Hallervorden-Spatz disease and infantile neuroaxonal dystrophy. Clinical characteristics and nosological considerations.

Abstract Two patients with the infantile onset of a non-familial neuroaxonal dystrophy are presented. One patient developed a gait disorder from 1 1 2 years of age, followed by deterioration of speech, severe torsion dystonia with opisthotonos, choreoathetosis of the limbs, and death at age 14. The neuropathology showed findings typical of Hallervorden-Spatz disease; spheroids and abnormal excessive pigment were confined to the basal ganglia. The second patient also developed a gait disorder at 1 1 2 years of age, followed by seizures, progressive spasticity with equinovarus deformities, and signs of cerebellar disorder, but without torsion dystonia or opisthotonos. Death occurred at 17 years. The neuropathology showed features characteristic of both Hallervorden-Spatz disease and of infantile neuroaxonal dystrophy; spheroids and excessive abnormal pigment in the basal ganglia were accompanied by widespread collections of spheroids throughout the gray matter, loss of cortical neurons, degeneration of the caudate nuclei, atrophy of elements in the cerebellar cortex, and degeneration of the posterior and lateral columns of the spinal cord and of the optic nerves. The first patient is discussed as an example of infantile Hallervorden-Spatz disease, the second as an example of a disease process intermediate between infantile Hallervorden-Spatz disease and infantile neuroaxonal dystrophy. The literature relating to infantile Hallervorden-Spatz disease and infantile neuroaxonal dystrophy is reviewed and the reported cases separated into three categories on the basis of the neuropathology. The findings which emerge from this review suggest that the entities previously described as infantile Hallervorden-Spatz disease and infantile neuroaxonal dystrophy are related disease processes which present a spectrum of clinical abnormalities and corresponding neuropathology. At one extreme (Category I) there are cases showing progressive loss of motor function, severe rigidity, torsion spasm with opisthotonos, athetosis, deterioration of mental and speech functions, and death at a mean age of 16 years. It is unusual for these patients to have seizures, hypotonia of the limbs, reduced vision, or siblings affected by a similar disease process. The neuropathology consists of spheroids and excessive abnormal pigment confined to the basal ganglia and thalamus. At the other extreme (Category III) there are cases showing progressive loss of motor functions with hypotonia of the limbs early in the evolution of the disease process, seizures, reduced vision, failure of speech and mental function, and death at a mean age of 4 years. These patients frequently have siblings affected by a similar disease process. Although some patients develop rigidity or spasticity of the limbs, it is rare to have torsion spasms, opisthotonos, or athetosis. The corresponding neuropathology consists of widespread spheroid collections in the nervous system without excessive pigment accumulation in the basal ganglia. In addition, there are variable degenerative changes in many central nuclei, generalized atrophy of the cerebellar cortex, and degeneration of the optic pathways, pyramidal and spinocerebellar tracts, and posterior columns. Between these extremes there are cases (Category II) showing progressive loss of motor functions with rigidity, spasticity, occasional hypotonia of the limbs, seizures, reduced vision, failure of speech and mental function and death at a mean age of 10 years. Equinovarus deformities and flexion contractures occur frequently and athetosis occurs in a few cases, but it is rare for these patients to have torsion spasm or opisthotonos. There are a few instances in which siblings are affected with a similar disease process. The neuropathology of these cases consists of a combination of the abnormalities described for Category I and those described for Category III. The disorders in all three groups present early psychomotor retardation, arrest of motor and speech development in the infantile or late-infantile period, a gait disorder in the late-infantile period, or with seizures. None of the cases has a history of a similar disease affecting antecedent generations. The etiology of the disorder is unknown.