Clinical Trials

Inclusion criteria:

• ≥ 20 years of age
• Pure UMN dysfunction (spasticity, pathological hyperreflexia, pathological reflexes with or without motor weakness) of undetermined etiology in at least both the arms and legs (to clinically exclude hereditary spastic paraplegia, HSP)
• Symptom onset (defined as subjective weakness or stiffness of the skeletal or bulbar muscles) less than 15 years prior to the baseline visit, exactly as in our current PLS COSMOS study
• Negative test result for HSP or HSP-related mutation (if a molecular diagnostic test for HSP was done
• Normal nerve conduction studies and normal needle electrode EMG examination when the diagnosis of PLS was made
• Expected to have at least some bulbar symptoms (dysarthria, dysphagia, drooling or pseudobulbar affect), but the absence of these symptoms will not exclude the patient when all other inclusion criteria have been met 
• Normal neuroimaging except for changes expected for PLS
• No active major neurological diseases other than PLS and no history of major neurological diseases
• No major unstable medical diseases that require treatment (i.e. active cancer, dialysis) in the past 6 months

Exclusion criteria:

• UMN symptoms and signs only in the legs.
• Residing outside of commutable distance and unwilling to visit the study site as required
• Unwilling to give informed consent.