The hereditary spastic paraplegias

Abstract

The hereditary spastic paraplegias (HSPs) are a large group of disorders that share the primary clinical feature of lower extremity spastic weakness. Lower extremity weakness and spasticity (occurring in varying proportions and to variable degree) may be isolated (“uncomplicated” HSP); or associated with additional neurologic abnormalities (“complicated” HSP) such as cognitive impairment, peripheral neuropathy, amyotrophy, or ataxia. In addition to variable clinical signs and symptoms, the course of disorders classified as HSP is highly variable. In general, HSP symptoms that begin in infancy may be nonprogressive. For example, subjects with early childhood-onset, uncomplicated HSP may resemble spastic diplegic cerebral palsy. In contrast, later onset symptoms typically worsen insidiously over many years. Nonetheless, even the course of progressive HSP may be variable. After a number of years, many (but not all) subjects with progressive worsening exhibit significant slowing of further functional decline. Postmortem studies in uncomplicated HSP have shown axon degeneration particularly involving the distal ends of corticospinal tract and dorsal column fibers. There are more than 90 genetic types of HSP. Genetic testing (either large panels of HSP genes or whole-exome sequencing) can confirm the diagnosis of HSP for approximately 50%-60% of subjects. The differential diagnosis of HSP includes treatable disorders [e.g., B12 deficiency, cervical spondylosis, dopa-responsive dystonia, and multiple sclerosis (MS)] as well as disorders, the prognosis of which is quite different than HSP (e.g., amyotrophic lateral sclerosis and MS). Treatment for HSP is symptomatic although research into disease-altering therapy (including gene therapy) is ongoing. In general, patient-specific, professionally developed, proactive physical therapy regimens and rehabilitation strategies to maintain and increase range of motion, reduce spasticity, improve balance, gait, and strength, and cardiovascular fitness are recommended.