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European Journal of Paediatric... Jan 2021Hemimegalencephaly is a rare malformation of cortical development characterised by enlargement of one cerebral hemisphere. The association between hemimegalencephaly and... (Review)
Review
Hemimegalencephaly is a rare malformation of cortical development characterised by enlargement of one cerebral hemisphere. The association between hemimegalencephaly and tuberous sclerosis complex, an autosomal dominant genetic disorder, is uncommon and has so far been reported only in a few cases. Intractable epilepsy and severe developmental delay are typical clinical manifestations. Aberrant activation of the mTOR signalling pathway is considered to be the hallmark of the pathogenesis of these two disorders. Thus, mTOR inhibitors such as everolimus represent a promising therapeutic approach to mTOR-associated manifestations. We present a thorough literature review of the association between hemimegaloencephaly and tuberous sclerosis complex.
Topics: Everolimus; Hemimegalencephaly; Humans; Male; TOR Serine-Threonine Kinases; Tuberous Sclerosis
PubMed: 33387903
DOI: 10.1016/j.ejpn.2020.12.007 -
Ryoikibetsu Shokogun Shirizu 2002
Review
Topics: Cerebral Cortex; Electroencephalography; Epilepsy; Humans; Intellectual Disability; Magnetic Resonance Imaging; Paresis; Prognosis; Syndrome
PubMed: 12483848
DOI: No ID Found -
Ultrasound Quarterly Jun 2011
Topics: Diagnosis, Differential; Hemispherectomy; Humans; Infant; Malformations of Cortical Development; Ultrasonography, Doppler, Transcranial
PubMed: 21606817
DOI: 10.1097/RUQ.0b013e31821c5dc7 -
Child's Nervous System : ChNS :... Jul 2022The aim of this report is to present a unique case of hemimegalencephaly and concomitant tuberous sclerosis complex (TSC1 mutation) with severe neonatal-onset epilepsy,... (Review)
Review
The aim of this report is to present a unique case of hemimegalencephaly and concomitant tuberous sclerosis complex (TSC1 mutation) with severe neonatal-onset epilepsy, which successfully underwent an anatomical hemispherectomy at 6.5 weeks of age for refractory seizures. Genetic testing confirmed a rare pathogenic, sporadic, heterozygous c.2041 + 1G > A gene mutation in intron 16 of the TSC1 gene, diagnostic for tuberous sclerosis. Post-operatively, the infant remained seizure free for at least 1 year. Following recurrence of her seizures, she has continued on multiple anti-seizure medications and everolimus therapy. We review the pathological and molecular features of this condition and highlight the ethics of intervention and steps taken toward safe neurosurgical intervention in this very young infant.
Topics: Epilepsy; Female; Hemimegalencephaly; Hemispherectomy; Humans; Infant; Infant, Newborn; Tuberous Sclerosis
PubMed: 35022853
DOI: 10.1007/s00381-021-05431-1 -
Neurology India 2015
PubMed: 26238918
DOI: 10.4103/0028-3886.162126 -
Child's Nervous System : ChNS :... Sep 2014Hemimegalencephaly is a rare sporadic brain malformation characterized by enlargement of one cerebral hemisphere. The classical clinical triad consists of intractable... (Review)
Review
Hemimegalencephaly is a rare sporadic brain malformation characterized by enlargement of one cerebral hemisphere. The classical clinical triad consists of intractable epilepsy, severe psychomotor delay and hemiparesis. In this report, we describe a case of a 3-year-old girl, with all the radiological features of severe hemimegalencephaly but with a comparatively benign clinical course. She had no hemiparesis, mild delay and no seizures. An extensive literature review reveals only one previously reported case of hemimegalencephaly with the absence of seizures, as part of case series. This is the first dedicated case report, with clinical description and radiological images, of this entity.
Topics: Child, Preschool; Epilepsy; Female; Frontal Lobe; Hemimegalencephaly; Humans; Magnetic Resonance Imaging
PubMed: 24589886
DOI: 10.1007/s00381-014-2392-9 -
Journal of Child Neurology May 2002Hemimegalencephaly is a rare hamartomatous malformation of the brain, remarkable for its extreme asymmetry. It can be isolated or associated with several neurocutaneous... (Review)
Review
Hemimegalencephaly is a rare hamartomatous malformation of the brain, remarkable for its extreme asymmetry. It can be isolated or associated with several neurocutaneous syndromes; less frequently, it also involves the brain stem and cerebellum. Traditionally, hemimegalencephaly has been considered a primary neuroblast migratory disturbance. At present, genetic theories of pathogenesis and modern histopathology provide a basis for this complex malformation as a primary disturbance in cellular lineage, differentiation, and proliferation, interacting with a disturbance in gene expression of body symmetry, with earlier onset than radial neuroblast migration. From my personal experience with 10 patients with hemimegalencephaly and review of the literature, I have found the same clinical neurologic, neuroimaging, and neuropathologic features in isolated and syndromic hemimegalencephaly. Magnetic resonance imaging (MRI) reveals abnormal gyration, ventriculomegaly, colpocephaly, an "occipital sign" (displacement of the occipital lobe across the midline), and increased volume and T2 signal of white matter, in addition to the overall increased size of the involved hemisphere. Mild, moderate, and severe grades of severity can be recognized, providing a functional neurologic prognosis and therapeutic plan. Early diagnosis is crucial because despite neuroimaging and pathologic evidence, hemimegalencephaly sometimes still is unrecognized. Also, misdiagnosis of obstructive hydrocephalus or cerebral neoplasm can lead to unnecessary surgical procedures. Although hemispherectomy has a high morbidity, it is recommended early for patients with severe, intractable epilepsy. The mildest forms of hemimegalencephaly are infrequent and the least recognized.
Topics: Brain; Brain Diseases; Child, Preschool; Electroencephalography; Epilepsy; Evoked Potentials; Female; Functional Laterality; Hamartoma; Humans; Magnetic Resonance Imaging; Male; Neurosurgical Procedures; Severity of Illness Index; Syndrome; Tomography, Emission-Computed; Tomography, X-Ray Computed
PubMed: 12150586
DOI: 10.1177/088307380201700512 -
Handbook of Clinical Neurology 2008
Topics: Brain; Humans; Magnetic Resonance Imaging; Malformations of Cortical Development
PubMed: 18809024
DOI: 10.1016/S0072-9752(07)87010-2 -
Current Opinion in Neurology Apr 2013Combining human genomics and molecular biology, recent studies have made pivotal progress toward understanding the cause of hemimegalencephaly (HME) and other cerebral... (Review)
Review
PURPOSE OF REVIEW
Combining human genomics and molecular biology, recent studies have made pivotal progress toward understanding the cause of hemimegalencephaly (HME) and other cerebral megalencephaly syndromes. The present article highlights recent advances of the genetic cause of these conditions, and considers the role of somatic postzygotic genetic lesions in brain maldevelopment.
RECENT FINDINGS
Studies over the past 12 months have identified de-novo somatic mutations as one possible cause in HME. The gene mutations involve components of the phosphatidylinositol 3-kinase (PI3K)-AKT (also known as protein kinase B)-mammalian target of rapamycin (mTOR) pathway and include PIK3CA, PIK3R2, AKT3, and MTOR. These mutations were identified by comparing genomic data obtained from surgically resected brain tissue with nondiseased tissue, and by single-neuron sequencing in combination with molecular biology techniques. The association between the somatic mutations and downstream activation of the PI3K-mTOR pathway suggests that HME is a neurodevelopmental disease caused by gain-of-function activation of the PI3K-AKT-mTOR pathway.
SUMMARY
The studies reviewed suggest that somatic mutations of the PI3K-AKT-mTOR pathway limited to the brain may represent one cause of HME. Dysregulation of this pathway has possible therapeutic potential in the identification of HME. Somatic mutations may be an important yet underappreciated disease mechanism in developmental neurological diseases.
Topics: Humans; Malformations of Cortical Development
PubMed: 23449172
DOI: 10.1097/WCO.0b013e32835ef373 -
Neurology India 2022
Topics: Adult; Hemimegalencephaly; Humans; Migraine Disorders
PubMed: 35532662
DOI: 10.4103/0028-3886.344681