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Cureus Jun 2024Bupropion is an antidepressant used in the treatment of major depressive disorder, seasonal affective disorder, nicotine addiction, and weight loss. It primarily...
Bupropion is an antidepressant used in the treatment of major depressive disorder, seasonal affective disorder, nicotine addiction, and weight loss. It primarily functions via norepinephrine and dopamine reuptake inhibition. At toxic doses, bupropion can elicit seizures, as well as precipitate corrected QT interval (QTc) and QRS prolongation. We describe a case of an 18-year-old female who reportedly ingested 28 grams of extended-release bupropion, a dose much higher than in previously reported cases. Toxic ingestion precipitated status epilepticus, prolonged QTc, widened QRS, pulseless ventricular tachycardia (pVT), and subsequent cardiovascular collapse necessitating veno-arterial extracorporeal membrane oxygenation (ECMO) and Impella support. Historically, the cardiotoxic effects of bupropion toxicity have largely been treated with supportive care, sometimes requiring ECMO. This patient's course was complicated by a widening QRS despite aggressive bicarbonate therapy and recurrent pVT, which was ultimately aborted with lidocaine. Neurological prognostication was further complicated by a lack of brainstem reflexes on the exam. With maximal supportive care, the patient was liberated from Impella, ECMO, and the ventilator by hospital day seven. At discharge, she was neurologically intact with full recovery of cardiac function. This case emphasizes the need for early consideration of transfer to an ECMO center in the setting of a bupropion overdose and offers a potentially effective treatment option for bupropion-induced ventricular arrhythmia.
PubMed: 38915842
DOI: 10.7759/cureus.62873 -
BioRxiv : the Preprint Server For... Jun 2024ADP-ribosylation is a post-translational modification involving the transfer of one or more ADP-ribose units from NAD+ to target proteins. Dysregulation of...
PURPOSE
ADP-ribosylation is a post-translational modification involving the transfer of one or more ADP-ribose units from NAD+ to target proteins. Dysregulation of ADP-ribosylation is implicated in neurodegenerative diseases. Here we report a novel homozygous variant in the gene (c.545A>G, p.His182Arg) encoding the mono(ADP-ribosyl) hydrolase ARH3 found in 2 patients with childhood-onset neurodegeneration with stress-induced ataxia and seizures (CONDSIAS).
METHODS
Genetic testing via exome sequencing was used to identify the underlying disease cause in two siblings with developmental delay, seizures, progressive muscle weakness, and respiratory failure following an episodic course. Studies in a cell culture model uncover biochemical and cellular consequences of the identified genetic change.
RESULTS
The ARH3 variant affects a highly conserved residue in the active site of ARH3, leading to protein instability, degradation, and reduced expression. ARH3 additionally fails to localize to the nucleus. The combination of reduced expression and mislocalization of ARH3 resulted in accumulation of mono-ADP ribosylated species in cells.
CONCLUSIONS
The children's clinical course combined with the biochemical characterization of their genetic variant develops our understanding of the pathogenic mechanisms driving CONDSIAS and highlights a critical role for ARH3-regulated ADP ribosylation in nervous system integrity.
PubMed: 38915701
DOI: 10.1101/2024.06.14.597428 -
Scientific Reports Jun 2024Epidural spinal cord stimulation (SCS) is indicated for the treatment of intractable pain and is widely used in clinical practice. In previous basic research, the...
Epidural spinal cord stimulation (SCS) is indicated for the treatment of intractable pain and is widely used in clinical practice. In previous basic research, the therapeutic effects of SCS have been demonstrated for epileptic seizure. However, the mechanism has not yet been elucidated. In this study, we investigated the therapeutic effect of SCS and the influence of epileptic seizure. First, SCS in the cervical spine was performed. The rats were divided into four groups: control group and treatment groups with SCS conducted at 2, 50, and 300 Hz frequency. Two days later, convulsions were induced by the intraperitoneal administration of kainic acid, followed by video monitoring to assess seizures. We also evaluated glial cells in the hippocampus by fluorescent immunostaining, electroencephalogram measurements, and inflammatory cytokines such as C-C motif chemokine ligand 2 (CCL2) by quantitative real-time polymerase chain reaction. Seizure frequency and the number of glial cells were significantly lower in the 300 Hz group than in the control group. SCS at 300 Hz decreased gene expression level of CCL2, which induces monocyte migration. SCS has anti-seizure effects by inhibiting CCL2-mediated cascades. The suppression of CCL2 and glial cells may be associated with the suppression of epileptic seizure.
Topics: Animals; Chemokine CCL2; Rats; Disease Models, Animal; Spinal Cord Stimulation; Male; Seizures; Epilepsy; Kainic Acid; Hippocampus; Neuroglia; Rats, Sprague-Dawley; Electroencephalography
PubMed: 38914629
DOI: 10.1038/s41598-024-64972-y -
Annals of Indian Academy of Neurology May 2024Epileptic spasms are a unique, age-dependent manifestation of epilepsies in infancy and early childhood, commonly occurring as part of infantile epileptic spasms...
Epileptic spasms are a unique, age-dependent manifestation of epilepsies in infancy and early childhood, commonly occurring as part of infantile epileptic spasms syndrome. Developmental stagnation and subsequent decline may occur in children with epileptic spasms, partly due to the abundant high-amplitude interictal epileptiform and slow wave abnormalities. Early recognition and treatment of epileptic spasms, along with the reversal of the electroencephalography (EEG) findings, are critical for improving outcomes. Recognizing hypsarrhythmia and its variations is key to confirming the diagnosis. The various patterns of hypsarrhythmia are not etiology specific, but could indicate the severity of the disease. Several scoring systems have been proposed to improve the inter-rater reliability of recognizing hypsarrhythmia and to assess EEG progress in response to treatment. Ictal patterns during spasms are brief and composed of slow waves, sharp transients, fast activity, and voltage attenuation, either in isolation or more commonly as a combination of these waveforms. Ictal patterns are commonly diffuse, but may be lateralized to one hemisphere in children with structural etiology. A subset of patients with epileptic spasms has a surgically remediable etiology, with readily identifiable lesions on neuroimaging in most cases. Asymmetry in epileptic spasms, concurrent focal seizures, and asymmetric interictal and ictal EEG findings may be present, but a lack of focality in electrophysiological findings is not uncommon. Intracranial EEG features of epileptic spasms have been described, but the utility of intracranial EEG monitoring in surgical candidates with overt focal epileptogenic lesions on magnetic resonance imaging is questionable, and surgery could be performed using noninvasive data.
PubMed: 38912539
DOI: 10.4103/aian.aian_445_24 -
Heliyon Jun 2024Neonatal seizure is a common medical emergency that signals severe insult to the neonatal brain. It is a major risk factor for neonatal morbidity and mortality. It has a...
BACKGROUND
Neonatal seizure is a common medical emergency that signals severe insult to the neonatal brain. It is a major risk factor for neonatal morbidity and mortality. It has a wide worldwide variation, ranging from 5 per 1000 live births in the United States of America to 39.5 per 1000 live births in Kenya. To decrease this significant figure, it is better to investigate its causes further. Therefore, this study aimed to assess its determinants since there was no prior evidence about it in the context of study area.
OBJECTIVE
Aim to assess the determinants of neonatal seizures among neonates admitted to neonatal intensive care units in the Awi Zone Hospitals, 2023.
METHODS
An institution based unmatched case-control study was conducted on 531 admitted eligible neonates from January 1, 2023, to May 30, 2023. A pretested tool was employed to collect data. The collected data were coded, edited, and entered into Epi-data version 3.1 and then exported to SPSS 26. Chi-square and odds ratios were used to assess the relationship between factors associated with the occurrence of neonatal seizure. Model goodness of fit was tested by Hosmer and Lemeshow. Bivariate and multivariate analysis was declared at P < 0.25 and P < 0.05 respectively to show a significant association with neonatal seizure at a 95 % level of significance.
RESULTS
A total of 506 (130 cases and 376 controls) of admitted neonates were used in the final analysis model. Neonates admitted within 24 h of birth [AOR; 5.98 (95 %, CI: 2.18-16.43)], gestational age <32 weeks [AOR; 2.89 (95 %, CI: 1.29-6.53)], body temperature >37.5 °C [AOR; 4.82 (95 %, CI: 1.82-12.76)], blood glucose level <40 g/dl [AOR; 4.95 (95 %, CI: 2.06,11.88)], neonatal sepsis [AOR; 2.79 (95 %, CI: 1.46-5.35)] and perinatal asphyxia [AOR; 8.25 (95 %, CI: 4.23, 16.12)] were found to be determinants of neonatal seizure.
CONCLUSION
and recommendations: In this study, neonatal seizure was determined by the factors of neonatal age, gestational age<32 weeks, body temperature >37.5 °C, blood glucose level <40 g/dl, neonatal sepsis, and perinatal asphyxia. Therefore, the presence of such factors requires prompt recognition and treatment.
PubMed: 38912494
DOI: 10.1016/j.heliyon.2024.e32537 -
ACG Case Reports Journal Jun 2024Biologic therapy is the mainstay of treatment of complicated inflammatory bowel diseases, which has numerous potential side effects. Among these is a rare condition...
Biologic therapy is the mainstay of treatment of complicated inflammatory bowel diseases, which has numerous potential side effects. Among these is a rare condition known as posterior reversible encephalopathy syndrome (PRES), which is a reversible neurological disorder that results in symptoms such as headache, nausea/vomiting, blurry vision, and seizure and is diagnosed based on specific clinical and radiological features. This report presents a case of a 19-year-old woman with fistulizing Crohn's disease who was treated with infliximab, but subsequently developed PRES, which was manifested as recurrent episodes of seizures and elevated blood pressure readings, was managed supportively with antiepileptic and antihypertensive medications and eventually made a full recovery, even after resuming infliximab. This case adds to the fewer than 10 previously reported cases of PRES associated with biological therapy for inflammatory bowel disease. It highlights the need to consider this complication when prescribing these drugs.
PubMed: 38912372
DOI: 10.14309/crj.0000000000001400 -
Degenerative Neurological and... 2024X-linked adrenoleukodystrophy (ALD) is a rare genetic disorder caused by a pathogenic variant of the ABCD1 gene, leading to impaired peroxisomal function and the...
BACKGROUND
X-linked adrenoleukodystrophy (ALD) is a rare genetic disorder caused by a pathogenic variant of the ABCD1 gene, leading to impaired peroxisomal function and the accumulation of very long-chain fatty acids (VLCFAs). ALD presents a wide range of neurological and adrenal symptoms, ranging from childhood cerebral adrenoleukodystrophy to adrenomyeloneuropathy and adrenal insufficiency. Newborn screening (NBS) for ALD is available in some regions but remains lacking in others, such as India.
CASE PRESENTATION
We present a case of a 10-year-old boy with ALD who presented with seizures, progressive weakness, visual impairment, and adrenal insufficiency. Despite symptomatic management and dietary adjustments, the disease progressed rapidly, leading to respiratory failure and eventual demise. The diagnosis was confirmed through molecular analysis and elevated VLCFA levels. Neuroimaging revealed characteristic white matter changes consistent with ALD.
CONCLUSION
ALD is a devastating disease with no cure, emphasizing the importance of early detection through newborn screening and genetic testing. Management strategies include adrenal hormone therapy, gene therapy, and allogenic stem cell transplantation, as well as investigational treatments such as VLCFA normalization. Our case advocates the need for worldwide NBS and pediatric neurologic follow-up to enable early intervention and improve patient outcomes. Additionally, the association between ALD, recurrent febrile seizures, and unexplained developmental delay warrants further investigation to better understand disease progression and potential therapeutic targets.
PubMed: 38912366
DOI: 10.2147/DNND.S442985 -
Frontiers in Cellular and Infection... 2024Invasive mold diseases of the central nervous (CNS IMD) system are exceedingly rare disorders, characterized by nonspecific clinical symptoms. This results in...
BACKGROUND
Invasive mold diseases of the central nervous (CNS IMD) system are exceedingly rare disorders, characterized by nonspecific clinical symptoms. This results in significant diagnostic challenges, often leading to delayed diagnosis and the risk of misdiagnosis for patients. Metagenomic Next-Generation Sequencing (mNGS) holds significant importance for the diagnosis of infectious diseases, especially in the rapid and accurate identification of rare and difficult-to-culture pathogens. Therefore, this study aims to explore the clinical characteristics of invasive mold disease of CNS IMD in children and assess the effectiveness of mNGS technology in diagnosing CNS IMD.
METHODS
Three pediatric patients diagnosed with Invasive mold disease brain abscess and treated in the Pediatric Intensive Care Unit (PICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2023 were selected for this study.
RESULTS
Case 1, a 6-year-old girl, was admitted to the hospital with "acute liver failure." During her hospital stay, she developed fever, irritability, and seizures. CSF mNGS testing resulted in a negative outcome. Multiple brain abscesses were drained, and was detected in pus culture and mNGS. The condition gradually improved after treatment with voriconazole combined with caspofungin. Case 2, a 3-year-old girl, was admitted with "acute B-lymphoblastic leukemia." During induction chemotherapy, she developed fever and seizures. was detected in the intracranial abscess fluid by mNGS, and the condition gradually improved after treatment with voriconazole combined with caspofungin, followed by "right-sided brain abscess drainage surgery." Case 3, a 7-year-old girl, showed lethargy, fever, and right-sided limb weakness during the pending chemotherapy period for acute B-lymphoblastic leukemia. and was detected in the cerebrospinal fluid by mNGS. The condition gradually improved after treatment with amphotericin B combined with posaconazole. After a six-month follow-up post-discharge, the three patients improved without residual neurological sequelae, and the primary diseases were in complete remission.
CONCLUSION
The clinical manifestations of CNS IMD lack specificity. Early mNGS can assist in identifying the pathogen, providing a basis for definitive diagnosis. Combined surgical treatment when necessary can help improve prognosis.
Topics: Humans; Female; High-Throughput Nucleotide Sequencing; Child; Metagenomics; Brain Abscess; Antifungal Agents; Invasive Fungal Infections; Male; Central Nervous System Fungal Infections; Child, Preschool; Aspergillus fumigatus; Caspofungin
PubMed: 38912204
DOI: 10.3389/fcimb.2024.1393242 -
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