Pedunculopontine Nucleus Stimulation Improves Gait Freezing in Parkinson Disease

Neurosurgery ◽  
2011 ◽  
Vol 69 (6) ◽  
pp. 1248-1254 ◽  
Author(s):  
Wesley Thevathasan ◽  
Terry J. Coyne ◽  
Jonathan A. Hyam ◽  
Graham Kerr ◽  
Ned Jenkinson ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Clinical Application ◽  
Rating Scale ◽  
Pedunculopontine Nucleus ◽  
Postural Instability ◽  
Bilateral Stimulation ◽  
Novel Therapy ◽  
Beneficial Effects ◽  
Disease Rating ◽  
Stimulation Of

Abstract BACKGROUND Pedunculopontine nucleus (PPN) stimulation is a novel therapy for Parkinson disease. However, controversies remain regarding the clinical application of this new therapy, including patient selection, electrode positioning, and how best to assess outcomes. OBJECTIVE To clarify the clinical application of PPN stimulation in Parkinson disease. METHODS Five consecutive patients with Parkinson disease complicated by severe gait freezing, postural instability, and frequent falls (all persisting even while the patient was on medication) received bilateral stimulation of the mid-lower PPN without costimulation of other brain targets. Outcomes were assessed prospectively over 2 years with gait-specific questionnaires and the Unified Parkinson Disease Rating Scale (part III). RESULTS The primary outcome, the Gait and Falls Questionnaire score, improved significantly with stimulation. Benefits were maintained over 2 years. Unified Parkinson Disease Rating Scale (part III) items assessing gait and posture were relatively insensitive to these treatment effects. Beneficial effects often appeared to outlast stimulation for hours or longer. Thus, single-session on- vs off-stimulation assessments may be susceptible to “delayed washout effects.” Stimulation of the PPN did not change akinesia scores or dopaminergic medication requirements. CONCLUSION Bilateral stimulation of the mid-lower PPN (more caudal than previous reports) without costimulation of other brain targets may be beneficial for the subgroup of patients with Parkinson disease who experience severe gait freezing and postural instability with frequent falls, which persist even while on medication. Choosing appropriate outcome measures and accounting for the possibility of prolonged stimulation washout effects appear to be important for detecting the clinical benefits.

Motor cortex stimulation in patients with Parkinson disease: 12-month follow-up in 4 patients

2008 ◽  
Vol 109 (1) ◽  
pp. 133-139 ◽  
Author(s):  
Jeffrey E. Arle ◽  
Diana Apetauerova ◽  
Janet Zani ◽  
D. Vedran Deletis ◽  
Dana L. Penney ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Motor Cortex ◽  
Parkinson Disease ◽  
Rating Scale ◽  
Motor Cortex Stimulation ◽  
Medline Search ◽  
Disease Rating ◽  
Chronic Pain Conditions ◽  
Stimulation Of

Object Since the initial 1991 report by Tsubokawa et al., stimulation of the M1 region of cortex has been used to treat chronic pain conditions and a variety of movement disorders. Methods A Medline search of the literature published between 1991 and the beginning of 2007 revealed 459 cases in which motor cortex stimulation (MCS) was used. Of these, 72 were related to a movement disorder. More recently, up to 16 patients specifically with Parkinson disease were treated with MCS, and a variety of results were reported. In this report the authors describe 4 patients who were treated with extradural MCS. Results Although there were benefits seen within the first 6 months in Unified Parkinson's Disease Rating Scale Part III scores (decreased by 60%), tremor was only modestly managed with MCS in this group, and most benefits seen initially were lost by the end of 12 months. Conclusions Although there have been some positive findings using MCS for Parkinson disease, a larger study may be needed to better determine if it should be pursued as an alternative surgical treatment to DBS.

The mechanism and effect of chronic electrical stimulation of the globus pallidus for treatment of Parkinson disease

2004 ◽  
Vol 100 (6) ◽  
pp. 997-1001 ◽  
Author(s):  
Mitsuhiro Ogura ◽  
Naoyuki Nakao ◽  
Ekini Nakai ◽  
Yuji Uematsu ◽  
Toru Itakura
Keyword(s):  
Electrical Stimulation ◽  
Parkinson Disease ◽  
Globus Pallidus ◽  
Rating Scale ◽  
Underlying Mechanism ◽  
Clinical Effects ◽  
Content Type ◽  
Chronic Electrical Stimulation ◽  
Fine Print ◽  
Stimulation Of

Object. Although chronic electrical stimulation of the globus pallidus (GP) has been shown to ameliorate motor disabilities in Parkinson disease (PD), the underlying mechanism remains to be clarified. In this study the authors explored the mechanism for the effects of deep brain stimulation of the GP by investigating the changes in neurotransmitter levels in the cerebrospinal fluid (CSF) during the stimulation. Methods. Thirty patients received chronic electrical stimulation of the GP internus (GPi). Clinical effects were assessed using the Unified PD Rating Scale (UPDRS) and the Hoehn and Yahr Staging Scale at 1 week before surgery and at 6 and 12 months after surgery. One day after surgery, CSF samples were collected through a ventricular tube before and 1 hour after GPi stimulation. The concentration of neurotransmitters such as γ-aminobutyric acid (GABA), noradrenaline, dopamine, and homovanillic acid (HVA) in the CSF was measured using high-performance liquid chromatography. The treatment was effective for tremors, rigidity, and drug-induced dyskinesia. The concentration of GABA in the CSF increased significantly during stimulation, although there were no significant changes in the level of noradrenaline, dopamine, and HVA. A comparison between an increased rate of GABA concentration and a lower UPDRS score 6 months postimplantation revealed that the increase in the GABA level correlated with the stimulation-induced clinical effects. Conclusions. Stimulation of the GPi substantially benefits patients with PD. The underlying mechanism of the treatment may involve activation of GABAergic afferents in the GP.

Bilateral stimulation of the subthalamic nucleus in patients with Parkinson disease: a study of efficacy and safety

2002 ◽  
Vol 96 (4) ◽  
pp. 666-672 ◽  
Author(s):  
Tanya Simuni ◽  
Jurg L. Jaggi ◽  
Heather Mulholland ◽  
Howard I. Hurtig ◽  
Amy Colcher ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Parkinson Disease ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Bilateral Stimulation ◽  
Content Type ◽  
Preoperative Status ◽  
Fine Print ◽  
Deep Brain ◽  
Stimulation Of

Object. Palliative neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson disease (PD) that is complicated by severe motor fluctuations. Despite great enthusiasm for long-term deep brain stimulation (DBS) of the subthalamic nucleus (STN), existing reports on this treatment are limited. The present study was designed to investigate the safety and efficacy of bilateral stimulation of the STN for the treatment of PD. Methods. In 12 patients with severe PD, electrodes were stereotactically implanted into the STN with the assistance of electrophysiological conformation of the target location. All patients were evaluated preoperatively during both medication-off and -on conditions, as well as postoperatively at 3, 6, and 12 months during medication-on and -off states and stimulation-on and -off conditions. Tests included assessments based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. The stimulation effect was significant in patients who were in the medication-off state, resulting in a 47% improvement in the UPDRS Part III (Motor Examination) score at 12 months, compared with preoperative status. The benefit was stable for the duration of the follow-up period. Stimulation produced no additional benefit during the medication-on state, however, when compared with patient preoperative status. Significant improvements were made in reducing dyskinesias, fluctuations, and duration of off periods. Conclusions. This study demonstrates that DBS of the STN is an effective treatment for patients with advanced, medication-refractory PD. Deep brain stimulation of the STN produced robust improvements in motor performance in these severely disabled patients while they were in the medication-off state. Serious adverse events were common in this cohort; however, only two patients suffered permanent sequelae.

scholarly journals Acoustic Voice Modifications in Individuals with Parkinson Disease Submitted to Deep Brain Stimulation

2019 ◽  
Vol 23 (02) ◽  
pp. 203-208 ◽  
Author(s):  
Aline Juliane Romann ◽  
Bárbara Costa Beber ◽  
Carla Aparecida Cielo ◽  
Carlos Roberto de Mello Rieder
Keyword(s):  
Deep Brain Stimulation ◽  
Parkinson Disease ◽  
Brain Stimulation ◽  
Statistical Difference ◽  
Rating Scale ◽  
Acoustic Measures ◽  
Disease Rating ◽  
The Voice ◽  
Stn Dbs ◽  
Deep Brain

Introduction Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor function in individuals with Parkinson disease (PD). The evidence about the effects of STN-DBS on the voice is still inconclusive. Objective To verify the effect of STN-DBS on the voice of Brazilian individuals with PD. Methods Sixteen participants were evaluated on the Unified Parkinson Disease Rating Scale—Part III, and by the measurement of the acoustic modifications in on and off conditions of stimulation. Results The motor symptoms showed significant improvement with STN-DBS on. Regarding the acoustic measures of the voice, only the maximum fundamental frequency (fhi) showed a statistical difference between on- and off-conditions, with reduction in off-condition. Conclusion Changes in computerized acoustic measures are more valuable when interpreted in conjunction with changes in other measures. The single finding in fhi suggests that DBS-STN increases vocal instability. The interpretation of this result should be done carefully, since it may not be of great value if other measures that also indicate instability are not significantly different.

Long-Term Improvement of Parkinson Disease Motor Symptoms Derived From Lesions of Prelemniscal Fiber Tract Components

2020 ◽  
Vol 19 (5) ◽  
pp. 539-550
Author(s):  
Maria Guadalupe García-Gomar ◽  
Luis Concha ◽  
Julian Soto-Abraham ◽  
Jacques D Tournier ◽  
Gustavo Aguado-Carrillo ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Rating Scale ◽  
Pedunculopontine Nucleus ◽  
Cerebellar Nuclei ◽  
Symptom Improvement ◽  
Fiber Tract ◽  
Fiber Tracts ◽  
Score Improvement ◽  
Updrs Score ◽  
Specific Symptoms

Abstract BACKGROUND Prelemniscal radiations (Raprl) are composed of different fiber tracts, connecting the brain stem and cerebellum with basal ganglia and cerebral cortex. In Parkinson disease (PD), lesions in Raprl induce improvement of tremor, rigidity, and bradykinesia in some patients, while others show improvement of only 1 or 2 symptoms, suggesting different fiber tracts mediate different symptoms. OBJECTIVE To search for correlations between improvements of specific symptoms with surgical lesions of specific fiber tract components of Raprl in patients with PD. METHODS A total of 10 patients were treated with unilateral radiofrequency lesions directed to Raprl. The improvement for tremor, rigidity, bradykinesia, posture, and gait was evaluated at 24 to 33 mo after operation through the Unified Parkinson's Disease Rating Scale (UPDRS) score, and the precise location and extension of lesions through structural magnetic resonance imaging and probabilistic tractography at 6 to 8 mo postsurgery. Correlation between percentage of fiber tract involvement and percentage of UPDRS-III score improvement was evaluated through Spearman's correlation coefficient. RESULTS Group average improvement was 86% for tremor, 62% for rigidity, 56% for bradykinesia, and 45% for gait and posture. Improvement in global UPDRS score correlated with extent of lesions in fibers connecting with contralateral cerebellar cortex and improvement of posture and gait with fibers connecting with contralateral deep cerebellar nuclei. Lesion of fibers connecting the globus pallidum with pedunculopontine nucleus induced improvement of gait and posture over other symptoms. CONCLUSION Partial lesion of Raprl fibers resulted in symptom improvement at 2-yr follow-up. Lesions of selective fiber components may result in selective improvement of specific symptoms.

scholarly journals Bilateral Subthalamic Nucleus Deep Brain Stimulation in Elderly Patients With Parkinson Disease: A Case-Control Study

2020 ◽  
Vol 19 (3) ◽  
pp. 234-240
Author(s):  
Kyle T Mitchell ◽  
John R Younce ◽  
Scott A Norris ◽  
Samer D Tabbal ◽  
Joshua L Dowling ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Parkinson Disease ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Intracerebral Hemorrhages ◽  
Disease Rating ◽  
Equivalent Reduction ◽  
Stn Dbs ◽  
Deep Brain

Abstract BACKGROUND Subthalamic nucleus deep brain stimulation (STN DBS) is an effective adjunctive therapy for Parkinson disease. Studies have shown improvement of motor function but often exclude patients older than 75 yr. OBJECTIVE To determine the safety and effectiveness of STN DBS in patients 75 yr and older. METHODS A total of 104 patients (52 patients >75 yr old, 52 patients <75 yr old) with STN DBS were paired and retrospectively analyzed. The primary outcome was change in Unified Parkinson Disease Rating Scale (UPDRS) subscale III at 1 yr postoperatively, OFF medication. Secondary outcomes were changes in UPDRS I, II, and IV subscales and levodopa equivalents. Complications and all-cause mortality were assessed at 30 d and 1 yr. RESULTS Both cohorts had significant improvements in UPDRS III at 6 mo and 1 yr with no difference between cohorts. Change in UPDRS III was noninferior to the younger cohort. The cohorts had similar worsening in UPDRS I at 1 yr, no change in UPDRS II, similar improvement in UPDRS IV, and similar levodopa equivalent reduction. There were similar numbers of postoperative intracerebral hemorrhages (2/52 in each cohort, more severe in the older cohort) and surgical complications (4/52 in each cohort), and mortality in the older cohort was similar to an additional matched cohort not receiving DBS. CONCLUSION STN DBS provides substantial motor benefit and reduction in levodopa equivalents with a low rate of complications in older patients, which is also noninferior to the benefit in younger patients. STN DBS remains an effective therapy for those over 75 yr.

scholarly journals Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease

Neurology ◽  
2017 ◽  
Vol 88 (23) ◽  
pp. 2198-2206 ◽  
Author(s):  
Fabrizio Stocchi ◽  
Olivier Rascol ◽  
Robert A. Hauser ◽  
Susan Huyck ◽  
Anjela Tzontcheva ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Active Control ◽  
Rating Scale ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Link Type ◽  
Parallel Group ◽  
Number Of Patients ◽  
Disease Rating ◽  
Post Hoc

Objective:To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy.Methods:This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving l-dopa or dopamine agonists. Patients with a Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS2+3).Results:The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS2+3 scores (with a negative difference indicating improvement vs placebo) were preladenant 2 mg = 2.60 (0.86, 4.30), preladenant 5 mg = 1.30 (−0.41, 2.94), preladenant 10 mg = 0.40 (−1.29, 2.11), and rasagiline 1 mg = 0.30 (−1.35, 2.03). Post hoc analyses did not identify a single causal factor that could explain the finding of a failed trial. Preladenant was generally well-tolerated with few patients discontinuing due to adverse events (preladenant 7%, rasagiline 3%, placebo 4%).Conclusions:No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results.Clinical trial registration:Clinicaltrials.gov: NCT01155479.Classification of evidence:This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg).

scholarly journals Metabolomic biomarkers as strong correlates of Parkinson disease progression

Neurology ◽  
2017 ◽  
Vol 88 (9) ◽  
pp. 862-869 ◽  
Author(s):  
Peter A. LeWitt ◽  
Jia Li ◽  
Mei Lu ◽  
Lining Guo ◽  
Peggy Auinger
Keyword(s):  
Parkinson Disease ◽  
High Performance ◽  
Rating Scale ◽  
High Positive Correlation ◽  
Metabolomic Profiling ◽  
Disease Rating ◽  
Nigrostriatal Neurons ◽  
Systemic Manifestations ◽  
Total Body ◽  
Selection Operator

Objective:To determine whether a Parkinson disease (PD)-specific biochemical signature might be found in the total body metabolic milieu or in the CSF compartment, especially since this disorder has systemic manifestations beyond the progressive loss of dopaminergic nigrostriatal neurons.Methods:Our goal was to discover biomarkers of PD progression. Using ultra-high-performance liquid chromatography linked to gas chromatography and tandem mass spectrometry, we measured concentrations of small-molecule (≤1.5 kDa) constituents of plasma and CSF from 49 unmedicated, mildly affected patients with PD (mean age 61.4 years; mean duration of PD 11.4 months). Specimens were collected twice (baseline and final) at intervals up to 24 months. During this time, mean Unified Parkinson’s Disease Rating Scale (UPDRS) parts 2 + 3 scores increased 47% (from 28.8 to 42.2). Measured compounds underwent unbiased univariate and multivariate analyses, including fitting data into multiple linear regression with variable selection using least absolute shrinkage and selection operator (LASSO).Results:Of 575 identified plasma and 383 CSF biochemicals, LASSO led to selection of 15 baseline plasma constituents with high positive correlation (0.87, p = 2.2e−16) to baseline-to-final change in UPDRS parts 2 + 3 scores. Three of the compounds had xanthine structures, and 4 were either medium- or long-chain fatty acids. For the 15 LASSO-selected biomarkers, pathway enrichment software found no overrepresentation among metabolic pathways. CSF concentrations of the dopamine metabolite homovanillate showed little change between baseline and final collections and minimal correlation with worsening UPDRS parts 2 + 3 scores (0.29, p = 0.041).Conclusions:Metabolomic profiling of plasma yielded strong prediction of PD progression and offered biomarkers that may provide new insights into PD pathogenesis.

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