Neurosurgical manifestations and management of mucopolysaccharidoses: A systematic review

Mucopolysaccharidoses (MPS) represent a group of rare inherited lysosomal storage disorders, of which neurosurgical issues arise during childhood and adolescence. The literature however remains fragmented in terms of these specific outcomes. Correspondingly, we sought to synthesize a primer for neurosurgeons in regard to MPS, summarizing the neurosurgical manifestations and management reported in the contemporary literature. A systematic interrogation of the literature was performed according to PRISMA guidelines. Electronic databases were searched from inception through June 2026. Studies reporting hydrocephalus, craniovertebral junction (CVJ) abnormalities, spinal cord compression, myelopathy, spinal deformity, neurosurgical interventions, or related outcomes in patients with any MPS subtype were included and their findings aggregated. Seventy-eight studies comprising 983 patients with 37.8% females and mean age of 12.4 years were included. MPS I (34%), MPS II (31%), and MPS IV (26%) represented the majority of reported subtypes. A total of 819 patients (83%) exhibited neurosurgical manifestations. Spinal deformity (29%) and hydrocephalus (28%) were the most frequently reported manifestations, followed by spinal cord compression/myelopathy (22%) and CVJ pathology (20%). Distinct subtype-specific patterns were observed: spinal deformity predominated in MPS I (24%), hydrocephalus in MPS II (20%), and CVJ instability/compression in MPS IV (12%). Overall, hydrocephalus was surgically treated in 74% of instances, whereas CVJ and spinal cord pathology were surgically treated in 41% and 23% of instances respectively. Patients in studies who were not treated by any prior systemic therapy reported higher rates of surgical intervention compared to those who had received treatment. Neurosurgical manifestations occur in over four-fifths of MPS patients and are clinically significant across all types of MPS. Hydrocephalus, CVJ instability, spinal cord compression, and progressive spinal deformity represent the major surgical morbidities. Early recognition, structured imaging surveillance, and timely neurosurgical intervention are essential components of MPS management.