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Friedreich ataxia (FA) is a rare mitochondrial disease characterized by sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy, and diabetes, for which there is no treatment. FA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of Fe-S clusters. To date, FA precise neuropathophysiology is not identified and despite significant progresses in recent the years, there was no good model to develop therapeutic approaches in order to stop or reverse the sensory ataxia associated to the FA. Thus, we have generated a new neuronal mouse model that recapitulates the sensory ataxia and the neuropathy associated to FXN deficiency. Several molecular mechanisms dysregulated in the absence of FXN in the proprioceptive neurons, primarily affected in FA, were identified. Furthermore, we have demonstrated the efficacy of a gene therapy (GT) approach, based on the delivery of adeno-associated vectors (AAV) expressing the human FXN, to reverse the sensitive neuropathy, thus establishing the preclinical proof of concept for the potential of GT in treating FA sensitive neuropathy., L’ataxie de Friedreich (AF) est une maladie mitochondriale caractérisée par une ataxie sensitive et spinocérébelleuse, une cardiomyopathie et du diabète, pour laquelle il n’existe pas de traitement. L’AF résulte de niveaux réduits de frataxine (FXN), une protéine mitochondriale impliquée dans la biosynthèse des centres Fe-S. La neurophysiopathologie précise de la maladie n’est pas identifiée et malgré d’intenses progrès ces dernières années, il n’existait pas de bon modèle pour développer des approches thérapeutiques visant à stopper ou réverser l’atteinte sensitive de l’AF. Nous avons donc généré un nouveau modèle murin qui récapitule l’ataxie sensitive et la neuropathie associée au déficit en FXN. Plusieurs mécanismes moléculaires affectés en absence de FXN dans les neurones proprioceptifs, primairement affectés dans l’AF, ont été identifiés. Nous avons également démontré l’efficacité d’une approche de thérapie génique, basée sur l’utilisation de vecteur adéno-associés (AAV) exprimant la FXN humaine, pour réverser la neuropathie, établissant la preuve de concept du potentiel d’une telle approche pour l’atteinte sensitive de l’AF.

Friedreich ataxia is a severe neurodegenerative disease caused by reduced expression of frataxin (FXN), a small mitochondrial protein involved in iron-sulfur (Fe/S) cluster biogenesis which are prostetic groups with essential cellular functions. It has been shown in vitro that mammalian FXN activates Fe/S cluster synthesis on the scaffold protein ISCU, by rising up suflide ion production by NFS1-ISD11-ISCU complex. However, the mechanism by which frataxin stimulates Fe/S cluster biogenesis has not been yet defined. We have studied the effect of FXN on the kinetics of formation and reduction of persulfides that are key intermediates of sulfide ion production generated by NFS1, using mass spectrometry and a new detection assay for persulfide based on gel-mobility shift following alkylation by maleimide-peptide compounds. We demonstrate that frataxin activates two similar reactions : sulfur transfer from cysteine desulfurase NFS1 to ISCU leading to accumulation of a persulfide on ISCUcysteine C104 and reduction of NFS1 persulfide by thiol reducers such as DTT, L-cysteine and glutathion. We have observed that FXN does not stimulate the rate of ISCU persulfide reduction by thiols and that this persulfide is reduced much more slowly than NFS1 persulfide. We have then correlated the reduction of NFS1 persulfide with Fe/S cluster assembly. Under our experimental conditions, the sulfur from ISCU persulfide is not incorporated into the Fe/S cluster. However, we cannot exclude that an as yet not identfiied reductase could reduces ISCU persulfide and trigger Fe/S cluster assembly. Overall, our data point to a regulatory function of FXN as an enhancer of persulfide reduction, stimulating the rates of sulfur transfer to ISCU and NFS1 persulfide.; L’ataxie de Friedreich est une maladie neurodégénérative sévère causée par un défaut d’expression de la frataxine (FXN), une petite protéine mitochondriale impliquée dans la biogenèse des centres fer-soufre (Fe/S), des groupement prosthétiques aux fonctions cellulaires essentielles. Chez les mammifères, il a été montré que la frataxine stimule la synthèse in vitro de centres Fe/S sur la protéine d’échaffaudage ISCU, grâce à l’augmentation de la production d’ions sulfures par le complexe NFS1-ISD11-ISCU. Cependant, le mécanisme par lequel la frataxine active la biogenèse des centres Fe/S n’a pas encore été défini. Nous avons étudié les effets de FXN sur les cinétiques de formation et de réduction des persulfures, des intermédiaires clés de la production d’ions sulfures, générés par la cystéiene désulfurase NFS1, à l’aide d’un test de détection des persulfures basé sur l’utilisation de composés synthétiques peptide-maléimide et de la spectrométrie de masse. Nous avons montré que FXN active deux réactions très similaires : la réduction du persulfure de NFS1 par des réducteurs à thiols comme le DTT, la L-cystéine et le glutathion et le transfert de soufre de NFS1 vers ISCU, conduisant à l’accumulation de persulfure sur la cystéine C104 d’ISCU. Nous avons constaté que la vitesse de réduction du persulfure d’ISCU par les thiols n’est pas affectée en présence de FXN et que ce persulfure est réduit plus lentement que celui de NFS1. Nous avons corrélé l’activation par FXN de la réduction du persulfure de NFS1 par les thiols à une stimulation de l’assemblage d’un centre Fe/S sur ISCU. Dans nos conditions expérimentales, l’atome de soufre du persulfure d’ISCU n’est pas incorporé dans le centre Fe/S synthétisé, mais nos résultats ne permettent pas d’exclure que ce persulfure puisse être réduit par une réductase dédiée, encore non identifiée. L’ensemble de nos données indiquent que le rôle de la frataxine est de contrôler la réduction du persulfure de NFS1, en augmentant les vitesses de transfert de soufre vers ISCU et de réduction du persulfure de NFS1 par les thiols.

Friedreich Ataxia (FA) is the most prevalent form of autosomal recessive ataxia in the Caucasian population. Frataxin is implicated in the biosynthesis of iron-sulfur (FeS). The first axis of my work was to better characterize the function of Frataxin in the “early” complex of FeS clusters biosynthesis (NFS1/ISD11/ISCU). I was able to show the crucial involvement of Frataxin in the control of iron entry in this complex, on the enzymatic activity of NFS1 and on the transfert of FeS cluster to apo-proteins. Thesecond axis was the development of a bio-informatic software (PredISC) that is able to predict potential iron-sulfur containing proteins. The software allows us to generate a list of candidates that will be compiled in a database. In the future transversal approaches have to be associated in order to reduced the number of candidates, and increase their interest.; L’Ataxie de Friedreich est une maladie génétique récessive neurodégénérative. Elle est due à un déficit dans l’expression d’une protéine mitochondriale, la frataxine. Cette protéine est impliquée dans l’assemblage des protéines fer-soufre (FeS). Le premier axe de ma thèse a consisté à mieux caractériser le rôle de la frataxine au sein du complexe précoce de biosynthèse des clusters FeS (NFS1/ISD11/ISCU). Mes résultats m’ont permis de mettre en évidence l’importance de la frataxine dans le contrôle de l’entrée du fer au sein du complexe de biosynthèse, sur l’activité enzymatique de NFS1 et sur le transfert des clusters FeS vers les apo-protéines. Le second axe a été le développement du programme de bioinformatique (PredISC) nous permettant des candidats de protéines FeS. Ce programme a permis de générer une liste de candidat qui pourra être compilée sous la forme d’une base de données. Par la suite, des approches transversales y seront associées à afin d’affiner les listes de candidats.

Friedreich ataxia is the most frequent recessive cerebral ataxia d should always be researched first. Ataxia with isolated vitamin E deficiency and abetalipoproteinemia have a specific treatment. Associated neurological signs such polyneuroapthy, ophtalmologic or oculomotor signs, pyramidal signs, and cerebellar MRI can lead to the etiological diagnosis. Biological tests should be: vitamin E, cholesterol, alpha-fetoprotein levels, acanthocytes, than phytanic acid, cholestanol, lysosomal enzymes. Numerous autosomal recessive cerebellar ataxia remain without etiology.

The monitoring of scoliosis treatment can lead to discover its cause.A 16-year-old patient was allowed in Center of Functional Rehabilitation for intensive orthopaedic treatment of a severe scoliosis. Electrophysiological explorations carried out within the framework of the monitoring of this treatment detected an axonal neuropathy with sensitive prevalence, whose association with clinical signs made it possible to diagnose Friedreich's disease, then confirmed by molecular biology.Electrophysiological examination is useful in a Rehabilitation Center within the framework of the monitoring of the treatment proposed, more especially as it can make it possible to direct a diagnosis.

Freidreich ataxia is the most frequent ataxia of early onset and of autosomal recessive transmission. It is associated with hypertrophic cardiomyopathy in 34 to 77% of cases. The purpose of this article is to describe the cardiac manifestations of two patients affected by this disease. The first case report is about a 34-years-old, bedridden male patient having muscular hypotony and osteotendinous areflexia of the lower limbs. Chest x-ray findings showed a cardiac silhouette distorted by scoliokyphosis. ECG revealed frequent auricular extrasystoles. Cardiac US examination disclosed a pattern of concentric hypertrophic cardiomyopathy with systolic and diastolic dysfonction.

A retrospective study of Friedreich's ataxia was conducted from january 1960 to december 1997. Eighten cases had been collected. Friedreich's ataxia was the second disorder after Pierre Marie's ataxia among inherited ataxia. Parental consanguinity has been found in 27.77% of cases. The sex-ratio was 2.6 for males. 66,67% of Friedreich's ataxia cases began after 25 years. Clinical signs were: cerebellar ataxia, sensitive disorders in 70%, pyramidal syndrom and cardiomyopathy in 22.22%, bones dysmorphy in 50% of cases. Electromyography indicated severe axonopathy of members with decreased somesthesic potentials in six cases. Glycaemia was normal in all cases. Clinical future presented wide variation between one and fourth years old.

The authors report the case of a 21 year old woman admitted to hospital for congestive cardiac failure due to concentric hypertrophic cardiomyopathy. Echocardiography showed severe systolo-diastolic left ventricular dysfunction without obstruction to ejection. Neurological examination showed a stato-kinetic cerebellar syndrome, a posterior radiculo-cordonal syndrome and a dysmorphic syndrome which characterise Friedreich's disease. In the light of this case and a review of the literature, the authors underline the rarity of cardiomyopathy in Friedreich's disease, its particular presentation and its poor prognostic significance in this disease.

Two sisters developed isolated cerebellar ataxia with pyramidal signs and preservation of reflexes at 49 and 63 years of age. Presence of two abnormal expansions GAA on both allels of the frataxine gene led to the diagnosis of Friedreich ataxia. These cases demonstrate the place of genetic tests in the diagnosis of late onset autosomal recessive ataxia.

Friedreich's ataxia (FRDA) is the most frequent cause of recessive ataxias. Neurological examination shows oculo-motor ataxia, dysarthria, limbs ataxia, tendon areflexia, pyramidal signs and sensory deficits. Extra-neurological involvement consists in osteoarticular deformities, cardiomyopathy and diabetes mellitus. Neurological deficits and osteoarticular deformities both contribute to the gait disorder, which is the main disabling deficit. In 98% of the cases, a trinucleotide repeat is found in chromosome 9. Gene implicated in FRDA codes for a protein called frataxin. Experimental studies have revealed iron accumulation in mitochondria of neurons and cardiomyocytes, suggesting that frataxin plays a determinant role in intramitochondrial iron homeostasis. These discoveries are now considered as a clue for new strategies of treatment in this hereditary disease.

The human genome, made of about 3 billion bases, encodes between 75 and 100,000 genes. However, most of the genome is made of non coding sequences, whose function is still unknown. When a base variation occurs in a DNA fragment, base change, deletion or insertion of one or several bases, a mutation or a polymorphism is generated depending whether this base change modifies or not the function of the encoded gene. In 1991, a new type of mutation has been discovered, namely the expansion beyond a critical length of a three-base repeat, called triplet. These anomalies due to genome instability are not rare and are now responsible for at least twelve diseases. It is expected that other diseases due to the same mechanism will be discovered in the near future. This article illustrates the concept of mutation by triplet expansion and presents 3 diseases frequently observed in Pediatrics: the fragile X syndrome, myotonic dystrophy and Friedreich's ataxia.

A 24-year-old patient, born from consanguineous parents, consulted for cerebellar syndrome, ataxia, loss of proprioception, bilateral Babinski sign and lower limbs areflexia. No mutation on Friedreich's ataxia gene was found. Plasmatic vitamin E level was extremely low. Point mutation on gene coding for alpha-tocopherol transfer protein (alpha-TTP) confirmed the diagnosis of familial isolated vitamin E deficiency (AVED). Vitamin E therapy restored normal serum levels and neurological symptoms were stabilized.

More than 10 genetic diseases, including 3 frequent ones (the fragile X mental retardation syndrome, myotonic dystrophy and Huntington's disease) are caused by unstable expansions of trinucleotide repeats. The instability of these mutations and their strong tendency to further expansion, account for the special characteristics of the mode of inheritance of these diseases. Unlike most other genetic diseases, that can be caused by a large number of different mutations, the trinucleotide expansion diseases are due to a single type of mutation. Detection of the expansion by DNA analysis allows thus easy and reliable diagnosis of these diseases. For several of them, the late but generally very deleterious clinical expression, raises the very delicate problem of genetic counselling and presymptomatic diagnosis.

Acoustic analysis of unvoiced diadochokinetic respiratory cycles helped identify two kinds of impairments in ten Friedreich's ataxia patients. Four patients manifested moderate problems maintaining regularity in the repetition of unvoiced respiratory cycles, and also showed moderate articulatory dysarthric problems in a syllabic repetition task. Six patients had severe respiratory insufficiency in the inspiration/expiration repetition task, and exhibited very important amplitude and fundamental frequency disturbances and a much slower rate of syllabic utterances. This respiratory insufficiency and aggravated speech disorders were linked to presence of pontine and medullary atrophy, sites comprising the respiratory centers of the brain stem.

Based on the hereditary ataxias concepts and a large field survey, the authors analyzed 392 cases of spino-cerebellar degeneration belonging to 188 families. Two main clinical groups were identified: 227 cases of Friedreich ataxia and 74 cases of cerebellar hereditary ataxia of P. Marie type. The association in the same patient of peroneal atrophy of Charcot Marie type with Friedreich ataxia (17 cases) or P. Marie cerebellar hereditary ataxia (13 definite cases and 13 probable) was the most striking finding. "Forme fruste", incomplete form or complex form of Friedreich ataxia were present in some families while in some others there was spastic paraplegia or pure Charcot Marie Tooth disease. This clinical heterogeneity in families of spino-cerebellar degeneration is discussed.

This study concerned VOT measurements of voiced and voiceless occlusives produced in a sample of spontaneous language from 16 French speakers with Friedreich's ataxia. The results revealed that average VOT values were positive for voiceless stops and negative for voiced stops and thus were in agreement with published data for French. There was, however, a reduction of the difference between the two voicing categories and large between-subject variability. The factors that could have contributed to the increase in between-subject variability and to the reduction of the difference between the two categories are discussed. Finally, some leads for the use of VOT in the therapeutic process are proposed.

This joint work has studied the cardiomyopathies occurring in hereditary neuro-muscular disorders (270 cases). The Duchenne type of disorder (74 cases) was responsible for asystole (4 cases), for cardiomegaly, and especially for abnormalities of the ECG (59 cases)--Q waves and large R waves in V1 and V6. The cardiomyopathy was of the hypokinetic type, with histological evidence of degeneration of the myocardial fibres. Dystrophia myotonica of Steinart (23 cases) caused conductive disorders (17 cases) which were either atrioventricular or intra-ventricular or both. Studies of the His pathway confirmed that these abnormalities were more diffuse in 5 cases. The main histological feature was interstitial fibrosis. There was a high risk of sudden death; ECG follow-up should be close. Friedreich's disease (20 cases) in its complete form led to later development of obstructive cardiomyopathy, with a systolic ejection murmur, cardiomegaly, and abnormalities of the ECG--left ventricular hypertrophy in the vertical axis, right ventricular and septal hypertrophy, repolarisation disorders similar to those found in coronary artery disease. Histology showed hypertrophy with degeneration of the myocardial fibres and interstitial fibrosis. This complete form was rare (7 cases out of 20); on the other hand, ECG abnormalites were very common (16 cases out of 20). The authors have tried to study the relationships between primary cardiomyopathies (50 cases) and peripheral neuromuscular disorders. 17 of the 39 peripheral muscle biopsies were abnormal, but a well-defined muscular dystrophy could not be found in them.

The authors performed ambulatory electro-vectorcardiography polycardiography and echocardiography in 18 patients with typical Friedreich's disease, and 6 patients with atypical forms of hereditary spino-cerebellar ataxia classified on e basis of the degree of neurological involvement, without clinical signs of cardiocirculatory failure. The ECG and VCG recording commonly showed appearances suggestive of myocardial "necrosis" and were of little value in the differential diagnosis between typical and atypical forms of Friedreich's ataxia. This limitation also applied to the kinetocardiogramme which was sometimes pathological confirming the echocardiographic diagnosis of symmetric LV hypertrophy and of septal hypokinesia despite normal ECG and VCG. The systolic time intervals and echocardiographic parameters of the interventricular septum were more helpful in the differential diagnosis. Hypertrophic cardiomyopathy, usually symmetric, was observed in about 70 p. 100 of typical and only rarely in atypical forms of Friedreich's disease. The symmetric or asymmetric hypertrophy was associated with reduced left ventricular performance in less than 20 p. 100 of typical Friedreich's disease, systolic anterior motion of the mitral valve and other signs of dynamic left ventricular outflow tract obstruction were not observed in any of these patients. The correlations between the degree of neurological disability and the cardiac abnormalities, were, in general, disappointing compared with other reported series. The cardiac investigation of patients with Friedreich's disease remains valuable from the point of view of recent pathological hypotheses of a metabolic abnormality with eventual therapeutic implications.

The case is reported of a patient with Charcot-Marie-Tooth disease and congestive cardiomyopathy. This is an exceptional association and suggests there could be transitional forms between Charcot-Marie-Tooth disease and Friedreich ataxia, which is frequently associated with hypertrophic cardiomyopathy. A disorder of pyruvate metabolism observed in our patient could explain both the neurologic and cardiac symptoms.

Urodynamic exploration with cystometry was performed at random on 55 of the 195 patients suffering from hereditary spinocerebellar degeneration (Friedreich's disease 43 cases, Pierre-Marie hereditary ataxia nine cases, Strumpell-Lorrain disease three cases). The authors observed disturbances in continence without urinary disorders, even when the bladder was atonic. In the case of Friedreich's disease, among the 18 patients with urgent urination or with urinary leakage, the bladder was found to be normal in only two cases. Although 25 patients evidenced no urinary disturbances, a through study revealed nine abnormal bladders. In the case of Pierre-Marie disease, six normal bladders and three pathological bladders were found. A single abnormal bladder was found in Strumpell-Lorrain disease. Two types of pathological bladder were observed: the atonic bladder was compared with the traumatic bladder, and was found primarily in conjunction with peripheral sensory disturbances. The hypertonic bladder appears when sensory involvement is not evident. The authors discuss the pathophysiology of these disturbances of continence.

Results of early auditory evoked potentials, recorded during exploration of spinocerebellar heredodegenerative lesions (21 cases of Friedreich's disease, 8 cases of Pierre-Marie's disease and 3 cases of Strumpell-Lorraine disease), are analyzed. Tracings showed alteration of auditory BER whereas tonal audiometry was normal. Analysis of BER demonstrated lengthening of the latency periods, a rise in thresholds without latency period increases and a tracing that was sometimes flat or with waves that were difficult to recognize.

18 patients with degenerative cerebellar ataxia were given for 12 months, high doses of D-L-5 Hydroxytryptophan (16 mg/kg/day) with a peripheral inhibitor of 5-HTP Decarboxylase. The ataxia was regularly evaluated with a semi-quantitative score and quantitative measurements, allowing a computerized processing of the data. A highly significant improvement of the static ataxia was observed at the 12th month, while adiadocokinesia, hypermetria and dysarthria were also influenced. These results could correspond to the presence of serotoninergic nerve terminals in the cerebellar cortex, the cerebellar deep nuclei and the inferior olivary complex. Moreover, the improvement of the ataxia continued for 3 months after treatment stopped, suggesting an effect distinct from the classical neuromediation phenomenon.

During a survey conducted in Tunisia in 1978, 204 cases of hereditary degenerative spinocerebellar diseases were discovered among members of 117 families. The cases included 109 patients with Friedreich's ataxia, 28 with Piere Marie's heredo-ataxia, 20 with Strumpell-Lorrain's disease, and 47 with intermediary forms. The latter group included incomplete forms of Friedreich's and Pierre Marie's diseases. The onset or progression of the disease was linked to a febrile episode in 25 p. cent of the cases. Emphasis is placed on the presence of bladder sphincter disorders in approximately one third of the patients with Friedreich's or Pierre Marie's diseases. Manometric studies in 17 cases demonstrated the presence of normal bladders in 4 cases, hypertonicity of the bladder in 5 patients, and hypesthesic retention-type bladders in 5 other cases. In 3 patients the disorder was difficult to classify. These results show that sphincter disorders should not constitute a criterium for exclusion of the diagnosis of spinocerebellar degeneration.

The literature contains few reports of investigations on the mental state of subjects with Friedreich's ataxia. Most are based on clinical findings and lead to differing conclusions. For some authors the neurological disease is associated with mental deficits of varying magnitude, for others the mental state of the patients is accompanied by any deficit. The authors discuss five cases and try to supplement clinical findings with a series of psychometric tests in three areas: intellectual efficiency, higher cortical functions and elements of personality. The clinical and psychometric results are summarized in a grid comprising the main psychopathological symptoms attached to cerebral organic suffering (psycho-organic syndrome). Comparison of the results with medical data confirm that, in Friedreich's ataxia, there are no specific disorders characteristic of a psycho-organic syndrome. Lastly, the authors discuss certain hypotheses (concerning methods used, precocious appearance of symptoms and reactions to the disease) which try to explain the divergence of conclusions reached in the literature for this type of study.

The results of NMR imaging in 8 cases of spinocerebellar degenerative diseases (age 4 to 19 years) are presented. In Friedreich ataxia (5 cases), spinal atrophy was constant and often severe, and was associated with a moderate cerebellar and/or bulbar atrophy in 3 cases. In hereditary spastic paraplegia, the only finding was a mild spinal atrophy in 2 of the 3 cases.

The authors describe the results of electrophoresis studies of 111 cerebrospinal fluids from 110 patients with various spinocerebellar degenerative diseases (58 cases of Friedreich's disease, 14 of Pierre-Marie's ataxia, 12 of Strumpell-Lorrain paraplegia, 23 cerebellar atrophies, and 4 cases of Roussy-Levy disease). The degenerative profile of the electrophoresis findings were characterized by an overall reduction in CSF proteins, an increase in pre-albumin, and a reduction in gammaglobulin, and this was noted in 82 cases (73.8 p. 100). Low levels (less than or equal to 0.17 g/l) of proteins were observed in 19 cases (17.1 p. 100), and increased pre-albumin in 43 cases (38.7 p. 100). Reduced gammaglobulin was present in 20 cases (18.0 p. 100), and the cerebrospinal fluid was normal in only 29 cases (26.1 p. 100). These modifications could result from a particular type of physiopathological process of cell degeneration in the nervous system.

This study presents the findings from a neuroradiological investigation of the cervical spinal canal in a number of diseases of the nervous system. It concerns the measurement of the sagittal and transversal diameters of the spinal canal at levels C3 through C6. The material for this investigation was made up of two main groups: A) 400 controls and B) 110 patients. The second group consisted of the following: 1) 20 patients suffering from Friedreich's Ataxia, 2) 14 patients with Steinert's disease, 3) 44 patients with lateral amyotrophic sclerosis, 4) 14 patients suffering from Charcot-Marie-Tooth's disease, and 5) 18 patients with muscular dystrophy. The results are as follow: 1) In patients with Friedreich's Ataxia both the sagittal and transversal diameters are smaller than those of the controls. 2) On the contrary, in Charcot-Marie-Tooth's disease the sagittal diameter is larger than the controls. 3) The transversal diameter in patients with muscular dystrophy is smaller than the controls and 4) the sagittal diameter of the vertebral canal decreases from the top (C3) downwards (C6) while the transversal diameter increases.

This survey of Roussy-Lévy disease begins with an historical account of the three neurological conditions from which this entity has been separated: Friedreich disease, described in 1861-1863, which proved with time to be a genuine anatomoclinical disorder: Charcot-Marie-Tooth atrophy, described in 1886, particular because of its morphology and evolution but due to various processes: Dejerine-Sottas hypertrophic neuritis, described in 1893, which was the first variant to be individualized within the heterogenous group of primary and familial hypertrophic neuritis. The initial description of Roussy-Lévy disease--in 1926, 1932, and 1934--and the controversies raised by this concept are recalled as well as the present state of the original family: five out of seven members have been examined since 1956 and it has been demonstrated that they are suffering from a form of hypertrophic neuritis. However it is this author's opinion that the concept of an autonomous Roussy-Lévy disease within hypertrophic neuritis is justified by the following criteria: dominant transmission, very precocious onset, extreme slowness of the evolution, remarkable benignity of the prognosis.

A preliminary report is presented of the audiovestibular findings in 16 cases of typical Friedreich ataxia. Many ENG abnormalities of the central type were found, the most frequent being square waves, ocular dysmetria, and disorganized pursuit of the pendulum. The other abnormal findings were less frequent or less specific. Peripheral vestibular and auditory impairment were not the rule. Eventually, the electronystagmogram could become an early paraclinical screening test of Friedreich's disease.

The authors describe a boy aged 16 presenting with a heredoataxia of Friedreichs type which began when the patient was eight and which was accompanied by a diffuse degeneration of the posterior pole of the retina developing at the same time. This syndrome is attended by dysmorphoses (slight craniofacial dysostosis and other developmental anomalies), retarded growth (height: 1 m. 36) and retardation of puberty. The authors advance the hypothesis that a recessive pleiotropic gene is responsible for both the neuroretinal syndrome and the dysmorphosis and quote the literature referring to this problem.

The sensitive potential of the median nerve is evoked by stimulating the second and third fingers while being recorded percutaneously at the wrist. Three parameters are calculated on control subjects: amplitude, duration and velocity, which is obtained from the negative peak latency. These parameters have been measured on children with Charcot-Marie-Tooth's disease. Friedreich's ataxia and Fukuyama's disease. The results are in good agreement with the literature. The interest of this investigation for early diagnosis of the disease and its classification is emphasized.