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.

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.

Generation of two human iPSC lines from dermal fibroblasts of adult- and juvenile-onset Huntington's disease patients and two healthy donors.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a mutation in the HTT gene. To generate human-induced pluripotent stem cells (hiPSCs), we used dermal fibroblasts from 1 healthy adult control (K-Pic2), 1 HD manifest patient (M-T2), 1 healthy juvenile control (jK-N1), and 1 juvenile HD patient (jHD-V1). HD stage of patients was assessed by neurological tests and donors were without comorbidities and were non-smokers. Characterization showed that the obtained hiPSCs have the same number of CAG repeats as the parental fibroblast lines, express pluripotency markers and have the ability to differentiate into all 3 germ layers.

Automated Vowel Articulation Analysis in Connected Speech Among Progressive Neurological Diseases, Dysarthria Types, and Dysarthria Severities.

PURPOSE: Although articulatory impairment represents distinct speech characteristics in most neurological diseases affecting movement, methods allowing automated assessments of articulation deficits from the connected speech are scarce. This study aimed to design a fully automated method for analyzing dysarthria-related vowel articulation impairment and estimate its sensitivity in a broad range of neurological diseases and various types and severities of dysarthria. METHOD: Unconstrained monologue and reading passages were acquired from 459 speakers, including 306 healthy controls and 153 neurological patients. The algorithm utilized a formant tracker in combination with a phoneme recognizer and subsequent signal processing analysis. RESULTS: Articulatory undershoot of vowels was presented in a broad spectrum of progressive neurodegenerative diseases, including Parkinson's disease, progressive supranuclear palsy, multiple-system atrophy, Huntington's disease, essential tremor, cerebellar ataxia, multiple sclerosis, and amyotrophic lateral sclerosis, as well as in related dysarthria subtypes including hypokinetic, hyperkinetic, ataxic, spastic, flaccid, and their mixed variants. Formant ratios showed a higher sensitivity to vowel deficits than vowel space area. First formants of corner vowels were significantly lower for multiple-system atrophy than cerebellar ataxia. Second formants of vowels /a/ and /i/ were lower in ataxic compared to spastic dysarthria. Discriminant analysis showed a classification score of up to 41.0% for disease type, 39.3% for dysarthria type, and 49.2% for dysarthria severity. Algorithm accuracy reached an F-score of 0.77. CONCLUSIONS: Distinctive vowel articulation alterations reflect underlying pathophysiology in neurological diseases. Objective acoustic analysis of vowel articulation has the potential to provide a universal method to screen motor speech disorders. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23681529.

Expiratory Muscle Strength Training in Multiple System Atrophy: A Pilot Study.

Background: The effects of expiratory muscle strength training (EMST) has not yet been investigated in MSA patients. Objective: The primary objective was to test the effects of EMST on expiratory muscle strength and voluntary peak cough flow (vPCF) in patients with multiple system atrophy (MSA). The secondary objective was to assess the suitability of the pulmonary dysfunction index as a tool for identifying MSA patients with expiratory muscle weakness and reduced voluntary peak cough flow. Methods: This was an open label, non-controlled study, with an 8-week intensive home-based EMST protocol. The outcome measures included: maximal expiratory pressure (MEP) and vPCF. The sensitivity and specificity of the index of pulmonary dysfunction in the respiratory diagnostic process were assessed using receiver operating characteristic (ROC) analysis. Results: Fifteen MSA patients were enrolled in the study. Twelve MSA patients completed the training period. After the training period, MEP significantly increased (P = 0.006). Differences in vPCF were not significant (P = 0.845). ROC analysis indicated that the overall respiratory diagnostic accuracy of the index of pulmonary dysfunction had an outstanding capability to detect patients at risk of less effective coughing and an acceptable capability of detecting patients with decreased expiratory muscle strength. Conclusions: These findings indicate non-significant differences in vPCF after 8 weeks of EMST. The index of pulmonary dysfunction appears to be a promising prognostic screening tool for identifying altered cough efficacy in MSA patients. Test cut-offs may be used to select an appropriate respiratory physiotherapy technique.

Establishing normative data for the evaluation of cognitive performance in Huntington's disease considering the impact of gender, age, language, and education.

BACKGROUND: A declining cognitive performance is a hallmark of Huntington's disease (HD). The neuropsychological battery of the Unified HD Rating Scale (UHDRS'99) is commonly used for assessing cognition. However, there is a need to identify and minimize the impact of confounding factors, such as language, gender, age, and education level on cognitive decline. OBJECTIVES: Aim is to provide appropriate, normative data to allow clinicians to identify disease-associated cognitive decline in diverse HD populations by compensating for the impact of confounding factors METHODS: Sample data, N = 3267 (60.5% females; mean age of 46.9 years (SD = 14.61, range 18-86) of healthy controls were used to create a normative dataset. For each neuropsychological test, a Bayesian generalized additive model with age, education, gender, and language as predictors was constructed to appropriately stratify the normative dataset. RESULTS: With advancing age, there was a non-linear decline in cognitive performance. In addition, performance was dependent on educational levels and language in all tests. Gender had a more limited impact. Standardized scores have been calculated to ease the interpretation of an individual's test outcome. A web-based online tool has been created to provide free access to normative data. CONCLUSION: For defined neuropsychological tests, the impact of gender, age, education, and language as factors confounding disease-associated cognitive decline can be minimized at the level of a single patient examination.

Höffding step and beyond: The impact of visual sensory impairment on cognitive performance in neuropsychological testing of survivors of acute methanol poisoning.

BACKGROUND: Sensory deficits can result in limitations regarding how well neuropsychological test findings can be interpreted. Only a few studies have investigated the influence of vision alteration on neuropsychological tests. In 2012 the Czech Republic experienced mass methanol poisoning. Methanol metabolites cause histotoxic hypoxia to the optic nerve. OBJECTIVE: In the current study, the effect of the toxic damage on the parts of the visual pathway on visual and non-visual neuropsychological measures was investigated using electrophysiological methods (visual evoked potential (VEP) and optical coherence tomography (OCT) with retinal nerve fibre layer (RNFL) thickness measurement. METHODS: 53 individuals who experienced methanol poisoning participated in this research (76% men; ages 24 to 74 years, mean = 43.8±14.6 years; education 11.9±1.4 years). Each participant underwent comprehensive neurological, ophthalmological, and neuropsychological examinations. RESULTS: The results of mixed-effect models revealed significant small to a medium association between the Stroop test weak interference and Grooved Pegboard with the left eye global, nasal and temporal RNFL thickness. Also, medium associations between the Finger Tapping test and the Stroop test weak interference and left eye temporal RNFL, right eye temporal RNFL, and the latency P1 of VEP in the left eye were significant. CONCLUSION: The results of this study found a small to medium association (r = .15- .33; p = .010- .046) between RNFL thickness and cognitive visual test performance. Careful interpretation is suggested regarding results obtained from visual tests of the executive or motor functioning with participants with RNFL decrease or other types of early visual processing damage.

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.

Is retina affected in Huntington's disease? Is optical coherence tomography a good biomarker?

AIM OF THE STUDY: Comparative cross-sectional study of retinal parameters in Huntington's disease and their evaluation as marker of disease progression. CLINICAL RATIONALE FOR THE STUDY: Huntington's disease (HD) is a neurodegenerative disorder with dominant motor and neuropsychiatric symptoms. Involvement of sensory functions in HD has been investigated, however studies of retinal pathology are incongruent. Effect sizes of previous findings were not published. OCT data of the subjects in previous studies have not been published. Additional examination of structural and functional parameters of retina in larger sample of patients with HD is warranted. MATERIALS AND METHODS: This is a prospective cross-sectional study that included: peripapillary retinal nerve fiber layer thickness (RNFL) and total macular volume (TMV) measured by spectral domain optical coherence tomography (OCT) of retina, Pelli-Robson Contrast Sensitivity test, Farnsworth 15 Hue Color discrimination test, ophthalmology examination and Unified Huntington's disease Rating Scale (UHDRS). Ninety-four eyes of 41 HD patients examined in total 47 visits and 82 eyes of 41 healthy controls (HC) examined in total 41 visits were included. Analyses were performed by repeated measures linear mixed effects model with age and gender as covariates. False discovery rate was corrected by Benjamini-Hochberg procedure. RESULTS: HD group included 21 males and 20 females (age 50.6±12.0 years [mean ± standard deviation], disease duration 7.1±3.6 years, CAG triplet repeats 44.1±2.4). UHDRS Total Motor Score (TMS) was 30.0±12.3 and Total Functional Capacity 8.2±3.2. Control group (HC) included 19 males and 22 females with age 48.2±10.3 years. There was no statistically significant difference between HD and HC in age. The effect of the disease was not significant in temporal segment RNFL thickness. It was significant in the mean RNFL thickness and TMV, however not passing false discovery rate adjustment and with small effect size. In the HD group, the effect of disease duration and TMS was not significant. The Contrast Sensitivity test in HD was within normal limits and the 15-hue-test in HD did not reveal any specific pathology. CONCLUSIONS: The results of our study support possible diffuse retinal changes in global RNFL layer and in macula in Huntington's disease, however, these changes are small and not suitable as a biomarker for disease progression. We found no other structural or functional changes in retina of Huntington's disease patients using RNFL layer and macular volume spectral domain OCT and Contrast Sensitivity Test and 15-hue-test. CLINICAL IMPLICATIONS: Current retinal parameters are not appropriate for monitoring HD 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.

Speech acoustic indices for differential diagnosis between Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.

While speech disorder represents an early and prominent clinical feature of atypical parkinsonian syndromes such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), little is known about the sensitivity of speech assessment as a potential diagnostic tool. Speech samples were acquired from 215 subjects, including 25 MSA, 20 PSP, 20 Parkinson's disease participants, and 150 healthy controls. The accurate differential diagnosis of dysarthria subtypes was based on the quantitative acoustic analysis of 26 speech dimensions related to phonation, articulation, prosody, and timing. A semi-supervised weighting-based approach was then applied to find the best feature combinations for separation between PSP and MSA. Dysarthria was perceptible in all PSP and MSA patients and consisted of a combination of hypokinetic, spastic, and ataxic components. Speech features related to respiratory dysfunction, imprecise consonants, monopitch, slow speaking rate, and subharmonics contributed to worse performance in PSP than MSA, whereas phonatory instability, timing abnormalities, and articulatory decay were more distinctive for MSA compared to PSP. The combination of distinct speech patterns via objective acoustic evaluation was able to discriminate between PSP and MSA with very high accuracy of up to 89% as well as between PSP/MSA and PD with up to 87%. Dysarthria severity in MSA/PSP was related to overall disease severity. Speech disorders reflect the differing underlying pathophysiology of tauopathy in PSP and α-synucleinopathy in MSA. Vocal assessment may provide a low-cost alternative screening method to existing subjective clinical assessment and imaging diagnostic approaches.

Generation of three human iPSC lines from patients with Huntington's disease with different CAG lengths and human control iPSC line from a healthy donor.

Huntington's disease (HD) is a progressive neurodegenerative disorder with autosomal-dominant heritability that affect the central nervous system and peripheral tissues. The human-induced pluripotent stem cells (hiPSC) lines were generated from dermal fibroblasts of patients without comorbidities, non-smokers, at the pre-manifest (IIMCBi004-A), early-manifest (IIMCBi005-A), and manifest (IIMCBi006-A) HD stage assessed by neurological tests, as well as from a healthy donor (IIMCBi003-A). Characterization showed that the obtained hiPSC lines contained different CAG repeats consistent with the number of CAG repeats in original fibroblasts. Moreover, hiPSCs expressed pluripotency markers and were able to differentiate into three-germ layers in vitro.

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.

Toward Automated Articulation Rate Analysis via Connected Speech in Dysarthrias.

PURPOSE: This study aimed to evaluate the reliability of different approaches for estimating the articulation rates in connected speech of Parkinsonian patients with different stages of neurodegeneration compared to healthy controls. METHOD: Monologues and reading passages were obtained from 25 patients with idiopathic rapid eye movement sleep behavior disorder (iRBD), 25 de novo patients with Parkinson's disease (PD), 20 patients with multiple system atrophy (MSA), and 20 healthy controls. The recordings were subsequently evaluated using eight syllable localization algorithms, and their performances were compared to a manual transcript used as a reference. RESULTS: The Google & Pyphen method, based on automatic speech recognition followed by hyphenation, outperformed the other approaches (automated vs. hand transcription: r > .87 for monologues and r > .91 for reading passages, p < .001) in precise feature estimates and resilience to dysarthric speech. The Praat script algorithm achieved sufficient robustness (automated vs. hand transcription: r > .65 for monologues and r > .78 for reading passages, p < .001). Compared to the control group, we detected a slow rate in patients with MSA and a tendency toward a slower rate in patients with iRBD, whereas the articulation rate was unchanged in patients with early untreated PD. CONCLUSIONS: The state-of-the-art speech recognition tool provided the most precise articulation rate estimates. If speech recognizer is not accessible, the freely available Praat script based on simple intensity thresholding might still provide robust properties even in severe dysarthria. Automated articulation rate assessment may serve as a natural, inexpensive biomarker for monitoring disease severity and a differential diagnosis of Parkinsonism.

Study Protocol for the Development of a European eHealth Platform to Improve Quality of Life in Individuals With Huntington's Disease and Their Partners (HD-eHelp Study): A User-Centered Design Approach.

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that affects the quality of life (QoL) of HD gene expansion carriers (HDGECs) and their partners. Although HD expertise centers have been emerging across Europe, there are still some important barriers to care provision for those affected by this rare disease, including transportation costs, geographic distance of centers, and availability/accessibility of these services in general. eHealth seems promising in overcoming these barriers, yet research on eHealth in HD is limited and fails to use telehealth services specifically designed to fit the perspectives and expectations of HDGECs and their families. In the European HD-eHelp study, we aim to capture the needs and wishes of HDGECs, partners of HDGECs, and health care providers (HCPs) in order to develop a multinational eHealth platform targeting QoL of both HDGECs and partners at home. Methods: We will employ a participatory user-centered design (UCD) approach, which focusses on an in-depth understanding of the end-users' needs and their contexts. Premanifest and manifest adult HDGECs (n = 76), partners of HDGECs (n = 76), and HCPs (n = 76) will be involved as end-users in all three phases of the research and design process: (1) Exploration and mapping of the end-users' needs, experiences and wishes; (2) Development of concepts in collaboration with end-users to ensure desirability; (3) Detailing of final prototype with quick review rounds by end-users to create a positive user-experience. This study will be conducted in the Netherlands, Germany, Czech Republic, Italy, and Ireland to develop and test a multilingual platform that is suitable in different healthcare systems and cultural contexts. Discussion: Following the principles of UCD, an innovative European eHealth platform will be developed that addresses the needs and wishes of HDGECs, partners and HCPs. This allows for high-quality, tailored care to be moved partially into the participants' home, thereby circumventing some barriers in current HD care provision. By actively involving end-users in all design decisions, the platform will be tailored to the end-users' unique requirements, which can be considered pivotal in eHealth services for a disease as complex and rare as HD.

Cognitive changes after methanol exposure: Longitudinal perspective.

BACKGROUND: From 2012 to 2013, there was a mass methanol poisoning outbreak in the Czech Republic. Methanol metabolites can cause specific lesions in the basal ganglia, subcortical white matter, and optic nerve. However, long-term sequelae of methanol poisoning on cognitive functioning have not yet been explored. The current study aimed to delineate the cognitive changes observed in methanol poisoning survivors in the seven years since 2012. METHODS: We conducted longitudinal research with repeated measurements in 2013, 2015, 2017 and 2019 to evaluate the development of cognitive changes after acute methanol poisoning. A complex neuropsychological battery consisted of tests of global cognitive performance, auditory and visual attention, executive functioning, learning and memory, working memory and language. Motor performance measures and depression scale were also included. RESULTS: Repeated measures ANOVA of four measurements with post-hoc tests showed a significant decline in the Mini-Mental State Examination (p = 0.007); however, other parameters were not significantly decreasing. In comparison to normative values, the z-scores for each test measure, in the memory domain, in particular, ranged from 43 to 60 % of participants below 1.5 SD. Mild to severe depression levels from the onset of poisoning improved during the seven years, returning to normal in up to 27 % of participants. CONCLUSION: In the longitudinal perspective, methanol poisoning survivors manifest progressive global cognitive decline and overall persistent below-average cognitive performance with some improvements in the frequency of depressive symptoms.

Validation Study of a German Cognitive Battery for Huntington's Disease: Relationship Between Cognitive Performance, Functional Decline, and Disease Burden.

OBJECTIVE: Cognitive decline is a key characteristic of Huntington's disease (HD). This study aimed to investigate the diagnostic accuracy of a cognitive battery with six tests used by most HD research centers to assess cognitive impairment in HD. METHOD: In total, 106 HD patients in different disease stages with more (HD-CD, N = 30) and less cognitive impairments (HD-NC, N = 70) and 100 healthy controls (NC) were matched by age, sex, and education and were examined using a standardized protocol including cognitive, motor, and functional assessments. RESULTS: One-way between-groups analysis of variance showed that controls performed significantly better than HD patients and that HD-NC significantly outperformed HD-CD patients in all cognitive tests (NC > HD-NC > HD-CD), with all Games-Howell post-hoc tests p < .001. Analyses using area under the receiver-operating characteristic curve (AUC) disclosed the diagnostic accuracy of all tests included in the battery to discriminate between NC and HD patients with AUC ranging from 0.809 to 0.862 (all p < .001) and between HD-CD and HD-NC patients with AUC ranging from 0.833 to 0.899 (all p < .001). In both analysis, Stroop Color Naming Test showed the highest discriminative potential. Additional analyses showed that cognitive deficits in all domains progressed with disease duration. Moreover, cognitive performance correlated with the severity of motor and functional impairment (all p < .001) and with the Disease Burden Score regardless of disease duration and age. CONCLUSION: Our results indicate that the cognitive battery is a suitable tool for assessing cognitive impairment in HD.

Comparison of Automated Acoustic Methods for Oral Diadochokinesis Assessment in Amyotrophic Lateral Sclerosis.

Purpose The purpose of this research note is to provide a performance comparison of available algorithms for the automated evaluation of oral diadochokinesis using speech samples from patients with amyotrophic lateral sclerosis (ALS). Method Four different algorithms based on a wide range of signal processing approaches were tested on a sequential motion rate /pa/-/ta/-/ka/ syllable repetition paradigm collected from 18 patients with ALS and 18 age- and gender-matched healthy controls (HCs). Results The best temporal detection of syllable position for a 10-ms tolerance value was achieved for ALS patients using a traditional signal processing approach based on a combination of filtering in the spectrogram, Bayesian detection, and polynomial thresholding with an accuracy rate of 74.4%, and for HCs using a deep learning approach with an accuracy rate of 87.6%. Compared to HCs, a slow diadochokinetic rate (p < .001) and diadochokinetic irregularity (p < .01) were detected in ALS patients. Conclusions The approaches using deep learning or multiple-step combinations of advanced signal processing methods provided a more robust solution to the estimation of oral DDK variables than did simpler approaches based on the rough segmentation of the signal envelope. The automated acoustic assessment of oral diadochokinesis shows excellent potential for monitoring bulbar disease progression in individuals with ALS.