Hereditary spastic paraplegia

Clinical features

Hereditary spastic paraplegia (HSP) (also known as Familial Spastic Paraparesis and Strumpell-Lorrain syndrome) is not a single disease entity but rather a group of clinically and genetically diverse disorders that share the primary feature of progressive, generally severe, lower extremity spasticity. HSP is classified as "uncomplicated" (symptoms confined to lower extremity weakness, bladder disturbance, and to a lesser extent impaired position sense in the legs); and "complicated" when additional neurologic deficits are present. Please refer to the following references for additional clinical descriptions: (McKusick, 1988a; Behan et al., 1974; Holmes et al., 1977; Cartlidge et al., 1973; Scheltens et al., 1990; Kenwrick et al., 1986; Polo et al., 1993; Baraitser, 1990; Sutherland, 1975; Schwarz et al., 1956; Boustany et al., 1987; Keppen et al., 1987; McKusick, 1988b; Rhein, 1914; Philipp, 1949; Skre, 1993; Roe, 1963; Harding, 1993; Durr et al., 1994; Fink et al., 1995)

Uncomplicated autosomal dominant HSP has been reviewed recently (Durr et al., 1994; Harding, 1993; Fink et al., 1996; Fink, 1997). Following normal gestation, delivery, and early childhood development, subjects develop leg stiffness and gait disturbance (stumbling and tripping) due to difficulty dorsiflexing the foot and weakness of hip flexion. Although the majority of patients experience symptom onset in the second through fourth decades, there is a wide range of age of symptom onset (from infancy through age 85) (Cooley et al., 1990; Durr et al., 1994; Hazan et al., 1993). Gait disturbance progresses insidiously without exacerbations, remissions, or step-wise worsening. Paresthesiae below the knees are not uncommon. Urinary urgency progressing to urinary incontinence is a frequent, although variable, late manifestation.

Neurologic examination of subjects with uncomplicated HSP reveals normal facial and extraocular movements and normal fundi. Although jaw jerk may be brisk in older subjects, there is no speech disturbance, difficulty swallowing or evidence of frank corticobulbar tract dysfunction. Upper extremity muscle tone and strength are normal. In the lower extremities, muscle tone is increased at the hamstrings, quadriceps and ankles. Weakness is most notable at the iliopsoas, tibialis anterior, and to a lesser extent, hamstring muscles. Muscle wasting may occur in uncomplicated HSP (Harding, 1981; Silver, 1966; Cross et al., 1967; Refsum et al., 1954) but in our experience, is mild in uncomplicated HSP patients and limited to atrophy of the shins in wheelchair-dependent elderly patients. Peripheral nerves are normal in uncomplicated HSP although decreased perception of sharp stimuli below the knees is noted occasionally. Vibratory sense is often diminished mildly in the distal lower extremities. When present, this is a useful diagnostic sign that helps distinguish HSP from other disorders. Slight terminal dysmetria is observed occasionally on finger-to-nose testing in older affected subjects. Deep tendon reflexes may be brisk (2 to 3+) in the upper extremities but are pathologically increased (3 to 4+) in the lower extremities. Gait demonstrates circumduction owing to difficulty with hip flexion and ankle dorsiflexion. Crossed adductor reflexes, ankle clonus, and extensor plantar responses are present uniformly. Hoffman's and Tromner's signs may be observed. High arched feet (pes cavus) are generally present and usually prominent in older affected subjects.

The age of symptom onset, rate of symptom progression, and extent of disability are variable both within and between HSP kindreds (Durr et al., 1994; Schady et al., 1990; Polo et al., 1993; Holmes and Shaywitz, 1977). In contrast to variable age of symptom onset and extent of disability, the distribution of neurologic deficits in uncomplicated HSP is invariant and consist of spastic weakness in the legs; variable impairment of vibratory sense in the feet; and variable urinary bladder disturbance. Additional deficits such as visual disturbance, marked muscle wasting, fasciculations, dementia, seizures, or peripheral neuropathy in subjects from uncomplicated HSP kindreds should not be attributed to variant presentations of uncomplicated HSP. Rather, such subjects should be evaluated thoroughly for concurrent or alternative neurologic disorders. Some autosomal dominant uncomplicated HSP kindreds that exhibit onset of progressive spastic paraplegia in childhood (before age 6 years) and relatively little progression of symptoms beyond adolescence. These patients often do not experience urinary bladder disturbances and generally remain ambulatory (with assistance).

Adapted with permission from (Fink et al., 1996) and (Fink, 1997).

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