THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES Positron Emission Tomography Study of Brain Benzodiazepine Receptors in Friedreich's Ataxia

Central type benzodiazepine receptors were studied in 9 patients with Friedreich's ataxia and 12 healthy subjects using positron emission tomography (PET) and ["C]Ro 15-1788, a specific antagonist of the central type benzodiazepine receptors, as radioligand. A standard PET procedure was used in 5 patients and 8 controls to obtain brain kinetics of the total binding of the radioligand. The remaining subjects were intravenously injected with a saturating dose of unlabeled Ro 15-1788, 30 minutes after the tracer injection, to determine the nondisplaceable binding of [C|Ro 15-1788. A semi-quantitative method was used to quantify the ["C]Ro 15-1788 data. None of the quantification indices in the cerebellar hemispheres, or in the other brain areas investigated, was significantly modified in patients with Friedreich's ataxia. These findings suggest that brain benzodiazepine receptors are unaffected in Friedreich's ataxia. RESUME: Etude des recepteurs des benzodiazepines par tomographic par emission de positons dans Pataxie de Friedreich Les recepteurs des benzodiazepines de type central ont ete etudies, par tomographie par emission de positions (PET), chez 9 patients atteints d'ataxie de Friedreich et chez 12 temoins, en utilisant le [C]Ro 15-1788 comme radioligand. Une procedure PET standard, permettant d'obtenir la cinetique de la liaison totale du radioligand au niveau du cerveau a et6 utilisee chez 5 patients et chez 8 temoins. Lea autres sujets ont reiju, 30 min apres l'administration du traceur, une injection intraveineuse d'une dose saturante de Ro 15-1788 non radioactif, afin de determiner la fraction non depla9able du [C]Ro 15-1788. Une methode semi-quantitative est proposee pour la quantification des donn^es. Quelle que soit la region cerebrate considered (hemispheres cerebelleux, cortex occipital, cortex temporal ou substance blanche), aucun des index de quantification n'etait significativement modifie chez les patients atteints d'ataxie de Friedreich. Ces resultats suggerent que les recepteurs des benzodiazepines ne sont pas alteres dans l'ataxie de Freidreich. Can. J. Neurol. Sci. 1990; 17: 404-409 Friedreich's ataxia (FA) is an autosomal recessive disorder characterized by severe degeneration of the spino-cerebellar pathways, the dorso-lateral columns of the spinal cord, and the dentate nuclei, with few changes in the cerebellar cortex itself. Four main reasons have prompted us to investigate whether the central type benzodiazepine receptors, known to be involved in the GABAergic inhibitory mechanisms, are involved in this disease: 1) These receptors are found at high concentration in the cerebellum. 2) Little is known about neurochemical changes in the brain of patients with FA although decreased cerebellar concentrations of GABA and glutamate have been found in two patients. 3) Benzodiazepine receptors have already been studied in other kinds of ataxic experimental and human diseases. For example, severe alterations of cerebellar benzodiazepine receptors have been reported in different strains of ataxic mutant mice." These changes are, however, associated with extensive pathological changes in the cerebellar cortex, which do not occur in FA. By contrast, a post-mortem analysis of some cases of olivo-ponto-cerebellar degeneration failed to detect marked changes of these receptors but the neuropathology of this progressive ataxic disease is also very different from FA. 4) In vivo examination of benzodiazepine receptors has become possible using positron emission tomography (PET) and [C]Ro 15-1788 as a radioligand." This could be an additional diagnostic element for the classification of cerebellar atrophies, which is still lacking in precision. Because of the well-known neuropathology of FA and its well-established clinical criteria that allow the determination of an homogeneous population of ataxic patients, we decided to study first the cerebellar benzodiazepine receptors in FA. This study must thus be considered as a first step towards further improvement in the classification of progressive cerebellar diseases. METHODS AND MATERIALS Nine patients with FA (mean age ± SD: 32 ± 12 years), members of the "Association Francaise de l'Ataxie de Friedreich", gave their informed consent to participate in the study. All subjects Du Service Hospitalier Fr£de>ic Joliot, CEA, Dgpartement de Biologie, Hopital d'Orsay, 91406 Orsay, France (C.C, Y.S., S.P., C.P., MM); Clinique de Neurologie et de Neuropsychologie and INSERM U289, Hopital de la Salpetriere, 75013 Paris, France (A.S., Y.A.) Received December 23, 1989. Accepted in final form July 16, 1990 Tir6sapart: Dr. C. Chavoix, National Institute of Health, Laboratory of Neuropsychology, Bdg9, Rm IN 107, Bethesda, Maryland 20892, USA