Jiří Klempíř

Variation of Selective Gray and White Matter Atrophy in Huntington's Disease

The relationship between the extent of local gray/white matter atrophy, genetic load, and clinical impairment was studied in Huntingtons disease (HD) by means of voxel‐based morphometry. T1‐weighted brain images from 33 patients (mean age 49.5, range 25–73 years) with HD duration of 1 to 15 years were analyzed by correlation of each voxel intensity with the number of CAG triplets and the UHDRS‐motor score (P < 0.001). The CAG number correlated inversely with gray matter intensity in the caudate nuclei and with white matter intensity in the both postcentral gyri and the right cerebellum. The UHDRS‐motor score correlated inversely with the atrophy of both caudates, right hippocampus, calcarine fissure, and with the white matter along the fourth and lateral ventricles. While atrophy of the caudate nucleus was related to a higher number of CAG triplets and higher UHDRS‐motor score, atrophy in other parts of the brain covaried with the two parameters differently: higher genetic load was associated with greater loss of cortical somatosensory projections and the worse UHDRS‐motor score was accompanied by increased atrophy of the internal capsule, lower brainstem, hippocampus, and visual cortex. According to our results, the genetic load in HD predicts partially the extent of selective gray/white brain matter atrophy, which is then reflected in the severity of motor impairment.

Acoustic assessment of voice and speech disorders in Parkinson's disease through quick vocal test.

The disorders of voice and speech in Parkinson’s disease (PD) result from involvements in several subsystems including respiration, phonation, articulation, and prosody. We investigated the feasibility of acoustic measures for the identification of voice and speech disorders in PD, using a quick vocal test consisting of sustained phonation, diadochokinetic task, and running speech. Various traditional and novel acoustic measurements have been designed in order to be gender independent, represent all speech subsystems, reduce the time required for voice investigation, and provide a reliable automated assessment in practice.

The Number of CAG Repeats Within the Normal Allele Does Not Influence the Age of Onset in Huntington's Disease

Huntingtons disease (HD) is caused by the expansion of the number of CAG repeats on the chromosome 4p16.3, which results in elongated glutamine tract of huntingtin. The purpose of this work was to examine the interaction between the normal and mutant alleles of this gene and their effect on the clinical onset of HD. We hypothesized that in patients with identical number of CAG repeats within the mutant allele, the age of onset of HD is influenced by the number of CAG repeats within the normal allele. We analyzed the relations between the number of CAG repeats within the normal and mutant alleles, the age at HD onset, and the character of initial symptoms in 468 patients with clinically expressed HD. Although the Cox regression coefficient of 0.15 was significant (P < 0.0001), the regression model explained only 28% of the variance of the age at onset related to the effect of the number of CAG repeats within normal allele. Within the groups of patients with the same number of CAG repeats of the mutant allele, number of CAG repeats of the normal allele was found uncorrelated to the age at onset. Furthermore, when analyzing subgroups of patients with the same allelic composition on both alleles, we failed to observe any correlation with the age at the onset. Our analysis gives no corroboration to the idea of a normal allele having a share in the modification of the age at HD onset. We believe that with the current state of knowledge it is not possible to devise a mathematical model for HD onset prediction because too many entirely unknown modifying factors are still involved.

Handedness does not predict side of onset of motor symptoms in Parkinson's disease

This study focused on the relationship between the asymmetry of initial motor symptoms of Parkinsons disease (PD) and premorbid handedness of patients. Structural equation modeling has been used for this purpose. The survey consisting of validated items measuring handedness and questions related to side of occurrence of initial symptoms was administered to 472 patients with PD [277 men, 195 women, mean age 66.5 (9.3), mean duration of the disease 10 (6.1) years]. The unidimensional model of handedness fits the data well (χ2 = 37.86, df = 20, P = 0.009, Root Mean Square Error of Approximation = 0.044, Comparative Fit Index = 1.00, Standardized Root Mean Square Residual = 0.042) and side of initial motor symptoms is not significantly related to the factor of handedness (r =0.11, SE = 0.07, P = 0.14). In contrast to several other studies, the results indicate that the side of first occurrence of PD signs cannot be predicted from premorbid handedness of patients.

Objective Acoustic Quantification of Phonatory Dysfunction in Huntington's Disease

Purpose Although speech motor changes are reported as a common sign of Huntington’s disease (HD), the most prominent signs of voice dysfunction remain unknown. The aim of the current study was to explore specific changes in phonatory function in subjects with HD. Method 34 subjects with HD and 34 age- and sex-matched healthy controls were examined. Participants performed sustained vowel phonation for subsequent analyses of airflow insufficiency, aperiodicity, irregular vibrations of vocal folds, signal perturbations, increased noise, and articulation deficiency. In total, 272 phonations were collected and 12 voice parameters were extracted. Subsequently, a predictive model was built to find the most salient patterns of voice disorders in HD. The results were also correlated with disease severity according to the Unified HD Rating Scale (UHDRS) motor score. Results Subjects with HD showed deterioration in all investigated phonatory functions. Irregular pitch fluctuations, sudden phonation interruption, increased noise, and misplacement of articulators were found to be most significant patterns of phonatory dysfunction in HD (p<0.001). The combination of these four dysphonia aspects contributed to the best classification performance of 94.1% (sensitivity: 95.1%; specificity: 93.2%) in the separation of HD patients from healthy participants. Our results further indicated stronger associations between sudden phonation interruption and voluntary components of the UHDRS (r = −0.48, p<0.01) and between misplacement of articulators and involuntary components of the UHDRS (r = 0.52, p<0.01). Conclusions Our configuration of phonatory features can detect subtle voice abnormalities in subjects with HD. As impairment of phonatory function in HD was found to parallel increasing motor involvement, a qualitative description of voice dysfunction may be helpful to gain better insight into the pathophysiology of the vocal mechanism.

Correlation between Relaxometry and Diffusion Tensor Imaging in the Globus Pallidus of Huntington's Disease Patients

Huntingtons disease (HD) is an inherited neurodegenerative disorder with progressive impairment of motor, behavioral and cognitive functions. The clinical features of HD are closely related to the degeneration of the basal ganglia, predominantly the striatum. The main striatal output structure, the globus pallidus, strongly accumulates metalloprotein-bound iron, which was recently shown to influence the diffusion tensor scalar values. To test the hypothesis that this effect dominates in the iron-rich basal ganglia of HD patients, we examined the globus pallidus using DTI and T2 relaxometry sequences. Quantitative magnetic resonance (MR), clinical and genetic data (number of CAG repeats) were obtained from 14 HD patients. MR parameters such as the T2 relaxation rate (RR), fractional anisotropy (FA) and mean diffusivity (MD) were analysed. A positive correlation was found between RR and FA (R2=0.84), between CAG and RR (R2=0.59) and between CAG and FA (R2=0.44). A negative correlation was observed between RR and MD (R2=0.66). A trend towards correlation between CAG and MD was noted. No correlation between MR and clinical parameters was found. Our results indicate that especially magnetic resonance FA measurements in the globus pallidus of HD patients may be strongly affected by metalloprotein-bound iron accumulation.

Hypernasality associated with basal ganglia dysfunction: evidence from Parkinson’s disease and Huntington’s disease

Background Although increased nasality can originate from basal ganglia dysfunction, data regarding hypernasality in Parkinson’s disease (PD) and Huntington’s disease (HD) are very sparse. The aim of the current study was to analyze acoustic and perceptual correlates of velopharyngeal seal closure in 37 PD and 37 HD participants in comparison to 37 healthy control speakers. Methods Acoustical analysis was based on sustained phonation of the vowel /i/ and perceptual analysis was based on monologue. Perceptual analysis was performed by 10 raters using The Great Ormond Street Speech Assessment ’98. Acoustic parameters related to changes in a 1/3-octave band centered on 1 kHz were proposed to reflect nasality level and behavior through utterance. Results Perceptual analysis showed the occurrence of mild to moderate hypernasality in 65% of PD, 89% of HD and 22% of control speakers. Based on acoustic analyses, 27% of PD, 54% of HD and 19% of control speakers showed an increased occurrence of hypernasality. In addition, 78% of HD patients demonstrated a high occurrence of intermittent hypernasality. Further results indicated relationships between the acoustic parameter representing fluctuation of nasality and perceptual assessment (r = 0.51, p < 0.001) as well as the Unified Huntington Disease Rating Scale chorea composite subscore (r = 0.42, p = 0.01). Conclusions In conclusion the acoustic assessment showed that abnormal nasality was not a common feature of PD, whereas patients with HD manifested intermittent hypernasality associated with chorea.

Changes of hand preference in Parkinson’s disease

This study focused on the difference between pre-morbid and current hand preference of patients with Parkinson’s disease (PD). A survey instrument comprised items measuring pre-morbid and current hand preference and question related to the side of occurrence of initial symptoms. These questions were administered to 471 PD patients. The results show a significant change of pre-morbid right hand preference toward using the left when the side of PD onset was on the right hand and vice versa. Disease duration does not predict the amount of hand preference shift.

Gait and balance impairment after acute methanol poisoning

Neurological sequelae including gait impairment were reported in survivors after methanol intoxication; however, no systematic study has been published so far. We aimed to analyse gait and balance impairment in a group of Czech methanol poisoning survivors. We examined 43 patients (age 46 ± 13 years) 2–8 months after methanol poisoning and 43 healthy controls. Investigations contained a shortened version of Falls Efficacy Scale (FES), clinical tests of gait and balance including Timed Up and Go test (TUG) and gait analysis using GaitRite® system, neurological and neuropsychological examination, brain imaging, EMG and tests of alcohol consumption. Nineteen patients admitted balance and gait impairment according to FES. Mild to moderate parkinsonian signs showed seven patients. Patients were slower (8.8 versus 5.7 s, p < 0.001) and performed more steps (11.1 versus 7.9, p < 0.001) in TUG compared with the controls. Gait analysis revealed shorter step length (76.5 versus 88.7 cm, p < 0.001), increased double support phase (18.8 versus 15.5%, p < 0.001) and wider base of support (11.3 versus 9.6 cm, p = 0.006) in patients. Eleven patients had deficit of executive function and performed higher cadence compared to the patients with normal execution (122.7 versus 115.0 step/min., p = 0.025). Lower limb polyneuropathy was verified in nine patients, without relation with gait or balance parameters. Neuroimaging revealed lesions mainly in the basal ganglia. Methanol poisoning survivors presented slower wide‐based gait with shortened steps corresponding with frontal gait disorder. Higher stepping cadence associated with executive deficit supported the evidence of frontal lobe dysfunction related to impairment of basal ganglia and connections in frontal cortico‐basal ganglia loops.

GABA spectra and remote distractor effect in progressive supranuclear palsy: A pilot study

Disturbances of the gamma-aminobutyric-acid (GABA) system have been suspected of contributing to the pathophysiology of progressive supranuclear palsy (PSP). The ability to rapidly resolve competitive action decisions, such as shifting the gaze to one particular stimulus rather than another, can be predicted by the concentration of GABA in the region of the frontal cortex relevant to eye movements. For this reason, our study measured GABA levels in seven PSP patients and eight healthy controls, using proton magnetic resonance spectroscopy, and assessed the relationship of these measurements to the remote distractor effect (RDE), an eye-movement paradigm investigating competitive action decisions. No significant differences were found in either frontal-eye-field GABA levels or RDE between PSP patients and controls.