Functional Outcomes in Hereditary Spastic Paraplegia: A Prospective Cohort Study (S43.005)

Objective: To describe the clinical, genetic, and epidemiological features of HSP (Hereditary Spatic Paraplegia) in Canada, and to identify which clinical, radiologic and genetic factors determine functional outcome for patients with HSP. Background: Many subtypes of HSP have been reported worldwide, but prevalence, clinical subtypes, genetic characterization, and functional impacts of this group of disease remain poorly assessed in Canada. These informations are crucial in the diagnosis and management of affected patients. Methods: We conducted a multicenter prospective observational study of patients who met the clinical criteria for diagnosis of HSP in the provinces of Alberta, Ontario and Quebec. Standardized clinical evaluations were carried out at all study sites. The characteristics of the participants were analyzed using descriptive statistics. The main outcome measure was the spastic paraplegia rating scale (SPRS). We also used the SPATAX-EUROSPA disability stage score to assess disability. Results: A total of 534 patients were identified with HSP across the country and 158 patients had a confirmed genetic diagnosis. Mutations were identified in 15 different genes; the most common were SPAST (SPG4, 46[percnt]), ATL1 (SPG3A, 20[percnt]), KIAA1840 (SPG11, 8[percnt]), PGN (SPG7, 6[percnt]), KIAA0196 (SPG8, 5[percnt]) and PLP1 (SPG 2, 3[percnt]). Diagnosis of SPG4 and SPG7 were associated with older age at symptom onset. SPG4 and SPG3A were less associated with learning disabilities compared to other subtypes of HSP and SPG11 was strongly associated with progressive cognitive deficits. SPG3A was associated with better functional outcome compared to other HSP subtypes. The strongest predictor for significant disability was an abnormal brain MRI (p=0.04). Conclusions: The most important predictors of disability in our patients with HSP were SPG11 mutations and abnormal brain MRI. Accurate molecular characterization of well-phenotyped cohorts and international collaboration will be essential to establish the natural history of these rare degenerative disorders. Disclosure: Dr. Chrestian has nothing to disclose. Dr. Dupre has nothing to disclose. Dr. Brisson has nothing to disclose. Dr. Gan-Or has nothing to disclose. Dr. Szuto has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Venkitachalam has nothing to disclose. Dr. Warman Chardon has nothing to disclose. Dr. Ahmed has nothing to disclose. Dr. Ashtiani has nothing to disclose. Dr. MacDonald has nothing to disclose. Dr. Provencher has nothing to disclose. Dr. Boycott has nothing to disclose. Dr. Stravropoulos has nothing to disclose. Dr. Dion has nothing to disclose. Dr. Ray has nothing to disclose. Dr. Suchowersky has received personal compensation for activities with Abbott, Merz, Allergan and Adamas as a consultant. Dr. Suchowersky has received personal compensation in an editorial capacity for UpToDate. Dr. Rouleau has nothing to disclose. Dr. Yoon has nothing to disclose.