Disease Delineation for Multiple Sclerosis, Friedreich Ataxia, and Healthy Controls Using Supervised Machine Learning on Speech Acoustics.

Neurodegenerative disease often affects speech. Speech acoustics can be used as objective clinical markers of pathology. Previous investigations of pathological speech have primarily compared controls with one specific condition and excluded comorbidities. We broaden the utility of speech markers by examining how multiple acoustic features can delineate diseases. We used supervised machine learning with gradient boosting (CatBoost) to delineate healthy speech from speech of people with multiple sclerosis or Friedreich ataxia. Participants performed a diadochokinetic task where they repeated alternating syllables. We subjected 74 spectral and temporal prosodic features from the speech recordings to machine learning. Results showed that Friedreich ataxia, multiple sclerosis and healthy controls were all identified with high accuracy (over 82%). Twenty-one acoustic features were strong markers of neurodegenerative diseases, falling under the categories of spectral qualia, spectral power, and speech rate. We demonstrated that speech markers can delineate neurodegenerative diseases and distinguish healthy speech from pathological speech with high accuracy. Findings emphasize the importance of examining speech outcomes when assessing indicators of neurodegenerative disease. We propose large-scale initiatives to broaden the scope for differentiating other neurological diseases and affective disorders.

Correlation of Visual Quality of Life With Clinical and Visual Status in Friedreich Ataxia.

BACKGROUND: The primary objective was to determine the association of patient-reported vision-specific quality of life to disease status and visual function in patients with Friedreich's ataxia (FRDA). METHODS: Patients with FRDA were assessed with the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) along with measures of disease status (ataxia stage) and visual function (low- and high-contrast letter acuity scores). The relations of NEI-VFQ-25 scores to those for disease status and visual function were examined. RESULTS: Scores for the NEI-VFQ-25 were lower in patients with FRDA (n = 99) compared with published disease-free controls, particularly reduced in a subgroup of FRDA patients with features of early onset, older age, and abnormal visual function. CONCLUSIONS: The NEI-VFQ-25 captures the subjective component of visual function in patients with FRDA.

Health-related quality of life and depressive symptoms in Friedreich ataxia.

PURPOSE: Friedreich ataxia (FRDA) is a chronic, progressive and highly disabling cerebellar degenerative disease. Despite this, little attention has been paid to the health-related quality of life (HRQOL) in this disease. The aim of the present study was to assess FRDA patients' perception of HRQOL and to determine the influence of depression, and demographic and clinical variables. METHOD: The sample consisted of 62 patients with genetically confirmed FRDA. The SF-36 Health Survey was used to assess HRQOL. Depressive symptoms were evaluated with the Beck Depression Inventory-II. RESULTS: FRDA patients' mean scores were significantly lower than the values for the Spanish population in all SF36 dimensions. Average z scores ranged from - 5.5 in physical functioning to - 0.48 in mental health. Age and clinical variables were significant predictors of HRQOL in only several dimensions, whereas BDI scores were able to predict a significant percentage of variance in all SF36 dimensions, except physical functioning. CONCLUSIONS: Our study demonstrates the high impact of Friedreich ataxia on quality of life. This impact does not only occur in those aspects most related to motor disability but it is also present in non-motor dimensions. Depressive symptomatology is the most relevant variable for predicting quality of life.

Impact of Mobility Device Use on Quality of Life in Children With Friedreich Ataxia.

OBJECTIVE: To determine how mobility device use impacts quality of life in children with Friedreich ataxia. STUDY DESIGN: Data from 111 pediatric patients with genetically confirmed Friedreich ataxia were collected from a prospective natural history study utilizing standardized clinical evaluations, including health-related quality of life using the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Module. RESULTS: Mobility device use was associated with worse mean PedsQL total, physical, emotional, social, and academic subscores, after adjusting for gender, age of disease onset, and Friedreich Ataxia Rating Scale score. The magnitude of the difference was greatest for the physical subscore (-19.5 points, 95% CI = -30.00, -8.99, P < .001) and least for the emotional subscore (-10.61 points, 95% CI = -20.21, -1.02, P = .03). Transition to or between mobility devices trended toward worse physical subscore (-16.20 points, 95% CI = -32.07, -0.33, P = .05). CONCLUSIONS: Mobility device use is associated with significant worsening of all domains of quality of life in children with Friedreich ataxia.

Depressive symptoms in Friedreich ataxia / Síntomas depresivos en la ataxia de Friedreich

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 (AU)

Antecedentes/Objetivo: La depresión en la ataxia de Friedreich (FRDA), una enfermedad degenerativa cerebelosa altamente incapacitante, ha recibido poca atención. Nuestro objetivo es evaluar la presencia y el perfil de los síntomas depresivos en FRDA y su relación con variables clínico-demográficas y la velocidad de procesamiento cognitivo. Método: Se estudiaron 57 pacientes con diagnóstico de FRDA. Se usó el Inventario de Depresión de Beck-II para evaluar los síntomas de depresión. La velocidad de procesamiento se midió con una tarea de tiempos de reacción. Resultados: La puntuación media de los pacientes en el BDI fue significativamente mayor que en la población general. El 21% de los participantes obtuvo puntuaciones en el rango moderado/grave. Se calculó una puntuación cognitiva-afectiva y una puntuación somática-motivacional para cada paciente. Las puntuaciones en ambas dimensiones fueron significativamente mayores que en la población general. Las variables clínico-demográficas no estaban relacionadas con los síntomas de depresión, a excepción de la gravedad de la ataxia. Los síntomas depresivos predicen los tiempos de reacción cognitivos. Conclusiones: Nuestros datos muestran que en la FRDA son frecuentes los síntomas de depresión, tanto los síntomas somáticomotivacionales como los cognitivo-afectivos. Además, los síntomas de depresión pueden influir en la cognición, especialmente, los de tipo cognitivo-afectivo (AU)

Emotion Recognition and Psychological Comorbidity in Friedreich's Ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive disease presenting with ataxia, corticospinal signs, peripheral neuropathy, and cardiac abnormalities. Little effort has been made to understand the psychological and emotional burden of the disease. The aim of our study was to measure patients' ability to recognize emotions using visual and non-verbal auditory hints, and to correlate this ability with psychological, neuropsychological, and neurological variables. We included 20 patients with FRDA, and 20 age, sex, and education matched healthy controls (HC). We measured emotion recognition using the Geneva Emotion Recognition Test (GERT). Neuropsychological status was assessed measuring memory, executive functions, and prosopagnosia. Psychological tests were Patient Health Questionnaire-9 (PHQ-9), State Trait Anxiety Inventory-state/-trait (STAI-S/-T), and Structured Clinical Interview for DSM Disorders II. FRDA patients scored worse at the global assessment and showed impaired immediate visuospatial memory and executive functions. Patients presented lower STAI-S scores, and similar scores at the STAI-T, and PHQ-9 as compared to HC. Three patients were identified with personality disorders. Emotion recognition was impaired in FRDA with 29% reduction at the total GERT score (95% CI - 44.8%, - 12.6%; p < 0.001; Cohen's d = 1.2). Variables associated with poor GERT scores were the 10/36 spatial recall test, the Ray Auditory Verbal Learning Test, the Montreal Cognitive Assessment, and the STAI-T (R2 = 0.906; p < 0.001). FRDA patients have impaired emotion recognition that may be secondary to neuropsychological impairment. Depression and anxiety were not higher in FRDA as compared to HC and should not be considered as part of the disease.

Personality and Neuropsychological Profiles in Friedreich Ataxia.

Friedreich ataxia, an autosomal recessive mitochondrial disease, is the most frequent inherited ataxia. Many studies have attempted to identify cognitive and affective changes associated with the disease, but conflicting results have been obtained, depending on the tests used and because many of the samples studied were very small. We investigated personality and neuropsychological characteristics in a cohort of 47 patients with genetically confirmed disease. The neuropsychological battery assessed multiple cognition domains: processing speed, attention, working memory, executive functions, verbal memory, vocabulary, visual reasoning, emotional recognition, and social cognition. Personality was assessed with the Temperament and Character Inventory, and depressive symptoms were assessed with the Beck Depression Inventory. We found deficits of sustained attention, processing speed, semantic capacities, and verbal fluency only partly attributable to motor deficit or depressed mood. Visual reasoning, memory, and learning were preserved. Emotional processes and social cognition were unimpaired. We also detected a change in automatic processes, such as reading. Personality traits were characterized by high persistence and low self-transcendence. The mild cognitive impairment observed may be a developmental rather than degenerative problem, due to early cerebellum dysfunction, with the impairment of cognitive and emotional processing. Disease manifestations at crucial times for personality development may also have an important impact on personality traits.

Dysphagia in Friedreich Ataxia.

The objective of the study was to comprehensively characterise dysphagia in Friedreich ataxia (FRDA) and identify predictors of penetration/aspiration during swallowing. We also investigated the psychosocial impact of dysphagia on individuals with FRDA. Sixty participants with FRDA were screened for dysphagia using a swallowing quality of life questionnaire (Swal-QOL) and case history. Individuals reporting dysphagia underwent a standardised oromotor assessment (Frenchay Dysarthria Assessment, 2, FDA-2) and videofluoroscopic study of swallowing (VFSS). Data were correlated with disease parameters (age at symptom onset, age at assessment, disease duration, FXN intron 1 GAA repeat sizes, and Friedreich Ataxia Rating Scale (FARS) score). Predictors of airway penetration/aspiration were explored using logistic regression analysis. Ninety-eight percent (59/60) of participants reported dysphagia, of whom 35 (58.3%) underwent FDA-2 assessment, and 38 (63.3%) underwent VFSS. Laryngeal, respiratory, and tongue dysfunction was observed on the FDA-2. A Penetration-Aspiration Scale score above 3 (deemed significant airway compromise based on non-clinical groups) was observed on at least one consistency in 13/38 (34.2%) participants. All of those who aspirated (10/38, 26.3%) did so silently, with no overt signs of airway entry such as reflexive cough. Significant correlations were observed between dysphagic symptoms and disease duration and severity. No reliable predictors of penetration or aspiration were identified. Oropharyngeal dysphagia is commonly present in individuals with FRDA and worsens with disease duration and severity. Individuals with FRDA are at risk of aspiration at any stage of the disease and should be reviewed regularly. Instrumental analysis remains the only reliable method to detect aspiration in this population. Dysphagia significantly affects the quality of life of individuals with FRDA.

Measuring Inhibition and Cognitive Flexibility in Friedreich Ataxia.

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with subtle impact on cognition. Inhibitory processes and cognitive flexibility were examined in FRDA by assessing the ability to suppress a predictable verbal response. We administered the Hayling Sentence Completion Test (HSCT), the Trail Making Test, and the Stroop Test to 43 individuals with FRDA and 42 gender- and age-matched control participants. There were no significant group differences in performance on the Stroop or Trail Making Test whereas significant impairment in cognitive flexibility including the ability to predict and inhibit a pre-potent response as measured in the HSCT was evident in individuals with FRDA. These deficits did not correlate with clinical characteristics of FRDA (age of disease onset, disease duration, number of guanine-adenine-adenine repeats on the shorter or larger FXN allele, or Friedreich Ataxia Rating Scale score), suggesting that such impairment may not be related to the disease process in a straightforward way. The observed specific impairment of inhibition and predictive capacity in individuals with FRDA on the HSCT task, in the absence of impairment in associated executive functions, supports cerebellar dysfunction in conjunction with disturbance to cortico-thalamo-cerebellar connectivity, perhaps via inability to access frontal areas necessary for successful task completion.

A longitudinal study of the Friedreich Ataxia Impact Scale.

BACKGROUND: Quality of life in Friedreich ataxia (FRDA) has been explored using various generic health status measurement tools, most commonly the Short Form Health Survey Version 2 (SF-36v2). The tool did not address many specific issues related to disease impact in people with FRDA. The Friedreich Ataxia Impact Scale (FAIS) was developed to examine clinically relevant areas in FRDA. The aims of the current study were to assess the relationship between the FAIS and clinical characteristics of FRDA, as well as to determine the responsiveness of the FAIS to change over one and two years. METHODS: One hundred and four individuals with FRDA, homozygous for the GAA expansion in intron 1 of FXN, completed the FAIS at baseline. Seventy individuals completed the FAIS again 12 months later and 49 completed the FAIS at 24 months. Clinical parameters and neurologic scales (Friedreich Ataxia Rating Scale (FARS)) were also recorded. RESULTS: The total FARS score, onset age and disease duration correlated significantly with FAIS subscales measuring symptoms and physical functioning. The physical and mental summary measures of the SF-36 V2 also correlated well with the FAIS subscales. Speech was the only subscale that demonstrated significant change over one and two years. CONCLUSIONS: The FAIS provides valuable insight into the perspective of individuals with FRDA on their health status, and is an important measure of morbidity. It has, however, limited responsiveness to change and its use in intervention studies is questionable.

"Both Sides of the Wheelchair": The Views of Individuals with, and Parents of Individuals with Friedreich Ataxia Regarding Pre-symptomatic Testing of Minors.

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder characterized by variable age of onset, with no treatment proven to alter its natural history. Siblings of individuals with FRDA have a 25 % risk of developing the condition, raising issues around genetic testing of asymptomatic minors. There is a lack of professional consensus and limited empirical evidence to support provision or refusal of testing. This study aimed to ascertain the opinions of individuals with and parents of individuals with FRDA regarding pre-symptomatic testing of minors. A qualitative research approach using semi-structured interviews and thematic analysis was employed. Interviews with ten individuals with FRDA, and ten parents of individuals with FRDA were conducted, recorded, transcribed and analyzed. Four findings emerged. First, a number of arguments for and against testing minors were identified. Second, strong support existed from parents about the parental right to test their at-risk immature children, but individuals with FRDA were of mixed opinions. Third, participants felt it was not the clinician's role to make a final decision about whether testing occurs. Finally, a specific issue of concern regarding testing was what and when to tell at-risk children about the test result. The findings highlight a dilemma of how to manage the desires of some individuals and families affected by FRDA to access testing, when there is a lack of professional consensus due to differing opinions regarding autonomy, confidentiality and risk of harm. Research regarding the impact of testing and the views of at-risk individuals and clinicians is required so an appropriate framework for dealing with this contentious issue is developed.

Friedreich ataxia: executive control is related to disease onset and GAA repeat length.

Friedreich ataxia (FRDA) is the most frequent inherited ataxia. Neuropsychological studies suggest that FRDA may be associated with specific cognitive impairment. Very little is known about the relation between cognitive performance, demographics and disease-related parameters, such as GAA repeat size, age of onset and disease duration. The present investigation aimed at assessing cognitive functions in a representative sample of FRDA patients and at identifying the most relevant disease-related parameters. Twenty-nine adult FRDA patients underwent neuropsychological tests assessing executive functions, attention, memory and visual perception. Performance was compared with 28 age- and education-matched controls as well as with standardized norms. The relation between neuropsychological outcome, demographical variables and disease-related parameters was assessed. Cognitive impairment affected only a subgroup of patients and mostly concerned attentional and executive functions. Good cognitive performance was associated with a later disease onset, shorter GAA repeat length and lower burden of disease. Age at disease onset has been found to be a good predictor when a cut-off of 14 years was chosen. No correlation was found between cognitive performance and education, age or disease duration. The present study extends earlier findings in FRDA showing that performance in attentional and executive function tasks is best predicted by the age at disease onset. Moreover, executive functions show a clear relationship to disease severity and repeat size of the shorter GAA allele. These findings therefore have important implications for patient counselling regarding education and career choices.

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.

Clinical features of Friedreich's ataxia: classical and atypical phenotypes.

One hundred and fifty years since Nikolaus Friedreich's first description of the degenerative ataxic syndrome which bears his name, his description remains at the core of the classical clinical phenotype of gait and limb ataxia, poor balance and coordination, leg weakness, sensory loss, areflexia, impaired walking, dysarthria, dysphagia, eye movement abnormalities, scoliosis, foot deformities, cardiomyopathy and diabetes. Onset is typically around puberty with slow progression and shortened life-span often related to cardiac complications. Inheritance is autosomal recessive with the vast majority of cases showing an unstable intronic GAA expansion in both alleles of the frataxin gene on chromosome 9q13. A small number of cases are caused by a compound heterozygous expansion with a point mutation or deletion. Understanding of the underlying molecular biology has enabled identification of atypical phenotypes with late onset, or atypical features such as retained reflexes. Late-onset cases tend to have slower progression and are associated with smaller GAA expansions. Early-onset cases tend to have more rapid progression and a higher frequency of non-neurological features such as diabetes, cardiomyopathy, scoliosis and pes cavus. Compound heterozygotes, including those with large deletions, often have atypical features. In this paper, we review the classical and atypical clinical phenotypes of Friedreich's ataxia.

Impact of Friedreich's Ataxia on health-care resource utilization in the United Kingdom and Germany.

BACKGROUND: Friedreich's Ataxia (FRDA) is a neurodegenerative disorder that causes progressive damage to the central and peripheral nervous systems having a significant impact upon quality of life. With little information in the literature, cross-sectional observational studies were conducted in the UK and Germany to collect data on resource use and the burden of the disease on individuals and their caregivers. METHODS: Cross-sectional observational studies were conducted in the UK and Germany to estimate the burden of FRDA on individuals and on the respective healthcare systems. A total of 75 individuals in the UK and 28 in Germany were recruited to the study. Participants in both countries were asked to complete a Patient and Caregiver Information Form (PCIF), regarding access to, and use of, healthcare resources, and the impact FRDA has on their lifestyle. In Germany, doctors were asked to complete a Patient Record Form (PRF). Analyses of annual direct and indirect resource utilization were conducted for both countries while costs were calculated for the UK only. These figures were compared to the costs associated with Parkinson's disease; one of the most common neurodegenerative conditions and the one most similar in terms of disease progression. RESULTS: The results showed that the annual burden of FRDA is significant and falls on the health and social care sectors, on society, on caregivers and on the individuals themselves. In the UK FRDA had a total annual cost per person of between £11,818 and £18,774 depending on whether the cost of long-term unemployment was included.Typically the largest component of direct costs is associated with professional care. Given the high proportion of children and young adults recruited and the long disease duration, (typically 40-50 years for FRDA, compared with 20 years for Parkinson's disease), these figures may underestimate the true burden of the disease. CONCLUSION: It is hoped that these estimates of resource utilization, can help in understanding the previously unquantified burden of FRDA. Given the long disease duration, management strategies should seek to minimise the impact of the condition on individuals and their caregivers, while maximising quality of life.

Binaural speech processing in individuals with auditory neuropathy.

Auditory neuropathy disrupts the neural representation of sound and may therefore impair processes contingent upon inter-aural integration. The aims of this study were to investigate binaural auditory processing in individuals with axonal (Friedreich ataxia) and demyelinating (Charcot-Marie-Tooth disease type 1A) auditory neuropathy and to evaluate the relationship between the degree of auditory deficit and overall clinical severity in patients with neuropathic disorders. Twenty-three subjects with genetically confirmed Friedreich ataxia and 12 subjects with Charcot-Marie-Tooth disease type 1A underwent psychophysical evaluation of basic auditory processing (intensity discrimination/temporal resolution) and binaural speech perception assessment using the Listening in Spatialized Noise test. Age, gender and hearing-level-matched controls were also tested. Speech perception in noise for individuals with auditory neuropathy was abnormal for each listening condition, but was particularly affected in circumstances where binaural processing might have improved perception through spatial segregation. Ability to use spatial cues was correlated with temporal resolution suggesting that the binaural-processing deficit was the result of disordered representation of timing cues in the left and right auditory nerves. Spatial processing was also related to overall disease severity (as measured by the Friedreich Ataxia Rating Scale and Charcot-Marie-Tooth Neuropathy Score) suggesting that the degree of neural dysfunction in the auditory system accurately reflects generalized neuropathic changes. Measures of binaural speech processing show promise for application in the neurology clinic. In individuals with auditory neuropathy due to both axonal and demyelinating mechanisms the assessment provides a measure of functional hearing ability, a biomarker capable of tracking the natural history of progressive disease and a potential means of evaluating the effectiveness of interventions.

Ataxia rating scales--psychometric profiles, natural history and their application in clinical trials.

We aimed to perform a comprehensive systematic review of the existing ataxia scales. We described the disorders for which the instruments have been validated and used, the time spent in its application, its validated psychometric properties, and their use in studies of natural history and clinical trials. A search from 1997 onwards was performed in the MEDLINE, LILACS, and Cochrane databases. The web sites ClinicalTrials.gov and Orpha.net were also used to identify the endpoints used in ongoing randomized clinical trials. We identified and described the semiquantitative ataxia scales (ICARS, SARA, MICARS, BARS); semiquantitative ataxia and non-ataxia scales (UMSARS, FARS, NESSCA); a semiquantitative non-ataxia scale (INAS); quantitative ataxia scales (CATSYS 2000, AFCS, CCFS and CCFSw, and SCAFI); and the self-performed ataxia scale (FAIS). SARA and ICARS were the best studied and validated so far, and their reliability sustain their use. Ataxia and non-ataxia scores will probably provide a better view of the overall disability in long-term trials and studies of natural history. Up to now, no clear advantage has been disclosed for any of them; however, we recommend the use of specific measurements of gait since gait ataxia is the first significant manifestation in the majority of ataxia disorders and comment on the best scales to be used in specific ataxia forms. Quantitative ataxia scales will be needed to speed up evidence from phase II clinical trials, from trials focused on the early phase of diseases, and for secondary endpoints in phase III trials. Finally, it is worth remembering that estimation of the actual minimal clinically relevant difference is still lacking; this, together with changes in quality of life, will probably be the main endpoints to measure in future therapeutic studies.

Utilisation of advance motor information is impaired in Friedreich ataxia.

Friedreich ataxia (FRDA) is the most common of the genetically inherited ataxias. We sought to examine motor planning ability in 13 individuals with FRDA and 13 age- and sex-matched control participants using two experimental paradigms that examined the ability to incorporate different levels of advance information to plan sequential movements. Individuals with FRDA demonstrated a differential pattern of motor response to advance information and were significantly disadvantaged by conditions requiring initiation of movement without a direct visual cue. There was also a significant negative correlation with age of disease onset and differing levels of advance information, suggesting an impact of FRDA on the development of motor cognition, independent of the effect of disease duration. We suggest that deficits are due to cerebellar impairment disrupting cerebro-ponto-cerebello-thalamo-cerebral loops (and thus cortical function), direct primary cortical pathology or a possible combination of the two.

Superior cerebellar peduncle atrophy in Friedreich's ataxia correlates with disease symptoms.

Friedreich's ataxia (FRDA) is the most common early onset inherited ataxia with clinical manifestations, including gradual progression of unremitting cerebellar-sensory ataxia, peripheral sensory loss, loss of lower limb tendon reflexes and hypertrophic cardiomyopathy. Although atrophy of the superior cerebellar peduncle (SCP) has been reported in several magnetic resonance imaging (MRI) studies of FRDA, the relationship of SCP changes to genetic and clinical features of FRDA has not been investigated. We acquired T1-weighted MRI scans in 12 right-handed individuals with FRDA, homozygous for a GAA expansion in intron 1 of FXN, as well as 13 healthy age-matched controls. The corrected cross-sectional areas of the right (left) SCP in the individuals with FRDA (R, 20 ± 7.9 mm(2); L, 25 ± 5.6 mm(2)) were significantly smaller than for controls (R, 68 ± 16 mm(2); L, 78 ± 17 mm(2)) (p < 0.001). The SCP volumes of individuals with FRDA were negatively correlated with Friedreich's ataxia rating scale score (r = -0.553) and disease duration (r = -0.541), and positively correlated with the age of onset (r = 0.548) (p < 0.05). These findings suggest that structural MR imaging of the SCP can provide a surrogate marker of disease severity in FRDA and support the potential role of structural MRI as a biomarker in the evaluation of neurodegenerative diseases and therapies.

Spectral measures of the effects of Friedreich's ataxia on speech.

This study identifies two measures of the effects of Friedreich's ataxia (FRDA) on speech motor control. Speech samples of 17 healthy controls and 37 speakers with dysarthria associated with FRDA were recorded during one structured and one unstructured speaking task. Two measures of spectral variation were used that relate to the rate and range of changes that occur in the spectral envelope. Linear mixed models revealed significant effects of GROUP, TASK, and GROUP*TASK. FRDA speech samples had slower rate of spectral change and reduced spectral range. Healthy speakers produced faster rates of spectral change in read text compared to conversation, but speakers with dysarthria did not. The results suggest that structured speaking tasks which demand large spectral variation may be particularly useful in assessing the dysarthria. It is concluded that the rate of spectral change is a useful measure of dysarthria associated with FRDA.