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Objectives To elucidate the phenotypes and pathophysiology of speech and voice disorders in Parkinson's disease (PD) with subthalamic nucleus deep brain stimulation (STN-DBS).
Methods We conducted a cross-sectional study on 76 PD patients treated with bilateral STN-DBS (PD-DBS) and 33 medically treated PD patients (PD-Med). Speech and voice functio...
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Introduction
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) using high-frequency (130–185 Hz) stimulation (HFS) is more effective for appendicular than for axial symptoms. Low-frequency stimulation (LFS) of the STN may reduce gait/balance and speech impairment but can result in worsened appendicular symptoms, limiting its clinical us...
Background:
Subthalamic nucleus deep brain stimulation (STN-DBS) is a widely used treatment for Parkinson's disease (PD) patients with motor complications, but can result in adverse effects (AEs) in a significant proportion of treated patients. The use of novel programming features including short pulse width (PW) and directional steering in allev...
Purpose
. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson’s disease (PD).
Methods
. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on...
Background
Beta-based adaptive Deep Brain Stimulation (aDBS) is effective in Parkinson’s disease (PD), when assessed in the immediate post-implantation phase. However, the potential benefits of aDBS in patients with electrodes chronically implanted, in whom changes due to the microlesion effect have disappeared, are yet to be assessed.
Methods
To...
Background:
Speech disorders are among the most common adverse effects after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients. However, longitudinal speech changes after STN-DBS are not fully understood.
Objective:
We performed a two-year prospective study on PD patients who underwent STN-DBS and analyzed...
Citations
... We and others have hypothesized that worsening dysarthria may occur because of current spread from DBS leads into the internal capsule with lateral placement [26][27][28] or current spread to cerebellothalamic fibers with medial placement. 12,13,29 Still others have suggested that lesions to the basal ganglia caused by the electrode trajectory or levodopa-induced dyskinesias may be responsible for degraded motor speech. ...
... Our findings are consistent with previously published reports. Tsuboi et al. 28 reported several distinct speech and voice changes after STN DBS and noted that stimulation of the corticobulbar and corticospinal tracts caused both dystonic speech changes and strained voice quality from abnormal laryngeal contraction. Tripoliti et al. 13 identified more medially placed electrode contacts in the left STN region as a predictive factor for motor speech deterioration. ...
Objective:
A motor speech disorder or dysarthria commonly arises in patients with Parkinson's disease (PD). The impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on motor speech and the potential of intraoperative motor speech testing to predict outcomes are unknown. This study examined 1) the types and prevalence of motor speech changes observed with STN DBS and their relation to the preoperative condition, 2) the ability of intraoperative testing to predict postoperative changes in motor speech, and 3) the spatial relationship between stimulation sites producing maximal motor improvement, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and maximal motor speech deterioration.
Methods:
Comprehensive preoperative, intraoperative, and postoperative motor speech/dysarthria evaluations were performed in consecutive patients with advanced idiopathic PD who underwent STN DBS surgery in the period from 2011 to 2016. Preoperative type of dysarthria and overall dysarthria severity rating along with intraoperative motor speech testing results were evaluated as predictors of postoperative change. Atlas-independent, fully individualized field modeling was used to identify stimulation sites associated with maximal MDS-UPDRS motor improvement and motor speech deterioration.
Results:
Forty-three patients with PD treated with STN DBS were prospectively studied. Improved MDS-UPDRS motor scores and worsened dysarthria were demonstrated by a subset of patients (16/43). Preoperative dysarthria characteristics did not predict postoperative deterioration. Intraoperative assessment of motor speech strongly predicted postoperative outcomes (OR 4.4, p = 0.02). Sites of maximal MDS-UPDRS motor improvement and worsened dysarthria were distinct. Worsened dysarthria was associated with capsular stimulation, anterior and ventral to the site of maximal MDS-UPDRS motor improvement.
Conclusions:
The predictive reliability of intraoperative motor speech testing, together with the identification of distinct stimulation sites for motor speech impairment and improved MDS-UPDRS motor function, raise the possibility that DBS lead repositioning or reprogramming could reduce adverse effects on motor speech without impacting MDS-UPDRS motor outcomes in patients undergoing STN DBS.
... Hence, it is possible that the various networks related to dysarthria, as observed here, reflect various behavioral effects. For instance, cerebellar circuits (DRTT) may be linked to ataxic dysarthria, whereas cortical circuits (SMA) may be linked to spastic dysarthria (Tsuboi et al., 2015). In addition, our clinical testing approach did not contain adequate assessment regarding verbal fluency; an issue that should also be further investigated in future studies. ...
Background:
Tractography based on diffusion-weighted magnetic resonance imaging (DWI) models the structural connectivity of the human brain. Deep brain stimulation (DBS) targeting the subthalamic nucleus is an effective treatment for advanced Parkinson's disease but may induce adverse effects. This study investigated the relationship between structural connectivity patterns of DBS electrodes and stimulation-induced side effects.
Methods:
Twenty-one patients with Parkinson's disease treated with bilateral subthalamic DBS were examined. Overall, 168 electrode contacts were categorized as inducing or non-inducing depending on their capability for inducing side effects like motor effects, paresthesia, dysarthria, oculomotor effects, hyperkinesia, and other complications as assessed during the initial programming session. Furthermore, the connectivity of each contact with target regions was evaluated by probabilistic tractography based on DWI. Finally, stimulation sites and structural connectivity patterns of inducing and non-inducing contacts were compared.
Results:
Inducing contacts differed across the various side effects and from those mitigating Parkinson's symptoms. Although contacts showed a largely overlapping spatial distribution within the sub-thalamic region, they could be distinguished by their connectivity patterns. In particular, inducing contacts were more likely connected with supplementary motor areas (hyperkinesia, dysarthria), frontal cortex (oculomotor), fibers of the internal capsule (paresthesia), and the basal ganglia-thalamo-cortical circuitry (dysarthria).
Discussion:
Side effects induced by DBS seem to be associated with distinct connectivity patterns. Cerebellar connections are hardly associated with side effects, although they seem relevant for mitigating motor symptoms in Parkinson's disease. A symptom-specific, connectivity-based approach for target planning in DBS may enhance treatment outcomes and reduce adverse effects.
... 6 STN-DBS in particular is known to exacerbate stuttering and hypophonia in PD patients. 7 Additionally, stimulation at contacts residing within specific regions of the STN may have differential effects on axial and appendicular symptoms. For example, stimulation of the dorsal half of the lateral STN been shown to improve step velocity, length and balance compared to stimulation of ventral regions. ...
Deep brain stimulation (DBS) is becoming increasingly central in the treatment of patients with Parkinson's disease and other movement disorders. Recent developments in DBS lead and implantable pulse generator design provide increased flexibility for programming, potentially improving the therapeutic benefit of stimulation. Directional DBS leads may increase the therapeutic window of stimulation by providing a means of avoiding current spread to structures that might give rise to stimulation-related side effects. Similarly, control of current to individual contacts on a DBS lead allows for shaping of the electric field produced between multiple active contacts. The following review aims to describe the recent developments in DBS system technology and the features of each commercially available DBS system. The advantages of each system are reviewed, and general considerations for choosing the most appropriate system are discussed.
... [1][2][3] Because of the limitations of L-dopa and other drug therapies, other treatment modalities such as deviceaided therapy have been attempted, [4] but at least in the case of deep brain stimulation, several side effects such as voice and speech disorders have been identified as problems. [5] Furthermore, none of the available treatments have been able to modify the course of the disease. ...
Background:
Cellular energetics play an important role in Parkinsons disease etiology, but no treatments directly address this deficiency. Our past research showed that treatment with febuxostat and inosine increased blood hypoxanthine and ATP in healthy adults, and a preliminary trial in 3 Parkinson's disease patients suggested some symptomatic improvements with no adverse effects.
Methods:
To examine the efficacy on symptoms and safety in a larger group of Parkinsons disease patients, we conducted a single-arm, open-label trial at 5 Japanese neurology clinics and enrolled thirty patients (nmales = 11; nfemales = 19); 26 patients completed the study (nmales = 10; nfemales = 16). Each patient was administered febuxostat 20 mg and inosine 500 mg twice-per-day (after breakfast and dinner) for 8 weeks. The primary endpoint was the difference of MDS-UPDRS Part III score immediately before and after 57 days of treatment.
Results:
Serum hypoxanthine concentrations were raised significantly after treatment (Pre = 11.4 μM; Post = 38.1 μM; P < .0001). MDS-UPDRS Part III score was significantly lower after treatment (Pre = 28.1 ± 9.3; Post = 24.7 ± 10.8; mean ± SD; P = .0146). Sixteen adverse events occurred in 13/29 (44.8%) patients, including 1 serious adverse event (fracture of the second lumbar vertebra) that was considered not related to the treatment.
Conclusions:
The results of this study suggest that co-administration of febuxostat and inosine is relatively safe and effective for improving symptoms of Parkinsons disease patients. Further controlled trials need to be performed to confirm the symptomatic improvement and to examine the disease-modifying effect in long-term trials.
... Surgery-related and device-related AEs included infection, intracerebral hemorrhage, cerebral infarction, and lead and connector breakages that are also commonly encountered in patients undergoing DBS for other indications [4,53,69]. Although the inconsistent reporting methods limited comparison of the frequency of AEs between GPi and STN studies, balance and gait disturbance, dysarthria, dysphagia, and cognitive decline were observed both after GPi and STN DBS. ...
Objective
To analyze deep brain stimulation (DBS) outcomes in patients with cervical dystonia (CD), the relationships between motor and disability/pain outcomes, and the differences in outcomes between globus pallidus internus (GPi) and subthalamic nucleus (STN) DBS, and to identify potential outcome predictors.
Methods
A systematic literature search identified individual patient data of CD patients who underwent DBS and whose outcomes were assessed with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Then, we performed a pooled meta-analysis on this cohort.
Results
A review of 39 papers yielded 208 patients with individual TWSTRS scores and demographic information. At a mean follow-up period of 23.3 months after either GPi or STN DBS, the TWSTRS total (58.8%), severity (53.9%), disability (61.3%), and pain (46.6%) scores significantly improved compared to baseline status (all p < 0.001). There were no significant outcome differences between short-term (< 23.3 months) and long-term (≥ 23.3 months). The TWSTRS outcomes after GPi and STN DBS were comparable, whereas these two targets showed different adverse effect profiles. The rates of responders to DBS according to the TWSTRS total and severity (defined as ≥ 25% improvement) were both 89%. Regression analyses demonstrated motor benefits associated with disability improvement more than pain relief (R² = 0.345 and 0.195, respectively). No clinically meaningful predictors for DBS outcomes were identified.
Conclusion
DBS improves motor symptoms, disability, and pain in CD patients and may provide sustained benefits over 2 years. GPi and STN appear to be equally effective targets with different adverse effect profiles.
... 9 Spread of the electrical field to adjacent structures, such as corticobulbar or internal capsule fibers, has been suggested to result in speech impairments, 38,39 by affecting laryngeal muscle, lip, and tongue circuits via stimulation that is too lateral to the STN target. [40][41][42] Tsuboi et al studied electrode location and voice outcomes but found conflicting results with lateral STN implants (with this location correlating with both worsening and improvement in voice outcomes depending on patient characteristics) which they explained as spread of electrical field to surrounding internal capsule or corticobulbar structures. 40 These previous results, however, do not explain the within STN location dependence of our findings. ...
... [40][41][42] Tsuboi et al studied electrode location and voice outcomes but found conflicting results with lateral STN implants (with this location correlating with both worsening and improvement in voice outcomes depending on patient characteristics) which they explained as spread of electrical field to surrounding internal capsule or corticobulbar structures. 40 These previous results, however, do not explain the within STN location dependence of our findings. ...
Background:
Despite the impact of Parkinson disease (PD) on speech communication, there is no consensus regarding the effect of lead location on voice-related outcomes in subthalamic nucleus (STN) deep brain stimulation (DBS).
Objective:
To determine the relationship of stimulation location to changes in cepstral analyses of voice following STN DBS.
Methods:
Speech pathology evaluations were obtained from 14 PD subjects, before and after STN DBS, including audio-perceptual voice ratings (overall severity, loudness, hoarseness changes), measured indices of dysphonia (cepstral peak prominence and cepstral spectral index of dysphonia), and phonatory aerodynamics. The contact locations used for active stimulation at the time of postoperative voice evaluations were determined and assessed in relation to voice outcomes.
Results:
Voice outcomes remained relatively unchanged on average. Stimulation locations in the anterior portion of the sensorimotor region of the left STN, however, were associated with improvements in voice severity scores, cepstral spectral index of dysphonia, shortness of breath, and phonatory airflow during connected speech. Posterior locations were associated with worsening of these outcomes. Variation in the medial-lateral or dorsal-ventral position on the left, and in any direction on the right, did not correlate with any voice outcome.
Conclusion:
Active contact placement within the anterior sensorimotor STN was associated with improved perceptual and acoustic-aerodynamic voice-related outcomes. These findings suggest an STN topography for improving airflow for speech, in turn improving how PD patients' voices sound.
... 18,19 In both groups, the most common AEs were dysarthria and gait and postural disorders that are presumably related to the current spread to adjacent pathways such as the corticobulbar and corticospinal fibers, the afferent and efferent fibers of the red nucleus, or the cerebellar efferent fibers from the vermis. [20][21][22][23][24] The patients with DT and patients with ET had similar outcomes of UE tremor total, postural tremor, action tremor, and hand function and the significant improvements in both groups were sustained for 6 years or beyond. However, the resting component of UE tremor did not demonstrate significant improvements at longer follow-ups in either group, which might be related to small sample size available for analysis. ...
Objective:
To assess longitudinal tremor outcomes with ventral intermediate nucleus deep brain stimulation (VIM DBS) in patients with dystonic tremor (DT) and to compare with DBS outcomes in essential tremor (ET).
Methods:
We retrospectively investigated VIM DBS outcomes for 163 patients followed at our center diagnosed with either DT or ET. The Fahn-Tolosa-Marin tremor rating scale (TRS) was used to assess change in tremor and activities of daily living (ADL) at 6 months, 1 year, 2-3 years, 4-5 years, and ≥6 years after surgery.
Results:
Twenty-six patients with DT and 97 patients with ET were analyzed. Compared to preoperative baseline, there were significant improvements in TRS motor up to 4-5 years (52.2%; p = 0.032) but this did not reach statistical significance at ≥6 years (46.0%, p = 0.063) in DT, which was comparable to the outcomes in ET. While the improvements in the upper extremity tremor, head tremor, and axial tremor were also comparable between DT and ET throughout the follow-up, the ADL improvements in DT were lost at 2-3 years follow-up.
Conclusion:
Overall, tremor control with VIM DBS in DT and ET was comparable and remained sustained at long term likely related to intervention at the final common node in the pathologic tremor network. However, the long-term ADL improvements in DT were not sustained, possibly due to inadequate control of concomitant dystonia symptoms. These findings from a large cohort of DT indicate that VIM targeting is reasonable if the tremor is considerably more disabling than the dystonic features.
Classification of evidence:
This study provides Class IV evidence that VIM DBS improves tremor in patients with DT or ET.
... The inconsistent findings of the effect of DBS on speech are not surprising considering the evidence that multiple neural mechanisms and neurotransmitters are affected in PD (Schapira et al., 2017). In addition, specific PD symptoms (Tsuboi et al., 2015), speech intelligibility prior to surgery, and surgical procedures can affect speech outcomes with DBS (Tripoliti et al., 2014). DBS implantation was initially developed to target motor symptoms (Limousin et al., 1995). ...
Purpose
Individuals with Parkinson disease (PD) present with complex and variable symptoms, with recent findings suggesting that the etiology of PD extends beyond the involvement of just the basal ganglia. These symptoms include significant impairments in the speech and swallowing domains, which can greatly affect quality of life and therefore require therapeutic attention. This research-based update reviews the neurophysiological basis for swallowing and speech changes in PD, the effectiveness of various types of treatments, and the implications for symptom evaluation and management.
Conclusion
The mechanisms responsible for swallowing and speech symptoms in PD remain largely unknown. Dopaminergic medication and deep brain stimulation do not provide consistent benefits for these symptoms, suggesting a nondopaminergic network is involved. Importantly, evidence suggests that symptoms of dysphagia and hypokinetic dysarthria may be early indications of PD, so it is critical to investigate the cause of these changes.
... Overall, STN DBS can differentially effect domains of speech, with phonation most likely to benefit [58,99,100]. This can be, however, at the cost of exacerbating articulatory disturbances, resulting in reduced speech intelligibility [4,[97][98][99][100]. Severity of dysarthria prior to STN-DBS, combined dopaminergic treatment, disease severity and left STN positioning of the active electrodes all appear to be critical determinants of STN-DBS efficacy to ameliorate speech deficits for individuals with PD [99]. ...
... Overall, STN DBS can differentially effect domains of speech, with phonation most likely to benefit [58,99,100]. This can be, however, at the cost of exacerbating articulatory disturbances, resulting in reduced speech intelligibility [4,[97][98][99][100]. Severity of dysarthria prior to STN-DBS, combined dopaminergic treatment, disease severity and left STN positioning of the active electrodes all appear to be critical determinants of STN-DBS efficacy to ameliorate speech deficits for individuals with PD [99]. ...
Introduction: Idiopathic Parkinson’s Disease (PD) results in a range of motor and non-motor impairments. Clinical diagnosis commonly occurs after substantial neurophysiological damage limiting the opportunity for neuroprotective treatments. Uncovering sensitive objective markers with the capacity to detect pre-symptomatic disease and track disease progression is therefore a priority. Speech may provide an ideal proxy marker for PD; a quantifiable biometric that displays salient changes in early disease and appears to evolve with disease progression.
Areas covered: This review describes the endophenotype of speech, voice, cognition and language modalities in PD and investigates the speech as a ‘proxy marker’ of PD disease state.
Expert opinion: Detailed characterization at different disease stages are needed and must incorporate longitudinal assessment to capture small but significant changes in speech, voice, cognition and language modalities within patient changes over time. Advances in technology are leading to new opportunities for acquiring data remotely and more frequently, offering more ecologically valid testing environments. Combined with automated signal processing and analysis, symptoms may also be tracked in-home readily. Features extracted may provide a ‘proxy marker’ for early identification of PD and objective monitoring of disease progression.
... Thus, the participants had relatively long disease duration (52 males; mean age: 64.8 ± 8.7 years; mean disease duration: 12.7 ± 5.9 years). Some of the patients enrolled in this study were those from our previous studies [11][12][13][14][15], and patients were assessed in the on-state under continued medication. ...
... In our previous cross-sectional study, 24% of 76 patients with PD who were treated with subthalamic nucleus DBS (STN-DBS) had stuttering as the chief characteristic of speech disorder [12]. Furthermore, our prospective study revealed that during the 1-year follow-up, 13% of patients with PD who were treated with STN-DBS and 18% of medically treated patients with PD developed stuttering. ...
Objectives:
This study aimed to explore clinical correlates of repetitive speech disorders in patients with Parkinson's disease (PD).
Methods:
This study investigated speech function (Assessment of Motor Speech for Dysarthria and Stuttering Severity Instrument-3), motor function (Unified Parkinson's Disease Rating Scale III [UPDRS-III] and UPDRS-IV), cognitive function (Mini-Mental State Examination [MMSE], Montreal Cognitive Assessment [MoCA], Stroop color-word test, verbal fluency, digit span tests, and line orientation), and activities of daily living of 113 PD patients. Comparison between groups (independent t-tests, Mann-Whitney U tests, or χ2 test) and linear regression analyses were performed to determine clinical correlates of repetitive speech disorders.
Results:
Totally, 65 patients (57.5%) had repetitive speech disorders. Patients with repetitive speech disorders had significantly worse UPDRS-III (P = .049), MoCA (P = .030), and speech function and higher levodopa equivalent daily dose (LEDD; P = .031) than those without repetitive speech disorders. Males were significantly predominant in patients with repetitive speech disorders (64.6%) compared to those without repetitive speech disorders (18.7%; P < .001). The univariate and subsequent multiple linear regression analyses revealed that the severity of repetitive speech disorders significantly correlated with gender (P < .001), MoCA (P = .006), and speech variables (abnormal rate, P = .007; imprecise consonants, P = .043), independent from disease duration, UPDRS III, and LEDD.
Conclusions:
PD patients with repetitive speech disorders had worse motor, cognitive, and speech functions than those without repetitive speech disorders. The most influential factor for repetitive speech disorders might be male gender.
