scholarly journals The efficacy and limits of magnetic resonance–guided focused ultrasound pallidotomy for Parkinson’s disease: a Phase I clinical trial

2019 ◽  
Vol 130 (6) ◽  
pp. 1853-1861 ◽  
Author(s):  
Na Young Jung ◽  
Chang Kyu Park ◽  
Minsoo Kim ◽  
Phil Hyu Lee ◽  
Young Ho Sohn ◽  
...  

OBJECTIVERecently, MR-guided focused ultrasound (MRgFUS) has emerged as an innovative treatment for numerous neurological disorders, including essential tremor, Parkinson’s disease (PD), and some psychiatric disorders. Thus, clinical applications with this modality have been tried using various targets. The purpose of this study was to determine the feasibility, initial effectiveness, and potential side effects of unilateral MRgFUS pallidotomy for the treatment of parkinsonian dyskinesia.METHODSA prospective, nonrandomized, single-arm clinical trial was conducted between December 2013 and May 2016 at a single tertiary medical center. Ten patients with medication-refractory, dyskinesia-dominant PD were enrolled. Participants underwent unilateral MRgFUS pallidotomy using the Exablate 4000 device (InSightec) after providing written informed consent. Patients were serially evaluated for motor improvement, neuropsychological effects, and adverse events according to the 1-year follow-up protocol. Primary measures included the changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) and Unified Dyskinesia Rating Scale (UDysRS) scores from baseline to 1 week, 1 month, 3 months, 6 months, and 1 year. Secondary measures consisted of neuropsychological batteries and quality of life questionnaire (SF-36). Technical failure and safety issues were also carefully assessed by monitoring all events during the study period.RESULTSUnilateral MRgFUS pallidotomy was successfully performed in 8 of 10 patients (80%), and patients were followed up for more than 6 months. Clinical outcomes showed significant improvements of 32.2% in the “medication-off” UPDRS part III score (p = 0.018) and 52.7% in UDysRS (p = 0.017) at the 6-month follow-up, as well as 39.1% (p = 0.046) and 42.7% (p = 0.046) at the 1-year follow-up, respectively. These results were accompanied by improvement in quality of life. Among 8 cases, 1 patient suffered an unusual side effect of sonication; however, no patient experienced persistent aftereffects.CONCLUSIONSIn the present study, which marks the first Phase I pilot study of unilateral MRgFUS pallidotomy for parkinsonian dyskinesia, the authors demonstrated the efficacy of pallidal lesioning using MRgFUS and certain limitations that are unavoidably associated with incomplete thermal lesioning due to technical issues. Further investigation and long-term follow-up are necessary to validate the use of MRgFUS in clinical practice.Clinical trial registration no.: NCT02003248 (clinicaltrials.gov)

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Nadeeka N. W. Dissanayaka ◽  
Farah Idu Jion ◽  
Nancy A. Pachana ◽  
John D. O’Sullivan ◽  
Rodney Marsh ◽  
...  

Background. Motor and nonmotor symptoms negatively influence Parkinson’s disease (PD) patients’ quality of life. Mindfulness interventions have been a recent focus in PD. The present study explores effectiveness of a manualized group mindfulness intervention tailored for PD in improving both motor and neuropsychiatric deficits in PD.Methods. Fourteen PD patients completed an 8-week mindfulness intervention that included 6 sessions. The Five Facet Mindfulness Questionnaire (FFMQ), Geriatric Anxiety Inventory, Hamilton Depression Rating Scale, PD Cognitive Rating Scale, Unified PD Rating Scale, PD Quality of Life Questionnaire, and Outcome Questionnaire (OQ-45) were administered before and after the intervention. Participants also completed the FFMQ-15 at each session. Gains at postassessment and at 6-month follow-up were compared to baseline using pairedt-tests and Wilcoxon nonparametric tests.Results. A significant increase in FFMQ-Observe subscale, a reduction in anxiety, depression, and OQ-45 symptom distress, an increase in PDCRS-Subcortical scores, and an improvement in postural instability, gait, and rigidity motor symptoms were observed at postassessment. Gains for the PDCRS were sustained at follow-up.Conclusion. The mindfulness intervention tailored for PD is associated with reduced anxiety and depression and improved cognitive and motor functioning. A randomised controlled trial using a large sample of PD patients is warranted.


2018 ◽  
Vol 128 (1) ◽  
pp. 202-210 ◽  
Author(s):  
Menashe Zaaroor ◽  
Alon Sinai ◽  
Dorith Goldsher ◽  
Ayelet Eran ◽  
Maria Nassar ◽  
...  

OBJECTIVEThalamotomy of the ventral intermediate nucleus (VIM) is effective in alleviating medication-resistant tremor in patients with essential tremor (ET) and Parkinson's disease (PD). MR-guided focused ultrasound (MRgFUS) is an innovative technology that enables noninvasive thalamotomy via thermal ablation.METHODSPatients with severe medication-resistant tremor underwent unilateral VIM thalamotomy using MRgFUS. Effects on tremor were evaluated using the Clinical Rating Scale for Tremor (CRST) in patients with ET and by the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with PD and ET-PD (defined as patients with ET who developed PD many years later). Quality of life in ET was measured by the Quality of Life in Essential Tremor (QUEST) questionnaire and in PD by the PD Questionnaire (PDQ-39).RESULTSThirty patients underwent MRgFUS, including 18 with ET, 9 with PD, and 3 with ET-PD. The mean age of the study population was 68.9 ± 8.3 years (range 46–87 years) with a mean disease duration of 12.1 ± 8.9 years (range 2–30 years). MRgFUS created a lesion at the planned target in all patients, resulting in cessation of tremor in the treated hand immediately following treatment. At 1 month posttreatment, the mean CRST score of the patients with ET decreased from 40.7 ± 11.6 to 9.3 ± 7.1 (p < 0.001) and was 8.2 ± 5.0 six months after treatment (p < 0.001, compared with baseline). Average QUEST scores decreased from 44.8 ± 12.9 to 13.1 ± 13.2 (p < 0.001) and was 12.3 ± 7.2 six months after treatment (p < 0.001). In patients with PD, the mean score of the motor part of the UPDRS decreased from 24.9 ± 8.0 to 16.4 ± 11.1 (p = 0.042) at 1 month and was 13.4 ± 9.2 six months after treatment (p = 0.009, compared with baseline). The mean PDQ-39 score decreased from 38.6 ± 16.8 to 26.1 ± 7.2 (p = 0.036) and was 20.6 ± 8.8 six months after treatment (p = 0.008). During follow-up of 6–24 months (mean 11.5 ± 7.2 months, median 12.0 months), tremor reappeared in 6 of the patients (2 with ET, 2 with PD, and 2 with ET-PD), to a lesser degree than before the procedure in 5. Adverse events that transiently occurred during sonication included headache (n = 11), short-lasting vertigo (n = 14) and dizziness (n = 4), nausea (n = 3), burning scalp sensation (n = 3), vomiting (n = 2) and lip paresthesia (n = 2). Adverse events that lasted after the procedure included gait ataxia (n = 5), unsteady feeling (n = 4), taste disturbances (n = 4), asthenia (n = 4), and hand ataxia (n = 3). No adverse event lasted beyond 3 months. Patients underwent on average 21.0 ± 6.9 sonications (range 14–45 sonications) with an average maximal sonication time of 16.0 ± 3.0 seconds (range 13–24 seconds). The mean maximal energy reached was 12,500 ± 4274 J (range 5850–23,040 J) with a mean maximal temperature of 56.5° ± 2.2°C (range 55°–60°C).CONCLUSIONSMRgFUS VIM thalamotomy to relieve medication-resistant tremor was safe and effective in patients with ET, PD, and ET-PD. Current results emphasize the superior adverse events profile of MRgFUS over other surgical approaches for treating tremor with similar efficacy. Large randomized studies are needed to assess prolonged efficacy and safety.


Author(s):  
Francesca Morgante ◽  
Valentina Oppo ◽  
Margherita Fabbri ◽  
Enrica Olivola ◽  
Chiara Sorbera ◽  
...  

Abstract Objectives Levodopa–Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson’s disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG. Methods Out of 512 PD subjects treated with LCIG at 9 Italian PD centers, we selected 25 LE-PD defined as age ≥ 80 years at last follow-up who were available to attend the study visit. Twenty-five PD patients (Control-PD, defined as age < 75 years at last follow-up) matched to LE-PD by disease and LCIG duration served as control group. The following motor and non-motor variables were ascertained: quality of life (PDQ-8), time spent in ON, wearing-off Questionnaire, Unified PD Rating Scale, freezing of gait questionnaire, Parkinson’s disease sleep scale-2, Non Motor Symptoms Scale (NMSS), and MOCA. Results No statistically significant differences were found between LE-PD and Control-PD on PDQ-8 and several motor and non-motor variables. LE-PD had less frequent and milder impulsive–compulsive behaviors and milder dyskinesia. At multivariable regression, worse quality of life was associated with UPDRS-III and NMSS scores but not to age at study visit and age at LICG implant. Rate of adverse effects was similar in both groups. Drop-out rate calculated in the whole PD cohort was comparable between the two groups. Conclusion Our data provide evidence that valuable LCIG infusion might be achieved in late elderly PD.


2021 ◽  
Vol 79 (8) ◽  
pp. 686-691
Author(s):  
Ingrid Estrada-Bellmann ◽  
Jesús Daniel Meléndez-Flores ◽  
Carlos Rodrigo Cámara-Lemarroy ◽  
Sergio Andrés Castillo-Torres

ABSTRACT Background: Self-efficacy is the individual’s assessment of his or hers ability to complete a specific task successfully and has been closely related to self-management and quality of life in several diseases. Objective: To investigate self-efficacy in a population of Parkinson’s disease (PD) patients in Mexico and study the factors that are associated with this measure. Methods: We carried out a cross-sectional observational study involving patients with PD in an outpatient neurology clinic in Mexico, using the following instruments: Spanish version of the Chronic Disease Self-Efficacy Scale (CDSES), Quality of Life Questionnaire PDQ-8, Movement Disorders Society-Unified Parkinson's disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), and Non-Motor Symptom Scale (NMSS). Clinical and demographic variables were also recorded. Results: We included 73 patients with a mean age of 65 years and most patients were male. Patients with lower CDSES scores (<7.75) had worse scores in MDS-UPDRS, NMSS, and PDQ-8 scales. CDSES scores were significantly correlated with MDS-UPDRS Part I (r=-0.497, p=<0.001), Part II (r= -0.271, p=0.020), Part III (r=-0.304, p=<0.001), PDQ-8 (r=-0.472, p=<0.001), and NMSS (r=-0.504, p=<0.001). Furthermore, when assessing the simultaneous effect of covariates associated with CDSES score, only Mood/Apathy domain of NMSS was significant (beta= -0.446, t= -3.807, p= 0.012). Conclusions: PD patients with lower self-efficacy scores had worse motor and non-motor symptomatology and quality of life. Mood/Apathy disorders were negatively associated with self-efficacy and contributed significantly to this measure.


2012 ◽  
Vol 70 (2) ◽  
pp. 119-124 ◽  
Author(s):  
Paula Luciana Scalzo ◽  
Carolina Reis Flores ◽  
Juliana Rúbia Marques ◽  
Simone Cristina de Oliveira Robini ◽  
Antônio Lúcio Teixeira

Parkinson's disease (PD) is characterized by motor symptoms that cause the decline of functional capacity and affect the quality of life (QoL). Objective: To evaluate the impact of changes in balance and walking capacity on the PD. Methods: The instruments used were: Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr Scale (HY), Schwab and England scale (SE), quality of life questionnaire (PDQ-39), Berg balance Scale (BBS) and six-minute walk test (6MWT). Results: Thirty-six patients with mean disease duration of 7.3 years were assessed. Lower scores on the BBS and shorter distances walked during the 6MWT correlated with a poorer perception of QoL. This correlation occurred at the expense of the mobility and daily living activities domains. Conclusion: Our results indicated that the impairment in balance while performing functional activities and the reduction in walking capacity are important factors that negatively affect the perception of QoL in PD patients.


2017 ◽  
Vol 95 (5) ◽  
pp. 419-424
Author(s):  
I. A. Zhukova ◽  
N. G. Zhukova ◽  
V. M. Alifirova ◽  
M. A. Nikitina ◽  
O. P. Izhboldina ◽  
...  

Background. The occurrence of emotional, cognitive, behavioral disorders associated with Parkinson’s disease is on the average 1.5-3 times higher than in the general population of the same age. At least one neuropsychiatric symptom is diagnosed in 77% of the patients and 46% have combination of three or more disturbances. Non-motor disturbances are manifested at all stages of Parkinson’s disease, but information about the relationship between their frequency and manifestations and the duration and severity of the disease is rather contradictory. Aim. To evaluate the prevalence and severity of depression and other non-motor symptoms in patients with Parkinson’s disease. Materials and methods. 206 patients at the average age 65.9±9.7 yr with Parkinson’s disease receiving pharmacotherapy were studied. The clinical assessment was carried out using the Unified Parkinson’s Disease Rating Scale, Hoehn & Yahr Scale, Beck depression inventory II, Hospital anxiety and depression scale, Apathy Scale, Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale, Montreal Cognitive Assessment, Parkinson’s Disease Quality of Life Questionnaire- 39, Medical Outcomes Study 36-Item Short Form. Results. 30.9% of the 62 patients with Parkinson’s disease suffered mild, 56 (27.4%) moderate, 21 (10.2%) severe depression and only 67 (32.5%) patients had no depression. The study revealed correlation of depression with apathy (r=0,488; p<0,001), low quality of life according to the PDQ-39 (r=0,471; p<0,001), cognition (r=0,451; p<0,001), emotional well-being (r=0,450; p≤0,001), anxiety (r=0,436; p<0,001). Conclusion. The prevalence of depression in patients with Parkinson’s disease is up to 67.5%. The proportion of patients with severe depression reaches 10.2%. Depression is one of the most frequent non-motor syndromes of Parkinson’s disease deteriorating the quality of life of the patients.


2021 ◽  
pp. 1-15
Author(s):  
Eduardo Tolosa ◽  
Georg Ebersbach ◽  
Joaquim J. Ferreira ◽  
Olivier Rascol ◽  
Angelo Antonini ◽  
...  

Background: A greater understanding of the everyday experiences of people with Parkinson’s disease (PD) and their carers may help improve clinical practice. Objective: The Parkinson’s Real-world Impact assesSMent (PRISM) study evaluated medication use, health-related quality of life (HRQoL) and the use of healthcare resources by people with PD and their carers. Methods: PRISM is an observational cross-sectional study, in which people with PD and their carers completed an online survey using structured questionnaires, including the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39), Non-Motor Symptoms Questionnaire (NMSQuest) and Zarit Burden Interview (ZBI). Results: Data were collected from 861 people with PD (mean age, 65.0 years; mean disease duration, 7.7 years) and 256 carers from six European countries. People with PD reported a large number of different co-morbidities, non-motor symptoms (mean NMSQuest score, 12.8), and impaired HRQoL (median PDQ-39 summary score, 29.1). Forty-five percent of people with PD reported at least one impulse control behaviour. Treatment patterns varied considerably between different European countries. Levodopa was taken in the last 12 months by 85.9% of participants, and as monotherapy by 21.8% . Carers, who were mostly female (64.8%) and the partner/spouse of the person with PD (82.1%), reported mild to moderate burden (mean ZBI total score, 26.6). Conclusions: The PRISM study sheds light on the lives of people with PD and those who care for them, re-emphasising the many challenges they face in everyday life. The study also provides insights into the current treatment of PD in Europe.


2021 ◽  
Vol 11 (4) ◽  
pp. 416
Author(s):  
Carla Piano ◽  
Francesco Bove ◽  
Delia Mulas ◽  
Enrico Di Stasio ◽  
Alfonso Fasano ◽  
...  

Previous investigations have reported on the motor benefits and safety of chronic extradural motor cortex stimulation (EMCS) for patients with Parkinson’s disease (PD), but studies addressing the long-term clinical outcome are still lacking. In this study, nine consecutive PD patients who underwent EMCS were prospectively recruited, with a mean follow-up time of 5.1 ± 2.5 years. As compared to the preoperatory baseline, the Unified Parkinson’s Disease Rating Scale (UPDRS)-III in the off-medication condition significantly decreased by 13.8% at 12 months, 16.1% at 18 months, 18.4% at 24 months, 21% at 36 months, 15.6% at 60 months, and 8.6% at 72 months. The UPDRS-IV decreased by 30.8% at 12 months, 22.1% at 24 months, 25% at 60 months, and 36.5% at 72 months. Dopaminergic therapy showed a progressive reduction, significant at 60 months (11.8%). Quality of life improved by 18.0% at 12 months, and 22.4% at 60 months. No surgical complication, cognitive or behavioral change occurred. The only adverse event reported was an infection of the implantable pulse generator pocket. Even in the long-term follow-up, EMCS was shown to be a safe and effective treatment option in PD patients, resulting in improvements in motor symptoms and quality of life, and reductions in motor complications and dopaminergic therapy.


2022 ◽  
Author(s):  
Manoela de Paula Ferreira ◽  
Adriano Zanardi da Silva ◽  
Bruna Yamaguchi ◽  
Sunita Mathur ◽  
Taina Ribas Melo ◽  
...  

BACKGROUND Many people with Parkinson’s disease (PD) have never received rehabilitation care due to lack of accessibility and transportation and high therapy costs for in-person rehabilitation. Home-based dance exercise is an innovative, low-cost therapy that may reduce accessibility barriers to exercise. Especially since the COVID-19 pandemic, home-exercise programs are a highly relevant, alternative approach for people with PD OBJECTIVE This clinical trial protocol aims to explore the effects of a Home-Based contemporary dance exercise program for people with moderate Parkinson’s Disease (PD), focusing on balance, functional mobility, quality of life (QOL), cognitive function, and depression. METHODS This protocol is for a non-randomized clinical trial for adults with moderate PD divided into control group (CG) and Experimental Group (EG). Participants from the EG will perform video-dances of the contemporary dance, delivered in a DVD format. The video-dances will be executed 16 weeks, three times per week, 30 minutes each day at home, with exercise intensity controlled by the BORG scale. Participants from the CG will not receive any new exercise therapy. As primary outcomes, the signs and symptoms of the PD assessed by the Unified Parkinson’s Disease Rating Scale – UPDRS II and III, Hoehn and Yahr for the PD severity, and health-related quality of life (HRQL), measured by the Parkinson’s Disease Questionnaire – PDQ-39) will be tested. Secondary outcomes include cognitive function by the Montreal Cognitive Assessment – MoCA, balance by the Mini-BESTest, functional mobility by the Timed “Up and Go” test – TUG and depression by the Geriatric Depression Scale – GDS. All outcomes will be assessed in an in-person evaluation by a blinded assessor before and after the 16 weeks of the program. RESULTS This protocol has a pilot study that included 10 participants (5 in each group). It was observed positive results favoring the EG over cognitive function (p = 0.034). In addition, HRQL, balance, and depression were improved after the pilot program in the EG, however, without significant difference. CONCLUSIONS This clinical trial has the potential to be a safe alternative exercise approach under COVID restrictions and travel-free therapy with effects on PD symptoms. CLINICALTRIAL RBR-58T68W (Brazilian Clinical Trials Registry)


Neurology ◽  
2019 ◽  
Vol 93 (24) ◽  
pp. e2284-e2293 ◽  
Author(s):  
Casey H. Halpern ◽  
Veronica Santini ◽  
Nir Lipsman ◽  
Andres M. Lozano ◽  
Michael L. Schwartz ◽  
...  

ObjectiveTo test the hypothesis that transcranial magnetic resonance–guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial.MethodsOutcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor–motor (scale of 0–32), functional disability (scale of 0–32), and postural tremor (scale of 0–4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0–100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported.ResultsMeasured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%–50% in hand tremor, 43%–56% in disability, 50%–75% in postural tremor, and 27%–42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0–2, p = 0.0098) and disability (95% CI 1–4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred.ConclusionsResults at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant.Clinicaltrials.gov identifierNCT01827904.Classification of evidenceThis study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.


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