Friedreich’s ataxia is a heredofamilial disease of early onset. It is characterized pathologically by degeneration of the lateral corticospinal tract and the posterior columns and the spinocerebellar pathways in the spinal cord, and clinically by progressive ataxia, nystagmus, absent or diminished deep tendon reflexes, and extensor plantar responses.
Etiology.
The disease is transmitted as an automatism recessive, and rarely as a dominant trait, with equal incidence in both sexes.
Pathology of Friedreich’s Ataxia.
The disease predominantly affects the posterior columns and peripheral nerves, where there is a selective degeneration of the large primary sensory neurons, the spinocerebellar tracts, and the lateral corticospinal tracts. Degeneration of the axis cylinders and their myelin sheaths with gliosis occurs. In the posterior columns, the degeneration is most obvious in the middle root zone. There may be associated loss of nerve cells in the dorsal root ganglia, and less commonly in the retinal ganglion cell layer. There is often diffuse fibrosis and focal degeneration of the myocardium.
Friedreich’s Ataxia;Clinical Manifestations.
Friedreich’s ataxia usually presents in the first decade of life as an abnormality of gait. At first, stumbling and awkwardness are seen, but as the disease progresses, the gait becomes markedly ataxic, with superimposed truncal titubation. Unsteadiness remains the most prominent and disabling symptom throughout the course of the disease. Later, ataxia in the arms and a progressive ataxic disorder of speech become evident. Words are unevenly scanned and syllables explosively uttered. As the disease progresses, the patient becomes confined to a chair and is unable to feed himself, and speech becomes unintelligible.
Examination discloses signs referable to the three primary neuronal systems involved. Degeneration of the spinocerebellar pathways results in a profound ataxia of all extremities. Until its final stages, the disease is most pronounced in the lower limbs. Impairment of function of the posterior columns leads to a loss of position sense, particularly in the lower extremities, which may further aggravate the ataxia. Corticospinal tract dysfunction is indicated by extensor plantar responses. Spasticity is not a feature of the disease. Weakness, as a consequence of combined cerebellar and pyramidal tract dysfunction, is evident. Deep tendon reflexes at the ankle are usually lost; those in the arms are diminished, but those of the knees may be retained for considerable periods. Choreic and pseudoathe- toid movements are sometimes observed.
Nystagmus is almost invariably present and is usually horizontal, but vertical nystagmus is occasionally seen. Involvement of other neuronal symptoms occurs rather commonly. Primary optic atrophy and, rarely, retinitis pigmentosa are sometimes seen in afflicted members of some families. Intellectual impairment is not uncommon and can be progressive. Loss of anterior horn cells in cervical and lumbar enlargements of the spinal cord may, in rare cases, lead to distal wasting of the extremities, suggesting a link to familial amyotrophic lateral sclerosis. Conduction velocity measurements of motor fibers fall within the range of normal.
Skeletal defects are commonly associated. Pescavus with clawing of the toes may be evident before ataxia develops, and is thought by some to be caused by muscle imbalance. Kyphoscoliosis is usual as the disease develops. Cardiac abnormalities, including cardiac enlargement, murmurs, and congestive failure, are well recognized and may cause the patient’s death. Bundle branch block, complete heart block, and inversion of the T-wave are the common electrocardiographic abnormalities. Patients with this disease have an unusually high incidence of diabetes mellitus.
Friedreich’s Ataxia Disease Course and Prognosis.
The usual course of Friedreich’s ataxia is steadily progressive. Although some patients with mild forms of the disease may live a normal life span, it is more common for the disease to run a progressive, downhill course. Total disability occurs within five to ten years in most cases, and death from inter current, infection, cardiac failure, or, rarely, from complication of associated diabetes, usually occurs sometime in the third or early part of the fourth decade. There is no specific treatment, and therapy is primarily effected through symptomatic treatment of the cardiac or metabolic abnormalities. However, in patients with very slowly evolving disease, physical therapy may offer useful training to help the patient compensate for his progressive motor impairment.
Laboratory tests are of little specific value in establishing the diagnosis. The cerebrospinal fluid, on examination, is usually normal. Electromyography may demonstrate signs of denervation in patients in whom anterior horn cell disease is evident. Nerve conduction velocity may be impaired. The differential diagnosis between Friedreich’s ataxia and multiple sclerosis must be made in patients with a sporadic form of the disease characterized by late onset and minimal skeletal abnormalities. The principal features by which the two diseases may be distinguished are the progressive course and the absence of deep tendon reflexes in Friedreich’s ataxia.
