Central Nervous System Hemangioblastoma, Von Hippel-Lindau Disease
Conditions
Keywords
Von Hippel-Lindau disease, Central nervous system hemangioblastoma, Pediatric neurosurgery, Natural history, Surgical indication, Long-term neurological outcome
Brief summary
Von Hippel-Lindau (VHL) disease is a rare hereditary cancer predisposition syndrome associated with the development of central nervous system hemangioblastomas from childhood. The natural history of these lesions in pediatric patients remains poorly characterized, particularly regarding the factors that predict progression from radiological surveillance to neurosurgical intervention. This multicenter retrospective observational study aims to identify clinical, radiological, and genetic predictors of surgical indication in children with VHL-associated CNS hemangioblastomas and to evaluate their long-term neurological and functional outcomes. The findings may contribute to optimizing surveillance strategies and improving clinical decision-making in this rare population.
Detailed description
Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary disorder caused by pathogenic variants in the VHL gene and characterized by the development of multiple benign and malignant tumors, including central nervous system (CNS) hemangioblastomas. In pediatric patients, CNS hemangioblastomas may remain asymptomatic for years before demonstrating periods of growth, cyst formation, neurological deterioration, or other complications requiring neurosurgical intervention. Despite regular radiological surveillance, there is currently no robust pediatric predictive model to identify lesions at highest risk of progression toward surgery. This multicenter retrospective observational study aims to establish a pediatric cohort of patients diagnosed with VHL before the age of 18 years and presenting at least one CNS hemangioblastoma. Clinical, radiological, genetic, therapeutic, and follow-up data collected between 2010 and 2025 will be retrospectively extracted from medical records. Variables of interest will include demographic characteristics, VHL genotype, tumor burden and localization, radiological evolution, symptom onset, neurological deficits, surgical indications, operative procedures, postoperative complications, and long-term neurological and functional outcomes. The primary objective is to identify clinical, radiological, and genetic factors associated with the transition from conservative surveillance to a neurosurgical indication. Secondary objectives include evaluating the relationship between surgical timing and functional outcome, describing long-term care pathways, identifying determinants of chronic neurological impairment, and defining high-risk subgroups that may benefit from personalized surveillance strategies. Statistical analyses will be performed using R software. By improving the understanding of the natural history and prognostic factors of pediatric VHL-associated CNS hemangioblastomas, this study seeks to support evidence-based management and improve long-term outcomes in affected children.
Interventions
None listed
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
* Age under 18 years at diagnosis of Von Hippel-Lindau disease * Presence of at least one central nervous system hemangioblastoma * Available clinical, radiological and genetic data
Exclusion criteria
* Insufficient follow-up data to assess clinical or radiological progression * Opposition from the child or his/her parents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Transition from radiological surveillance to neurosurgical intervention for a CNS hemangioblastoma. | From diagnosis of CNS hemangioblastoma to last available follow-up, assessed retrospectively over the 2010-2025 study period | Occurrence of a neurosurgical procedure performed for a previously monitored central nervous system hemangioblastoma, regardless of the indication (radiological progression, symptom development, neurological deficit, cyst formation, syringomyelia, hydrocephalus, hemorrhage, or other documented clinical reasons). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Association between timing of surgery and neurological outcome | From neurosurgical intervention to last available follow-up, assessed retrospectively over the 2010-2025 study period | Evaluation of whether neurosurgical intervention performed before the occurrence of severe neurological deficit, hemorrhage, or hydrocephalus is associated with a better neurological outcome at last follow-up. |
| Number of neurosurgical interventions | From diagnosis of CNS hemangioblastoma to last available follow-up, assessed retrospectively over the 2010-2025 study period | Total number of neurosurgical procedures performed for CNS hemangioblastomas during follow-up. |
| Chronic neurological deficit | From diagnosis of CNS hemangioblastoma to last available follow-up, assessed retrospectively over the 2010-2025 study period | Occurrence or persistence of chronic neurological deficits during follow-up, including motor, sensory, cerebellar, cranial nerve, or sphincter deficits. Time Frame: From diagnosis to last available follow-up. |
| Number of high-risk patient subgroups identified | Through study completion, up to 15 years. | Number of high-risk patient subgroups identified according to clinical, radiological, and genetic characteristics. |
Countries
France
Contacts
CONTACTAmr ABDELHAKAM
Outcome results
None listed