Vocal Responses to Perturbations in Voice Auditory Feedback in Individuals with Parkinson's Disease

One of the most common symptoms of speech deficits in individuals with Parkinson's disease (PD) is significantly reduced vocal loudness and pitch range. The present study investigated whether abnormal vocalizations in individuals with PD are related to sensory processing of voice auditory feedback. Perturbations in loudness or pitch of voice auditory feedback are known to elicit short latency, compensatory responses in voice amplitude or fundamental frequency.Twelve individuals with Parkinson's disease and 13 age- and sex-matched healthy control subjects sustained a vowel sound (/α/) and received unexpected, brief (200 ms) perturbations in voice loudness (±3 or 6 dB) or pitch (±100 cents) auditory feedback. Results showed that, while all subjects produced compensatory responses in their voice amplitude or fundamental frequency, individuals with PD exhibited larger response magnitudes than the control subjects. Furthermore, for loudness-shifted feedback, upward stimuli resulted in shorter response latencies than downward stimuli in the control subjects but not in individuals with PD.The larger response magnitudes in individuals with PD compared with the control subjects suggest that processing of voice auditory feedback is abnormal in PD. Although the precise mechanisms of the voice feedback processing are unknown, results of this study suggest that abnormal voice control in individuals with PD may be related to dysfunctional mechanisms of error detection or correction in sensory feedback processing

Using “Functional” Target Coordinates of the Subthalamic Nucleus to Assess the Indirect and Direct Methods of the Preoperative Planning: Do the Anatomical and Functional Targets Coincide?

Objective: To answer the question of whether the anatomical center of the subthalamic nucleus (STN), as calculated indirectly from stereotactic atlases or by direct visualization on magnetic resonance imaging (MRI), corresponds to the best functional target. Since the neighboring red nucleus (RN) is well visualized on MRI, we studied the relationships of the final target to its different borders. Methods: We analyzed the data of 23 PD patients (46 targets) who underwent bilateral frame-based STN deep brain stimulation (DBS) procedure with microelectrode recording guidance. We calculated coordinates of the active contact on DBS electrode on postoperative MRI, which we referred to as the final “functional/optimal” target. The coordinates calculated by the atlas-based “indirect” and “direct” methods, as well as the coordinates of the different RN borders were compared to these final coordinates. Results: The mean ± SD of the final target coordinates was 11.7 ± 1.5 mm lateral (X), 2.4 ± 1.5 mm posterior (Y), and 6.1 ± 1.7 mm inferior to the mid-commissural point (Z). No significant differences were found between the “indirect” X, Z coordinates and those of the final targets. The “indirect” Y coordinate was significantly posterior to Y of the final target, with mean difference of 0.6 mm (p = 0.014). No significant differences were found between the “direct” X, Y, and Z coordinates and those of the final targets. Conclusions: The functional STN target is located in direct proximity to its anatomical center. During preoperative targeting, we recommend using the “direct” method, and taking into consideration the relationships of the final target to the mid-commissural point (MCP) and the different RN borders

Severe topiramate-associated hyperthermia resulting in persistent neurological dysfunction.

Topiramate has recently been reported to cause hyperthermia as a result of oligohydrosis, primarily in pediatric patients. All cases reported to date were clinically mild, without permanent systemic or neurologic dysfunction. We report a case of severe hyperthermia and subsequent ataxia and tremor in an adult treated with topiramate. To our knowledge, this is the first case of topiramate-associated hyperthermia to result in residual cerebellar and cognitive dysfunction

Long-Term Satisfaction and Patient-Centered Outcomes of Deep Brain Stimulation in Parkinson’s Disease

Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective and proven treatment option for patients with advanced Parkinson’s disease (PD). Long-term outcomes (>5 years) have demonstrated sustained improvement in objective motor symptoms; however, few studies have evaluated patient-centered outcomes other than quality of life (QOL). A locally developed DBS-patient-centered outcomes questionnaire was administered to PD patients >5 years post-DBS. All questions were scored on a ten-point scale, whereby 0 represented the most ‘positive’ answer and 10 the most ‘negative’ answer. Pre-operative scales were repeated at the time of survey. Fifty-two patients (mean 8.2 ± 2.6 years post-DBS) were included. Satisfaction was high with median score (range) of 1/10 (0–8) at the time of survey. Patients endorsed having made the correct decision by undergoing DBS, with a score of 0 (0–10), would choose to have DBS again, with a score of 0 (0–10), and would recommend DBS to others, with a score of 0 (0–10). Pre-operative expectation target was set at a high level with a score of 2 (0–10). Parkinson’s Disease QOL (PDQ-39) Questionnaire Summary Index (SI) scores were, mean (SD), 2.1 (18.2) above baseline (p = 0.44). Those with worsening in PDQ-39-SI scores had less satisfaction with DBS (rs = 0.57, p ≤ 0.0001). This is the first study to assess long-term patient satisfaction with STN DBS. We are currently collecting data prospectively to confirm the results of these preliminary findings

Accuracy of Intraoperative Computed Tomography during Deep Brain Stimulation Procedures: Comparison with Postoperative Magnetic Resonance Imaging

To determine the accuracy of intraoperative computed tomography (iCT) in localizing deep brain stimulation (DBS) electrodes by comparing this modality with postoperative magnetic resonance imaging (MRI). Optimal lead placement is a critical factor for the outcome of DBS procedures and preferably confirmed during surgery. iCT offers 3-dimensional verification of both microelectrode and lead location during DBS surgery. However, accurate electrode representation on iCT has not been extensively studied. DBS surgery was performed using the Leksell stereotactic G frame. Stereotactic coordinates of 52 DBS leads were determined on both iCT and postoperative MRI and compared with intended final target coordinates. The resulting absolute differences in X (medial-lateral), Y (anterior-posterior), and Z (dorsal-ventral) coordinates (ΔX, ΔY, and ΔZ) for both modalities were then used to calculate the euclidean distance. Euclidean distances were 2.7 ± 1.1 and 2.5 ± 1.2 mm for MRI and iCT, respectively (p = 0.2). Postoperative MRI and iCT show equivalent DBS lead representation. Intraoperative localization of both microelectrode and DBS lead in stereotactic space enables direct adjustments. Verification of lead placement with postoperative MRI, considered to be the gold standard, is unnecessar

Effect of Concomitant Medications on the Safety and Efficacy of Extended-Release Carbidopa-Levodopa (IPX066) in Patients With Advanced Parkinson Disease: A Post Hoc Analysis

OBJECTIVES: Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in off time, on time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine). METHODS: ADVANCE-PD (n = 393) assessed safety and efficacy of ER CD-LD versus IR CD-LD. ASCEND-PD (n = 91) evaluated ER CD-LD versus CLE. In both studies, IR- and CLE-experienced patients underwent a 6-week, open-label dose-conversion period to ER CD-LD prior to randomization. For analysis, the randomized population was divided into 3 subgroups: dopaminergic agonists, rasagiline or selegiline, and amantadine. For each subgroup, changes from baseline in PD diary measures ( off time and on time with and without troublesome dyskinesia), Unified Parkinson Disease Rating Scale Parts II + III scores, and adverse events were analyzed, comparing ER CD-LD with the active comparator. RESULTS AND CONCLUSIONS: Concomitant dopaminergic agonist or MAO-B inhibitor use did not diminish the efficacy (improvement in off time and on time without troublesome dyskinesia) of ER CD-LD compared with IR CD-LD or CLE, whereas the improvement with concomitant amantadine failed to reach significance. Safety and tolerability were similar among the subgroups, and ER CD-LD did not increase troublesome dyskinesia. For patients on oral LD regimens and taking a dopaminergic agonist, and/or a MAO-B inhibitor, changing from an IR to an ER CD-LD formulation provides approximately an additional hour of good on time