Quantitative brain morphometry identifies cerebellar, cortical, and subcortical gray and white matter atrophy in late-onset Tay-Sachs disease.

Cerebellar atrophy is a characteristic sign of late-onset Tay-Sachs disease (LOTS). Other structural neuroimaging abnormalities are inconsistently reported. Our study aimed to perform a detailed whole-brain analysis and quantitatively characterize morphometric changes in LOTS patients. Fourteen patients (8 M/6F) with LOTS from three centers were included in this retrospective study. For morphometric brain analyses, we used deformation-based morphometry, voxel-based morphometry, surface-based morphometry, and spatially unbiased cerebellar atlas template. The quantitative whole-brain morphometric analysis confirmed the finding of profound pontocerebellar atrophy with most affected cerebellar lobules V and VI in LOTS patients. Additionally, the atrophy of structures mainly involved in motor control, including bilateral ventral and lateral thalamic nuclei, primary motor and sensory cortex, supplementary motor area, and white matter regions containing corticospinal tract, was present. The atrophy of the right amygdala, hippocampus, and regions of occipital, parietal and temporal white matter was also observed in LOTS patients in contrast with controls (p < 0.05, FWE corrected). Patients with dysarthria and those initially presenting with ataxia had more severe cerebellar atrophy. Our results show predominant impairment of cerebellar regions responsible for speech and hand motor function in LOTS patients. Widespread morphological changes of motor cortical and subcortical regions and tracts in white matter indicate abnormalities in central motor circuits likely coresponsible for impaired speech and motor function.

The impact of expiratory muscle strength training on voluntary cough effectiveness in Huntington's disease.

BACKGROUND AND PURPOSE: Dysfunction of the airway defence system in Huntington's disease (HD) is a significant but often overlooked problem. Although expiratory muscle strength training (EMST) is frequently utilized in cough effectiveness treatment, its specific impact in HD patients has not yet been explored. This study investigated the effects of EMST on voluntary peak cough flow (vPCF) in HD patients and evaluated the retention of potential gains post-intervention. METHODS: In this prospective case-controlled trial, 29 HD patients completed an 8-week wait-to-start period, which served to identify the natural development of expiratory muscle strength and vPCF. This was followed by 8 weeks of EMST training and an additional 8 weeks of follow-up. The study's outcome parameters, vPCF and maximum expiratory pressure (MEP), were measured against those of age- and sex-matched healthy controls. RESULTS: Huntington's disease patients had significantly lower MEP (p < 0.001) and vPCF (p = 0.012) compared to healthy controls at baseline. Following the EMST, significant improvements in MEP (d = 1.39, p < 0.001) and vPCF (d = 0.77, p = 0.001) were observed, with HD patients reaching the cough performance levels of healthy subjects. However, these gains diminished during the follow-up, with a significant decline in vPCF (d = -0.451, p = 0.03) and in MEP (d = -0.71; p = 0.002). CONCLUSIONS: Expiratory muscle strength training improves expiratory muscle strength and voluntary cough effectiveness in HD patients, but an ongoing maintenance programme is necessary to sustain the improvements.

Speech biomarkers in Huntington's disease: A cross-sectional study in pre-symptomatic, prodromal and early manifest stages.

BACKGROUND AND PURPOSE: Motor speech alterations are a prominent feature of clinically manifest Huntington's disease (HD). Objective acoustic analysis of speech can quantify speech alterations. It is currently unknown, however, at what stage of HD speech alterations can be reliably detected. We aimed to explore the patterns and extent of speech alterations using objective acoustic analysis in HD and to assess correlations with both rater-assessed phenotypical features and biological determinants of HD. METHODS: Speech samples were acquired from 44 premanifest (29 pre-symptomatic and 15 prodromal) and 25 manifest HD gene expansion carriers, and 25 matched healthy controls. A quantitative automated acoustic analysis of 10 speech dimensions was performed. RESULTS: Automated speech analysis allowed us to differentiate between participants with HD and controls, with areas under the curve of 0.74 for pre-symptomatic, 0.92 for prodromal, and 0.97 for manifest stages. In addition to irregular alternating motion rates and prolonged pauses seen only in manifest HD, both prodromal and manifest HD displayed slowed articulation rate, slowed alternating motion rates, increased loudness variability, and unstable steady-state position of articulators. In participants with premanifest HD, speech alteration severity was associated with cognitive slowing (r = -0.52, p < 0.001) and the extent of bradykinesia (r = 0.43, p = 0.004). Speech alterations correlated with a measure of exposure to mutant gene products (CAG-age-product score; r = 0.60, p < 0.001). CONCLUSION: Speech abnormalities in HD are associated with other motor and cognitive deficits and are measurable already in premanifest stages of HD. Therefore, automated speech analysis might represent a quantitative HD biomarker with potential for assessing disease progression.

Could hyperlipidemia be a risk factor for corticobasal syndrome? - a pilot study.

INTRODUCTION: Corticobasal syndrome (CBS) is a specific clinical manifestation shared by multiple pathologies. The exact mechanism of this phenomenon remains unclear. Differential diagnosis of CBS in everyday clinical practice is challenging, as this syndrome can overlap with other entities, especially progressive supranuclear palsy Richardson-Steele phenotype (PSP-RS). Several papers have suggested a possible role of vascular pathology as a linking factor in the pathogenesis of CBS based on different neuropathologies. This paper analyses differences in the occurrence of the most common vascular risk factors such as hypertension and lipid profile with respect to dietary habits among patients who fulfill the diagnostic criteria for probable/possible CBS and PSP-RS. MATERIAL AND METHODS: Seventy (70) patients in total were included in the study. Exclusion criteria comprised hydrocephalus, stroke in the past, the presence of marked vascular changes in white matter defined as the presence of vascular change ≥ 1 mm in 3T MRI, medical history of hyperlipidemia or the use of drugs that could impact upon lipid metabolism before the initiation of the neurodegenerative disease, and neoplastic focuses in the central nervous system. Patients with diabetes, or with BMI exceeding 18-25, or who were smokers, or who were affected by chronic stress were also excluded. Data was analysed statistically using the Shapiro-Wilk test, the U Mann-Whitney test for group comparison, and a Bonferroni correction to control the false discovery rate (FDR). RESULTS: Our obtained results indicated a statistically significantly higher level of total cholesterol in the CBS group (p = 0.0039) without a correlation with dietary habits. CONCLUSIONS AND CLINICAL IMPLICATIONS: The results obtained in our study may suggest a possible role of vascular pathology in CBS development. This issue requires further research.

Mitochondrial organization and structure are compromised in fibroblasts from patients with Huntington's disease.

Huntington´s disease (HD) is a progressive neurodegenerative disease with onset in adulthood that leads to a complete disability and death in approximately 20 years after onset of symptoms. HD is caused by an expansion of a CAG triplet in the gene for huntingtin. Although the disease causes most damage to striatal neurons, other parts of the nervous system and many peripheral tissues are also markedly affected. Besides huntingtin malfunction, mitochondrial impairment has been previously described as an important player in HD. This study focuses on mitochondrial structure and function in cultivated skin fibroblasts from 10 HD patients to demonstrate mitochondrial impairment in extra-neuronal tissue. Mitochondrial structure, mitochondrial fission, and cristae organization were significantly disrupted and signs of elevated apoptosis were found. In accordance with structural changes, we also found indicators of functional alteration of mitochondria. Mitochondrial disturbances presented in fibroblasts from HD patients confirm that the energy metabolism damage in HD is not localized only to the central nervous system, but also may play role in the pathogenesis of HD in peripheral tissues. Skin fibroblasts can thus serve as a suitable cellular model to make insight into HD pathobiochemical processes and for the identification of possible targets for new therapies.

Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington's Disease and Human Blood Plasma.

(1) Background: Huntington's disease (HD) is rare incurable hereditary neurodegenerative disorder caused by CAG repeat expansion in the gene coding for the protein huntingtin (HTT). Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuronal cell death. Porcine models of HD are used in preclinical testing of currently emerging disease modifying therapies. Such therapies are aimed at reducing mHTT expression, postpone the disease onset, slow down the progression, and point out the need of biomarkers to monitor disease development and therapy efficacy. Recently, extracellular vesicles (EVs), particularly exosomes, gained attention as possible carriers of disease biomarkers. We aimed to characterize HTT and mHTT forms/fragments in blood plasma derived EVs in transgenic (TgHD) and knock-in (KI-HD) porcine models, as well as in HD patients' plasma. (2) Methods: Small EVs were isolated by ultracentrifugation and HTT forms were visualized by western blotting. (3) Results: The full length 360 kDa HTT co-isolated with EVs from both the pig model and HD patient plasma. In addition, a ~70 kDa mutant HTT fragment was specific for TgHD pigs. Elevated total huntingtin levels in EVs from plasma of HD groups compared to controls were observed in both pig models and HD patients, however only in TgHD were they significant (p = 0.02). (4) Conclusions: Our study represents a valuable initial step towards the characterization of EV content in the search for HD biomarkers.

Dysarthria enhancement mechanism under external clear speech instruction in Parkinson's disease, progressive supranuclear palsy and multiple system atrophy.

Clear speech refers to intentionally modifying conversational speech to maximise intelligibility. This study aimed to compare the speech behaviour of patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and Parkinson's disease (PD) under conversational and clear speech conditions to gain greater pathophysiological insight. A total of 68 participants including 17 PD, 17 MSA, 17 PSP and 17 healthy controls (HC) performed two readings of the same standardized passage. During the first reading, participants were instructed to read the text in an ordinary way, while during the second reading to read the text as clearly as possible. Acoustic analyses were based upon measurements of mean loudness, loudness variability, pitch variability, vowel articulation, articulation rate and speech severity. During clear speech production, PD patients were able to achieve improvements mainly in loudness (p < 0.05) and pitch variability (p < 0.001), leading to a reduction in overall speech severity (p < 0.001), whereas PSP and MSA patients were able to modulate only articulation rate (p < 0.05). Contrary to HC and PD groups, which slowed or maintained articulation rate, PSP and MSA groups employed a markedly faster articulation rate under the clear speech condition indicating an opposing approach to speech adaptation. Patients with atypical Parkinsonism showed a different strategy to intentionally improve their speech performance following a simple request to produce speech more clearly compared to PD, suggesting important therapeutic implications for speech rehabilitation management.

Methanol Poisoning as an Acute Toxicological Basal Ganglia Lesion Model: Evidence from Brain Volumetry and Cognition.

BACKGROUND: Acute methanol poisoning leads to optic neuropathy and necrotic lesions of basal ganglia (BG) and subcortical white matter. Survivors of methanol poisoning exhibit long-term executive and memory deficits. Associations between brain volumetry parameters and cognitive sequelae of methanol poisoning are not known. The aim of our study was to identify long-term associations between the cognitive performance of survivors of methanol poisoning and the volume of the brain structures that are selectively vulnerable to methanol. METHODS: We conducted a cross-sectional follow-up study on a sample of patients (n = 33, age 50 ± 14 years, 82% males) who survived acute methanol poisoning during methanol mass poisoning outbreak from September 2012 till January 2013 in the Czech Republic. A battery of neuropsychological tests and brain magnetic resonance imaging were included in the clinical examination protocol. Specific brain structures (putamen, globus pallidus, nucleus caudatus, and frontal white matter) were selected as regions of interest, and their volumes were estimated using the MorphoBox prototype software. RESULTS: In robust multiple regression models, sustained visual attention performance (as assessed by Trail Making Test and Prague Stroop Test) was positively associated with BG structures and frontal white matter volumes (Wald = 9.03 to 85.50, p < 0.01), sensitivity to interference (as assessed by Frontal Battery Assessment) was negatively associated with frontal white matter volume (Wald = 35.44 to 42.25, p < 0.001), and motor performance (as assessed by Finger Tapping Test) was positively associated with globus pallidus and frontal white matter volumes (Wald = 9.66 to 13.29, p < 0.01). CONCLUSIONS: Our results demonstrate that smaller volumes of elements of BG-thalamocortical circuitry, namely the BG and frontal white matter, relate to attention and motor performance in methanol poisoning from a long-term perspective. Disruption of those functional circuits may underlie specific cognitive deficits observed in methanol poisoning.

Effects of dopaminergic replacement therapy on motor speech disorders in Parkinson's disease: longitudinal follow-up study on previously untreated patients.

Although speech disorders represent an early and common manifestation of Parkinson's disease (PD), little is known about their progression and relationship to dopaminergic replacement therapy. The aim of the current study was to examine longitudinal motor speech changes after the initiation of pharmacotherapy in PD. Fifteen newly-diagnosed, untreated PD patients and ten healthy controls of comparable age were investigated. PD patients were tested before the introduction of antiparkinsonian therapy and then twice within the following 6 years. Quantitative acoustic analyses of seven key speech dimensions of hypokinetic dysarthria were performed. At baseline, PD patients showed significantly altered speech including imprecise consonants, monopitch, inappropriate silences, decreased quality of voice, slow alternating motion rates, imprecise vowels and monoloudness. At follow-up assessment, preservation or slight improvement of speech performance was objectively observed in two-thirds of PD patients within the first 3-6 years of dopaminergic treatment, primarily associated with the improvement of stop consonant articulation. The extent of speech improvement correlated with L-dopa equivalent dose (r = 0.66, p = 0.008) as well as with reduction in principal motor manifestations based on the Unified Parkinson's Disease Rating Scale (r = -0.61, p = 0.02), particularly reflecting treatment-related changes in bradykinesia but not in rigidity, tremor, or axial motor manifestations. While speech disorders are frequently present in drug-naive PD patients, they tend to improve or remain relatively stable after the initiation of dopaminergic treatment and appear to be related to the dopaminergic responsiveness of bradykinesia.

Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars.

BACKGROUND: Huntington's disease is induced by CAG expansion in a single gene coding the huntingtin protein. The mutated huntingtin (mtHtt) primarily causes degeneration of neurons in the brain, but it also affects peripheral tissues, including testes. OBJECTIVE: We studied sperm and testes of transgenic boars expressing the N-terminal region of human mtHtt. METHODS: In this study, measures of reproductive parameters and electron microscopy (EM) images of spermatozoa and testes of transgenic (TgHD) and wild-type (WT) boars of F1 (24-48 months old) and F2 (12-36 months old) generations were compared. In addition, immunofluorescence, immunohistochemistry, Western blot, hormonal analysis and whole-genome sequencing were done in order to elucidate the effects of mtHtt. RESULTS: Evidence for fertility failure of both TgHD generations was observed at the age of 13 months. Reproductive parameters declined and progressively worsened with age. EM revealed numerous pathological features in sperm tails and in testicular epithelium from 24- and 36-month-old TgHD boars. Moreover, immunohistochemistry confirmed significantly lower proliferation activity of spermatogonia in transgenic testes. mtHtt was highly expressed in spermatozoa and testes of TgHD boars and localized in all cells of seminiferous tubules. Levels of fertility-related hormones did not differ in TgHD and WT siblings. Genome analysis confirmed that insertion of the lentiviral construct did not interrupt any coding sequence in the pig genome. CONCLUSIONS: The sperm and testicular degeneration of TgHD boars is caused by gain-of-function of the highly expressed mtHtt.

Effect of dopaminergic medication on speech dysfluency in Parkinson's disease: a longitudinal study.

Although speech dysfluencies have been hypothesized to be associated with abnormal function of dopaminergic system, the effects of dopaminergic medication on speech fluency in Parkinson's disease (PD) have not been systematically studied. The aim of the present study was, therefore, to investigate the long-term effect of dopaminergic medication on speech fluency in PD. Fourteen de novo PD patients with no history of developmental stuttering and 14 age- and sex-matched healthy controls (HC) were recruited. PD subjects were examined three times; before the initiation of dopaminergic treatment and twice in following 6 years. The percentage of dysfluent words was calculated from reading passage and monolog. The amount of medication was expressed by cumulative doses of L-dopa equivalent. After 3-6 years of dopaminergic therapy, PD patients exhibited significantly more dysfluent events compared to healthy subjects as well as to their own speech performance before the introduction of dopaminergic therapy (p < 0.05). In addition, we found a strong positive correlation between the increased occurrence of dysfluent words and the total cumulative dose of L-dopa equivalent (r = 0.75, p = 0.002). Our findings indicate an adverse effect of prolonged dopaminergic therapy contributing to the development of stuttering-like dysfluencies in PD. These findings may have important implication in clinical practice, where speech fluency should be taken into account to optimize dopaminergic therapy.

Imaging findings after methanol intoxication (cohort of 46 patients).

OBJECTIVES: Our goal is to demonstrate the variability of imaging findings, primarily in the MRI, in 46 patients who survived acute methanol poisoning. This cohort of patients is the largest such sample group examined by MRI. METHODS: Patients were examined by means of imaging methods (42 patients by MRI and 4 by CT). All had an identical protocol of MR examination (T2WI, FLAIR, T1WI with or without application of contrast medium and T2WI/FFE, DWI in the transversal plane of the scan, and with focus on the optic nerves in the coronal plane of the scan in T2WI-SPIR). RESULTS: Imaging methods revealed a positive finding associated with methanol intoxication in 21 patients (46%). These consisted of symmetrical lesions in the putamen--13 patients (28%), haemorrhage--13 cases (28%), deposits in white matter with localization primarily subcortically--4 cases (9%), lesions in the region of the globus pallidus--7 cases (15%) (in 6 cases without combination with the lesions in the putamen), lesions in the brainstem afflicted 6 patients (13%), and lesion in the cerebellum was found in one case. A pathological finding was found only in the patients examined by MRI. CONCLUSION: Almost half of the patients who survived acute methanol poisoning had pathological findings by MRI. The most common finding concerned an affliction of the putamen, which is a predilection area. An interesting finding was the relatively frequent occurrence of selective lesion of the globus pallidus, which is more usually associated with other types of intoxication.

Characteristics and occurrence of speech impairment in Huntington's disease: possible influence of antipsychotic medication.

Although motor speech impairment is a common manifestation of Huntington's disease (HD), its description remains limited. The aim of the current study was therefore to estimate the occurrence and characteristics of speech disorder in HD and to explore the influence of antipsychotic medication on speech performance. Speech samples, including reading passage and monologue, were acquired from 40 individuals diagnosed with HD and 40 age- and sex-matched healthy controls. Objective acoustic analyses were used to evaluate key aspects of speech including vowel articulation, intensity, pitch and timing. A predictive model was constructed to detect the occurrence and most prominent patterns of speech dysfunction in HD. We revealed that 93% of HD patients manifest some degree of speech impairment. Decreased number of pauses, slower articulation rate, imprecise vowel articulation and excess intensity variations were found to be the most salient patterns of speech dysfunction in HD. We further demonstrated that antipsychotic medication may induce excessive loudness and pitch variations perceptually resembling excess patterns of word stress, and may also accentuate general problems with speech timing. Additionally, antipsychotics induced a slight improvement of vowel articulation. Specific speech alterations observed in HD patients indicate that speech production may reflect the pathophysiology of the disease as well as treatment effects, and may therefore be considered a valuable marker of functional disability in HD.

Development of the Huntington Support App (HD-eHelp study): a human-centered and co-design approach.

Introduction: eHealth seems promising in addressing challenges in the provision of care for Huntington's disease (HD) across Europe. By harnessing information and communication technologies, eHealth can partially relocate care from specialized centers to the patients' home, thereby increasing the availability and accessibility of specialty care services beyond regional borders. Previous research on eHealth (development) in HD is however limited, especially when it comes to including eHealth services specifically designed together with HD gene expansion carriers (HDGECs) and their partners to fit their needs and expectations. Methods: This article describes the qualitative human-centered design process and first evaluations of the Huntington Support App prototype: a web-app aimed to support the quality of life (QoL) of HDGECs and their partners in Europe. Prospective end-users, i.e., HDGECs, their partners, and healthcare providers (HCPs), from different countries were involved throughout the development process. Through interviews, we captured people's experiences with the disease, quality of life (QoL), and eHealth. We translated their stories into design directions that were further co-designed and subsequently evaluated with the user groups. Results: The resulting prototype centralizes clear and reliable information on the disease, HD-related news and events, as well as direct contact possibilities with HCPs via an online walk-in hour or by scheduling an appointment. The app's prototype was positively received and rated as (very) appealing, pleasant, easy to use and helpful by both HDGECs and partners. Discussion: By involving end-users in every step, we developed a healthcare app that meets relevant needs of individuals affected by HD and therefore may lead to high adoption and retention rates. As a result, the app provides low-threshold access to reliable information and specialized care for HD in Europe. A description of the Huntington Support App as well as implications for further development of the app's prototype are provided.

Spinocerebellar ataxias type 8, 12, and 17 and dentatorubro-pallidoluysian atrophy in Czech ataxic patients.

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders currently associated with 27 genes. The most frequent types are caused by expansions in coding CAG repeats. The frequency of SCA subtypes varies among populations. We examined the occurrence of rare SCAs, SCA8, SCA12, SCA17 and dentatorubro-pallidoluysian atrophy (DRPLA), in the Czech population from where the data were missing. We analyzed causal gene expansions in 515 familial and sporadic ataxic patients negatively tested for SCA1-3 and SCA6-7. Pathogenic SCA8 and SCA17 expansions were identified in eight and five patients, respectively. Tay-Sachs disease was later diagnosed in one patient with an SCA8 expansion and the diagnosis of multiple sclerosis (MS) was suspected in two other patients with SCA8 expansions. These findings are probably coincidental, although the participation of SCA8 expansions in the susceptibility to MS and disease progression cannot be fully excluded. None of the patients had pathogenic SCA12 or DRPLA expansions. However, three patients had intermediate SCA12 alleles out of the normal range with 36 and 43 CAGs. Amyotrophic lateral sclerosis (ALS) was probable in the patient with 43 CAGs. This coincidence is remarkable, especially in the context with the recently identified predisposing role of longer SCA2 alleles in ALS. Five families with SCA17 represent a significant portion of ataxic patients and this should be reflected in the diagnostics of SCAs in the Czech population. SCA8 expansions must be considered after careful clinical evaluation.

Evaluation of speech impairment in early stages of Parkinson's disease: a prospective study with the role of pharmacotherapy.

Despite the initial reports showing beneficial effects of dopaminergic treatment on speech in Parkinson's disease (PD), more recent studies based upon valid measurements have not approved any improvement of speech performance under pharmacotherapy. The aim of this study was to analyze the effect of treatment initiation on the progression of speech impairment in PD, using novel evaluation criteria. Nineteen de novo patients with PD were tested and retested within 2 years after the introduction of antiparkinsonian therapy. As controls, 19 age-matched individuals were recorded. Speech examination included sustained phonation, fast syllable repetition, reading text, and monolog. Quantitative acoustic analyses of the key aspects of speech based on Gaussian kernel distribution, statistical decision-making theory, and healthy speech observation were used to assess the improvement or deterioration of speech. A trend for speech performances to improve was demonstrated after treatment mainly in quality of voice, intensity variability, pitch variability, and articulation. The treatment-related improvement differed in various aspects of speech for individual PD patients. Improvements in vowel articulation and pitch variability correlated with treatment-related changes in bradykinesia and rigidity, whereas voice quality and loudness variability improved independently. Using a novel approach of acoustic analysis and advanced statistics, improvements in speech performance can be demonstrated in PD patients after the introduction of antiparkinsonian therapy. Moreover, changes in speech articulation and pitch variability appear to be related with dopaminergic responsiveness of bradykinesia and rigidity. Therefore, speech may be a valuable marker of disease progression and treatment efficacy in PD.

Imprecise vowel articulation as a potential early marker of Parkinson's disease: effect of speaking task.

The purpose of this study was to analyze vowel articulation across various speaking tasks in a group of 20 early Parkinson's disease (PD) individuals prior to pharmacotherapy. Vowels were extracted from sustained phonation, sentence repetition, reading passage, and monologue. Acoustic analysis was based upon measures of the first (F1) and second (F2) formant of the vowels /a/, /i/, and /u/, vowel space area (VSA), F2i/F2u and vowel articulation index (VAI). Parkinsonian speakers manifested abnormalities in vowel articulation across F2u, VSA, F2i/F2u, and VAI in all speaking tasks except sustained phonation, compared to 15 age-matched healthy control participants. Findings suggest that sustained phonation is an inappropriate task to investigate vowel articulation in early PD. In contrast, monologue was the most sensitive in differentiating between controls and PD patients, with classification accuracy up to 80%. Measurements of vowel articulation were able to capture even minor abnormalities in speech of PD patients with no perceptible dysarthria. In conclusion, impaired vowel articulation may be considered as a possible early marker of PD. A certain type of speaking task can exert significant influence on vowel articulation. Specifically, complex tasks such as monologue are more likely to elicit articulatory deficits in parkinsonian speech, compared to other speaking tasks.

Importance of psychiatric examination in predictive genetic testing for Huntington disease.

BACKGROUND AND PURPOSE: Huntington disease (HD) is an au-tosomal dominant hereditary neurodegenerative disease with multiplication of CAG triplet in the short arm of chromoso-me 4, manifested by motor symptoms, cognitive dysfunction progressing to dementia, and various types of neuropsychiat-ric disorders. The diagnosis of HD is confirmed by a gene-tic test, which may also be carried out presymptomatically. MATERIAL AND METHODS: We studied differences in psychiatric examination and psychometric measures among the 52 people at risk of HD, who were recommended to postpone or to continue in the predictive protocol. In addition to the psychiatric examination, we administered the Eysenck Personality Questionnaire (EPQ-A), the Symptom Checklist 90 (SCL-90), and quality of life questionnaire (MANSA). RESULTS: People at risk of HD with the recommended test postponement showed lower rate of neuroticism and EPQ-A lie score, higher values on the phobia and the so-called 'positive symptom distress index' in SCL-90 and lower quality of life than people at risk of HD with the recommendation to continue. CONCLUSIONS: Our results indicate that the formalized testing does not bring significant information whereas the clinical psychiatric examination remains the main decisive factor in the recommendation to perform a predictive genetic test. The motivation of applicants is considered as the most important factor in the decision-making process.

Coenzyme Q10: A Biomarker in the Differential Diagnosis of Parkinsonian Syndromes.

Multiple system atrophy (MSA) is generally a sporadic neurodegenerative disease which ranks among atypical Parkinson's syndromes. The main clinical manifestation is a combination of autonomic dysfunction and parkinsonism and/or cerebellar disability. The disease may resemble other Parkinsonian syndromes, such as Parkinson's disease (PD) or progressive supranuclear palsy (PSP), from which MSA could be hardly distinguishable during the first years of progression. Due to the lack of a reliable and easily accessible biomarker, the diagnosis is still based primarily on the clinical picture. Recently, reduced levels of coenzyme Q10 (CoQ10) were described in MSA in various tissues, including the central nervous system. The aim of our study was to verify whether the level of CoQ10 in plasma and lymphocytes could serve as an easily available diagnostic biomarker of MSA. The study reported significantly lower levels of CoQ10 in the lymphocytes of patients with MSA compared to patients with PD and controls. The reduction in CoQ10 levels in lymphocytes correlated with the increasing degree of clinical involvement of patients with MSA. CoQ10 levels in lymphocytes seem to be a potential biomarker of disease progression.

The Role of Micronutrients in Neurological Disorders.

Trace elements and vitamins, collectively known as micronutrients, are essential for basic metabolic reactions in the human body. Their deficiency or, on the contrary, an increased amount can lead to serious disorders. Research in recent years has shown that long-term abnormal levels of micronutrients may be involved in the etiopathogenesis of some neurological diseases. Acute and chronic alterations in micronutrient levels may cause other serious complications in neurological diseases. Our aim was to summarize the knowledge about micronutrients in relation to selected neurological diseases and comment on their importance and the possibilities of therapeutic intervention in clinical practice.