A randomized trial of deep-brain stimulation for Parkinson's disease.

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

fMRI and acoustic analyses reveal neural correlates of gestural complexity and articulatory effort within bilateral inferior frontal gyrus during speech production.

In an event-related fMRI study of overt speech production, we investigated the relationship between gestural complexity and underlying brain activity within bilateral inferior frontal gyrus (IFG). We operationalized gestural complexity as the number of active articulatory tiers (glottal, oral, nasal) and the degree of fine-grained temporal coordination between tiers (low, high). Forty-three neurotypical participants produced three types of highly-frequent non-word CV-syllable sequences, which differ systematically in gestural complexity (simple: ['dadada], intermediate: ['tatata], complex: ['nanana]). Comparing blood oxygen level-dependent (BOLD) responses across complexity conditions revealed that syllables with greater gestural complexity elicited increased activation patterns. Moreover, when durational parameters were included as covariates in the analyses, significant effects of articulatory effort were found over and above the effects of complexity. The results suggest that these differences in BOLD-response reflect the differential contribution of articulatory mechanisms that are required to produce phonologically distinct speech sounds.

Effect of deep brain stimulation on different speech subsystems in patients with multiple sclerosis.

The effect of deep brain stimulation on articulation and phonation subsystems in seven patients with multiple sclerosis (MS) was examined. Production parameters in fast syllable-repetitions were defined and measured, and the phonation quality during vowel productions was analyzed. Speech material was recorded for patients (with and without stimulation) and for a group of healthy control speakers. With stimulation, the precision of glottal and supraglottal articulatory gestures is reduced, whereas phonation has a greater tendency to be hyperfunctional in comparison with the healthy control data. Different effects on the two speech subsystems are induced by electrical stimulation of the thalamus in patients with MS.

Evaluation of Phonatory Behavior and Voice Quality in Patients with Multiple Sclerosis Treated with Deep Brain Stimulation.

OBJECTIVES: The effect of deep brain stimulation (DBS) on phonatory behavior and voice quality in eight patients with multiple sclerosis (MS) was examined instrumentally and perceptually. The acoustic signals of vowel productions obtained from patients (produced with and without stimulation) and from a group of 16 healthy control speakers were analyzed to prove statistically the changes of phonatory behavior and voice quality. STUDY DESIGN: This is a randomized study. METHODS: Firstly, a new parametrization was used to determine phonatory behavior. Secondly, a perceptual evaluation of voice quality of the same speech material was performed. RESULTS: With stimulation, phonation has a greater tendency to be strained. The results of perceptual evaluation support this strained phonation behavior under stimulation, resulting in a smaller degree of breathiness ratings of all raters. Without stimulation, an impaired and partly disturbed adduction of the vocal folds can be shown. These findings are also supported in the perceptual experiment providing a higher degree of hoarseness ratings of all raters for these signals. CONCLUSIONS: High-frequency electrical impulses to the thalamus in patients with MS influence the phonatory behavior of their vocal folds. The results suggest the need for long-term monitoring of phonatory behavior during DBS to initiate adequate treatments without delay.

Clinical value of iodine-123-alpha-methyl-L-tyrosine single-photon emission tomography in the differential diagnosis of recurrent brain tumor in patients pretreated for glioma at follow-up.

PURPOSE: To assess the clinical potential of iodine-123-alpha-methyl-L-tyrosine (IMT) and single-photon emission tomography (SPET) in the differential diagnosis of recurrences in patients pretreated for gliomas at follow-up. PATIENTS AND METHODS: Seventy-eight patients were examined after primary therapy over 36 months. Histopathologic diagnoses of all patients was known at first treatment; magnetic resonance and/or computed tomography examination was performed in addition to IMT-SPET. Cerebral SPET images were acquired 20 minutes after intravenous application of 190 +/- 10 MBq of IMT. SPET images were classified as positive or negative for recurrent tumor visually and by calculating the ratios between tracer accumulation in the lesion and the unaffected contralateral regions of reference using region of interest. Final diagnoses were based on prospective clinicopathologic findings obtained independently of IMT-SPET. RESULTS: IMT-SPET detected all high-grade recurrent gliomas (grade 4; sensitivity, 100%). A difference could be demonstrated in grade 2 and 3 recurrences (sensitivity, 84% and 92%, respectively). Moreover, benign posttherapeutic lesions (postoperative scars, radiation necrosis) were correctly diagnosed as negative for tumor recurrence. In general, IMT uptake in grade 2 (1.45 +/- 0.24) was significantly lower than that in grades 3 (1.70 +/- 0.41) and 4 (1.88 +/- 0.32). However, it was difficult to evaluate tumor grade only from the IMT accumulation in individual cases. CONCLUSION: IMT-SPET seems highly useful for detecting and delineating recurrent gliomas and differentiating between benign posttherapeutic lesions and malignant tumor tissue. It may be a valuable clinical tool to diagnose recurrences in patients pretreated for gliomas at follow-up. However, it showed limitations in determining histologic tumor grade.

Peroperative transcranial sonography for electrode placement into the targeted subthalamic nucleus of patients with Parkinson disease: technical note.

BACKGROUND: In the search for a better preoperative knowledge of the position of probes and electrodes, we assessed the feasibility and the usefulness of transcranial sonography during surgery for the implantation of stimulation electrodes into the subthalamic nucleus (STN) of patients with Parkinson's disease. METHODS: Transcranial sonography was carried out during stereotactic surgery in 8 patients with Parkinson's disease who had a suitable temporal bone window on the side receiving the electrode. Test stimulation parameters were 130 Hz, 0.1 ms, up to 0 to 4.5 V. RESULTS: The test probe with a diameter of 0.8 mm was visualized through the temporal preauricular window. The correct anatomic position of the electrode tip could be indirectly assessed thanks to the topographic relationship of the STN with the hyperechogenic substantia nigra and the nucleus ruber. The tip position of the final electrode was easily documented. A laterality of 10.5 to 11.5 mm, verified by teleradiographic ventriculography and plain films, was correlated with the best response of symptoms of Parkinson's disease to electrical impulses delivered to the STN. CONCLUSIONS: Transcranial sonography is easily feasible during stereotactic surgery. In combination with the clinical effects of electrostimulation on the symptoms of Parkinson's disease and with stereotactic x-ray images, it enables the assessment and the documentation of the correct position of implanted STN electrodes in real time.

Transient dystonia following magnetic resonance imaging in a patient with deep brain stimulation electrodes for the treatment of Parkinson disease. Case report.

Data from previous studies have shown that magnetic resonance (MR) imaging of the head can be performed safely in patients with deep brain stimulators. The authors report on a 73-year-old patient with bilaterally implanted deep brain electrodes for the treatment of Parkinson disease, who exhibited dystonic and partially ballistic movements of the left leg immediately after an MR imaging session. Such dystonic or ballistic movements had not been previously observed in this patient. In the following months, this focal movement disorder resolved completely. This case demonstrates the possible risks of MR imaging in patients with deep brain stimulators.

Effect of bilateral stimulation of the subthalamic nucleus on different speech subsystems in patients with Parkinson's disease.

The effect of deep brain stimulation on the two speech-production subsystems, articulation and phonation, of nine Parkinsonian patients is examined. Production parameters (stop closure voicing; stop closure, VOT, vowel) in fast syllable-repetitions were defined and measured and quantitative, objective metrics of vocal fold function were obtained during vowel production. Speech material was recorded for patients (with and without stimulation) and for a reference group of healthy control speakers. With stimulation, precision of the glottal and supraglottal articulation as well as the phonatory function is reduced for some individuals, whereas for other individuals an improvement is observed. Importantly, the improvement or deterioration is determined not only on the basis of the direction of parameter change but also on the individuals' position relative to the healthy control data. This study also notes differences within an individual in the effects of stimulation on the two speech subsystems. These findings qualify the value of global statements about the effect of neurostimulatory operations on Parkinsonian patients. They also underline the importance of careful consideration of individual differences in the effect of deep brain stimulation on different speech subsystems.

Bilateral high-frequency electrical impulses to the thalamus reduce voice tremor: acoustic and electroglottographic analysis. A case report.

An 81-year-old female patient suffering from disabling Holmes' tremor affecting both upper extremities, the head and additionally the vocal apparatus underwent bilateral thalamic ventralis intermedius nucleus (v.i.m.) stimulation. With the stimulation ON, the patient experienced complete suppression of the limb and head tremor and thorough voice normalization. Acoustic and electroglottographic (EGG) analysis showed a tendency towards hyperfunctional phonation with the stimulation ON as well as OFF, but a less disturbed vocal cord vibration pattern with the stimulation ON in comparison with a group of normal female speakers. This example shows that long-term monitoring of the vocal apparatus under deep brain stimulation therapy (DBS) of movement disorders must be planned in order to modify the stimulation parameters, if necessary, or to initiate logopaedic treatment.

Improvement of upper limb ataxia and intention tremor allowing cessation of thalamic electrostimulation after four years.

A 34-year-old female patient suffering from multiple sclerosis was treated with thalamic electrostimulation for right dominant brachial ataxia and intention tremor. At the end of the fourth year, the energy of the battery of the impulse generator was depleted. However, the patient was able to use her hands without major impairment with the stimulator OFF; due to a stable reduction of the degree of ataxia and intention tremor. The opposite thalamus received an electrode that was never activated because of a permanent thalamotomy effect. Thus, it can be concluded that restoration of function by means of deep brain stimulation might have been beneficial towards achieving a reorganization and stabilization of subcortico-cortical and cerebellar circuitry, supporting the process of self-repair in this patient with a less aggressive course of multiple sclerosis. However, scientific proof has yet to be found. This exceptional observation emphasizes the need for longterm studies.

[Effect of deep brain stimulation on glottal phonation in patients with Parkinson's disease and multiple sclerosis]. / Auswirkungen der Elektrostimulation subkortikaler Hirnstrukturen auf das glottale Schwingungsverhalten bei Patienten mit Morbus Parkinson und multipler Sklerose.

The present study examines the effect of neurostimulatory operations on glottal phonation of 3 parkinsonian patients and 3 patients with multiple sclerosis. With the help of two voice analysis programs (MDVP from Kay Elemetrics and EEG Program by Marasek) for the acoustic and electroglottographic definition of voice characteristics, vowel productions of the patients, which were recorded under two conditions (with and without stimulation), were analysed. In a first step, significantly different intrasubject means in the two conditions indicate the effect of neurostimulation. The strength of the effect differs among subjects, particularly in the case of patients with Parkinson's disease. In a second step, a gender-differentiated comparison of the individual patient's data (recorded with and without stimulation) with a group of normal voice speakers (150 male and 150 female speakers) is carried out. This intersubject comparison proves useful in that it relativizes the results from the intrasubject comparison. It is shown for the parkinsonian patients that stimulation causes a relative deterioration of the glottal cycle, while for the patients with multiple sclerosis a tendency for hyperfunctional phonation is observed. In the latter case, the results suggest the need for long-term monitoring of phonation behaviour during chronic electrical stimulation.