Differentiation of hereditary spastic paraparesis from primary lateral sclerosis in sporadic adult-onset upper motor neuron syndromes

Objective: To study whether clinical characteristics can differentiate sporadic presentations of hereditary spastic paraparesis(HSP) from primary lateral sclerosis(PLS). Differentiation between these diseases is important for genetic counseling and prognostication. Design: Case series. Setting: Tertiary referral center. Patients: One hundred four Dutch patients with an adult- onset, sporadic upper motor neuron syndrome of at least 3 years' duration. Hereditary spastic paraparesis was genetically confirmed in 14 patients(7 with SPG4 and 7 with SPG7 mutations). Results: All 14 patients with the SPG4 or SPG7 mutation had symptom onset in the legs, and 1 of the patients with the SPG7 mutation also developed symptoms in the arms. Of the other 90 patients, 78(87%) had symptom onset in the legs. Thirty-six patients developed a PLS phenotype(bulbar region involvement), 15 had a phenotype that was difficult to classify as similar to HSP or PLS(involvement of legs and arms only), and 39 continued to have a phenotype similar to typical HSP(involvement of the legs only). Median age at onset was lower in patients with the SPG4 or SPG7 mutation(39 [range, 29-69] years), but there was considerable overlap with patients with the PLS phenotype(52 [range, 32-76] years). No differences were found in the features used by previous studies to distinguish HSP from PLS, including evidence of mild dorsal column impairment(decreased vibratory sense or abnormal leg somatosen- sory evoked potentials), symptoms of urinary urgency, or mild electromyographic abnormalities. Conclusions: In most patients with a sporadic adult- onset upper motor neuron syndrome, differentiation of sporadic presentations of HSP from PLS based on clinical characteristics is unreliable and therefore depends on results of genetic testing.