Population Characteristics and Progressive Disability in Neurofibromatosis Type 2 in Japan

Background: Neurofibromatosis type 2 (NF2) is a genetic disease characterized by multiple, progressive, and recurrent tumors of the central nervous system with significant neurological disabilities. The clinical features and prognosis are highly variable with little data available to inform management decisions. The purpose of this study was to characterize the clinical features of the NF2 population and determine prognostic risk factors for progressive disabilities.

Method: This retrospective cohort study of the Japanese national NF2 registry between 2009–2013 analyzed demographic, history, oncological, and neurological data in 807 patients. The overall severity of neurological disability was assessed using a comprehensive 25-points scoring system. In 587 patients in whom longitudinal data were available, multivariate logistic regression was performed to identify risk factors of disability progression. P-values < 0.05 were considered statistically significant.

Findings: The clinical characteristics of the Japanese NF2 population were heterogeneous: median onset age [range] 24 years [1–80]; male-to-female ratio 1:1·29; initial severity score 4 [0–22] out of 25; family history present in 33%. Most frequent clinical features were bilateral cranial nerve VIII nerve sheath tumor (CN8 NST, 87%), spinal NST (80%), hearing loss (65%), spinal dysfunction (50%), intracranial meningioma (49%), and facial paresis (36%). Disability progressed by ≥5-points in 6·1% of patients over the study period. Based on multivariate logistic regression, the significant independent risk factors of progression (p-value) included: onset age <25 years (0·015), positive family history (0·007), positive treatment history (0·026) hearing loss (0·014), facial paresis (0·015), blindness (0·011), hemiparesis (0·025).

Interpretation: The clinical characteristics of the Japanese NF2 population was heterogeneous. Risk factors of progressive disability included younger onset age, positive family history, positive treatment history, and specific neurological deficits.