Jan Roth

Functional magnetic resonance imaging during deep brain stimulation: a pilot study in four patients with Parkinson's disease.

Functional magnetic resonance imaging (fMRI) was performed in patients with Parkinsons disease during deep brain stimulation of the subthalamic nucleus (three patients) and during deep brain stimulation of the ventral intermedius nucleus of the thalamus (one patient). All showed an increase in blood oxygenation level‐dependent signal in the subcortical regions ipsilateral to the stimulated nucleus. This effect cannot be simply explained by a mechanism of depolarization blockade; rather, it is caused by overstimulation of the target nucleus, resulting in the suppression of its spontaneous activity. We confirm that fMRI during deep brain stimulation is a safe method with considerable potential for elucidating the functional connectivity of the stimulated nuclei.

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.

Deep brain stimulation of the subthalamic nucleus affects resting EEG and visual evoked potentials in Parkinson's disease

OBJECTIVE We studied changes of the EEG spectral power induced by deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinsons disease (PD). Also analyzed were changes of visual evoked potentials (VEP) with DBS on and off. METHODS Eleven patients with advanced PD treated with bilateral DBS STN were examined after an overnight withdrawal of L-DOPA and 2 h after switching off the neurostimulators. All underwent clinical examination followed by resting EEG and VEP recordings, a procedure repeated after DBS STN was switched on. RESULTS With DBS switched on, the dominant EEG frequency increased from 9.44+/-1.3 to 9.71+/-1.3 Hz (P<0.01) while its relative spectral power dropped by 11% on average (P<0.05). Switching on the neurostimulators caused a decrease in the N70/P100 amplitude of the VEP (P<0.01), which inversely correlated with the intensity of DBS (black-and-white pattern: P<0.01; color pattern: P<0.05). CONCLUSIONS Despite artifacts generated by neurostimulators, the VEP and resting EEG were suitable for the detection of effects related to DBS STN. The acceleration of dominant frequency in the alpha band may be evidence of DBS STN influence on speeding up of intracortical oscillations. The spectral power decrease, seen mainly in the fronto-central region, might reflect a desynchronization in the premotor and motor circuits, though no movement was executed. Similarly, desynchronization of the cortical activity recorded posteriorly may by responsible for the VEP amplitude decrease implying DBS STN-related influence even on the visual system. SIGNIFICANCE Changes in idling EEG activity observed diffusely over scalp together with involvement of the VEP suggest that the effects of DBS STN reach far beyond the motor system influencing the basic mechanisms of rhythmic cortical oscillations.

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

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

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

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

VIM thalamic stimulation for tremor in a patient with IgM paraproteinaemic demyelinating neuropathy

We demonstrate the effect of deep brain stimulation of the ventral intermediate thalamic nucleus on intractable action tremor, in a 72‐year‐old man suffering from neuropathy associated with monoclonal gammopathy.

Effects of Ropinirole Prolonged-Release on Sleep Disturbances and Daytime Sleepiness in Parkinson Disease

This study evaluated the effects of ropinirole prolonged-release (RPR) in comparison with ropinirole immediate-release (RIR) on sleep-related disorders in Parkinson disease (PD).Thirty-three PD patients (aged 62.5 [SD, 8] years; PD duration, 9 [SD, 4] years) were evaluated on a stable dose of RIR and 5 to 13 weeks after switch to the closest possible dose of RPR. The following questionnaires were administered: Epworth Sleepiness Scale, PD Sleep Scale, Pittsburgh Sleep Quality Index, REM Sleep Behavior Disorder Screening Questionnaire, and PD Questionnaire 39. We further monitored the occurrence of restless legs syndrome and sleep attacks (SAs). Motor disability was evaluated by PD diary and by Unified Parkinson Disease Rating Scale part 3 on medication (ON) and after medication withdrawal (OFF). In 8 patients with marked subjective sleep disturbance, polysomnography, and multiple sleep latency test were performed.After switching to RPR, there was an improvement in PD Sleep Scale (94.9 [SD, 23] vs 102.2 [SD, 27]; P < 0.05 corrected), Pittsburgh Sleep Quality Index (7.2 [SD, 3] vs 5.8 [SD, 3]; P < 0.05 corrected), Epworth Sleepiness Scale (14.1 [SD, 5] vs 12.0 [SD, 6]; P < 0.05 corrected) and Unified Parkinson Disease Rating Scale part 3 in the ON state (20.9 [SD, 10] 10 vs 17.6 [SD, 10]; P < 0.05 corrected). Thirteen patients reported disappearance of SAs on RPR. Polysomnography and multiple sleep latency test showed no changes in a subgroup of 8 patients after the switch to RPR.Ropinirole prolonged-release compared with RIR improved subjective quality of sleep, reduced daytime sleepiness, and led to disappearance of SAs in some patients possibly due to a more stable plasma level of ropinirole.

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

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

Validity of the Montreal Cognitive Assessment in the Detection of Cognitive Dysfunction in Huntington's Disease

The purpose of this study was to assess the convergent and discriminative validity of the Montreal Cognitive Assessment (MoCA) as a screening tool for cognitive dysfunction in Huntingtons disease (HD). Twenty HD patients with cognitive deficit and 23 normal controls (NC) without cognitive deficit were matched for age, sex, and education. The mean MoCA score was 20.5 (SD = 5.5) in HD and 27.5 (SD = 2.2) in NC. The MoCA correlated in both samples with the brief cognitive battery composite score (r = .81, p < .001). With the screening and diagnostic cutoff scores determined at <26 points, the MoCA showed a sensitivity of 94% and a specificity of 84% in the detection of cognitive dysfunction in HD. The area under the receiver-operating characteristics curve (95% confidence interval) for the MoCA was 0.90 (0.809–0.997), p < .001. Our results show that the MoCA is a suitable tool for assessing cognitive dysfunction in patients with HD.