Spinal deformities have been evaluated in a five year retrospective study where 28 boys and 25 girls all having Friedreich's ataxia were on the average assessed once a year in a multidisciplinary clinic. Scoliosis seems somewhat more progressive in girls than in boys and more severe in non-ambulatory than ambulatory patients. Some of those scolioses are very progressive reaching 60° to 100° Cobb angle values requiring spinal surgery while other progress less rapidly and do well on their own. In addition it was shown that the intrinsic geometric spine curve parameters namely that of curvature and torsion are a powerful diagnostic tool in the assessment of evolutive scoliosis.

l-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) selectively destroys dopaminergic neurons in the pars compacta of the substantia nigra (A8 and A9 cells). MPTP or its metabolite enters nerve cells at the level of their terminals in the caudate nucleus and putamen leading to a disturbance in axoplasmic flow and retrograde degeneration. The species-dependent neurotoxicity of MPTP (primate vs. rodent) suggests that a biochemical property of the cell related to neuromelanin may be important in the mechanism of cell injury.

Myocardial scanning after the intravenous administration of Thallium 201 was used to evaluate regional myocardial perfusion in 14 patients with Friedreich's ataxia. Isotopic ventriculography was also used to assess left ventricular contractility. Myocardial images in patients with Friedreich's ataxia were found to be precociously abnormal irrespective of the degree of neurological impairment or of the severity of myocardial hypertrophy.

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson’s disease using 18F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra.

We present the pathological data from the autopsies performed on 6 Friedreich's disease patients since the start of the Quebec Cooperative Study. All patients met the strict diagnostic criteria of the QCSFA. The anatomical lesions found in the peripheral and central nervous system were similar in all 6 cases and do not differ from those described in the literature. The clinical findings correlate closely with the histological lesions found in the peripheral nervous system and spinal cord. The evidence of segmental demyelination and remyelination in the spinal ganglia and posterior roots further supports the dying-back axonopathy hypothesis.

[18F] 6-fluoro-L-dopa and positron emission tomography has been used to study intracerebral dopamine distribution in five control subjects and six patients with hemiparkinsonism. In the control subjects striatal, frontal and cingulate accumulations were clearly seen. In addition 18F concentrated in the region of the insula and the parietal lobe.

In the patients striatal accumulation 18F was reduced in the contralateral striatum, especially in the putamen. The uniformity of distribution of 18F in the striatum on the side of the parkinsonian signs was also irregular. This finding is consonant with the suggestion that intracerebral compensatory mechanisms prevent the manifestation of intracerebral dopamine deficiency from becoming obvious until a late stage of the disease.

We have measured in leukocytes the following lysosomal enzymes in II Friedreich disease cases, 11 “atypical” recessive ataxias, 13 neurological controls and 16 normal controls: hexosaminidase A and B; (3-galactosidase and neuraminidase (labile and cold stable, or A and B). The lysosomal enzyme deficiencies known to produce certain forms of spinocerebellar degeneration were not present in Friedreich's disease or the Charievoix-Saguenay syndrome. The very small scale survey of “atypical” recessive ataxias revealed 3 cases of severe deficiencies in hexosaminidase activity. Two adult brothers presenting with the clinical phenotype of Kugelberg-Welander disease (one also with ataxia), were shown to have a severe deficiency of both HEX A and HEX B activity (Sandhoff biochemical pattern). This is the first such report. A further adult female patient, unrelated to the others, had a severe isolated deficiency of HEX B and presented with a very slowly progressive and mild ataxia with severe internal strabismus. These patients and their families are being studied clinically and biochemically in greater detail and will be reported elsewhere. However these preliminary findings justify screening for such lysosomal defects in all cases of “atypical” recessive ataxia.