Nasality in Friedreich ataxia.

Perceptual speech research in Friedreich ataxia (FRDA) has identified altered nasality as a key component of the dysarthria profile, however the incidence and severity of abnormal nasality remains unknown. Utilizing objective and perceptual methods, data on the relationship between resonance, disease duration, severity, age of onset and genetic profiles were collated. Thirty-seven participants with FRDA and 24 healthy controls provided contemporaneous speech samples for perceptual analysis, and single word samples for acoustic analysis. A subset of participants (eight participants with FRDA and eight controls) underwent nasometry assessment. Twenty-seven participants with FRDA presented with hypernasality and five with hyponasality on perceptual assessment. Acoustic analysis revealed participants with FRDA had greater nasality than controls (p < 0.05). Perceptual ratings of hypernasality correlated with GAA2 repeat length (ρ = 0.37, p = 0.03). Findings highlight the variability of nasality in FRDA, potentially reflecting variation in the neuropathological profile. Data also suggest the influence of genetic profiles on nasality.

Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes.

BACKGROUND: Hereditary ataxia syndromes can result in significant speech impairment, a symptom thought to be responsive to treatment. The type of speech impairment most commonly reported in hereditary ataxias is dysarthria. Dysarthria is a collective term referring to a group of movement disorders affecting the muscular control of speech. Dysarthria affects the ability of individuals to communicate and to participate in society. This in turn reduces quality of life. Given the harmful impact of speech disorder on a person's functioning, treatment of speech impairment in these conditions is important and evidence-based interventions are needed. OBJECTIVES: To assess the effects of interventions for speech disorder in adults and children with Friedreich ataxia and other hereditary ataxias. SEARCH METHODS: On 14 October 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, PsycINFO, Education Resources Information Center (ERIC), Linguistics and Language Behavior Abstracts (LLBA), Dissertation Abstracts and trials registries. We checked all references in the identified trials to identify any additional published data. SELECTION CRITERIA: We considered for inclusion randomised controlled trials (RCTs) or quasi-RCTs that compared treatments for hereditary ataxias with no treatment, placebo or another treatment or combination of treatments, where investigators measured speech production. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias of included studies using the standard methodological procedures expected by The Cochrane Collaboration. The review authors collected information on adverse effects from included studies. We did not conduct a meta-analysis as no two studies utilised the same assessment procedures within the same treatment. MAIN RESULTS: Fourteen clinical trials, involving 721 participants, met the criteria for inclusion in the review. Thirteen studies compared a pharmaceutical treatment with placebo (or a low dose of the intervention), in heterogenous groups of degenerative cerebellar ataxias. Three compounds were studied in two trials each: a levorotatory form of 5-hydroxytryptophan (L-5HT), idebenone and thyrotropin-releasing hormone tartrate (TRH-T); each of the other compounds (riluzole, varenicline, buspirone, betamethasone, coenzyme Q10 with vitamin E, α-tocopheryl quinone and erythropoietin) were studied in one trial. The 14th trial, involving a mixed group of participants with spinocerebellar ataxia, compared the effectiveness of nonspecific physiotherapy and occupational therapy within an inpatient hospital setting to no treatment. No studies utilised traditional speech therapies. We defined the primary outcome measure in this review as the percentage change (improvement) in overall speech production immediately following completion of the intervention or later, measured by any validated speech assessment tool. None of the trials included speech as a primary outcome or examined speech using any validated speech assessment tool. Eleven studies reported speech outcomes derived from a subscale embedded within disease rating scales. The remaining three studies used alternative assessments to measure speech, including mean time to produce a standard sentence, a subjective rating of speech on a 14-point analogue scale, patient-reported assessment of the impact of dysarthria on activities of daily living and acoustic measures of syllable length. One study measured speech both subjectively as part of a disease rating scale and with further measures of speech timing. Three studies utilised the Short Form-36 Health Survey (SF-36) and one used the Child Health Questionnaire as measures of general quality of life. A further study utilised the Functional Independence Measure to assess functional health.Five studies reported statistically significant improvement on an overall disease rating scale in which a speech subscale was included. Only three of those studies provided specific data on speech performance; all were comparisons with placebo. Improvements in overall disease severity were observed with α-tocopheryl quinone; however, no significant changes were found on the speech subscale in a group of individuals with Friedreich ataxia. A statistically significant improvement in speech according to a speech disorders subscale was observed with betamethasone. Riluzole was found to have a statistically significant effect on speech in a group of participants with mixed hereditary, sporadic and unknown origin ataxias. No significant differences were observed between treatment and placebo in any other pharmaceutical study. A statistically significant improvement in functional independence occurred at the end of the treatment period in the rehabilitation study compared to the delayed treatment group but these effects were not present 12 to 24 weeks after treatment. Of the four studies that assessed quality of life, none found a significant effect. A variety of minor adverse events were reported for the 13 pharmaceutical therapies, including gastrointestinal side effects and nausea. Serious adverse effects were reported in two participants in one of the L-5HT trials (participants discontinued due to gastrointestinal effects), and in four participants (three taking idebenone, one taking placebo) in the idebenone studies. Serious adverse events with idebenone were gastrointestinal side effects and, in people with a previous history of these events, chest pain and idiopathic thrombocytopenic purpura. The rehabilitation study did not report any adverse events.We considered six studies to be at high risk of bias in some respect. We suspected inadequate blinding of participants or assessors in four studies and poor randomisation in a further two studies. There was a high risk of reporting bias in two studies and attrition bias in four studies. Only one study had a low risk of bias across all criteria. Taken together with other limitations of the studies relating to the validity of the measurement scales used, we downgraded the quality of the evidence for many of the outcomes to low or very low. AUTHORS' CONCLUSIONS: There is insufficient and low or very low quality evidence from either RCTs or observational studies to determine the effectiveness of any treatment for speech disorder in any of the hereditary ataxia syndromes.

Differentiating profiles of speech impairments in Friedreich's ataxia: a perceptual and instrumental approach.

BACKGROUND: The speech disorder associated with Friedreich's ataxia (FRDA) is classically described as ataxic dysarthria. However, variable neuropathology beyond the cerebellum, which may include the corticospinal and corticobulbar tracts, means that the dysarthria can be mixed rather than a pure ataxic dysarthria. AIMS: To characterize physiological features of the dysarthria associated with FRDA and identify differential patterns of deviation that may occur across the subsystems of the speech-production mechanism in a series of seven case studies. METHODS & PROCEDURES: The assessment battery included a perceptual analysis of a speech sample using an interval rating scale, and a range of instrumental measures to investigate the respiratory, laryngeal, velopharyngeal and articulatory systems. OUTCOMES & RESULTS: The results demonstrated the variability that exists in the dysarthria associated with FRDA, highlighting the existence of differential profiles of speech impairment. A particular distinction was observed between the presence of hypernasality and phonatory dysfunction, as evidenced by the instrumental results. CONCLUSIONS & IMPLICATIONS: The distinct profiles of dysarthria associated with FRDA indicate that approaches that address multiple subsystems are necessary for the accurate characterization and quantification of the motor speech disorder. Further research is required to investigate the decline in speech function as the disease progresses, as changes in speech function over time may be a good indicator of neurological decline in FRDA.

Kinematic analysis of lingual movements during consonant productions in dysarthric speakers with Friedreich's ataxia: A case-by-case analysis.

Articulatory kinematics were investigated using electromagnetic articulography (EMA) in four dysarthric speakers with Friedreich's ataxia (FRDA). Specifically, tongue-tip and tongue-back movements were recorded by the AG-200 EMA system during production of the consonants /t/ and /k/ as produced within a sentence utterance and during a rapid syllable repetition task. The results obtained for each of the participants with FRDA were individually compared to those obtained by a control group (n = 10). Results revealed significantly greater movement durations and increased articulatory distances, most predominantly during the approach phase of consonant production. A task difference was observed with lingual kinematics more disturbed during the syllable repetition task than during the sentence utterance. Despite expectations of slowed articulatory movements in FRDA dysarthria, the EMA data indicated that the observed prolongation of consonant phase durations was generally associated with greater articulatory distances, rather than slowed movement execution.

Dysarthria in Friedreich's ataxia: a perceptual analysis.

The aims of this study were to: (1) evaluate the perceptual speech dimensions, speech intelligibility and dysarthria severity of a group of individuals diagnosed with Friedreich's ataxia (FRDA); (2) determine the presence of subgroups within FRDA dysarthria; (3) investigate the relationship between the speech outcome and the clinical factors of disease progression. The study included 38 individuals (21 female, 17 male) with a confirmed diagnosis of FRDA. A group of 20 non-neurologically impaired individuals served as controls. Perceptual analysis, investigating 30 different dimensions of speech, was conducted on a speech sample obtained from each participant. In addition, the Assessment of Intelligibility of Dysarthria Speech was administered. All FRDA participants presented with dysarthria with severities ranging from mild to moderate. Cluster analysis revealed 3 subgroups, the first presenting with mild dysarthric symptoms, the second with increased velopharyngeal involvement and the third characterized by increased laryngeal dysfunction. Dysarthria severity showed a significant correlation to disease duration but to no other clinical measure. The findings support the notion of subgroups in FRDA dysarthria, representing distinct impairments of the speech mechanism and perhaps reflective of differing evolutions beyond the cerebellum.

Automatic method of pause measurement for normal and dysarthric speech.

This study proposes an automatic method for the detection of pauses and identification of pause types in conversational speech for the purpose of measuring the effects of Friedreich's Ataxia (FRDA) on speech. Speech samples of approximately 3 minutes were recorded from 13 speakers with FRDA and 18 healthy controls. Pauses were measured from the intensity contour and fit with bimodal lognormal distributions using the Expectation-Maximization algorithm in Matlab. In the speakers with FRDA, both modes in the pause distributions had significantly larger means, with disproportionately fewer pauses associated with the first mode. From this preliminary study, it is concluded that distributional analysis of pause duration holds promise as a useful method of measuring the effects of FRDA on functional speech.

Voice in Friedreich Ataxia.

BACKGROUND: Friedreich Ataxia (FRDA) is the most common hereditary ataxia, with dysarthria as one of its key clinical signs. OBJECTIVE: To describe the voice profile of individuals with FRDA to inform outcome marker development and goals of speech therapy. METHODS: Thirty-six individuals with FRDA and 30 age-matched controls provided sustained vowel and connected speech samples. Speech and voice samples were analyzed acoustically using the Analysis of Dysphonia in Speech and Voice program and perceptually using the Consensus Auditory-Perceptual Evaluation of Voice form. Correlations between dysphonia and overall dysarthria severity, demographic, clinical, and genetic information were explored. RESULTS: Individuals with FRDA presented with mild dysphonia characterized by hoarseness (combined roughness and breathiness), increased strain, and altered pitch variability (increased in vowel productions; slightly decreased on reading samples). Acoustically, individuals with FRDA had significantly higher scores on the Cepstral Spectral Index of Dysphonia during vowel production. A combination of perceptual and acoustic measures of dysphonia used in this study was quite effective in categorizing the FRDA versus control participants, with >80% overall accuracy. CONCLUSIONS: Although dysphonia severity in FRDA did not correlate significantly with overall disease severity, speaking rate and syllabic duration significantly correlated with age at disease onset and disease duration, and also have an effect on listener perception of dysphonia. The relationship between dysphonia and dysarthria in FRDA suggests that reducing overall dysphonia severity via therapeutic techniques that improve phonatory stability and increase speaking rate is a viable target for speech therapy.

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.

Longitudinal change in dysarthria associated with Friedreich ataxia: a potential clinical endpoint.

CNS functions that show change across short periods of time are particularly useful clinical endpoints for Friedreich ataxia. This study determined whether there is measurable acoustical change in the dysarthria associated with Friedreich ataxia across yearly intervals. A total of 29 participants diagnosed with Friedreich ataxia were recorded across 4 years at yearly intervals. A repeated measures ANOVA was used to determine which acoustic measures differed across time, and pairwise t tests were used to assess the consistency of the change across the time intervals. The relationship between the identified measures with perceptual severity was assessed with stepwise regression. Significant longitudinal change was observed with four measures that relate to the utterance duration and spectral changes in utterances. The spectral measures consistently detected change across time intervals of two or more years. The four measures combined moderately predicted perceptual severity. Together, the results implicate longitudinal change in speaking rate and utterance duration. Changes in speech associated with Friedreich ataxia can be measured across intervals of 2 years and therefore show rich potential for monitoring disease progression and therapy outcomes.

Articulatory kinematics in the dysarthria associated with Friedreich's ataxia.

Electromagnetic articulography (EMA) was used to investigate the tongue kinematics in the dysarthria associated with Friedreich's ataxia (FRDA). The subject group consisted of four individuals diagnosed with FRDA. Five nonneurologically impaired individuals, matched for age and gender, served as controls. Each participant was assessed using the AG-200 EMA system during six repetitions of the tongue tip sentence Tess told Dan to stay fit and the tongue back sentence Karl got a croaking frog. Results revealed reduced speed measures (i.e., maximum acceleration / deceleration / velocity), greater movement durations and increased articulatory distances for the approach phases of consonant productions. The approach phase, involving movement up to the palate, was more affected than the release phase. It is suggested that deviant lingual kinematics could be the outcome of disturbances to cerebellar function, or possibly in combination with disturbances to upper motor neuron systems.

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.

Measures of spectral change and their application to habitual, slow, and clear speaking modes.

Spectral measures are sensitive to dysarthric speech. However, it is unclear whether the spectral differences in dysarthric and healthy speech are due to slow articulation rate or reflect other qualitative changes in speech. Spectral measures were used to detect differences between habitual, slow, and "clear" speaking modes in 12 healthy speakers. Matched t-tests were used to determine differences in the rate and degree of spectral change between the speaking modes. Pearson's correlation coefficients were calculated to assess how well rate of spectral change predicts articulation rate (syllables per second). Clear speech had a significantly higher degree of spectral change than habitual speech, and slow speech had a significantly slower rate of spectral change than habitual and clear speaking modes. These differences occurred in all 12 speakers. The rate of spectral change was correlated with articulation rate across all speakers (range of r = .8-.9 within individual speaking modes) and therefore is a gross predictor of articulation rate. These results suggest that measures of the degree and rate of spectral change together can be used to detect changes between clear, slow, and habitual speaking modes, and hold potential as performance measures.

Differentiating impairment levels in temporal versus spatial aspects of linguopalatal contacts in Friedreich's ataxia.

Electropalatography (EPG) was used to describe the pattern of linguopalatal contact and the consonant phase durations exhibited by a group of seven individuals with dysarthria associated with Friedreich's ataxia (FRDA). A group of 14 non-neurologically impaired individuals served as controls. The Reading Electropalatograph (EPG3) system was used to record linguopalatal contact during production of the target consonants (/t/, /l/, /s/, /k/) elicited in five words of CV and CVC construction, with the target consonants in word initial position. These words were embedded into short sentences and repeated five times by each participant. The FRDA group exhibited significantly increased consonant durations compared with the controls while maintaining normal linguopalatal contact patterns. These findings suggest that the articulatory impairment in FRDA manifests as a temporal rather than spatial disturbance.