Levodopa may modulate specific speech impairment in Parkinson's disease: an fMRI study.

Hypokinetic dysarthria (HD) is a difficult-to-treat symptom affecting quality of life in patients with Parkinson's disease (PD). Levodopa may partially alleviate some symptoms of HD in PD, but the neural correlates of these effects are not fully understood. The aim of our study was to identify neural mechanisms by which levodopa affects articulation and prosody in patients with PD. Altogether 20 PD patients participated in a task fMRI study (overt sentence reading). Using a single dose of levodopa after an overnight withdrawal of dopaminergic medication, levodopa-induced BOLD signal changes within the articulatory pathway (in regions of interest; ROIs) were studied. We also correlated levodopa-induced BOLD signal changes with the changes in acoustic parameters of speech. We observed no significant changes in acoustic parameters due to acute levodopa administration. After levodopa administration as compared to the OFF dopaminergic condition, patients showed task-induced BOLD signal decreases in the left ventral thalamus (p = 0.0033). The changes in thalamic activation were associated with changes in pitch variation (R = 0.67, p = 0.006), while the changes in caudate nucleus activation were related to changes in the second formant variability which evaluates precise articulation (R = 0.70, p = 0.003). The results are in line with the notion that levodopa does not have a major impact on HD in PD, but it may induce neural changes within the basal ganglia circuitries that are related to changes in speech prosody and articulation.

Repetitive transcranial magnetic stimulation for hypokinetic dysarthria in Parkinson's disease enhances white matter integrity of the auditory-motor loop.

BACKGROUND AND PURPOSE: In our previous study, repeated sessions of repetitive transcranial magnetic stimulation (rTMS) over the auditory feedback area were shown to improve hypokinetic dysarthria (HD) in Parkinson's disease (PD) and led to changes in functional connectivity within the left-sided articulatory networks. We analyzed data from this previous study and assessed the effects of rTMS for HD in PD on the diffusion parameters of the left anterior arcuate fasciculus (AAF), which connects the auditory feedback area with motor regions involved in articulation. METHODS: Patients were assigned to 10 sessions of real or sham 1-Hz stimulation over the right posterior superior temporal gyrus. Stimulation effects were evaluated using magnetic resonance diffusion tensor imaging and by a speech therapist using a validated tool (Phonetics score of the Dysarthric Profile) at baseline, immediately after 2 weeks of stimulation, and at follow-up visits at Weeks 6 and 10 after the baseline. RESULTS: Altogether, data from 33 patients were analyzed. A linear mixed model revealed significant time-by-group interaction (p = 0.006) for the relative changes of fractional anisotropy of the AAF; the value increases were associated with the temporal evolution of the Phonetics score (R = 0.367, p = 0.028) in the real stimulation group. CONCLUSIONS: Real rTMS treatment for HD in PD as compared to sham stimulation led to increases of white matter integrity of the auditory-motor loop during the 2-month follow-up period. The changes were related to motor speech improvements.

Small-nerve-fiber pathology in critical illness documented by serial skin biopsies.

INTRODUCTION: Small-fiber pathology can develop in the acute phase of critical illness and may explain chronic sensory impairment and pain in critical care survivors. METHODS: Eleven adult ischemic stroke patients in a neurocritical care unit were enrolled in an observational cohort study. Intraepidermal nerve fiber density (IENFD) in the distal leg was assessed on admission to the intensive care unit and 10-14 days later, together with electrophysiological testing. RESULTS: Of the 11 patients recruited, 9 (82%) had sepsis or multiple-organ failure. Median IENFD on admission (5.05 fibers/mm) decreased significantly to 2.18 fibers/mm (P < 0.001), and abnormal IENFD was found in 6 patients (54.5%). Electrodiagnostic signs of large-fiber neuropathy and/or myopathy were found in 6 patients (54.5%), and autonomic dysfunction was found in 2 patients (18.2%). CONCLUSION: Serial IENFD measurements confirmed the development of small-fiber sensory involvement in the acute phase of critical illness.

Screening and differential diagnosis of delirium in neurointensive stroke patients.

Diagnosing delirium in neurointensive care is difficult because symptoms of delirium, such as inappropriate speech, may be related to aphasia due to primary brain injury. Therefore, validated screening tools are needed. The aim of this study was to compare two Czech versions of already validated screening tools - the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) - in a cohort of acute stroke patients. We also aimed to assess the pitfalls of delirium detection in the context of non-convulsive status epilepticus (NCSE). We analysed 138 stroke patients admitted to the neurological intensive care unit (ICU) or stroke unit. According to expert judgement, which was used as the gold standard, 38 patients (27.54%) developed delirium. The sensitivity and specificity of the ICDSC were 91.60% and 95.33%, respectively, and the positive and negative predictive values were 76.76% and 98.54%, respectively. Similarly, the sensitivity and specificity of CAM-ICU were 75.63% and 96.74%, respectively, and the positive and negative predictive values were 79.65% and 95.93%, respectively. We did not detect an episode of NCSE mimicking delirium in any of our stroke patients who were judged to be delirious by expert assessment. Our results suggest that the ICDSC may be a more suitable tool for delirium screening than the CAM-ICU in patients with neurological deficit. NCSE as a mimic of delirium seems to be less common in the acute phase of stroke than previously reported.

Poststroke delirium incidence and outcomes: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).

OBJECTIVE: To describe the epidemiology and time spectrum of delirium using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and to validate a tool for delirium assessment in patients in the acute poststroke period. DESIGN: A prospective observational cohort study. SETTING: The stroke unit of a university hospital. PATIENTS: A consecutive series of 129 patients with stroke (with infarction or intracerebral hemorrhage, 57 women and 72 men; mean age, 72.5 yrs; age range, 35-93 yrs) admitted to the stroke unit of a university hospital were evaluated for delirium incidence. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Criterion validity and overall accuracy of the Czech version of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) were determined using serial daily delirium assessments with CAM-ICU by a junior physician compared with delirium diagnosis by delirium experts using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria that began the first day after stroke onset and continued for at least 7 days. Cox regression models using time-dependent covariate analysis adjusting for age, gender, prestroke dementia, National Institutes of Stroke Health Care at admission, first-day Sequential Organ Failure Assessment, and asphasia were used to understand the relationships between delirium and clinical outcomes. An episode of delirium based on reference Diagnostic and Statistical Manual assessment was detected in 55 patients with stroke (42.6%). In 37 of these (67.3%), delirium began within the first day and in all of them within 5 days of stroke onset. A total of 1003 paired CAM-ICU/Diagnostic and Statistical Manual of Mental Disorders daily assessments were completed. Compared with the reference standard for diagnosing delirium, the CAM-ICU demonstrated a sensitivity of 76% (95% confidence interval [CI] 55% to 91%), a specificity of 98% (95% CI 93% to 100%), an overall accuracy of 94% (95% CI 88% to 97%), and high interrater reliability (κ = 0.94; 95% CI 0.83-1.0). The likelihood ratio of the CAM-ICU in the diagnosis of delirium was 47 (95% CI 27-83). Delirium was an independent predictor of increased length of hospital stay (hazard ratio 1.63; 95% CI 1.11-2.38; p = .013). CONCLUSIONS: Poststroke delirium may frequently be detected provided that the testing algorithm is appropriate to the time profile of poststroke delirium. Early (first day after stroke onset) and serial screening for delirium is recommended. CAM-ICU is a valid instrument for the diagnosis of delirium and should be considered an aid in delirium screening and assessment in future epidemiologic and interventional studies in patients with stroke.

Towards a predictive model for post-stroke delirium.

PRIMARY OBJECTIVE: To assess predisposing and precipitating risk factors and create a predictive model for post-stroke delirium. RESEARCH DESIGN: A prospective observational study in a cohort of consecutive patients with ischemic stroke or intracerebral haematoma admitted within 24 hours of stroke onset. METHODS: Patients were assessed daily for delirium during the first week by means of DSM-IV criteria and risk factors were recorded. RESULTS: One hundred patients completed a 7-day evaluation (47 women and 53 men, median age 77 years). An episode of delirium was detected in 43 patients (43%). Using multivariate logistic regression, a predictive statistical model was developed that utilized independent risk factors: age (OR = 1.08; 95% CI = 1.02-1.15); intracerebral haemorrhage (OR = 6.11; 95% CI = 1.62-22.98), lesion volume > 40 ccm (OR = 3.99; 95% CI = 1.29-12.39) and either elevated gamma-glytamyl transferase (OR = 4.88; 95% CI = 1.45-16.35) and elevated serum bilirubin (OR = 3.70; 95% CI = 1.32-10.38) or maximum sequential organ failure assessment score >2 (OR = 3.33; 95% CI = 1.06-10.45) with acceptable sensitivity and specificity (69.0% and 80.7%). In ischemic strokes, total anterior circulation infarctions were more frequently associated with delirium (73.3% developed delirium) compared with the remainder of the groups combined (p = 0.004; OR = 6.66; 95% CI = 1.85-24.01). CONCLUSION: Higher age, metabolic disturbances, intracerebral haemorrhage and larger ischemic hemispheric strokes increase the risk of post-stroke delirium.

Non-invasive brain stimulation for speech in Parkinson's disease: A randomized controlled trial.

BACKGROUND: Hypokinetic dysarthria is a common but difficult-to-treat symptom of Parkinson's disease (PD). OBJECTIVES: We evaluated the long-term effects of multiple-session repetitive transcranial magnetic stimulation on hypokinetic dysarthria in PD. Neural mechanisms of stimulation were assessed by functional MRI. METHODS: A randomized parallel-group sham stimulation-controlled design was used. Patients were randomly assigned to ten sessions (2 weeks) of real (1 Hz) or sham stimulation over the right superior temporal gyrus. Stimulation effects were evaluated at weeks 2, 6, and 10 after the baseline assessment. Articulation, prosody, and speech intelligibility were quantified by speech therapist using a validated tool (Phonetics score of the Dysarthric Profile). Activations of the speech network regions and intrinsic connectivity were assessed using 3T MRI. Linear mixed models and post-hoc tests were utilized for data analyses. RESULTS: Altogether 33 PD patients completed the study (20 in the real stimulation group and 13 in the sham stimulation group). Linear mixed models revealed significant effects of time (F(3, 88.1) = 22.7, p < 0.001) and time-by-group interactions: F(3, 88.0) = 2.8, p = 0.040) for the Phonetics score. Real as compared to sham stimulation led to activation increases in the orofacial sensorimotor cortex and caudate nucleus and to increased intrinsic connectivity of these regions with the stimulated area. CONCLUSIONS: This is the first study to show the long-term treatment effects of non-invasive brain stimulation for hypokinetic dysarthria in PD. Neural mechanisms of the changes are discussed.

Vowel Articulation Dynamic Stability Related to Parkinson's Disease Rating Features: Male Dataset.

Neurodegenerative pathologies as Parkinson's Disease (PD) show important distortions in speech, affecting fluency, prosody, articulation and phonation. Classically, measurements based on articulation gestures altering formant positions, as the Vocal Space Area (VSA) or the Formant Centralization Ratio (FCR) have been proposed to measure speech distortion, but these markers are based mainly on static positions of sustained vowels. The present study introduces a measurement based on the mutual information distance among probability density functions of kinematic correlates derived from formant dynamics. An absolute kinematic velocity associated to the position of the jaw and tongue articulation gestures is estimated and modeled statistically. The distribution of this feature may differentiate PD patients from normative speakers during sustained vowel emission. The study is based on a limited database of 53 male PD patients, contrasted to a very selected and stable set of eight normative speakers. In this sense, distances based on Kullback-Leibler divergence seem to be sensitive to PD articulation instability. Correlation studies show statistically relevant relationship between information contents based on articulation instability to certain motor and nonmotor clinical scores, such as freezing of gait, or sleep disorders. Remarkably, one of the statistically relevant correlations point out to the time interval passed since the first diagnostic. These results stress the need of defining scoring scales specifically designed for speech disability estimation and monitoring methodologies in degenerative diseases of neuromotor origin.

Non-invasive stimulation of the auditory feedback area for improved articulation in Parkinson's disease.

INTRODUCTION: Hypokinetic dysarthria (HD) is a common symptom of Parkinson's disease (PD) which does not respond well to PD treatments. We investigated acute effects of repetitive transcranial magnetic stimulation (rTMS) of the motor and auditory feedback area on HD in PD using acoustic analysis of speech. METHODS: We used 10 Hz and 1 Hz stimulation protocols and applied rTMS over the left orofacial primary motor area, the right superior temporal gyrus (STG), and over the vertex (a control stimulation site) in 16 PD patients with HD. A cross-over design was used. Stimulation sites and protocols were randomised across subjects and sessions. Acoustic analysis of a sentence reading task performed inside the MR scanner was used to evaluate rTMS-induced effects on motor speech. Acute fMRI changes due to rTMS were also analysed. RESULTS: The 1 Hz STG stimulation produced significant increases of the relative standard deviation of the 2nd formant (p = 0.019), i.e. an acoustic parameter describing the tongue and jaw movements. The effects were superior to the control site stimulation and were accompanied by increased resting state functional connectivity between the stimulated region and the right parahippocampal gyrus. The rTMS-induced acoustic changes were correlated with the reading task-related BOLD signal increases of the stimulated area (R = 0.654, p = 0.029). CONCLUSION: Our results demonstrate for the first time that low-frequency stimulation of the temporal auditory feedback area may improve articulation in PD and enhance functional connectivity between the STG and the cortical region involved in an overt speech control.

Neuromechanical Modelling of Articulatory Movements from Surface Electromyography and Speech Formants.

Speech articulation is produced by the movements of muscles in the larynx, pharynx, mouth and face. Therefore speech shows acoustic features as formants which are directly related with neuromotor actions of these muscles. The first two formants are strongly related with jaw and tongue muscular activity. Speech can be used as a simple and ubiquitous signal, easy to record and process, either locally or on e-Health platforms. This fact may open a wide set of applications in the study of functional grading and monitoring neurodegenerative diseases. A relevant question, in this sense, is how far speech correlates and neuromotor actions are related. This preliminary study is intended to find answers to this question by using surface electromyographic recordings on the masseter and the acoustic kinematics related with the first formant. It is shown in the study that relevant correlations can be found among the surface electromyographic activity (dynamic muscle behavior) and the positions and first derivatives of the first formant (kinematic variables related to vertical velocity and acceleration of the joint jaw and tongue biomechanical system). As an application example, it is shown that the probability density function associated to these kinematic variables is more sensitive than classical features as Vowel Space Area (VSA) or Formant Centralization Ratio (FCR) in characterizing neuromotor degeneration in Parkinson's Disease.

A standardization study of the Czech version of the Mississippi Aphasia Screening Test (MASTcz) in stroke patients and control subjects.

PRIMARY OBJECTIVE: To assess the criterion and construct validity and inter-rater reliability of the Czech version of the Mississippi Aphasia Screening Test (MASTcz). RESEARCH DESIGN: Prospective evaluation of consecutive inpatients admitted to the stroke unit of a university hospital within 60 days of onset of a unilateral left hemispheric ischaemic or haemorrhagic stroke with documented aphasia (LHA + ; n = 149). As control groups, unilateral right hemisphere stroke patients without aphasia (RHA-; n = 45) and healthy volunteers recruited from the community to comprise a non-patient control group (CG; n = 243) were examined. METHODS: Data collection included administration of MASTcz (in 52 LHA + patients, repeated by two blinded observers within 24 hours), Edinburgh inventory, Minimental State Examination score and chart review. The presence of aphasia was documented with a standard clinical logopaedic examination and also with the Western Aphasia Battery (WAB) in 45 LHA+ patients. RESULTS: MASTcz displayed high criterion validity (with sensitivity and specificity above 90%) in discrimination between stroke aphasia patients and both control subjects and RHA- stroke patients, high construct validity (close correlation with WAB score; r = 0.933), and acceptable interrater reliability. CONCLUSION: Analyses suggest the usefulness of MASTcz as a reliable and valid screening tool for the detection of aphasia and tracking of its progress.

Quantitative Analysis of Relationship Between Hypokinetic Dysarthria and the Freezing of Gait in Parkinson's Disease.

Hypokinetic dysarthria (HD) and freezing of gait (FOG) are both axial symptoms that occur in patients with Parkinson's disease (PD). It is assumed they have some common pathophysiological mechanisms and therefore that speech disorders in PD can predict FOG deficits within the horizon of some years. The aim of this study is to employ a complex quantitative analysis of the phonation, articulation and prosody in PD patients in order to identify the relationship between HD and FOG, and establish a mathematical model that would predict FOG deficits using acoustic analysis at baseline. We enrolled 75 PD patients who were assessed by 6 clinical scales including the Freezing of Gait Questionnaire (FOG-Q). We subsequently extracted 19 acoustic measures quantifying speech disorders in the fields of phonation, articulation and prosody. To identify the relationship between HD and FOG, we performed a partial correlation analysis. Finally, based on the selected acoustic measures, we trained regression models to predict the change in FOG during a 2-year follow-up. We identified significant correlations between FOG-Q scores and the acoustic measures based on formant frequencies (quantifying the movement of the tongue and jaw) and speech rate. Using the regression models, we were able to predict a change in particular FOG-Q scores with an error of between 7.4 and 17.0 %. This study is suggesting that FOG in patients with PD is mainly linked to improper articulation, a disturbed speech rate and to intelligibility. We have also proved that the acoustic analysis of HD at the baseline can be used as a predictor of the FOG deficit during 2 years of follow-up. This knowledge enables researchers to introduce new cognitive systems that predict gait difficulties in PD patients.

Parkinson Disease Detection from Speech Articulation Neuromechanics.

Aim: The research described is intended to give a description of articulation dynamics as a correlate of the kinematic behavior of the jaw-tongue biomechanical system, encoded as a probability distribution of an absolute joint velocity. This distribution may be used in detecting and grading speech from patients affected by neurodegenerative illnesses, as Parkinson Disease. Hypothesis: The work hypothesis is that the probability density function of the absolute joint velocity includes information on the stability of phonation when applied to sustained vowels, as well as on fluency if applied to connected speech. Methods: A dataset of sustained vowels recorded from Parkinson Disease patients is contrasted with similar recordings from normative subjects. The probability distribution of the absolute kinematic velocity of the jaw-tongue system is extracted from each utterance. A Random Least Squares Feed-Forward Network (RLSFN) has been used as a binary classifier working on the pathological and normative datasets in a leave-one-out strategy. Monte Carlo simulations have been conducted to estimate the influence of the stochastic nature of the classifier. Two datasets for each gender were tested (males and females) including 26 normative and 53 pathological subjects in the male set, and 25 normative and 38 pathological in the female set. Results: Male and female data subsets were tested in single runs, yielding equal error rates under 0.6% (Accuracy over 99.4%). Due to the stochastic nature of each experiment, Monte Carlo runs were conducted to test the reliability of the methodology. The average detection results after 200 Montecarlo runs of a 200 hyperplane hidden layer RLSFN are given in terms of Sensitivity (males: 0.9946, females: 0.9942), Specificity (males: 0.9944, females: 0.9941) and Accuracy (males: 0.9945, females: 0.9942). The area under the ROC curve is 0.9947 (males) and 0.9945 (females). The equal error rate is 0.0054 (males) and 0.0057 (females). Conclusions: The proposed methodology avails that the use of highly normalized descriptors as the probability distribution of kinematic variables of vowel articulation stability, which has some interesting properties in terms of information theory, boosts the potential of simple yet powerful classifiers in producing quite acceptable detection results in Parkinson Disease.

Prosodic analysis of neutral, stress-modified and rhymed speech in patients with Parkinson's disease.

BACKGROUND AND OBJECTIVE: Hypokinetic dysarthria (HD) is a frequent speech disorder associated with idiopathic Parkinson's disease (PD). It affects all dimensions of speech production. One of the most common features of HD is dysprosody that is characterized by alterations of rhythm and speech rate, flat speech melody, and impairment of speech intensity control. Dysprosody has a detrimental impact on speech naturalness and intelligibility. METHODS: This paper deals with quantitative prosodic analysis of neutral, stress-modified and rhymed speech in patients with PD. The analysis of prosody is based on quantification of monopitch, monoloudness, and speech rate abnormalities. Experimental dataset consists of 98 patients with PD and 51 healthy speakers. For the purpose of HD identification, sequential floating feature selection algorithm and random forests classifier is used. In this paper, we also introduce a concept of permutation test applied in the field of acoustic analysis of dysarthric speech. RESULTS: Prosodic features obtained from stress-modified reading task provided higher classification accuracies compared to the ones extracted from reading task with neutral emotion demonstrating the importance of stress in speech prosody. Features calculated from poem recitation task outperformed both reading tasks in the case of gender-undifferentiated analysis showing that rhythmical demands can in general lead to more precise identification of HD. Additionally, some gender-related patterns of dysprosody has been observed. CONCLUSIONS: This paper confirms reduced variation of fundamental frequency in PD patients with HD. Interestingly, increased variability of speech intensity compared to healthy speakers has been detected. Regarding speech rate disturbances, our results does not report any particular pattern. We conclude further development of prosodic features quantifying the relationship between monopitch, monoloudness and speech rate disruptions in HD can have a great potential in future PD analysis.

Speech prosody impairment predicts cognitive decline in Parkinson's disease.

BACKGROUND: Impairment of speech prosody is characteristic for Parkinson's disease (PD) and does not respond well to dopaminergic treatment. OBJECTIVES: We assessed whether baseline acoustic parameters, alone or in combination with other predominantly non-dopaminergic symptoms may predict global cognitive decline as measured by the Addenbrooke's cognitive examination (ACE-R) and/or worsening of cognitive status as assessed by a detailed neuropsychological examination. METHODS: Forty-four consecutive non-depressed PD patients underwent clinical and cognitive testing, and acoustic voice analysis at baseline and at the two-year follow-up. Influence of speech and other clinical parameters on worsening of the ACE-R and of the cognitive status was analyzed using linear and logistic regression. RESULTS: The cognitive status (classified as normal cognition, mild cognitive impairment and dementia) deteriorated in 25% of patients during the follow-up. The multivariate linear regression model consisted of the variation in range of the fundamental voice frequency (F0VR) and the REM Sleep Behavioral Disorder Screening Questionnaire (RBDSQ). These parameters explained 37.2% of the variability of the change in ACE-R. The most significant predictors in the univariate logistic regression were the speech index of rhythmicity (SPIR; p = 0.012), disease duration (p = 0.019), and the RBDSQ (p = 0.032). The multivariate regression analysis revealed that SPIR alone led to 73.2% accuracy in predicting a change in cognitive status. Combining SPIR with RBDSQ improved the prediction accuracy of SPIR alone by 7.3%. CONCLUSIONS: Impairment of speech prosody together with symptoms of RBD predicted rapid cognitive decline and worsening of PD cognitive status during a two-year period.

Addenbrooke's Cognitive Examination and Individual Domain Cut-Off Scores for Discriminating between Different Cognitive Subtypes of Parkinson's Disease.

Objective. The main aim of this study was to verify the sensitivity and specificity of Addenbrooke's Cognitive Examination-Revised (ACE-R) in discriminating between Parkinson's disease (PD) with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI) and between PD-MCI and PD with dementia (PD-D). We also evaluated how ACE-R correlates with neuropsychological cognitive tests in PD. Methods. We examined three age-matched groups of PD patients diagnosed according to the Movement Disorder Society Task Force criteria: PD-NC, PD-MCI, and PD-D. ROC analysis was used to establish specific cut-off scores of ACE-R and its domains. Correlation analyses were performed between ACE-R and its subtests with relevant neuropsychological tests. Results. Statistically significant differences between groups were demonstrated in global ACE-R scores and subscores, except in the language domain. ACE-R cut-off score of 88.5 points discriminated best between PD-MCI and PD-NC (sensitivity 0.68, specificity 0.91); ACE-R of 82.5 points distinguished best between PD-MCI and PD-D (sensitivity 0.70, specificity 0.73). The verbal fluency domain of ACE-R demonstrated the best discrimination between PD-NC and PD-MCI (cut-off score 11.5; sensitivity 0.70, specificity 0.73) while the orientation/attention subscore was best between PD-MCI and PD-D (cut-off score 15.5; sensitivity 0.90, specificity 0.97). ACE-R scores except for ACE-R language correlated with specific cognitive tests of interest.