Broadened Friedreich's ataxia phenotype after gene cloning
M. RagnoGiovanna De MicheleFrancesca CavalcantiLuigi PianeseAntonella MonticelliL. CuratolaF. BollettiniSergio CocozzaGiuseppe CarusoLucio SantoroAlessandro Filla
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We describe three siblings from an Italian family affected by an autosomal recessive spinocerebellar degeneration. Gait ataxia, presenting between 38 and 45 years, was the first symptom in all three patients. Dysarthria, dysmetria, brisk tendon reflexes, extensor plantar response, and scoliosis were constant features. Disease progression was slow. Electrophysiologic studies demonstrated a slight reduction in sural nerve sensory action potential in only one patient. Analysis of GAA expansion within the X25 gene showed that patients were homozygous for the expansion, with the shorter expanded allele ranging from 120 to 156 triplets. The size of the GAA expansion may be smaller than we previously described. Such minimal expansions may result in atypical forms of Friedreich's ataxia.Keywords:
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Dysarthria
Intention tremor
Acoustic analysis was conducted to investigate symptomatic differences in decreased oral alternating motion rates (AMRs) between individuals with spastic and with ataxic dysarthria. The subjects were 6 individuals with spastic dysarthria, 6 with ataxic dysarthria and 6 normal speakers. Monosyllables /pa/ and /ta/ were used to examine alternating motions of the lips and tongue, respectively. In the decreased AMRs of the spastic group, the mean syllable durations were generally longer in the individuals where the mean total syllable durations were longer, and in the decreased AMRs of the ataxic group, the mean gap durations were generally longer in the individuals where the mean total syllable durations were longer. It was suggested that each syllable component could represent a separate function and contribute differently to the decreased AMRs in these dysarthric groups.
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Dysmetria ("wrong length") is a clinical sign that manifests in the upper extremity as the inability to alternatively touch another person's fingertip with one's own fingertip and then touch the tip of one's own nose. Although dysmetria can indicate cerebellar damage and is usually taken as a sign of such damage, lesions affecting other structures also can cause dysmetria. Recently we have treated a number of patients with unilateral thalamic lesions resulting from stroke who have no cerebellar damage but have exhibited the sign of dysmetria. For example, a 63-year-old patient with a history of hypertension presented with right-sided weakness and speech difficulties. Upon examination the patient had an ataxic gait, 4+/5 weakness on the right side (normal 5/5 strength on the left side), right arm dysmetria (Video 1), and mild right facial droop with normal sensation bilaterally. Findings of the remainder of the neurologic and general physical examination were normal. Magnetic resonance imaging (Figure 1) showed a left thalamic hemorrhage and no cerebellar lesions. With physical and occupational therapy the patient improved over 10 days from a moderate assistance level for ambulation (with a rolling walker) and activities of daily living to a supervision level for these activities. The right arm dysmetria and gait ataxia improved concomitantly. A T1-weighted magnetic resonance imaging scan shows a left thalamic hemorrhage (arrowhead) with intraventricular extension without hydrocephalus. Patients with cerebellar dysmetria typically both start on an incorrect initial trajectory and cannot make the necessary correction 1. In contrast, our patient reaches more slowly with the affected right hand (Video 1) than with the unaffected left hand (Video 2), and while starting off on a grossly correct trajectory, fluid online guidance of the reaching finger seems to be lacking, requiring multiple subtle discrete corrections to arrive correctly at the target. Dysmetria has been noted to be part of a thalamic ataxia syndrome 2, although we are not aware of the availability of video of the thalamic dysmetria sign. This case illustrates the subtle but crucial—and still incompletely understood—role that the thalamus plays in motor control. Clinically it is important to appreciate that (1) dysmetria does not equate with cerebellar damage, (2) physical examination may be useful in parsing the lesion site, and (3) patients with dysmetria may have different rehabilitation issues, trajectories, and outcomes depending on the lesion site. Supplementary materials Video 1 Supplementary materials Video 2 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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This study compared orofacial muscle strength between normal and dysarthric speakers and across types of dysarthria, and examined correlations between strength and dysarthria severity. Participants included 79 speakers with flaccid, spastic, mixed spastic-flaccid, ataxic, or hypokinetic dysarthria and 33 healthy controls. Maximum pressure generation (Pmax) by the tongue, lips, and cheeks represented strength. Pmax was lower for speakers with mixed spastic-flaccid dysarthria for all tongue and lip measures, as well as for speakers with flaccid or spastic dysarthria for anterior tongue elevation and lip compression. Anterior tongue elevation and cheek compression tended to be lower than normal for the hypokinetic group. Pmax did not differ significantly between controls and speakers with ataxic dysarthria on any measure. Correlations were generally weak between dysarthria severity and orofacial weakness but were stronger in the dysarthria groups with more prominent orofacial weakness. The results generally support predictions that orofacial weakness accompanies flaccid and/or spastic dysarthria but not ataxic dysarthria. The findings support including type of dysarthria as a variable of interest when examining orofacial weakness in motor speech disorders.
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Abstract Using magnetic resonance imaging, we studied 6 patients with the dysarthria–clumsy hand syndrome. All were found to have pontine infarctions contralateral to the symptomatic side. Clinically, these patients exhibited dysarthria; “clumsiness,” characterized by dysmetria, dysrhythmia, dysdiadochokinesia and sometimes truncal and gait ataxia; and mild ipsilateral weakness. Previous clinical‐anatomical correlations for this syndrome are limited by inconsistencies in clinical diagnostic criteria and low‐resolution imaging methods. In our patients, and in a review of the literature, the overwhelming majority of patients with the dysarthria–clumsy hand syndrome had pontine infarcts. We conclude that if rigid clinical criteria are used, the label of the dysarthria–clumsy hand syndrome predicts a lesion in the contralateral basis pontis.
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This study aims to investigate acoustic change over time as biomarkers to differentiate among spastic-flaccid dysarthria associated with amyotrophic lateral sclerosis (ALS), spastic dysarthria associated with primary lateral sclerosis (PLS), flaccid dysarthria associated with spinal and bulbar muscular atrophy (SBMA), and to explore how these acoustic parameters are affected by dysarthria severity.Thirty-three ALS patients with mixed flaccid-spastic dysarthria, 17 PLS patients with pure spastic dysarthria, 18 SBMA patients with pure flaccid dysarthria, and 70 controls, all French speakers, were included in the study. Speakers produced vowel-glide sequences targeting different vocal tract shape changes. The mean and coefficient of variation of the total squared change of mel frequency cepstral coefficients were used to capture the degree and variability of acoustic changes linked to vocal tract modifications over time. Differences in duration of acoustic events were also measured.All pathological groups showed significantly less acoustic change compared to controls, reflecting less acoustic contrast in sequences. Spastic and mixed spastic-flaccid dysarthric speakers showed smaller acoustic changes and slower sequence production compared to flaccid dysarthria. For dysarthria subtypes associated with a spastic component, reduced degree of acoustic change was also associated with dysarthria severity.The acoustic parameters partially differentiated among the dysarthria subtypes in relation to motor neuron diseases. While similar acoustic patterns were found in spastic-flaccid and spastic dysarthria, crucial differences were found between these two subtypes relating to variability. The acoustic patterns were much more variable in ALS. This method forms a promising clinical tool as a diagnostic marker of articulatory impairment, even at mild stage of dysarthria progression in all subtypes.
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Symptomatic tremors are labeled in the literature under different names including rubral tremor, midbrain tremor, thalamic tremor, myorhythmia, Holmes' tremor, cerebellar tremor, and goal-directed tremor. The most common tremor is a delayed-onset postural and action tremor with a low frequency of 3 Hz and a proximal distribution. Resting irregular tremor is sometimes present. Mild cerebellar dysmetria is often detected. The lesions are mainly located in the thalamus, the brain stem, and the cerebellum, with secondary interruption and degeneration of various pathways and olivary hypertrophy. The more consistent lesions are found in the cerebello-thalamocortical and dentato-rubro-olivary pathways. The role of superimposed dysfunction of the nigrostriatal system may account for the rest component. The role of the basal ganglia in the emergence and control of tremor is poorly understood.
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Chief, Audiology/Speech Pathology, Long Beach VA Medical Center, Long Beach, California, Clinical Faculty Member, Department of ENT/Head-Neck Surgery, University of California, Irvine, Irvine, California
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Diseases affecting the cerebellum typically cause ataxia, coupled with dysmetria and tremor. Dysmetria is a condition in which there is improper measuring of distance in muscular acts; hypermetria is overreaching (overstepping) and hypometria is underreaching (understepping). Tremor refers to an involuntary, rhythmic, oscillatory movement of a body part. The tremor of cerebellar disease typically is exaggerated by goal-oriented movements (intention tremor). Cerebellar lesions also often cause loss of the menace response, despite the presence of normal vision. The anatomic basis for this phenomenon is obscure. The principal disease affecting the cerebellum in cats is cerebellar hypoplasia due to in utero infection with the panleukopenia virus. This disease will be discussed here. Neurologic signs of cerebellar involvement also may be seen in association with those diseases that affect the CNS multifocally. In these cats, there may be additional signs indicating involvement of other anatomic areas or the cerebellar deficits may occur alone (see discussion of multifocal diseases in Multiple Neurologic Deficits: Inflammatory Diseases [page 426] and Multiple Neurologic Deficits: Noninfectious Diseases [page 440]).
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Dysarthrias are speech disorders that result from neurological impairments associated with weakness,slowness,or incoordination of the musculature used to produce speech.According to the lesion sites and the severity of the speech impairments,it is identified 6 types of dysarthria:spastic,flaccid,mixed spastic-flaccid,ataxic,hypokinetic,and hyperkinetic.And spastic is the most common.The incidence of dysarthria in cerebrovascular disease is 30%～40%.There are many researches and data on this speech disorder abroad.But because of different language,most of the data is not appropriate to Chinese.
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Diadochokinetic Syllable Rate and Regularity in Normal and in Spastic and Ataxic Dysarthric Subjects
Rate and regularity of diadochokinetic syllable repetitions of /pΛ/, /tΛ/, and /kΛ/ in 30 normal subjects, 30 subjects with spastic dysarthria, and 30 subjects with ataxic dysarthria were measured by computer. Normal subjects had rates (syllables per second) of 6.4, 6.1, and 5.7; spastic dysarthric subjects, 4.6, 4.2, and 3.5; and ataxic dysarthric subjects, 3.8, 3.9, and 3.4 for /pΛ/, /tΛ/, and /kΛ/, respectively. Spastic and ataxic subjects were significantly slower and more variable than normal subjects and ataxic subjects were significantly more variable than spastic subjects. The significantly slower than normal rate of repetition in the ataxic subjects and the significantly more variable than normal rhythm of repetition in the spastic subjects were unexpected findings and are in contrast with results from perceptually based investigations of dysarthria. The study demonstrates that slowness of syllable repetition is not restricted to spastic dysarthria and that dysrhythmia of syllable repetition is not restricted to ataxic dysarthria, thus suggesting the need for additional quantitative measurements of acoustic features on which certain notions about the dysarthrias are currently based.
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