We report a clinical and biochemical survey of 23 patients with Friedreich's ataxia from southern Italy. They were studied clinically and by means of a clinical rating scale devised by us (Inherited Ataxias Clinical Rating Scale). Laboratory tests, based on the Quebec Cooperative Study, were also performed on our patients. No major clinical or biochemical differences were found between Italian and Canadian patients. Investigation of CSF monoamine metabolites showed that HVA decreased after probenecid and metoclopramide loading

During the past decade a number of reports have appeared suggesting that alterations in GABAergic transmission may play a role in the symptoms of a variety of neurosychiatric disorders (Enna, 1980; Enna and Maggi, 1979). In the present communication, some of the evidence supporting this contention will be briefly summarized and reviewed.

In this brief review it will be possible to mention only superficially the bioclinical, behavioral, neurochemical, neuropharmacological and neurophysiological evidence to support the view that some of the trace amines [meta- and paratyramine (m-TA, p-TA), β-phenylethylamine (PE) and tryptamine (T)] may play a significant role in the propagation of nervous impulses and perhaps be involved in the etiology of certain mental disorders. More detailed comments will be found in some recent papers and reviews (Axelrodet al, 1976; Boulton, 1974, 1976, 1978, 1979; Boulton and Baker, 1975; Boulton and Juorio, 1979; Faurbye, 1968; Mosnaim and Wolfe, 1978; Sandler and Reynolds, 1976; Wyatl et al, 1977).

Eighteen patients with the presumptive diagnosis of Friedreich's ataxia were studied. Clinical, neurophysiological and biochemical data were concordant in 14 patients and led to the diagnosis of typical Friedreich's ataxia in this group of patients. The remaining 4 patients differed from the typical patients in several respects, but mainly in the cardiological findings. It is concluded that no single clinical or laboratory finding is typical of F.A. Multidisciplinary approaches are essential to the diagnosis of Friedreich's ataxia.

Dynamic muscle function was evaluated in nine patients with Friedreich's ataxia (FA) and eight with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The measurement of torque throughout maximum voluntary isokinetic knee movements was used to quantitatively describe muscle weakness in the ataxic patients. Both FA and ARSACS patients were shown to have decreased dynamic strength in comparison to normal values during knee extension and flexion movements at 30% /s. In the FA patients a lower torqueproducing capacity was seen in the older patients.

The electromyographic (EMG) activity was recorded in lower extremity muscles during the movements. In the vastus lateralis (VL), deviations from the normal EMG activation pattern were described in both groups of patients. A reduced amplitude in the EMG activity in the medial hamstrings (MH) was seen in the majority of the patients. An index of coactivation was defined by comparing the EMG activity when a muscle lengthened (antagonistic) to the EMG activity when the same muscle shortened (agonistic) during the isokinetic contractions. In comparison to normal values increased coactivation indexes were present in the VL and MH in patients of both groups. The characteristics of dynamic muscle strength and the activation of agonistic and antagonistic muscles described in the present study will provide the basis of evaluation for the effects of therapy in these patients.

In studies of post-partum women, the oral tyramine loading test is shown to be of predictive value in identifying those subjects with a lifetime history of depressive illness. The cause of the decreased output of conjugated tyramine, after tyramine ingestion, is still unclear. Some possible mechanisms have been under scrutiny.

We evaluated 15 patients with Friedreich's ataxia (FA) to define the incidence of myocardial involvement and the type of cardiomyopathy observed.

All patients with FA had either ECG, vectocardiographic or echocardiography abnormalities, suggesting some degree of myocardial involvement. In contrast to reports indicating that asymmetric septal hypertrophy (ASH), often obstructive, is associated with FA, symmetric, concentric hypertrophic cardiomyopathy (SCH) was the predominant abnormality (sixty-seven percent of patients). Echocardiograms should be performed periodically in all FA patients since this technique allows the detection of cardiac hypertrophy.

Antithetical hypotheses as to CNS noradrenergic function in depressed patients can be constructed from results of pharmacological studies of the effects of antidepressant drugs. The experimental data supporting each of these opposing propositions is briefly reviewed in this paper. Finally, the results of clinical studies of noradrenergic function in depressed patients are noted and discussed in terms of these disparate hypotheses.

Benzodiazepine derivatives are neuropharmacologically similar but may appear clinically distinct due to pharmacokinetic differences. The clinical effects of single doses depend mainly on rates of drug absorption and distribution, whereas drug accumulation is a major determinant of clinical action during multiple dosage. This paper outlines potential clinical implications of benzodiazepine pharmacokinetics.

The preliminary results based on a one year study on the evolution and management of scoliosis are presented. Twenty-one patients were followed in the Neuro- Muscular Disease Clinic at Ste- Justine Hospital where standardized spinal radiographs were taken periodically with the Scoliosis Chariot and the Throne. The short period of observation as well as the relatively small number of Friedreich ataxia patients followed requires that these results and the following remarks be interpreted with caution.

Pathomechanics — Between the age groups I (5- 10 years) and 11(10-15 years), a substantial increase in the Cobb values occurs. Associated with it, an increase was observed in the thoracic and thoraco lumbar projected surface area indices. The relative rotation between the thoracic and lumbar segments was presumed to be the cause of the sudden increase in the Cobb measurements.

For the non-ambulatory patients, a decrease in the lumbar lordosis towards a thoraco-lumbar kyphosis as well as a sudden increase in the sacral angle and a drop in the lumbosacral angle were associated with the seated posture assumed by the patient.

Management — Prevention of the progression of established curves was our main objective. Careful examination of the spine, depending on the age of the child, in our preliminary study, stimulated early orthopaedic treatment in any curve of 20° or more. There was always concern for curves of 30° or more. In the growing child, bracing was recommended.

In the older child, the curve was usually stable after sixteen years of age. Surgery was usually attempted in curves over 40° in the growing child. The same curve was usually stable after the growth period.

For the non-ambulatory patients, the present study suggested the prescription of a molded seat with the following characteristics: i) a posterior lumbar support, ii) low thoracic lateral supports and iii) a slight inclination of the seating system. This was presumed to be beneficial in maintaining stability of the spine. Presently, an evaluation of such a device is under investigation.

In the light of the recent finding of deposits of calcium salts and iron in myocardial cells in one case of Friedreich's ataxia, we have made a detailed morphological study of 3 new cases of this cardiomyopathy. Calcium deposits were not found in the muscle fibers but lipofuscin granules and deposits of iron were observed in our 3 cases. In addition to the usual findings of interstitial fibrosis, hypertrophy and degeneration of myocardial fibers, foci of segmental active muscle necrosis were constantly present. There is a possibility that Friedreich's ataxia could be a neurocardiac degenerative disease with a membrane defect which could be related to defective metabolism of vitamin E or other micronutrienls.

Glucose tolerance and insulin release were evaluated in 16 families with Friedrich's ataxia. Impaired glucose tolerance differed in incidence according to the method of evaluation, but was increased in number in parents' and siblings of Friedreich's cases. Insulin output was not quantitatively different from normal, although the insulin peak was often delayed. This finding, in association with impaired glucose tolerance, suggest a defect in glucose entry into cells.