Evzen Ruzicka

Quantitative acoustic measurements for characterization of speech and voice disorders in early untreated Parkinson’s disease

An assessment of vocal impairment is presented for separating healthy people from persons with early untreated Parkinsons disease (PD). This studys main purpose was to (a) determine whether voice and speech disorder are present from early stages of PD before starting dopaminergic pharmacotherapy, (b) ascertain the specific characteristics of the PD-related vocal impairment, (c) identify PD-related acoustic signatures for the major part of traditional clinically used measurement methods with respect to their automatic assessment, and (d) design new automatic measurement methods of articulation. The varied speech data were collected from 46 Czech native speakers, 23 with PD. Subsequently, 19 representative measurements were pre-selected, and Wald sequential analysis was then applied to assess the efficiency of each measure and the extent of vocal impairment of each subject. It was found that measurement of the fundamental frequency variations applied to two selected tasks was the best method for separating healthy from PD subjects. On the basis of objective acoustic measures, statistical decision-making theory, and validation from practicing speech therapists, it has been demonstrated that 78% of early untreated PD subjects indicate some form of vocal impairment. The speech defects thus uncovered differ individually in various characteristics including phonation, articulation, and prosody.

Selecting deep brain stimulation or infusion therapies in advanced Parkinson's disease: an evidence-based review

Motor complications in Parkinson’s disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.

Efficacy and safety of a standardised 500 unit dose of Dysport® (Clostridium botulinum toxin type A haemaglutinin complex) in a heterogeneous cervical dystonia population: results of a prospective, multicentre, randomised, double-blind, placebo-controlled, parallel group study

Abstract Results from a dose-ranging study in a selected group of de novo patients with rotational cervical dystonia (CD) suggest that 500 units of Dysport (Clostridium botulinum toxin type A haemaglutinin complex) is the optimal starting dose. The present study aimed to confirm the efficacy and safety profile of this dose in a population of CD patients more representative of those seen in a typical dystonia clinic.A total of 68 patients with moderate to severe CD (Tsui score ≥ 9) were randomly assigned to receive placebo or Dysport 500 units. Treatment was administered according to the clinical pattern of head deviation, using a standardised injection protocol. A total of 21 patients (11 Dysport, 10 placebo) had not previously received botulinum toxin type A (BtxA) injections, and 47 patients (24 Dysport, 23 placebo) had received BtxA more than 12 weeks previously. Assessments were performed at baseline and weeks 4, 8 and 16. Patients defined as non-responders at week 4 were re-treated in an open phase with 500 units of Dysport at week 6, and were followed up at week 10.Significant between-group differences in Tsui scores were present at weeks 4 (p=0.001) and 8 (p=0.002). Similarly, there were significant between-group differences (p < 0.001) in patient and investigator assessments of response in favour of Dysport at weeks 4 and 8. Also, more Dysport (49 %) than placebo (33 %) patients were pain-free at week 4 (p=0.02). Overall, 30/35 (86 %) Dysport patients and 14/33 (42 %) placebo patients were classified as responders at week 4. Adverse events were reported by 15/35 Dysport patients and 9/33 placebo patients. Open phase treatment produced improvements in Tsui (p < 0.001) and pain scores (p=0.011), and 23/24 patients were classified as responders.Although individual dose titration and muscle selection is desirable, this study demonstrated that a dose of 500 units of Dysport injected into clinically identified neck muscles without electromyographic guidance is safe and effective in the treatment of patients with the major clinical types of cervical dystonia.

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 Parkinsons 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.

Safety and efficacy of perampanel in advanced Parkinson's disease: A randomized, placebo-controlled study†

Perampanel, a novel, noncompetitive, selective AMPA‐receptor antagonist demonstrated evidence of efficacy in reducing motor symptoms in animal models of Parkinsons disease (PD). We assessed the safety and efficacy of perampanel for treatment of “wearing off” motor fluctuations in patients with PD. Patients (N = 263) were randomly assigned to once‐daily add‐on 0.5, 1, or 2 mg of perampanel or placebo. The primary objective was to determine whether there was a dose‐response relationship for efficacy among the 3 perampanel doses and placebo. The primary efficacy endpoint for each treatment was measured as the least‐squares (LS) mean change from baseline to week 12 in percent “off” time reduction during the waking day, as recorded by patient diaries. The primary efficacy analysis was a 1‐sided Williams test for dose‐response trend at the 0.025 level of significance. At week 12, dose‐response trends, as determined by the Williams test, were not statistically significant for LS mean reduction in percent “off” time during the waking day (P = 0.061, with significance defined as P ≤ 0.025). The 2 higher perampanel doses (ITT population; n = 258) produced nonsignificant reductions from baseline to week 12 in percent “off” time during the waking day versus placebo (7.59%, P= 0.421 [1 mg], 8.60%, P = 0.257 [2 mg] versus 5.05% [placebo]; significance for pairwise comparisons defined as P ≤ 0.05). There were no significant changes in dyskinesia or cognitive function in any perampanel group versus placebo. Adverse events were similar across treatment groups. Perampanel treatment was well tolerated and safe, but failed to achieve statistical significance in primary and secondary endpoints.

Costs of illness and care in Parkinson's disease: an evaluation in six countries.

We investigated the costs of Parkinsons Disease (PD) in 486 patients based on a survey conducted in six countries. Economic data were collected over a 6-month period and presented from the societal perspective. The total mean costs per patient ranged from EUR 2620 to EUR 9820. Direct costs totalled about 60% to 70% and indirect costs about 30% to 40% of total costs. The proportions of costs components of PD vary notably; variations were due to differences in country-specific health system characteristics, macro economic conditions, as well as frequencies of resource use and price differences. However, inpatient care, long-term care and medication were identified as the major expenditures in the investigated countries.

Czech Version of the Trail Making Test: Normative Data and Clinical Utility

The Trail Making Test (TMT) comprises two psychomotor tasks that measure a wide range of visual-perceptual and executive functions. The purpose of this study was to provide Czech normative data and to examine the relationship between derived TMT indices and demographic variables. The TMT was administered to 421 healthy adults. Two clinical groups (n = 126) were evaluated to investigate the clinical utility of the TMT-derived scores: amnestic mild cognitive impairment (n = 90) and Alzheimers disease (n = 36). Statistical analyses showed that age and education, but not gender, were significantly associated with TMT completion times and derived scores. Of all the indices, only the TMT ratio score was insensitive to age. We present normative values for the Czech version of the TMT, providing a reference for measuring individual performance in native Czech speakers. Moreover, we found that accuracy on the TMT was improved with the attenuation of age.

Measurement instruments to assess posture, gait, and balance in Parkinson's disease: Critique and recommendations

Disorders of posture, gait, and balance in Parkinsons disease (PD) are common and debilitating. This MDS‐commissioned task force assessed clinimetric properties of existing rating scales, questionnaires, and timed tests that assess these features in PD.

On the structure of motor symptoms of Parkinson's disease

This study aims to investigate the structure of the motor symptoms of Parkinsons disease (PD), as measured by the Motor Section of the Unified Parkinsons Disease Rating Scale (UPDRS). The dimensionality of the Motor Section of the UPDRS was studied using structural equation modeling. The UPDRS measures were obtained from 405 patients with PD [237 men (39 “off”, 170 “on”, 28 unknown) and 168 women (21 “off”, 140 “on”, 7 unknown)]. The ordinal character of UPDRS scores and sample size substantiated the use of robust diagonally weighted least squares model estimation. It was shown that the Motor Section of the UPDRS incorporates five main latent symptom factors (rigidity, tremor, bradykinesia of the extremities, axial/gait bradykinesia, speech/hypomimia) plus two additional factors for laterality, which account for asymmetry of tremor, rigidity and bradykinesia of the extremities. Tremor seems to be an independent symptom factor of PD. Other latent variables are substantially correlated.

Long-term visual damage after acute methanol poisonings: Longitudinal cross-sectional study in 50 patients

Context. Visual disturbances due to the toxic effect of formic acid in acute methanol poisonings are generally transient. The subjective symptoms of visual toxicity may resolve within few weeks and fundoscopic signs of acute optic neuropathy subside within 1–2 months; therefore, the prevalence of long-term visual sequelae in the population of survivors of poisonings may be underestimated. Objective. To study the prevalence and character of long-term visual sequelae of acute methanol poisonings based on the data from the Czech mass methanol outbreak in 2012. Patients and methods. A total of 50 patients with confirmed methanol poisoning were included in this longitudinal cross-sectional study, median age: 48 (range, 23–73) years. The following tests were performed: optical coherence tomography or OCT with evaluation of the retinal nerve fibers layer (RNFL), visual evoked potentials (VEP), magnetic resonance imaging (MRI) of brain, complete ocular examination (visual acuity/field, color vision, contrast sensitivity, and fundus), neurological examinations, and biochemical tests. Results. Of 50 patients, 7/50 (14%) were discharged with diagnosed visual sequelae and 6/50 (12%) were discharged with both visual and central nervous system sequelae of poisoning. On the follow-up examination, 20/50 (40%) of the patients had long-term visual sequelae, with 8% of blindness. A total of 38% of the patients had abnormal (28% borderline) findings on RNFL, and 40% had abnormal (18% borderline) VEP. Among the patients discharged without detected visual sequelae, 8/37 (22%) had abnormal RNFL and VEP. Patients with visual sequelae had brain lesions more often (70% vs. 27%, p < 0.01). MRI identified optic nerve lesions in 2/20 cases with abnormal VEP only. The groups with and without visual sequelae differed in serum methanol, ethanol, HCO3-, formate, pH, anion gap, and base deficit (all p < 0.01). Visual disturbances on admission and coma were more prevalent in the patients with visual sequelae (p < 0.05). Patients with positive serum ethanol on admission were 93% less likely to have optical axonal damage (OR: 0.07 (95% CI: 0.01–0.8); p < 0.05). No association was found between visual sequelae and type of antidote administered, mode of hemodialysis, or folate substitution. Pre-hospital administration of ethanol seemed beneficial: these patients were 90% less likely to have abnormal RNFL findings (OR: 0.10 (95% CI: 0.02–0.52); p < 0.01). Conclusions. The long-term visual sequelae were clearly underestimated on discharge, suggesting a significantly higher amount of patients with long-term sequelae than earlier reported. Thorough examinations before discharge and during follow-up will likely uncover a higher morbidity also after methanol poisonings in general.