SPG11-related parkinsonism: Clinical profile, molecular imaging and l-dopa response.

Background: Molecular imaging has proven to be a powerful tool to elucidate degenerated paths in a wide variety of neurological diseases and has not been systematically studied in hereditary spastic paraplegias.

Objectives: To investigate dopaminergic degeneration in a cohort of 22 patients with hereditary spastic paraplegia attributed to SPG11 mutations and evaluate treatment response to l-dopa.

Methods: Patients and controls underwent single-photon emission computed tomography imaging utilizing Tc-TRODAT-1 tracer. A single-blind trial with 600 mg of l-dopa was performed comparing UPDRS scores.

Results: Reduced dopamine transporter density was universal among patients. Nigral degeneration was symmetrical and correlated with disease duration and motor and cognitive handicap. No statistically significant benefit could be demonstrated with l-dopa intake during the trial.

Conclusion: Disruption of presynaptic dopaminergic pathways is a widespread phenomenon in patients with SPG11 mutations, even in the absence of parkinsonism. Unresponsiveness to treatment could be related to postsynaptic damage that needs to be further investigated.