Autosomal dominant cerebellar ataxias: a systematic review of clinical features.

BACKGROUND AND PURPOSE: To assess, through systematic review, distinctive or common clinical signs of autosomal dominant cerebellar ataxias (ADCAs), also referred to as spinocerebellar ataxias (SCAs) in genetic nomenclature. METHODS: This was a structured search of electronic databases up to September 2012 conducted by two independent reviewers. Publications containing proportions or descriptions of ADCA clinical features written in several languages were selected. Gray literature was included and a back-search was conducted of retrieved publication reference lists. Initial selection was based on title and abstract screening, followed by full-text reading of potentially relevant publications. Clinical findings and demographic data from genetically confirmed patients were extracted. Data were analyzed using the chi-squared test and controlled for alpha-error inflation by applying the Holms step-down procedure. RESULTS: In all, 1062 publications reviewing 12 141 patients (52% male) from 30 SCAs were analyzed. Mean age at onset was 35 ± 11 years. Onset symptoms in 3945 patients revealed gait ataxia as the most frequent sign (68%), whereas overall non-ataxia symptom frequency was 50%. Some ADCAs often presented non-ataxia symptoms at onset, such as SCA7 (visual impairment), SCA14 (myoclonus) and SCA17 (parkinsonism). Therefore a categorization into two groups was established: pure ataxia and mainly non-ataxia forms. During overall disease course, dysarthria (90%) and saccadic eye movement alterations (69%) were the most prevalent non-ataxia findings. Some ADCAs were clinically restricted to cerebellar dysfunction, whilst others presented additional features. CONCLUSIONS: Autosomal dominant cerebellar ataxias encompass a broad spectrum of clinical features with high prevalence of non-ataxia symptoms. Certain features distinguish different genetic subtypes. A new algorithm for ADCA classification at disease onset is proposed.

Kinematic evaluation of gestural and repetitive single joint movements of the arm after posteroventral pallidotomy, subthalamotomy or both procedures combined in two Parkinson's disease patients: two case studies.

Two patients with severe Parkinson's disease undergoing partial or complete ablative interruption of basal ganglia (BG) output are presented. One patient who underwent bilateral subthalamotomy, and a second who underwent unilateral posteroventral pallidotomy, followed 7 years later by a bilateral subthalamotomy because of contralateral disease progression, were studied. In addition to the usual clinical evaluation, changes in joint kinematics observed during unconstrained, skilled multi-joint movement and repetitive single joint (RSJ) movement of the wrist were studied. Clinical UPDRS items referred to hand movements contralateral to the procedure, and instrumental measurement of RSJ improved in both patients after either pallidotomy or subthalamotomy. When both BG outflow paths were interrupted as was the case in the second patient (bilateral subthalamotomy after the initial pallidotomy), no added clinical improvement was observed, RSJ even deteriorated slightly. Instrument-based studies for movement alteration detection after simultaneous ablation of the globus pallidus and the subthalamic nucleus of these two patients showed greater sensitivity than clinical evaluation alone. Complex gestural movement performance remained unaffected after partial (subthalamotomy or pallidotomy) or complete interruption of BG outflow (case 2), indicating BG compensatory capacity after total outflow interruption remained intact.

Disruption of spatial organization and interjoint coordination in Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy.

Patients with basal ganglia diseases may exhibit ideomotor apraxia. To define the nature of the impairment of the action production system, we studied a repetitive gesture of slicing bread by three-dimensional computergraphic analysis in eight nondemented patients with Parkinson's disease in the "on" state, five with progressive supranuclear palsy and four with multiple system atrophy. Two patients with Parkinson's disease and two with progressive supranuclear palsy showed ideomotor apraxia for transitive movements on standard testing. A Selspott II system was used for kinematic analysis of wrist trajectories and angular motions of the shoulder and elbow joints. Patients with Parkinson's disease, progressive supranuclear palsy, and even some with multiple system atrophy exhibited kinematic deficits in the spatial precision of movement and velocity-curvature relationships; in addition, they failed to maintain proper angle/angle relationships and to apportion their relative joint amplitudes normally. Spatial disruption of wrist trajectories was more severe in patients with ideomotor apraxia. We posit that the basal ganglia are part of the parallel parieto-frontal circuits devoted to sensorimotor integration for object-oriented behavior. The severity and characteristics of spatial abnormalities of a transitive movement would therefore depend on the location and distribution of the pathologic process within these circuits.

GPi firing rate modification during beginning-of-dose motor deterioration following acute administration of apomorphine.

We present a patient with clinically evident beginning-of-dose motor deterioration who had undergone posteroventral pallidotomy. This patient underwent an intrasurgical apomorphine test followed by single cell recording of the internal globus pallidus (GPi) to determine changes in GPi firing rate during the occurrence of such phenomenon. A significant increase in GPi firing rate coincident with worsening of patient disabilities prior to improvement was found. This finding suggests that beginning-of-dose motor deterioration may be mediated by enhanced thalamic inhibition.

Apomorphine induces changes in GPi spontaneous outflow in patients with Parkinson's disease.

OBJECTIVE: To determine the effect of a single dose of apomorphine on internal globus pallidus (GPi) neuronal discharge in patients with Parkinson's disease (PD). PATIENTS AND METHODS: Nine PD patients who underwent microelectrode-guided posteroventral pallidotomy (PVP) were studied. After identification of a single GPi unit discharge with sufficient spike S/N ratio to allow reliable thresholding, basal recording was followed by a single 3-mg subcutaneous injection. One-minute samples were recorded 10', 30', and 60' after apomorphine. RESULTS: In four patients, recording was lost after 5-10 minutes. In two, changes were observed at peak-of-dose but recording was then lost, whereas three completed recording and returned to baseline, all five showing significant reduction in GPi firing rate (mean +/- standard deviation for basal and post-apomorphine were 143+/-55.6 and 52+/-19.2, respectively; p <0.002). CONCLUSION: In patients with PD, apomorphine induces changes in GPi spontaneous discharge and modifies firing rates resembling recordings in normal primates. These findings show that clinical improvement as well as induction of dyskinesias following DA administration could be mediated by reduction of GPi outflow.

Movement quality of repetitive self-paced single joint rapid arm movements on Parkinson's disease: acute effect of 1-dopa.

Most studies on single-joint ballistic movements in PD have reported smaller differences between ON and OFF states than those exhibited when PD patients are compared with normal controls. We developed a mathematical model (quality of movement coefficient, QMC), which represents a combination of the diverse kinematic variables applicable to repetitive ballistic movements and depicting the differences between normal subjects and PD patients as well as disclosing changes induced by 1-dopa. Seven patients were evaluated in ON and OFF states. An optoelectronic system (SELSPOT II) was used to digitize movement trajectories. Patients were instructed to repetitively flex and extend the forearms maximizing speed during 20 s. Seven normal controls were also evaluated. Significant differences were found in the QMC between ON and OFF states (ANOVA p < 0.0 1) and between patients and normal controls (ANOVA p < 0.04). Moreover, QMC significantly correlated with UPDRS motor score in both ON and OFF states [R2 F(1,5) = 12.06; p < 0.01]. In conclusion, we found that QMC seems to be a sensitive indicator of Parkinsonian disabilities as well as of 1-dopa effect.