Outcome Comparison of Emerging Molecular Therapies with Ventriculoperitoneal Shunt in Neonatal Post-hemorrhagic Hydrocephalus

Introduction: Post-hemorrhagic hydrocephalus (PHH) is a multifaceted neurological disorder that arises as a sequela of intraventricular hemorrhage or germinal matrix hemorrhage in neonates. PHH leads to elevated intracranial pressure and progressive ventriculomegaly that are associated with significant morbidity and mortality. Currently, ventriculoperitoneal (VP) shunt remains the standard and most frequently performed neurosurgical procedure to manage PHH, despite its high rates of complications and failures. This systematic review aims to elucidate the underlying mechanisms of PHH and examine the potential advantages of novel therapeutic approaches.

Methods: This systematic review was conducted following PRISMA guidelines. Two reviewers performed a comprehensive literature search in PubMed, Cochrane Library, and Scopus, retrieving publications from 2020 to August 2024. Following the retrieval of 706 studies, 431 duplicates were removed, and the remaining studies were screened for eligibility based on predefined criteria. Data extracted included author, year of publication, study design, population, model, control group, treatment, method of administration, and outcomes. Outcomes of interest included structural, clinical, and molecular parameters to assess the effects of various treatments. Methodological quality was assessed using the SYRCLE risk of bias tool for animal studies and the Newcastle-Ottawa Scale for observational studies, with discrepancies resolved by a third reviewer. Narrative synthesis was employed to summarize qualitative data, organized in an evidentiary table.

Results: Of 8 included studies, 5 were animal studies and 3 were observational studies of neonates. Molecular therapies investigated in PHH models ameliorated PHH by regulating cerebrospinal fluid absorption and reducing neuroinflammation through complement cascade inhibition or transporter modulation. Notable reductions in ventricular area and improvements in cognitive and motor outcomes were observed across all molecular treamtents. VP shunt placement was associated with suboptimal neurodevelopmental outcomes in neonates, particularly delayed motor development.

Conclusion : This systematic review represents the first comprehensive analysis that directly compares molecular therapies targeting specific mechanisms of PHH with VP shunt. Molecular therapies demonstrated superior functional outcomes relative to the shunt. Further research is warranted to investigate the potential of combining molecular treatments with temporary CSF diversion methods.