Hereditary Spastic Paraplegia

Symptoms/Findings/Disorder Classification

Hereditary spastic paraplegia (HSP) is primarily characterized by varying degrees of stiffness (rigidity and weakness of leg muscles and hip abductors (muscles that spread the legs apart), with associated gait disturbances and increasing difficulties walking. Onset tends to be gradual (insidious), with symptoms typically becoming progressively severe over time. The age at symptom onset may be extremely variable among different families as well as affected members of the same family (kindred). Many patients initially develop symptoms during the second to fourth decades; however, reports indicate that symptoms may begin as early as infancy or early childhood to as late as the eighth or ninth decade of life. In some kindreds, symptoms appear to occur at a progressively younger age with successive generations, a phenomenon referred to as "genetic anticipation." However, it is important to note that apparent anticipation may result from increased awareness and earlier detection of the disease.

As mentioned previously, HSP that is characterized by progressive spasticity as an isolated finding—i.e., without other associated neurologic features—is often described as uncomplicated or "pure" HSP. In those with uncomplicated HSP, initial findings may include...

• Rigidity and increased tone (hypertonicity) of certain leg muscles, including those of the inner thigh, front and back of the thighs and of the calves.
• Weakness of certain leg muscles, such as those at the sides of the shin bones that flex the feet up and down, muscle groups that flex the thighs and the lower back (lumbar spinal column), and muscles at the back of the thighs that bend the knees
• Delayed walking (a relatively rare finding that may occur with childhood onset)
• Repeated tripping or falling
• Abnormal manner of walking (gait), such as dragging the toes and/or crossing the legs when a leg is not on the floor

Uncomplicated HSP may also be associated with additional symptoms and findings. These may include the following:

• Ankle clonus or abnormal reflex movements of the foot. More specifically, sudden upward bending (dorsiflexion) of the foot results in alternating muscular contraction and relaxation of the calf muscles.
• Highly arched feet (pes cavus)
• Diminished vibration sense in the feet
• Abnormal sensations (paresthesias), such as numbness, below the knees
• Muscle spasms
• Leg cramps
• Relatively mild muscle wasting (atrophy). According to reports in the medical literature, atrophy may be confined to certain muscle groups (e.g., of the shins) and primarily affect patients late in the disease course who have become dependent on wheelchairs.
• Bladder control problems, such as a sudden, compelling urge to urinate (urinary urgency) that may progress to an inability to control urination (urinary incontinence). Such symptoms may develop as a late manifestation of HSP in some patients

As with the age at onset, the rate of disease progression, symptom severity, and degree of associated disability may vary greatly, including among affected members of the same family. For example, in some patients with uncomplicated HSP, particularly those with childhood onset, symptoms may become apparent, gradually worsen over a number of years, and eventually stabilize following adolescence. In such cases, patients often maintain an ability to walk (ambulant) with assistive devices. In other cases, once symptoms develop, they slowly become increasingly severe throughout the patients' lifetimes. Although walking typically becomes increasingly difficult, HSP patients may only rarely experience a complete loss of leg mobility.

In addition, less commonly, families (kindreds) have been described in which progressive weakness and spasticity occurs in association with additional neurological features. This is often described as "complicated HSP." In certain, isolated kindreds, such findings have included the following:

• Mental retardation
• Dementia
• Sudden, recurrent, uncontrolled electrical discharges from neurons of the cerebral cortex or the outer region of the brain (epilepsy)
• Peripheral neuropathy
• Degenerative changes or dysfunction of the nerve-rich, innermost membranes of the eyes (retinopathy)
• Destruction or dysfunction of optic nerve tissues (optic neuropathy)
• Deafness
• Impaired ability to coordinate voluntary movements (ataxia)
• Slurred speech (dysarthria)
• Rapid, involuntary, rhythmic eye movements (nystagmus)
• Disturbances of the extrapyramidal system, characterized by changes in muscle tone, postural abnormalities, impairments in the execution of voluntary actions, and/or the development of abnormal involuntary movements
• Ichthyosis or abnormal thickening, dryness, and scaling of the skin