Diagnosis Of Friedreich Ataxia Research Articles

Uniparental IsoDisomy: a case study on a new mechanism of Friedreich ataxia.

Friedreich's Ataxia (FRDA) is the most common hereditary ataxia and is mainly caused by biallelic GAA repeat expansion in the FXN gene. Rare patients carrying FXN point mutations or intragenic deletions are reported. We describe the first FRDA patient with a chromosome 9 segmental Uniparental isoDisomy (UPiD) unmasking a homozygous FXN expansion initially undetected by TP-PCR. The child presented with a progressive proprioceptive ataxia associated with peripheral sensory neuronopathy and severe scoliosis. Whole genome sequencing (WGS) identified a maternal segmental Uniparental Isodisomy (UPiD) encompassing FXN. Short tandem repeats analysis on WGS showed a biallelic FXN expansion. The identification of a deletion in the primer-annealing region of the TP-PCR explained the initial TP-PCR failure. This is the first documented case of FRDA caused by segmental UPiD. This case highlights the complexity of the molecular diagnosis of FRDA, and emphasises the importance of integrating results from various technical diagnostic approaches.

Evaluating mFARS in pediatric Friedreich's ataxia: Insights from the FACHILD study.

Friedreich ataxia (FRDA) is a rare genetic disorder caused by mutations in the FXN gene, leading to progressive coordination loss and other symptoms. The recently approved omaveloxolone targets this condition but is limited to patients over 16 years of age, highlighting the need for pediatric treatments due to the disorder's early onset and more rapid progression in children. This population also experiences increased non-neurological complications; the FACHILD study aimed to augment and expand the knowledge about the natural history of the disease and clinical outcome assessments for trials in children in FRDA. The study enrolled 108 individuals aged 7-18 years with a confirmed FRDA diagnosis, with visits occurring from October 2017 to November 2022 across three institutions. Several measures were introduced to minimize the impact of the COVID-19 pandemic, including virtual visits. Outcome measures centered on the mFARS score and its subscores, and data were analyzed using mixed models for repeated measures. For context and to avoid misinterpretation, the analysis was augmented with data from patients enrolled in the Friedreich's Ataxia Clinical Outcome Measures Study. Results confirmed the general usefulness of the mFARS score in children, but also highlighted issues, particularly with the upper limb subscore (FARS B). Increased variability, limited homogeneity across study subgroups, and potential training effects might limit mFARS application in clinical trials in pediatric populations. The FARS E (Upright Stability) score might be a preferred outcome measure in this patient population.

Characterization of Cardiac-Onset Initial Presentation in Friedreich Ataxia.

We examined the clinical features of Friedreich ataxia (FRDA) patients who present first with cardiac disease in order to understand the earliest features of the diagnostic journey in FRDA. We identified a group of subjects in the FACOMS natural history study whose first identified clinical feature was cardiac. Only 0.5% of the total cohort belonged to this group, which was younger on average at the time of presentation. Their cardiac symptoms ranged from asymptomatic features to heart failure with severe systolic dysfunction. Two of those individuals with severe dysfunction proceeded to heart transplantation, but others spontaneously recovered. In most cases, diagnosis of FRDA was not made until well after cardiac presentation. The present study shows that some FRDA patients present based on cardiac features, suggesting that earlier identification of FRDA might occur through enhancing awareness of FRDA among pediatric cardiologists who see such patients. This is important in the context of newly identified therapies for FRDA.

Vestibular Pathology as Early Finding of Friedreich's Ataxia in a 16 Years Old Woman.

Friedreich's ataxia is degenerative disease frequently starting around puberty and it's characterized by a progressive gait ataxia, limb weakness, apparition of Babinsky sign, loss of deep tendon reflex, dysarthria and skeletal deformities. The development of vestibular pathology is common but not completely understood. A 16 years old woman with early vestibular defects in relation to a latter Friedreich's ataxia diagnosis is reported.

Scoliosis in Patients With Friedreich Ataxia: Results of a Consecutive Prospective Series

Study DesignProspective monocentric study. ObjectivesTo describe the radiologic characteristics and evolution of spinal shapes in a pediatric cohort of patients with Friedreich ataxia (FA). Summary of Background DataFA is a spinocerebellar degenerative disorder responsible for gait impairment in children and young adults, and several orthopedic deformities can occur during growth, including scoliosis. However, curves' characteristics and their natural evolution have been poorly described, and the subsequent therapeutic management remains controversial. MethodsSixty six FA patients were prospectively included between 2008 and 2017. Clinical, functional, and radiologic records were conducted twice a year. Coronal curve types, segmental measurements, and skeletal maturity were assessed. ResultsA scoliotic deformity was reported in 71% of the patients at a mean age of 11.7 ± 3.1 years. Average follow-up was 6 years, including 75% of patients with closed triradiate cartilage at latest examination. Mean Cobb angle was 34° ± 2°. Main right thoracic curves were the most frequent curves observed (36%), followed by double major (21%), thoracolumbar and left thoracic curves (13%), main lumbar (11%), and long C-shape curves (6%). Hyperkyphosis (>40°) was present in 66%, with an average kyphosis angle of 50° ± 3°, and anterior misalignment (>5°) occurred in 53%. The severity of the Cobb angle was neither correlated to the FA severity scores nor the age at FA diagnosis. An arthrodesis was performed in 9 patients, including 5 patients (45%) who were ambulatory at least 1 year after surgery. ConclusionsThe prevalence of scoliosis in FA was high (71%), and thoracic hyperkyphosis, with anterior misalignment, was frequently observed, which might be related to the anterior imbalance frequently encountered in patients with an ataxia. Posterior fusion including sacral instrumentation was only performed in nonambulatory patients, and the loss of ambulation was not associated with spinal surgery. Level of EvidenceLevel IV.

Heart disease in Friedreich's ataxia.

Friedreich’s ataxia (FRDA), which occurs in 1/50000 live births, is the most prevalent inherited neuromuscular disorder. Nearly all FRDA patients develop cardiomyopathy at some point in their lives. The clinical manifestations of FRDA include ataxia of the limbs and trunk, dysarthria, diabetes mellitus, and cardiac diseases. However, the broad clinical spectrum makes FRDA difficult to identify. The diagnosis of FRDA is based on the presence of suspicious clinical factors, the use of the Harding criteria and, more recently, the use of genetic testing for identifying the expansion of a triplet nucleotide sequence. FRDA is linked to a defect in the mitochondrial protein frataxin; an epigenetic alteration interferes with the folding of this protein, causing a relative deficiency of frataxin in affected patients. Frataxins are small essential proteins whose deficiency causes a range of metabolic disturbances, including oxidative stress, iron-sulfur cluster deficits, and defects in heme synthesis, sulfur amino acid metabolism, energy metabolism, stress responses, and mitochondrial function. The cardiac involvement seen in FRDA is a consequence of mitochondrial proliferation as well as the loss of contractile proteins and the subsequent development of myocardial fibrosis. The walls of the left ventricle become thickened, and different phenotypic manifestations are seen, including concentric or asymmetric hypertrophy and (less commonly) dilated cardiomyopathy. Dilated cardiomyopathy and arrhythmia are associated with mortality in patients with FRDA, whereas hypertrophic cardiomyopathy is not. Systolic function tends to be low-normal in FRDA patients, with an acute decline at the end of life. However, the literature includes only a few long-term prospective studies of cardiac progression in FRDA, and the cause of death is often attributed to heart failure and arrhythmia postmortem. Cardiomyopathy tends to be correlated with the clinical neurologic age of onset and the nucleotide triplet repeat length (i.e., markers of phenotypic disease severity) rather than the duration of disease or the severity of neurologic symptoms. As most patients are wheelchair-bound within 15 years of diagnosis, the clinical determination of cardiac involvement is often complicated by comorbidities. Researchers are currently testing targeted therapies for FRDA, and a centralized database, patient registry, and natural history study have been launched to support these clinical trials. The present review discusses the pathogenesis, clinical manifestations, and spectrum of cardiac disease in FRDA patients and then introduces gene-targeted and pathology-specific therapies as well as screening guidelines that should be used to monitor cardiac disease in this mitochondrial disorder.

Depressive symptoms in Friedreich ataxia

Background/Objective: Almost no attention has been paid to depression in Friedreich ataxia (FRDA), a highly disabling cerebellar degenerative disease. Our aim was to study the presence and the profile of depressive symptoms in FRDA and their relationship with demographic-disease variables and cognitive processing speed. Method: The study groups consisted of 57 patients with a diagnosis of FRDA. The Beck Depression Inventory-II was used to assess symptoms of depression. Speed of information processing was measured with a Choice Reaction time task. Results: The mean BDI score for patients was significantly higher than the mean score in the general population. Twenty one percent of participants scored in the moderate/severe range. A Cognitive-Affective score and a Somatic-Motivational score was calculated for each patient. Patients’ scores in both dimensions were significantly higher than the scores in the general population. Demographic and disease variables were not related with symptoms of depression, except for severity of ataxia. Depressive symptoms predict cognitive reaction times. The greater proportion of variance was explained by the Cognitive-Affective dimension. Conclusions: Our data show that both somatic-motivational and cognitive affective symptoms of depression are frequent in individuals with FRDA. In addition, depressive symptoms may influence cognition, especially, the cognitive and affective symptoms.

Milestones in Friedreich ataxia: more than a century and still learning.

Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia worldwide. This review highlights the main clinical features, pathophysiological mechanisms, and therapeutic approaches for FRDA patients. The disease is characterized by a combination of neurological involvement (ataxia and neuropathy), cardiomyopathy, skeletal abnormalities, and glucose metabolism disturbances. FRDA is caused by expanded guanine-adenine-adenine (GAA) triplet repeats in the first intron of the frataxin gene (FXN), resulting in reduction of messenger RNA and protein levels of frataxin in different tissues. The molecular and metabolic disturbances, including iron accumulation, lead to pathological changes characterized by spinal cord and dorsal root ganglia atrophy, dentate nucleus atrophy without global cerebellar volume reduction, and hypertrophic cardiomyopathy. DNA analysis is the hallmark for the diagnosis of FRDA. There is no specific treatment to stop the disease progression in FRDA patients. However, a number of drugs are under investigation. Therapeutic approaches intend to improve mitochondrial functioning and to increase FXN expression.

Friedreich Ataxia in Classical Galactosaemia.

Movement disorders such as ataxia are a recognized complication of classical galactosaemia, even in diet-compliant patients. Here, we report the coexistence of classical galactosaemia and Friedreich ataxia (FRDA) in nine children from seven Irish Traveller families. These two autosomal recessive disorders, the loci for which are located on either side of the centromere of chromosome 9, appear to be in linkage disequilibrium in this subgroup. Both conditions are known to occur with increased frequency amongst the Irish Traveller population.Each member of our cohort had been diagnosed with galactosaemia in the neonatal period, and all are homozygous for the common Q188R mutation in the GALT gene. Eight of the nine patients later presented with progressive ataxia, between the ages of 5-13 years. Another child presented in cardiac failure secondary to dilated cardiomyopathy at 7 years of age. He was not ataxic at presentation and, one year from diagnosis, his neurological examination remains normal. The diagnosis of FRDA was confirmed by detecting the common pathogenic GAA expansion in both alleles of the frataxin gene (FXN) in each patient.Neurological symptoms are easily attributed to an underlying diagnosis of galactosaemia. It is important to consider a diagnosis of Friedreich ataxia in a child from the Irish Traveller population with galactosaemia who presents with ataxia or cardiomyopathy.

Dysphagia and swallowing-related quality of life in Friedreich ataxia

Dysphagia in Friedreich ataxia (FRDA) and its impact on quality of life is not adequately understood. The objective of this study was to characterise dysphagia in FRDA and to determine the impact of swallowing dysfunction on activities, participation, and sense of well-being. Thirty-six individuals with a confirmed diagnosis of FRDA were assessed via a clinical bedside examination (CBE), the Royal Brisbane Hospital outcome measure for swallowing, an oral-motor examination and the Australian therapy outcome measures for speech and swallowing (AusTOMS). Data on swallowing function, diet modification and swallowing strategies were collated. Thirty-three (91.67%) participants exhibited clinical signs of dysphagia according to the CBE, and all participants received ratings indicating swallowing difficulties on at least one other measure. Dysphagia in FRDA is characterised by oral and pharyngeal stage impairment relating to incoordination, weakness and spasticity. A significant positive correlation was found between the severity of impairment, activity, participation and distress/well-being on the AusTOMS, suggesting that swallowing function decreases with overall reductions in quality of life. A significant correlation was found between activity on the AusTOMS and disease duration (r=-0.283, p=0.012). No significant correlations were found between dysphagia severity and GAA repeat length, age of onset or disease severity. Participants employing diet modification and swallowing strategies demonstrated higher dysphagia severity, activity limitations and participation restrictions. These data advocate a holistic approach to dysphagia management in FRDA. Early detection of swallowing impairment and consideration of the potential impact dysphagia has on quality of life should be key aspects in disease management.

Molecular Diagnosis of Friedreich Ataxia Using Analysis of GAA Repeats and FXN Gene Exons in Population from Western India

The diagnosis of Friedreich ataxia is based on the clinical symptoms and GAA repeats expansions. In our experience, checking FXN gene exons for mutations along with GAA repeat analysis may give better clue for its diagnosis. In the present study, total 49 suspected Friedreich ataxia patients were analyzed for GAA repeat expansion. Eleven patients have normal number of GAA repeats, thereby termed as FRDA negative patients. Thirty-eight patients showed no amplification using GAA repeat analysis. Since no conclusion was possible based on these results, these patients were designated as uninformative. We have analyzed 5 exons of the FXN gene in FRDA negative and uninformative patients to check for possible mutations. It was observed that there were no mutations found in any of FRDA negative and most uninformative patients. We further used long range PCR to check for deletion of exon 5a. It was found that 18 patients showed expression for exon 5a PCR but none in long range PCR. Five patients showed no expression for exon 5a PCR as well as long range PCR indicating that these 5 patients may be positive FRDA patients. These findings need to be correlated with clinical history of these patients for confirmation.

Friedreich Ataxia: Dysarthria Profile and Clinical Data

Friedreich ataxia (FRDA) is the most frequent recessive ataxia in the Western world. Dysarthria is a cardinal feature of FRDA, often leading to severe impairments in daily functioning, but its exact characteristics are only poorly understood so far. We performed a comprehensive evaluation of dysarthria severity and the profile of speech motor deficits in 20 patients with a genetic diagnosis of FRDA based on a carefully selected battery of speaking tasks and two widely used paraspeech tasks, i.e., oral diadochokinesis and sustained vowel productions. Perceptual ratings of the speech samples identified respiration, voice quality, voice instability, articulation, and tempo as the most affected speech dimensions. Whereas vocal instability predicted ataxia severity, tempo turned out as a significant correlate of disease duration. Furthermore, articulation predicted the overall intelligibility score as determined by a systematic speech pathology assessment tool. In contrast, neurologists' ratings of intelligibility--a component of the "Scale for the Assessment and Rating of Ataxia"--were found to be related to perceived speech tempo. Obviously, clinicians are more sensitive to slowness of speech than to any other feature of spoken language during dysarthria evaluation. Our results suggest that different components of speech production and trunk/limb motor functions are differentially susceptible to FRDA pathology. Furthermore, evidence emerged that paraspeech tasks do not allow for an adequate scaling of speech deficits in FRDA.

Feasibility of Implantable Cardioverter Defibrillator Treatment in Five Patients With Familial Friedreich's Ataxia—A Case Series

Friedreich's ataxia (FRA) is an autosomal recessive disease of the central nervous system that is associated with familial cardiomyopathy. Cardiac involvement is seen in more than 90% of the patients and is the most common cause of death in these patients. We present a case series and discuss the indications for implantable cardioverter defibrillator (ICD) implantation in FRA with review of the literature. Five pediatric patients who suffer from FRA (four female and one male, mean age 17.4 years) underwent ICD implantation between 2007 and 2008 in the University Hospital of Goettingen. The diagnosis of FRA was established by standard clinical criteria and proven in each case by genotyping at the frataxin locus. The time from diagnosis to ICD implantation was 10.4±1.73 years (range 8-15 years). All patients received transvenous lead systems. There were no intraoperative and postoperative complications. At the latest follow-up, the neuromuscular symptoms exhibited no further progress and no ICD activations were noticed. Only minor repolarization changes were seen on electrocardiogram. All patients had normal echocardiographic findings and no angina has been reported. Coronary angiographies were normal. It is evident that many FRA patients develop ventricular dysfunction. In the absence of a definitive surgical cure an ICD is generally indicated in young patients with hemodynamically significant sustained ventricular tachyarrhythmias for prevention of sudden cardiac death. Our experience implies the safe use of ICD in children with FRA.

Protocol proposal for Friedreich ataxia molecular diagnosis using fluorescent and triplet repeat primed polymerase chain reaction

Friedreich ataxia (FRDA) is the most common hereditary ataxia that is caused mainly by an unstable GAA trinucleotide expansion in the first intron of the frataxin gene. Molecular tests for FRDA diagnosis and carrier detection include polymerase chain reaction (PCR) for the GAA expansion, triplet repeat primed PCR (TP-PCR), and/or Southern blotting. TP-PCR is a method developed to detect trinucleotide expansions successfully applied to FRDA diagnosis. In our laboratory, we have included a PCR for the GAA expansion using fluorescent primers polymerase chain reaction (F-PCR) to identify normal heterozygous and affected individuals unambiguously. The purpose of our study was to reanalyze 310 samples previously diagnosed in our laboratory and compare the results with those obtained by F-PCR and TP-PCR. Eight percent of the discrepancies between the carrier and the normal individuals were identified correctly by this protocol. No discrepancy was detected in the affected individuals. These techniques are effective, and compared with Southern blotting, they are less labor-intensive and suitable for automation. We suggest a new routine protocol for FRDA diagnosis that includes F-PCR and TP-PCR.

Characterizing Gait, Locomotor Status, and Disease Severity in Children and Adolescents with Friedreich Ataxia

The purpose of this study was to describe gait parameters in children and adolescents with a diagnosis of Friedreich ataxia (FA) and examine the relationship between disease severity, measured by the Friedreich Ataxia Rating Scale (FARS) and gait parameters. The study examined whether FARS scores can discriminate between those who walk independently and those who require assistance. Thirty-eight children (aged 5-11 years) and adolescents (aged 12-17 years) with genetically confirmed FA were divided into two groups based on locomotor status: group 1, subjects who were able to walk independently, and group 2, subjects who required assistance for walking. Temporal and spatial gait parameters were collected using the Stride Analyzer computerized foot switch system and compared with age-matched normative data. The FARS was used to measure disease severity. Correlation coefficients and the Mann-Whitney U test of differences were used to evaluate associations and discern differences between groups. In subjects with FA, gait parameters of velocity and cadence were slower and stride length was shorter compared with age-matched children without disabilities. These parameters were significantly correlated with FARS score (r = 0.696, 0.667, 0.537; respectively, all P values <0.001). Total FARS scores were correlated with locomotor status (ç value r = 0.623; P < 0.01) and could categorize subjects into groups based on independent walking or need for assistance, 73% and 87% of the time, respectively. Subjects with FA exhibited specific abnormal gait characteristics relative to age-matched individuals. Disease severity, as measured by the FARS, was associated with gait velocity, stride length, and cadence. FARS scores can be used to categorize subjects by locomotor status and may be a useful screening tool to identify those requiring assistance.

Comparison of three clinical rating scales in Friedreich ataxia (FRDA)

To test the validity and reliability of the scale for the assessment and rating of ataxia (SARA) in Friedreich ataxia (FRDA). SARA is limited to eight items and can be performed rapidly. Ninety-six patients with a molecular genetic diagnosis of FRDA were rated using three different clinical scales, the FRDA Rating Scale (FARS), the International Cooperative Ataxia Rating Scale (ICARS), and SARA. Despite considerable discrepancies in scale size and subscale structure, SARA total scores were significantly correlated with ICARS (r = 0.953, P < 0.0001) and FARS (r = 0.938, P < 0.0001) total scores. SARA total scores also correlated with the activities of daily living (ADL, r = 0.929, P < 0.0001). Although originally developed for the use in dominantly inherited ataxias, which are primarily ataxias of the cerebellar type, SARA can also be used successfully to assess afferent ataxia, which is the predominant form in FRDA. Because SARA is characterized by high interrater reliability and practicability, SARA is applicable and well suited forclinical trials of FRDA.

Low-dose idebenone treatment in Friedreich’s ataxia with and without cardiac hypertrophy

Left ventricular hypertrophy (LVH) is a frequent finding in Friedreich's ataxia (FRDA). In previous studies treatment with idebenone, a synthetic analogue of coenzyme Q10, has been associated with a substantial decrease in myocardial hypertrophy, despite great variability in cardiac responsiveness among patients. Here we present the results of a retrospective analysis of a cohort of 35 patients (20 with LVH, 15 without LVH) with confirmed molecular diagnosis of FRDA, treated with idebenone 5 mg/kg/day for up to five years. At the end of the study, we found an increase of interventricular septum and posterior wall thickness in the group without LVH before treatment and no change in the group with LVH before treatment. The neurological picture of the disease significantly deteriorated with time in both groups.

The Longitudinal Course of Cardiomyopathy in Friedreich’s Ataxia During Childhood

Clinical heart disease was recognized in the first descriptions of Friedreich's ataxia (FA). Cardiac manifestations reported for this progressive neurologic disease include hypertrophic cardiomyopathy, dilated cardiomyopathy, and electrophysiologic disturbances. Longitudinal data for childhood cases are limited. This study aimed to define the longitudinal course of the cardiac abnormalities with FA diagnosed during childhood and to correlate the presence of cardiomyopathy with clinical and genetic factors. A retrospective chart review was conducted, with prospective, blinded interpretation of echocardiograms and electrocardiograms. All the patients with a diagnosis of FA referred to the cardiology department of a single institution from 1974 to 2004 were included in the study. This study investigated a total of 113 echocardiograms for 28 patients. Overall, the group had left ventricular hypertrophy and normal systolic function, with a median mass z-score of 2.48 (range, -3.8 to 35.6) and a median ejection fraction (EF) of 61% (range, 23-81%). Of the 28 patients, 23 (82%) had two or more echocardiograms. The median follow-up time to the most recent echocardiogram was 5.1 years (range, 0.4-16.5 years). Many in this longitudinal follow-up cohort (57%) showed hypertrophic cardiomyopathy on at least one echocardiogram, with the last follow-up assessment showing systolic dysfunction for 38% of these patients. There was a slow nonlinear decline in systolic function over time, with the mean EF decreasing more rapidly as age increased (p = 0.02) and maintenance of EF in the normal range until the age of 22 years. Of the 12 patients with systolic dysfunction and follow-up echocardiograms, 10 showed improvement to the normal EF range on at least one echocardiogram, and 5 remained normal through the last study. None of the trends in cardiac function and morphology correlated with frataxin GAA repeat length (the primary genetic defect in FA) or ambulatory status. One patient required an implantable defibrillator. There were no deaths or heart transplantations. Overall, patients with FA have preserved cardiac function with increased mass throughout childhood. Because many patients who experience depressed systolic function show improvement in subsequent studies, evaluation for potentially reversible causes of heart failure should be conducted. Relative clinical stability during childhood and maintenance of normal systolic function into the second decade may be helpful for parent and patient education.

Triplet Repeat Primed PCR (TP PCR) in Molecular Diagnostic Testing for Friedreich Ataxia

Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disease, is associated with an unstable expansion of a GAA trinucleotide repeat in the first intron of the frataxin gene on chromosome 9q13. Unequivocal molecular characterization of the FRDA triplet expansion requires the use of different PCR protocols to amplify normal and mutated alleles combined with Southern blotting analysis to accurately size the expansion. Nevertheless, expansion detection by PCR may be somewhat problematic in heterozygous individuals. The purpose of this study was to evaluate triplet repeat primed PCR (TP PCR) as a screening method for FRDA diagnosis in the diagnostic laboratory. Fifty-four cases referred either to confirm the diagnosis of FRDA or to detect carrier status were re-evaluated by the TP PCR method. The TP PCR assay correctly identified the FRDA status in all 54 individuals tested including homozygous expansions (9 individuals), heterozygous expansions (20 individuals), and non-carriers (25 individuals). Results showed 100% concordance with those obtained by Southern blot analysis. TP PCR allowed us to identify the expanded alleles or to demonstrate their absence in DNA samples where conventional PCR procedures failed to give a reliable result. TP PCR represents an additional valuable tool for mutation detection in FRDA patients and carriers, but also can be used as screening test in a diagnostic laboratory.

Ataxia de Friedreich: análisis de parámetros de resonancia magnética y correlatos con el enlentecimiento cognitivo y motor

The heredodegenerative ataxias are a heterogeneous group of disorders affecting especially the cerebellum and its tracts. Magnetic resonance imaging (MRI) studies using quantitative methodology are scarce, particularly in Friedreich's ataxia (FA). On the other hand, slowness of information processing speed has been described in FA, but no empirical relation with MRI parameters has been established.The aim of the present study was to quantitatively assess infra and supratentorial atrophy in patients with clinical diagnosis of FA and to establish the relationship with a information processing speed measure.Twelve FA patients that fulfilled clinical diagnostic criteria and twelve control subjects were studied. A computerized system that differentiate reaction time and movement time, as well as a semiautomated technique of binarization and analysis of MRI were used.Patients showed a poorer performance in movement time and in reaction time. Analyzing the frequency of pathologic changes, vermal atrophy was present in 67% of the patients and cerebellar hemisphere atrophy in 50%. Only a minority of patients showed signs of supratentorial cerebral atrophy (17%). Statistically significant negative correlations were obtained between reaction time and the size of the cerebellum.Cerebellar hemisphere atrophy is a usual finding in FA, although vermal atrophy is more frequent. The relation between cerebellar atrophy and reaction time supports the claim about cerebellar involvement in the information processing and response speed.