Neuromotor microalterations in subjects with spasmophilia symptoms: a preliminary study.

Spasmophilia is a relatively unknown condition characterized by perturbations of the neuromuscular system. We hypothesized that spasmophilia may negatively affect neuromotor functions in subtle ways. Three tests including tremor, rapid pointing movements, and alternating movements were quantified in a group of subjects with spasmophilia symptoms (SS) (n = 10) and a healthy control group (n = 10). Most of the characteristics used to evaluate motor functions in these three tests revealed no significant differences between the two groups except for two characteristics in alternating movements and two characteristics in rapid pointing movements. In terms of variances, a dissociation between voluntary movements and involuntary movements was observed for the two groups. Control subjects had significantly higher variances in involuntary movements such as tremor, while subjects with SS had significantly higher variances in voluntary movements such as alternating and rapid pointing movements. A significant increase in asymmetry in hand laterality was also noted for some characteristics in subjects with SS.

Manganese neurotoxicity, a continuum of dysfunction: results from a community based study.

Excessive manganese (Mn) has been associated with neurobehavioral deficits and neurological and/or neuropsychiatric illness, but the level at which this metal can cause adverse neurotoxic effects, particularly with long-term exposure, is still unknown. The objective of the present study was to assess nervous system functions in residents exposed to manganese from a variety of environmental sources. A random stratified sampling procedure was used to select participants; persons with a history of workplace exposure to Mn and other neurotoxic substances were excluded. A self-administered questionnaire provided data on socio-demographic variables. Blood samples were analyzed for total manganese (MnB), lead, mercury and serum iron. Nervous system assessment included computer and hand-administered neurobehavioral tests, computerized neuromotor tests, sensory evaluation and a neurological examination. The present analyses include 273 persons (151 women and 122 men); MnB range: 2.5 micrograms/L-15.9 micrograms/L (median: 7.3 micrograms/L). Multivariate analyses were used and neuro-outcomes were examined with respect to MnB, taking into account potential confounders and covariables. Results were grouped according to neurofunctional areas and MANOVA analyses revealed that higher MnB (7.5 micrograms/L) was significantly associated with changes in coordinated upper limb movements (Wilks' lambda = 0.92; p = 0.04) and poorer learning and recall (men: Wilks' lambda = 0.77; p = 0.002; women: Wilks' lambda = 0.86; p = 0.04). Further analyses revealed that with increasing log MnB (Simple regression: p < 0.05) performance on a pointing task was poorer, frequency dispersion of hand-arm tremor decreased, while harmonic index increased, and the velocity of a pronation/supination arm movement was slower. An Mn-age interaction was observed for certain motor tasks, with the poorest performance observed among those _50 y and in the higher MnB category. Differences between genders suggest that men may be at greater risk than women, although effects were also observed in women. These findings are consistent with the hypothesis that Mn neurotoxicity can be viewed on a continuum of dysfunction, with early, subtle changes at lower exposure levels.

Quantitative analysis of rapid pointing movements in Cree subjects exposed to mercury and in subjects with neurological deficits.

To quantify rapid and precise proximo-distal movements, we have developed a simple system (eurythmokinesimeter or EKM) which requires the subject to touch alternately the center of proximal and distal targets with a stylus. Ninety-six participants, including 30 controls subjects, 36 Cree subjects exposed to mercury, 21 subjects with Parkinson disease, 6 with presumed cerebellar deficit, and 3 with essential tremor, participated in the study. A total of nine measures, including precision, imprecision, contact duration, unsureness, tremor, transit time, irregularity, speed, and Fitts' constant, were calculated. Test-retest reliability was above 0.8 for most measures and above 0.9 for many measures. Correlations between measures and number of outliers with respect to the control group distribution for each measure were used to reduce the set of measures to five (i.e., precision, imprecision, tremor, Fitts' constant, and irregularity). An ANOVA on the three largest groups generated significant results for tremor, Fitts' constant, and irregularity between the Cree and the control subjects and on Fitts' constant and irregularity between the subjects with Parkinson's disease and the control subjects. Three subgroups of the same mean age composed of six subjects each were selected. One was composed of Cree subjects with the highest level of mercury exposure, another with Cree subjects having a low level of mercury exposure, and a third with control subjects. An ANOVA on these three groups revealed a significant difference between both groups of Cree subjects and the control group for Fitts' constant and irregularity. These preliminary results suggest that the EKM system is able to discriminate the performance of different groups of subjects.

Analysis of rapid alternating movements in Cree subjects exposed to methylmercury and in subjects with neurological deficits.

To quantify rapid alternating movements (RAMs) we used a simple prototype developed in our laboratory that requires the subject to rotate two hand-held foam spheres connected to optical encoders via flexible rods. Ninety-six participants, including 30 control subjects, 36 Cree subjects exposed to methylmercury, 21 subjects with Parkinson's disease, 6 subjects with cerebellar deficits, and 3 subjects with essential tremor, were involved in the study (though data for 5 were later removed). Twelve characteristics were developed and calculated from the raw data. Conditions examined included two hands at natural cadence (NC2), right and left hands separately at fast cadence (FCl), and both hands at fast cadence (FC2). Two ratios (FC2/NC2) and (FC2/FC1) combining these conditions were also examined. Test-retest reliability was >0.80 for most characteristics but was <0.70 for some characteristics, especially in the conditions executed at normal cadence. Correlations between characteristics and numbers of outliers with respect to the control group distribution were used to reduce the set of characteristics from 12 to 7 (i.e., duration, range, maximum slope, similarity in shape, smoothness, sharpness, and coherence). ANOVAs on the three largest groups generated significant results for most characteristics in the three conditions and the two ratios for Cree subjects and subjects with Parkinson's disease. ANOVAs on 3 age-matched groups (n=6) suggest that methylmercury affects the performance of the Cree subjects with the higher exposure, especially in terms of smoothness, sharpness, and coherence. These preliminary results suggest that this test is sufficiently specific and sensitive to characterize the performance of different groups of subjects. Ratios tend to improve discrimination for Cree subjects in a few characteristics but not for patients with Parkinson's disease.

Can tremor be used to measure the effect of chronic mercury exposure in human subjects?

Clinical and quantitative studies in which tremor was used to evaluate the effect of chronic exposure to organic and inorganic mercury in human subjects during the last 20 years were identified in MEDLINE and BIOLOGICAL ABSTRACTS. In the selected studies, methods varied widely by types of transducers used, anatomical locations of tremor testing, tasks executed by the subjects, types of tremor recorded and durations of trials. Measurements of tremor in these studies also varied by frequency, amplitude, waveform and reproducibility. Typically measures of variability were not included. Results obtained depended heavily on the methods and analyses used. We suggest that, although many contradictions and discrepancies have been noted in these studies, tremor can probably be used to measure the effect of chronic mercury exposure. This would involve more rigorous and uniform recording procedures and analyses. Specific suggestions proposed include: realizing the limitations of accelerometric data; considering the effect of weight on the tested limb; controlling recording conditions; selecting samples more carefully; recording other physiological variables besides tremor; using tasks and manoeuvres that unmask subclinical abnormalities in tremor; reporting frequency, amplitude, waveform and variability of tremor; understanding the limitations of power spectra analysis; separating tremor characteristics according to types of mercury exposure; and considering supraspinal influences that both vision and voluntary movements have on tremor.

The measurement of tremor using simple laser systems.

Quantification of movement pathologies is an important challenge of the clinical and research laboratories today. Basically, two problems must be addressed. The first one is to find the appropriate technology; the second is to develop adequate measures from the raw data which will best discriminate between health and pathology. In this paper, we propose a simple method to record and analyse tremor and other microdisplacements of the upper extremities based on the recording of position by laser analog sensors. Any microcomputer equipped to perform analog-digital conversion is compatible for use with this system. The performance of the laser system is examined and compared with the performance of accelerometers. Finally, data recorded with a laser analog sensor from a patient with Parkinson's disease and a control subject are presented. This new laser-based quantitative method may prove to be an important tool in early and differential diagnosis of neurodegenerative diseases of the central nervous system.

Diadochokinesimetry: a study of patients with Parkinson's disease and manganese exposed workers.

Diadochokinesia, the ability to perform rapid alternating movements is often impaired in patients with extrapyramidal disease. It is a common sign among patients with Parkinsonism or manganism. In the present study we compare patients with Parkinson's disease (n = 11), workers formerly exposed to manganese (n = 10) and control subjects (n = 11) performing rapid alternating hand movements for 5 s under four conditions repeated twice (natural cadence and maximal speed with one or two hands). Data recorded using a diadochokinesimeter built in our laboratory and connected to a 486/33 microcomputer were digitized in real time while subjects rotated back and forth hand held foam spheres connected to flexible rods articulated with optical encoders. Significant differences were found between control subjects and patients with Parkinson's disease, but not with manganese exposed workers, in most variables examined. However, trajectory length (a combination of movement amplitude and velocity) indicated that manganese exposed workers and patients with Parkinson's disease were significantly different from the controls in functional asymmetries between right and left hand. In addition, workers and patients tend to have marked differences between the performance of right and left hands. Improved quantitative measurement of rapid alternating movements may prove to be an important tool in early and differential diagnosis of Parkinson's disease and manganese exposure.