Hemimegalencephaly

• Electrical Status Epilepticus in Sleep in a Patient with Hemimegalencephaly and Tuberous Sclerosis Complex
• Transarterial embolization for infants under 3 months of age with refractory seizures due to hemimegalencephaly: complication analysis and evolution of treatment strategy
• mTORopathies in Epilepsy and Neurodevelopmental Disorders: The Future of Therapeutics and the Role of Gene Editing
• Uncrossed Cerebellar Diaschisis in Hemimegalencephaly: Evaluated by FDG-PET and Diffusion Tensor Tractography
• Corpus Callosotomy for Atonic Drop Seizures in Bilateral Malformations of Cortical Development: A Systematic Review of Literature
• Effectiveness and Safety of High-Dose Oral Phenobarbital in Children With Recurrent and Treatment-Refractory Seizures
• The fetal neurologist: Strategies to improve training, practice, and clinical care
• A Novel RHEB Germline Variant Associated With Intellectual Disability and Epilepsy: Expanding the Spectrum of mTORopathies

Hemimegalencephaly (HME), or unilateral megalencephaly, is a rare congenital disorder affecting all or a part of a cerebral hemisphere.

It causes severe seizures, which are often frequent and hard to control. A minority might have seizure control with medicines, but most will need removal or disconnection of the affected hemisphere as the best chance. Uncontrolled, they often cause progressive intellectual disability and brain damage and stop development.

Hemimegalencephaly treatment.

A case report of hemimegalencephaly with super-refractory status epilepticus and brain atrophy associated with NPRL3 gene mutation ¹⁾

Koboldt et al. from the Nationwide Children's Hospital, reported two somatic variants of PTEN affecting a single patient presenting with intractable epilepsy and hemimegalencephaly that varied in clinical severity throughout the left cerebral hemisphere. High-throughput sequencing analysis of affected brain tissue identified two somatic variants in PTEN. The first variant was present in multiple cell lineages throughout the entire hemisphere and associated with mild cerebral overgrowth. The second variant was restricted to posterior brain regions and affected the opposite PTEN allele, resulting in a segmental region of more severe malformation, and the only neurons in which it was found by single-nuclei RNA-seq had a unique disease-related expression profile. This study reveals brain mosaicism of PTEN as a disease mechanism of hemimegalencephaly and furthermore demonstrates the varying effects of single- or bi-allelic disruption of PTEN on cortical phenotypes ²⁾.

2: Weil AG, Fallah A, Wang S, Ibrahim GM, Elkaim LM, Jayakar P, Miller I, Bhatia S, Niazi TN, Ragheb J. Functional hemispherectomy: can preoperative imaging predict outcome? J Neurosurg Pediatr. 2020 Jun 1;25(6). doi: 10.3171/2019.12.PEDS19370. Epub 2020 Feb 21. PMID: 33988937.

3: Chang JW, Reyes SD, Faure-Kumar E, Lam SK, Lawlor MW, Leventer RJ, Lew SM, Lockhart PJ, Pope K, Weiner HL, Salamon N, Vinters HV, Mathern GW, Fallah A, Owens GC. Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures. Front Immunol. 2021 Apr 6;12:664344. doi: 10.3389/fimmu.2021.664344. PMID: 33889159; PMCID: PMC8056262.

4: Kim S, Baldassari S, Sim NS, Chipaux M, Dorfmüller G, Kim DS, Chang WS, Taly V, Lee JH, Baulac S. Detection of Brain Somatic Mutations in Cerebrospinal Fluid from Refractory Epilepsy Patients. Ann Neurol. 2021 Jun;89(6):1248-1252. doi: 10.1002/ana.26080. Epub 2021 Apr 20. PMID: 33834539.

5: Goldstein HE, Hauptman JS. The Putative Role of mTOR Inhibitors in Non- tuberous Sclerosis Complex-Related Epilepsy. Front Neurol. 2021 Feb 12;12:639319. doi: 10.3389/fneur.2021.639319. PMID: 33643212; PMCID: PMC7907183.

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7: Lee WS, Baldassari S, Chipaux M, Adle-Biassette H, Stephenson SEM, Maixner W, Harvey AS, Lockhart PJ, Baulac S, Leventer RJ. Gradient of brain mosaic RHEB variants causes a continuum of cortical dysplasia. Ann Clin Transl Neurol. 2021 Feb;8(2):485-490. doi: 10.1002/acn3.51286. Epub 2021 Jan 12. PMID: 33434304; PMCID: PMC7886042.

8: Kurwale NS, Patil SB, Jagtap SA, Joshi A, Nilegaonkar S, Bapat D, Chitnis S. Failed Hemispherotomy: Insights from Our Early Experience in 40 Patients. World Neurosurg. 2021 Feb;146:e685-e690. doi: 10.1016/j.wneu.2020.10.170. Epub 2020 Nov 7. PMID: 33171323.

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11: Kobow K, Jabari S, Pieper T, Kudernatsch M, Polster T, Woermann FG, Kalbhenn T, Hamer H, Rössler K, Mühlebner A, Spliet WGM, Feucht M, Hou Y, Stichel D, Korshunov A, Sahm F, Coras R, Blümcke I, von Deimling A. Mosaic trisomy of chromosome 1q in human brain tissue associates with unilateral polymicrogyria, very early-onset focal epilepsy, and severe developmental delay. Acta Neuropathol. 2020 Dec;140(6):881-891. doi: 10.1007/s00401-020-02228-5. Epub 2020 Sep 26. PMID: 32979071; PMCID: PMC7666281.

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19: Pan PJ, Ullman HE, Mathern GW, Salamon N. Physical Growth of the Contralateral Cerebrum is Preserved After Hemispherotomy in Childhood. Pediatr Neurol. 2019 Jul;96:48-52. doi: 10.1016/j.pediatrneurol.2019.02.007. Epub 2019 Feb 13. PMID: 30928301.

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21: Owens GC, Garcia AJ, Mochizuki AY, Chang JW, Reyes SD, Salamon N, Prins RM, Mathern GW, Fallah A. Evidence for Innate and Adaptive Immune Responses in a Cohort of Intractable Pediatric Epilepsy Surgery Patients. Front Immunol. 2019 Jan 29;10:121. doi: 10.3389/fimmu.2019.00121. PMID: 30761153; PMCID: PMC6362260.

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29: Griffin NG, Cronin KD, Walley NM, Hulette CM, Grant GA, Mikati MA, LaBreche HG, Rehder CW, Allen AS, Crino PB, Heinzen EL. Somatic uniparental disomy of Chromosome 16p in hemimegalencephaly. Cold Spring Harb Mol Case Stud. 2017 Sep 1;3(5):a001735. doi: 10.1101/mcs.a001735. PMID: 28864461; PMCID: PMC5593155.

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41: Chrastina J, Novak Z, Brazdil M, Hermanova M. Glioblastoma Multiforme in a Patient with Isolated Hemimegalencephaly. J Neurol Surg Rep. 2015 Jul;76(1):e160-3. doi: 10.1055/s-0035-1554929. Epub 2015 Jun 26. PMID: 26251796; PMCID: PMC4520982.

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