Hemimegalencephaly in Children: A Systematic Review of Diagnosis, Management, and Outcomes in 161 Reported Cases

Background/Objectives: To describe the clinical and genetic features of hemimegalencephaly in pediatric patients, and to highlight treatment outcomes in this population. Methods: This is a systematic literature review following PRISMA guidelines. We used PubMed, Google Scholar, and Scopus for this systematic literature review as databases. Clinical data, imaging findings, EEG patterns, genetic variants, associated syndromes and treatment modalities and outcomes were reviewed, analyzed and summarized in tables. A total of 161 pediatric patients with hemimegalencephaly are described. A risk of bias and sensitivity analysis was conducted. Results: Hemimegalencephaly is more frequently reported in males. The most common subtype was isolated hemimegalencephaly followed by the syndromic subtype, in particular the association with Ito’s hypomelanosis. The most common seizure type was focal onset with impaired awareness. Genetic analysis showed variants in TSC1, TSC2, NPRL3, and PIK3CA, supporting mTOR pathway involvement. Drug-resistant epilepsy was present in approximately 73.2% (118/161) of the sample size. Hemispherectomy, especially functional, in our sample was more frequently reported and the current limited available literature suggests potentially comparable seizure outcomes compared to anatomical hemispherectomy in terms of seizure reduction. Our biggest limitation is the lack of long-term neurological follow-up in the existing literature. Conclusions: Hemimegalencephaly presents with a wide clinical and genetic spectrum and frequently results in drug-resistant epilepsy and developmental impairment. Although surgery may offer seizure relief, outcomes vary and the optimal approach remains individualized. Early diagnosis is essential to enable timely intervention and coordinated care. A multidisciplinary team including neurology, genetics, radiology and neurosurgery is key to optimizing outcomes. Broader studies including milder cases and long follow-up are needed to fully understand disease progression and guide management.