Hemimegalencephaly with Seizure: A Rare Congenital Malformation in a 22 months Old Boy

Abstract Isolated hemimegalencephaly (HME) is a rare congenital malformation of brain development, remarkable for its extreme asymmetry, and is characterized by the overgrowth of part or whole hemisphere. The enlarged hemisphere is manifested by hamartomatous characteristics with a dysplastic cell array of atypical morphology. Traditionally the genetic theories regarding the pathogenesis of HME are considered due to disturbance in cell signaling during neuroblast migration, cell differentiation, and proliferation, pattering, and symmetry. HME can present as isolated or associated with several neurocutaneous syndromes. The clinical picture varies depending on the severity of the malformation; however, HME patients typically exhibit refractory epilepsy, macrocephaly, colpocephaly, global developmental delay, intellectual disability, hemibody hypertrophy, and hemiparesis. Early diagnosis is crucial because despite neuroimaging and pathologic evidence, hemimegalencephaly sometimes still is unrecognized. Also, misdiagnosed as obstructive hydrocephalus or cerebral neoplasm can lead to unnecessary surgical procedures. Although hemispherectomy has high morbidity, it is recommended early for patients with severe, intractable epilepsy. We report a diagnosed case of a 22-month-old boy hemimegalencephaly who presented with seizures attack and was successfully treated with antiepileptic medications.

Download Full-text

Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novoGRIN2Amutation

Epilepsia ◽

10.1111/epi.12663 ◽

2014 ◽

Vol 55 (7) ◽

pp. e75-e79 ◽

Cited By ~ 19

Author(s):

Sunita Venkateswaran ◽

Ken A. Myers ◽

Amanda C. Smith ◽

Chandree L. Beaulieu ◽

Jeremy A. Schwartzentruber ◽

...

Keyword(s):

Exome Sequencing ◽

Developmental Delay ◽

Whole Exome Sequencing ◽

Intractable Epilepsy ◽

Global Developmental Delay ◽

Whole Exome

Download Full-text

Boricua Founder Variant in FRRS1L Causes Epileptic Encephalopathy With Hyperkinetic Movements

Journal of Child Neurology ◽

10.1177/0883073820953001 ◽

2020 ◽

Vol 36 (2) ◽

pp. 93-98

Author(s):

Imane Abdelmoumen ◽

Sandra Jimenez ◽

Ignacio Valencia ◽

Joseph Melvin ◽

Agustin Legido ◽

...

Keyword(s):

Movement Disorder ◽

Puerto Rican ◽

Cerebellar Atrophy ◽

Intractable Epilepsy ◽

Brain Magnetic Resonance Imaging ◽

Epileptic Encephalopathy ◽

Pathogenic Variant ◽

Global Developmental Delay ◽

Neurodevelopmental Outcomes ◽

Developmental Regression

Objective: To describe a founder mutation effect and the clinical phenotype of homozygous FRRS1L c.737_739delGAG (p.Gly246del) variant in 15 children of Puerto Rican (Boricua) ancestry presenting with early infantile epileptic encephalopathy (EIEE-37) with prominent movement disorder. Background: EIEE-37 is caused by biallelic loss of function variants in the FRRS1L gene, which is critical for AMPA-receptor function, resulting in intractable epilepsy and dyskinesia. Methods: A retrospective, multicenter chart review of patients sharing the same homozygous FRRS1L (p.Gly246del) pathogenic variant identified by clinical genetic testing. Clinical information was collected regarding neurodevelopmental outcomes, neuroimaging, electrographic features and clinical response to antiseizure medications. Results: Fifteen patients from 12 different families of Puerto Rican ancestry were homozygous for the FRRS1L (p.Gly246del) pathogenic variant, with ages ranging from 1 to 25 years. The onset of seizures was from 6 to 24 months. All had hypotonia, severe global developmental delay, and most had hyperkinetic involuntary movements. Developmental regression during the first year of life was common (86%). Electroencephalogram showed hypsarrhythmia in 66% (10/15), with many older children evolving into Lennox-Gastaut syndrome. Six patients demonstrated progressive volume loss and/or cerebellar atrophy on brain magnetic resonance imaging (MRI). Conclusions: We describe the largest cohort to date of patients with epileptic encephalopathy. We estimate that 0.76% of unaffected individuals of Puerto Rican ancestry carry this pathogenic variant due to a founder effect. Children homozygous for the FRRS1L (p.Gly246del) Boricua variant exhibit a very homogenous phenotype of early developmental regression and epilepsy, starting with infantile spasms and evolving into Lennox-Gastaut syndrome with hyperkinetic movement disorder.

Download Full-text

Gamma knife surgery for hypothalamic hamartomas accompanied by medically intractable epilepsy and precocious puberty: experience in Mexico

Journal of Neurosurgery ◽

10.3171/jns.2005.102.s_supplement.0053 ◽

2005 ◽

Vol 102 ◽

pp. 53-55 ◽

Cited By ~ 29

Author(s):

Marco A. Barajas ◽

Maria G. Ramírez-Guzmán ◽

Carlos Rodríguez-Vázquez ◽

Vinicio Toledo-Buenrostro ◽

Abel Cuevas-Solórzano ◽

...

Keyword(s):

Gamma Knife ◽

Precocious Puberty ◽

Intractable Epilepsy ◽

Gamma Knife Surgery ◽

Sleep Cycle ◽

Hypothalamic Hamartoma ◽

High Morbidity ◽

Content Type ◽

Hypothalamic Hamartomas ◽

Fine Print

Object.Hypothalamic hamartoma is a nonneoplastic malformative mass of neurons and glia in the region of the hypothalamus. Because of its location, open surgery is associated with high morbidity and mortality rates. Gamma knife surgery (GKS) may be an efficient and safe treatment approach, which produces little morbidity. The authors describe the results of GKS in three patients with hypothalamic hamartomas.Methods.All patients were male, aged 3, 12, and 15 years. The lesions were classified according to the Valdueza scale: one was Type IIb and two were Type IIa. The patients presented with gelastic seizures (15–20 per day), generalized epilepsy, behavioral abnormalities, and alterations of the sleep cycle. Precocious puberty was present in one patient. The Type IIb tumor had a volume of 1.8 cm3, and the Type IIa tumors were 597 mm3and 530.1 mm3. The lesions received 12.5 Gy, 14 Gy, and 15 Gy, respectively, to the 50% isodose line. The patients were followed for 30 to 50 months. After 3 months, all patients showed improvement of their sleep, behavior, and epilepsy. At the present time, these patients are receiving low-dose antiepileptic agents and have achieved adequate social development and school integration.Conclusions.Gamma knife surgery appears to be a good, safe, and effective option for the treatment of selected hypothalamic hamartomas. No morbidity or mortality was associated with these three cases.

Download Full-text

Gamma knife surgery for hypothalamic hamartomas accompanied by medically intractable epilepsy and precocious puberty: experience in Mexico

Journal of Neurosurgery ◽

10.3171/sup.2005.102.s_supplement.0053 ◽

2005 ◽

Vol 102 (Special_Supplement) ◽

pp. 53-55 ◽

Cited By ~ 10

Author(s):

Marco A. Barajas ◽

Maria G. Ramírez-Guzmán ◽

Carlos Rodríguez-Vázquez ◽

Vinicio Toledo-Buenrostro ◽

Abel Cuevas-Solórzano ◽

...

Keyword(s):

Gamma Knife ◽

Precocious Puberty ◽

Intractable Epilepsy ◽

Gamma Knife Surgery ◽

Sleep Cycle ◽

Hypothalamic Hamartoma ◽

High Morbidity ◽

Content Type ◽

Hypothalamic Hamartomas ◽

Fine Print

Object. Hypothalamic hamartoma is a nonneoplastic malformative mass of neurons and glia in the region of the hypothalamus. Because of its location, open surgery is associated with high morbidity and mortality rates. Gamma knife surgery (GKS) may be an efficient and safe treatment approach, which produces little morbidity. The authors describe the results of GKS in three patients with hypothalamic hamartomas. Methods. All patients were male, aged 3, 12, and 15 years. The lesions were classified according to the Valdueza scale: one was Type IIb and two were Type IIa. The patients presented with gelastic seizures (15–20 per day), generalized epilepsy, behavioral abnormalities, and alterations of the sleep cycle. Precocious puberty was present in one patient. The Type IIb tumor had a volume of 1.8 cm3, and the Type IIa tumors were 597 mm3 and 530.1 mm3. The lesions received 12.5 Gy, 14 Gy, and 15 Gy, respectively, to the 50% isodose line. The patients were followed for 30 to 50 months. After 3 months, all patients showed improvement of their sleep, behavior, and epilepsy. At the present time, these patients are receiving low-dose antiepileptic agents and have achieved adequate social development and school integration. Conclusions. Gamma knife surgery appears to be a good, safe, and effective option for the treatment of selected hypothalamic hamartomas. No morbidity or mortality was associated with these three cases.

Download Full-text

Quinine in the Treatment of Malignant Migrating Partial Seizures in Infancy: A Case Report

10.53350/pjmhs211592986 ◽

2021 ◽

Vol 15 (9) ◽

pp. 2986-2988

Author(s):

Abeer Yousaf ◽

Ali Matter ◽

Aalia Akhtar Hayat

Keyword(s):

Ketogenic Diet ◽

Intractable Epilepsy ◽

Psychomotor Development ◽

Partial Seizures ◽

Ictal Eeg ◽

Electrographic Seizures ◽

Poor Outcomes ◽

Antiepileptic Medications ◽

Migrating Partial Seizures ◽

International League

The syndrome of malignant migrating partial seizures in infancy was first described by Coppola and colleagues in 1995. The International League Against Epilepsy defines this form of epilepsy as a seizure onset in the first 6 months of life, occurrence of almost continuous migrating polymorphous focal seizures, combined with multifocal ictal EEG discharges, and progressive deterioration of psychomotor development. Most cases are pharmacoresistant and have poor outcomes. A lot of publications described the trial of several medications such as Stiripentol, Rufinamide, Cannabidiol, and finally Ketogenic diet, to control the refractory devastating seizures. We describe a 13-month-old girl with malignant migrating partial seizures in infancy who was started on Quinine for the control of her refractory seizures after the trial of multiple antiepileptic medications that failed to control her seizures, including Clonazepam, Carbamazepine, Phenobarbitone, Phyntion, Midazolam, Valproate, Perampanel & Ketogenic diet, all were tried by different combination at different times. Finally, as malignant migrating partial seizures in infancy are sometimes linked to K channelopathy, a trial of Quinine was given in a dose of 30mg/kg/d. Patients showed an excellent response with control of clinical & electrographic seizures. Now she is seizure-free for five months and undergoing physiotherapy. She started rolling over but doesn't have much improvement in motor milestones, is not following or cooing, and is unable to say clear words. Keywords: MMPSI – malignant migrating partial seizures in infancy- Quinine – Intractable epilepsy- CPLANE-1 gene defect

Download Full-text

Management of Infantile Spasms: An Updated Review

International Journal of Epilepsy ◽

10.1055/s-0040-1708562 ◽

2020 ◽

Vol 06 (01) ◽

pp. 04-14

Author(s):

Mary Iype ◽

Kiren George Koshy

Keyword(s):

Early Recognition ◽

Intractable Epilepsy ◽

Epileptic Encephalopathy ◽

Infantile Spasms ◽

Response To Treatment ◽

High Dose ◽

Ohtahara Syndrome ◽

Oral Steroids ◽

Antiepileptic Medications ◽

Infancy And Early Childhood

AbstractInfantile spasms remain the most challenging of the epileptic encephalopathies of childhood. Infantile spasms are classified as an epileptic encephalopathy, as the adverse cognitive and behavioral burden of the condition is out of proportion to the burden one would expect from the underlying etiology or the accompanying magnetic resonance imaging. The ictal and interictal electroencephalographic (EEG) activity is presumed to contribute to the progressive cerebral dysfunction. In many of these children, the underlying etiology also contributes to the severe mental subnormality and autistic behavior. Though it is the syndromic approach that guides the pediatric epileptologist, it is best to keep in mind that one syndrome may evolve into another in infancy and early childhood. A baby with Ohtahara syndrome may, after 2 to 7 months, begin to have spasms. Lennox-Gastaut syndrome with its typical seizure types and EEG may evolve in a child with infantile spasms.The unique modalities used in the treatment of infantile spasms make early recognition important. It is, however, also of paramount importance to make an etiological diagnosis as the underlying etiology may be eminently treatable. The treating physician cannot abandon them as wholly “intractable” epilepsy. The excellent response to treatment in the few who just cannot be defined or accurately predicted drives the physician to exercise his brain. Use of the two well-accepted modalities of treatment; vigabatrin and adrenocorticotrophic hormone singly or in combination, oral steroids in high dose, ketogenic diet, the conventional antiepileptic medications, and strategies to target the basic cause have been tried out by various clinicians. Here, we have made an attempt to collate evidence and describe the progress in the management of infantile spasms.

Download Full-text

Transcallosal Resection of Hypothalamic Hamartomas, with Control of Seizures, in Children with Gelastic Epilepsy

Neurosurgery ◽

10.1097/00006123-200101000-00019 ◽

2001 ◽

Vol 48 (1) ◽

pp. 108-118 ◽

Cited By ~ 31

Author(s):

Jeffrey V. Rosenfeld ◽

A. Simon Harvey ◽

Jacquie Wrennall ◽

Margaret Zacharin ◽

Samuel F. Berkovic

Keyword(s):

Third Ventricle ◽

Intractable Epilepsy ◽

Frameless Stereotaxy ◽

Seizure Freedom ◽

Gelastic Seizures ◽

Complete Excision ◽

Transcallosal Approach ◽

Hypothalamic Hamartomas ◽

Gelastic Epilepsy ◽

Antiepileptic Medications

Abstract OBJECTIVE Hypothalamic hamartomas (HHs) are associated with precocious puberty and gelastic epilepsy; the seizures are often refractory to antiepileptic medications and associated with delayed development and disturbed behavior. The current opinion is that surgery to treat intrahypothalamic lesions is formidable and that complete excision is not technically achievable. We report our experience with a transcallosal approach to the resection of HHs. METHODS Five children (age, 4–13 yr) with intractable epilepsy and HHs underwent preoperative clinical, electroencephalographic, and imaging evaluations. Two patients experienced only gelastic seizures, and three patients experienced mixed seizure disorders with drop attacks; all experienced multiple daily seizures. Patients were evaluated with respect to seizures, cognition, behavior, and endocrine status 9 to 37 months (mean, 24 mo) after surgery. The HHs were approached via a transcallosal-interforniceal route to the third ventricle and were resected using a microsurgical technique and frameless stereotaxy. RESULTS Complete or nearly complete (>95%) excision of the HHs was achieved for all patients, with no adverse neurological, psychological, or visual sequelae. Two patients experienced mild transient diabetes insipidus after surgery. Two patients developed appetite stimulation, but no other significant endocrinological sequelae were observed. Three patients are seizure-free and two patients have experienced only occasional, brief, mild gelastic seizures after surgery, all with reduced antiepileptic medications. On the basis of parental reports and our own subjective observations, the children also exhibited marked improvements in behavior, school performance, and quality of life. CONCLUSION Complete or nearly complete resection of HHs can be safely achieved via a transcallosal approach, with the possibility of seizure freedom and neurobehavioral improvements.

Download Full-text

Biological Bases of Symptomatic Generalized Epilepsies in Children

10.1093/med/9780199937837.003.0040 ◽

2017 ◽

Author(s):

Dragos A. Nita ◽

Miguel A. Cortez ◽

Jose Luis Perez Velazquez ◽

O. Carter Snead

Keyword(s):

Mental Retardation ◽

Intractable Epilepsy ◽

Epileptic Encephalopathy ◽

Global Developmental Delay ◽

Epilepsy Syndrome ◽

Mortality And Morbidity ◽

Age Related ◽

Ohtahara Syndrome ◽

Brain Involvement ◽

Myoclonic Encephalopathy

Symptomatic generalized epilepsies represent a group of challenging epilepsy syndromes, most often seen in children, which share the hallmark of a triad encompassing multiple seizure types, electroencephalographical (EEG) evidence of diffuse brain involvement, and dysfunction in the intellectual domain (global developmental delay or mental retardation). SGEs include the early myoclonic encephalopathy, early infantile epileptic encephalopathy (Ohtahara syndrome), West syndrome, epilepsy with myoclonic-astatic seizures, epilepsy with myoclonic absence, Lennox-Gastaut syndrome, and the progressive myoclonic epilepsies. SGEs may arise from various genetic, developmental, or acquired brain pathologies and also can be associated with other cerebral or systemic defects and thus being part of a broader epilepsy syndrome phenotype. SGEs are associated with significant mortality and morbidity and most patients with SGE grow up to have intractable epilepsy, mental retardation, and depend on parents and institutions for the activities of the daily living. The mechanisms of SGE are numerous and heterogeneous and the EEG findings usually reflect the age-related changes as the brain matures.

Download Full-text

A Potential Role for Felbamate in TSC- and NF1-Related Epilepsy: A Case Report and Review of the Literature

Case Reports in Neurological Medicine ◽

10.1155/2015/960746 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Natanya M. Mishal ◽

Dimitrios Arkilo ◽

Ju Tang ◽

John R. Crawford ◽

Sonya G. Wang

Keyword(s):

Potential Role ◽

Maternal Inheritance ◽

Intractable Epilepsy ◽

Neurofibromatosis Type ◽

Mechanisms Of Action ◽

Review Of The Literature ◽

Aspartate Receptor ◽

Cortical Tubers ◽

Antiepileptic Medications

A 15-year-old girl with maternal inheritance of neurofibromatosis type 1 (NF1) and paternal inheritance of tuberous sclerosis complex (TSC) developed intractable epilepsy at age 5. Her seizures were refractory to adequate doses of four antiepileptic medications until felbamate was initiated at age 7. She has since remained seizure-free on felbamate monotherapy. Although felbamate has multiple mechanisms of action, it is thought to have its most potent antiepileptic effects through inhibition of theN-methyl-D-aspartate receptor (NMDAR). Previous studies have shown that the NMDAR is altered in varying epilepsy syndromes and notably in the cortical tubers found in TSC. The aim of this paper is to examine how felbamate monotherapy was able to achieve such robust antiepileptic effects in a unique patient and possibly offer a novel therapeutic approach to patients suffering from TSC- and NF-related epilepsy.

Download Full-text

Complementing the phenotypical spectrum of TUBA1A tubulinopathy and its role in early-onset epilepsies

European Journal of Human Genetics ◽

10.1038/s41431-021-01027-0 ◽

2022 ◽

Author(s):

Julian Schröter ◽

Bernt Popp ◽

Heiko Brennenstuhl ◽

Jan H. Döring ◽

Stephany H. Donze ◽

...

Keyword(s):

Protein Interactions ◽

Early Onset ◽

Neurodevelopmental Disorder ◽

Motor Impairment ◽

Case Series ◽

Intractable Epilepsy ◽

Global Developmental Delay ◽

Protein Structure Analysis ◽

Brain Malformations ◽

Subcortical Band Heterotopia

AbstractTUBA1A tubulinopathy is a rare neurodevelopmental disorder associated with brain malformations as well as early-onset and intractable epilepsy. As pathomechanisms and genotype-phenotype correlations are not completely understood, we aimed to provide further insights into the phenotypic and genetic spectrum. We here present a multicenter case series of ten unrelated individuals from four European countries using systematic MRI re-evaluation, protein structure analysis, and prediction score modeling. In two cases, pregnancy was terminated due to brain malformations. Amongst the eight living individuals, the phenotypic range showed various severity. Global developmental delay and severe motor impairment with tetraparesis was present in 63% and 50% of the subjects, respectively. Epilepsy was observed in 75% of the cases, which showed infantile onset in 83% and a refractory course in 50%. One individual presented a novel TUBA1A-associated electroclinical phenotype with evolvement from early myoclonic encephalopathy to continuous spike-and-wave during sleep. Neuroradiological features comprised a heterogeneous spectrum of cortical and extracortical malformations including rare findings such as cobblestone lissencephaly and subcortical band heterotopia. Two individuals developed hydrocephalus with subsequent posterior infarction. We report four novel and five previously published TUBA1A missense variants whose resulting amino acid substitutions likely affect longitudinal, lateral, and motor protein interactions as well as GTP binding. Assessment of pathogenic and benign variant distributions in synopsis with prediction scores revealed sections of variant enrichment and intolerance to missense variation. We here extend the clinical, neuroradiological, and genetic spectrum of TUBA1A tubulinopathy and provide insights into residue-specific pathomechanisms and genotype-phenotype correlations.

Download Full-text