Infantile Neurodegeneration and Hair Changes: A Rare Case of Menkes Disease

A 4-month-old, previously healthy boy presented with acute onset of prolonged, recurrent seizure activity followed by neurodevelopmental deterioration and concurrent hair shaft hypopigmentation with fragility. Initial evaluation revealed significant low serum copper and ceruloplasmin, electrical status epilepticus on electroencephalography, and generalized subcortical white matter changes with diffuse tortuosity of intracranial vessels on MRI brain. In addition, a genetic study with whole-genome sequencing demonstrated a hemizygous pathogenic variant at c.2179G>A p(Gly727Arg) on ATP7A, thereby confirming the diagnosis of Menkes disease. Symptomatic treatment with antiepileptic medications was provided along with an urgent referral to an advanced center for multidisciplinary care and copper histidine replacement therapy.

Experience in Diagnosing Neuronal Ceroid Lipofuscinosis Type-2

Introduction: Developmental regression is always an alarming symptom in children as it is an early sign of some genetic disorders, one of which is neuronal ceroid lipofuscinosis (NCL). NCL is a group of rare neurodegenerative disorder caused by accumulation of intracellular ceroid lipofuscin. Since 2017 an enzyme replacement therapy (ERT) has been approved by Food and Drug Administration (FDA) for this disease. The symptoms of NCL could be managed by ERT if detected early, and the child could live normally.Case: We present a case of a 6-year-and-5-month-old boy with developmental regression, speech delay, recurrent seizure, and visual impairment, who was diagnosed with NCL type 2 after genetic testing. Compound heterozygous mutations in tripeptidyl-peptidase 1 (TPP1) gene was revealed, consistent with very low level of TPP1 enzyme in this patient.Discussion: NCL is a fatal disease which is often misdiagnosed in early stage. Diagnostic delay of NCL often occurs due to lack of awareness which often leads to premature death.Conclusion: Knowledge regarding the disease is important for early detection and to slow down the disease progression.

Recurrent Generalized Seizures with Postictal Todd’s Paralysis Caused by Medication-Associated Severe Hypomagnesemia: A Case Report

Hypomagnesemia is one of the electrolyte disturbances that can cause seizures. It is common in the hospitalized patients and can be induced by long-term usage of many medications. A 68-year-old male known to have hypertension and gastroesophageal reflux presented to the Emergency Department with an unprovoked first seizure at home followed by a temporary right-sided hemiparesis, dysphasia, and facial asymmetry. The hemiparesis, dysphasia, and facial asymmetry resolved within less than an hour after the seizure. His serum potassium was low with prolonged QT interval in the electrocardiogram (serum magnesium was not checked in the Emergency Department). He received intravenous IV potassium chloride infusion, and his serum potassium level was corrected, but he had a recurrent seizure after 10 h. At that time, his serum magnesium was found to be very low, he received IV magnesium sulfate infusion, and his indapamide, omeprazole, and metformin medications were stopped. He had no further seizures, the rest of his blood tests were normal, and his CT brain was unremarkable. He was treated for aspiration pneumonia, and his outpatient MRI brain and EEG came to be normal too.

Takotsubo Cardiomyopathy as a Complication/ Sequelae of Prolonged Refractory Seizure: A Case Report from Nepal

Takotsubo cardiomyopathy(TC) is a reversible, yet underdiagnosed cause of mortality and morbidity in the intensive care units. It occurs secondary to sudden catecholamine surge precipitated by any form of emotional or pathological stress. Association between central nervous system disorders and Takotsubo cardiomyopathy is being increasingly reported. Epilepsy is the second most common CNS disorder to trigger TC, SAH being the first. We report a case of TC in an elderly man with prolonged, recurrent seizure episodes refractory to the commonly used antiepileptic drugs (AEDs), who developed unexplained tachycardia, hypotension and elevated cardiac enzymes.

CLINICAL PROFILE AND OUTCOME OF CHILDREN ADMITTED WITH STATUS EPILEPTICS

Background: Objective of this study was to study epidemiology and clinical profile of Status epilepticus Methods: Hospital based cross sectional study conducted on 50 children All children aged between 1 month to 12 years who at presentation or during the PICU stay had convulsive status epilepticus - defined as continuous seizure activity or recurrent seizure activity without regaining consciousness lasting for >5 min. Results: Among 50 children 56.00 % were in the age group were less than 5 years ,24 % were between 6-10 years ,20.00 % were above 10 yrs. The mean age group was 6.21±1.26 years. Incidence was higher in males (64%) when compared to females (36%). Generalized tonic clonic seizure were observed in 46 (92.00%) and partial seizure was noted in 4 (8%) of the children. About 36 (72%) of the children developed SE for the first time. Conclusion: Status epilepticus is one of the common neurological emergency which requires admission to PICU. In our study epilepsy is one of the most common causes of status epilepticus. Early and appropriate treatment with anticonvulsants and use of mechanical ventilation may improve the outcome. Keywords: Status epilepticus, mortality, clinical profile

Hemosiderin, a possible biomarker for sudep?

Epilepsy is one of the neurological diseases of complex etiology that affects around 50 million people worldwide and is characterized by abnormal electrical activity and recurrent seizures. Uncontrolled generalized repetitive tonic-clonic seizures (GTCS) are the main causes of unexpected sudden death in epilepsy (SUDEP). Hypoxic stress induced by seizure results in neurocardiogenic dysfunctions, including iron overload and cardiomyopathy (IOC) which is related to severe lipid peroxidation caused by the production of reactive oxygen species (ROS). ROS induces recurrent seizure activity, favoring the overexpression of P glycoprotein (P-gp) in the heart. P-gp plays a depolarizing role in cardiomyocyte membranes and potassium (Kir) channels control cellular excitability regarding the repolarization of the cardiac action potential. All these events result in a possible appearance of severe bradycardia and fatal arrhythmia. Several studies have sought evidence for different possible biomarkers for potential prediction of the risk of SUDEP avoiding its fatal outcome.

Association of the Intronic Polymorphism rs3773364 A>G in Synapsin-2 Gene with Epilepsy Patients in Iraq

Epilepsy is a central nervous system disease which is characterized by a recurrent seizure that distinguishes it from other similar diseases. Epilepsy may occur due to defects in genes that encode some receptors in the brain. For this reason, this study aimed to understand the association between Synapsin-2 (SYN2) gene and susceptibility to epilepsy. Blood samples were collected from 40 volunteers, including 30 patients suffering epilepsy with an age range of 26-49 years old and 10 healthy individuals with an age range of 25-53 years old. The study sample involved 16 males and 14 females with epilepsy along with 6 males and 4 females healthy subjects. DNA was isolated from the volunteers for PCR-RFLP assay. Genotyping of rs3773364 A>G SYN2 was conducted and the results refer to a highly significant difference in the distribution of AG genotype (P=0.0001), while there is no significant difference in the distribution of AA and GG genotypes, with p values of 0.1702 and 1.00, respectively. The results also showed that gender did not significantly affect the results when comparing patients with the control (p=0.0934). Our findings indicates that SYN2 rs3773364 A>G confers risk to epilepsy and may be implicated in epileptogenesis.

Sex Differences and Olfactory Bulb Alterations Contribute to Limbic Circuit Dysfunction and Behavioral Disturbances in Pilocarpine Model of Epilepsy

The olfactory bulb at the sensory and circuit level transmits information to the limbic and cortical systems for behavioral outputs, and disruption of such circuits induces behavioral disturbances in rodents. Previously, data from our laboratory showed the occurrence of behavioral disturbances in Wistar rats submitted to the pilocarpine model of epilepsy (PME) and that these alterations were sex related. Here we deepen our findings that sex-linked differences are present in PME and that male epileptic rats exhibit profound recurrent seizure patterns, namely seizure duration, severity, and distribution along the light/dark cycle different from that observed in epileptic female rats. Further, using isotropic fractionator we observed significant alterations in the number of neuronal and non-neuronal cells of the olfactory bulb, amygdala, and hippocampus following 3 months of spontaneous recurrent seizures in epileptic male and female rats. Altogether, our study suggests that neuronal and non-neuronal cell death in olfactory bulb may interfere with sex-related differential recurrent seizure patterns, limbic circuit dysfunction, and behavioral disturbances in PME. Lastly, the pilocarpine epilepsy model provides an evidence-based tool to study mechanisms of behavioral disturbances in epileptogenesis that may provide future therapeutic insights in our quest to improve the life of people with epilepsy.

Neurons and mechanism of epileptic associated genes in brain network: current concepts and future perspectives.

Neurons are the basic cell structure of the nervous system and responsible for the communication between brain and body. Brain networks are formed from a single neuron to highly complexed interconnected (˷ 100 billion) neurons. Imbalances between excitation and inhibition mechanism of neuronal cells leads to altered brain network causing seizure/epileptic activity. The mechanism is known as an ictogenic mechanism. In particular, epilepsy is characterized by abnormal neuronal cells and several genetic factors are attributed for their development. CHRNA4 is the first epileptic gene discovered in an autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Since, the era of epileptic genetics has reached to peaks and still extending the branches to study in detail to solve the mysteries behind the brain and epileptic/seizure genes. However, genes such as AQP4, SESN3, ARX, NTNG1, NTNG2, TSC1 and TSC2 need more attention in epilepsy genetic studies. Therefore, this review describes brain network during epilepsy (recurrent seizure) as well as deals with recent studies on molecular genetics and identification methods of epilepsy.