEG.
CONCLUSION
Neurological features were frequently associated with influenza infection in children; most were transient. Effects on long-term neurodevelopmental outcomes need to be clarified as our follow-up was limited, especially in children with pre-existing neurological conditions.
PubMed: 38908343
DOI: 10.1016/j.ejpn.2024.05.012 -
Annals of General Psychiatry Jun 2024This study aimed to assess the incidence of EEG abnormalities (EEG-ab) in children diagnosed with ADHD, investigate the risk of epileptic seizures (SZ) and maintenance...
PURPOSE
This study aimed to assess the incidence of EEG abnormalities (EEG-ab) in children diagnosed with ADHD, investigate the risk of epileptic seizures (SZ) and maintenance on methylphenidate (MPH) over a three-year period.
METHODS
A total of 517 ADHD children aged 6-14 years were included. Baseline assessments included the identification of EEG-ab, ADHD inattentive subtype (ADHD-I), comorbid epilepsy, the use of antiepileptic drugs (AEDs) and the use of MPH. At the 3-year follow-up, assessments included the presence of EEG-ab, maintenance on MPH, AED usage, SZ risk in cases with EEG-epileptiform abnormalities (EEG-epi-ab), compared with control ADHD cases without EEG-epi-ab matched for age and gender.
RESULTS
EEG-ab were identified in 273 (52.8%) cases. No statistically significant differences were observed between the EEG-ab and EEG-non-ab groups in terms of age, gender, ADHD-I type or initial use of MPH. EEG non-epileptiform abnormalities (EEG-non-epi-ab) were found in 234 out of 478 (49%) cases without EEG-epi-ab. Notably, EEG-non-epi-ab occurred more frequently in the group of 39 cases with EEG-epi-ab (30/39 (76.9%) vs. 9/39, (21.3%), a subset selected for 3-year follow-up. At 3-year-follow-up no statistically significant difference was found in maintenance on MPH in ADHD cases with and without EEG-epi-ab. Nobody of ADHD cases without comorbid epilepsy or with comorbid epilepsy with achieved SZ freedom developed new SZ. Only 3 children with drug resistant epilepsy experienced SZs, without increase in SZ frequency. The disappearance rate of EEG-epi-ab was higher than that EEG-non-epi-ab (71.8% vs. 33.3%).
CONCLUSIONS
Children with and without EEG-ab exhibited similar patterns of MPH use (initial use, positive response, and maintenance on MPH). The presence of comorbid epilepsy and EEG-ab, with or without EEG-epi-ab, was not associated with an increased risk of SZ despite the use of MPH.
PubMed: 38907242
DOI: 10.1186/s12991-024-00510-4