Two-Weeks of Twice-Daily Prism Adaptation Treatment does not Improve Posture or Gait in Parkinson’s Disease: A Double-Blind Randomized Controlled Trial

2021 ◽  
Author(s):  
Janet H Bultitude ◽  
Dawna M Pidgeon ◽  
Pauline R LeBlanc ◽  
Charlotte A Jeffreys ◽  
Faith P Alexandre ◽  
...  

Abstract BackgroundGait difficulties in Parkinson’s disease have been related to problems shifting center of gravity forward. We previously showed reduced forward stepping latencies for people with Parkinson’s disease after one session of adaptation to upward visual shifts, which produces downward motor after-effects and potentially shifts center of gravity forward. Here we tested if repeated prism adaptation improved gait and postural control in Parkinson’s disease through a parallel, double-blind, randomized, sham-controlled trial.MethodsWe recruited participants with idiopathic Parkinson’s disease aged 40 – 80 and meeting any one of three clinical criteria: 1) Hoehn and Yahr Stage II.5 – IV; 2) Scoring > 0 on the gait, freezing of gait, and/or postural stability items of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale; or 3) Timed Up and Go > 12 seconds. Sealed envelope style randomization allocated participants to two weeks of twice-daily prism adaptation or sham treatment. Participants, care givers, and those assessing the outcomes were blinded to group assignment. Primary outcomes were changes in postural control measured using the Berg Balance Scale; and the Limits of Stability, Sensory Organisation, and Motor Control tests from the Smart EquiTest system. Secondary outcomes included other physiotherapy and questionnaire measures. Outcomes were assessed at the Dartmouth Hitchcock Medical Center immediately before and after the treatment period, with further long-term postal follow-up over two months. Outcomes were analysed using Analyses of Variance with follow-up t-tests. ResultsEighteen participants were allocated to undergo prism adaptation, of which sixteen were analysed. Thirteen participants were allocated to undergo sham treatment, and all were analysed. The prism adaptation group showed increased forward stepping velocity on the Limits of Stability test (Pre: M=2.33, SEM=0.24; post: M=2.88, SEM=0.26; t(15)=3.2, p=.005, d=.819). The sham group showed no such change (Pre: M=2.13, SEM=0.22; 1d post: M=2.24, SEM=0.22; t(13)=.636, p=.537, d=.176). However, there were no group differences for any other outcome measures, and no indications that prism adaptation produced functional improvements in posture, gait, or activities of daily living. ConclusionsPrism adaptation does not improve gait or postural control in Parkinson’s disease. Trial RegistrationRegistered prospectively at ClinicalTrials.gov, 5th March 2015, NCT02380859, https://clinicaltrials.gov/ct2/show/NCT02380859.

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Janet H. Bultitude ◽  
Dawna M. Pidgeon ◽  
Pauline R. LeBlanc ◽  
Charlotte A. Jeffreys ◽  
Faith P. Alexandre ◽  
...  

Abstract Background Gait difficulties in Parkinson’s disease have been related to problems shifting the center of gravity forward. We previously showed reduced forward stepping latencies for people with Parkinson’s disease after one session of adaptation to upward visual shifts, which produces downward motor after-effects and potentially shifts the center of gravity forward. Here we tested if repeated prism adaptation improved gait and postural control in Parkinson’s disease through a parallel, double-blind, randomized, sham-controlled trial. Methods We recruited participants with idiopathic Parkinson’s disease aged 40–85 and meeting any one of three clinical criteria: (1) Hoehn and Yahr Stage II.5–IV; (2) scoring > 0 on the gait, freezing of gait, and/or postural stability items of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale; or (3) Timed Up and Go > 12 s. Sealed envelope style randomization allocated participants to two weeks of twice-daily prism adaptation or sham treatment. Participants, care givers, and those assessing the outcomes were blinded to group assignment. Primary outcomes were changes in postural control measured using the Berg Balance Scale and the Limits of Stability, Sensory Organization, and Motor Control tests from the Smart EquiTest system. Secondary outcomes included other physiotherapy and questionnaire measures. Outcomes were assessed at the Dartmouth Hitchcock Medical Center immediately before and after the treatment period, with further long-term postal follow-up over 3 months. Outcomes were analyzed using analyses of variance with follow-up t tests. Results Eighteen participants were allocated to undergo prism adaptation, of which sixteen were analyzed. Thirteen participants were allocated to undergo sham treatment, and all were analyzed. The prism adaptation group showed increased forward stepping velocity on the Limits of Stability test (pre: M=2.33, SEM=0.24; post: M=2.88, SEM=0.26; t(15)=3.2, p=.005, d=.819). The sham group showed no such change (pre: M=2.13, SEM=0.22; 1d post: M=2.24, SEM=0.22; t(13)=.636, p=.537, d=.176). However, there were no group differences for any other outcome measures and no indications that prism adaptation produced functional improvements in posture, gait, or activities of daily living. Conclusions Prism adaptation does not improve gait or postural control in Parkinson’s disease. Trial registration ClinicalTrials.govNCT02380859. Registered prospectively on 5 March 2015.


BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040527
Author(s):  
Julia C Greenland ◽  
Emma Cutting ◽  
Sonakshi Kadyan ◽  
Simon Bond ◽  
Anita Chhabra ◽  
...  

IntroductionThe immune system is implicated in the aetiology and progression of Parkinson’s disease (PD). Inflammation and immune activation occur both in the brain and in the periphery, and a proinflammatory cytokine profile is associated with more rapid clinical progression. Furthermore, the risk of developing PD is related to genetic variation in immune-related genes and reduced by the use of immunosuppressant medication. We are therefore conducting a ‘proof of concept’ trial of azathioprine, an immunosuppressant medication, to investigate whether suppressing the peripheral immune system has a disease-modifying effect in PD.Methods and analysisAZA-PD is a phase II randomised placebo-controlled double-blind trial in early PD. Sixty participants, with clinical markers indicating an elevated risk of disease progression and no inflammatory or immune comorbidity, will be treated (azathioprine:placebo, 1:1) for 12 months, with a further 6-month follow-up. The primary outcome is the change in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale gait/axial score in the OFF state over the 12-month treatment period. Exploratory outcomes include additional measures of motor and cognitive function, non-motor symptoms and quality of life. In addition, peripheral and central immune markers will be investigated through analysis of blood, cerebrospinal fluid and PK-11195 positron emission tomography imaging.Ethics and disseminationThe study was approved by the London-Westminster research ethics committee (reference 19/LO/1705) and has been accepted by the Medicines and Healthcare products Regulatory Agency (MHRA) for a clinical trials authorisation (reference CTA 12854/0248/001–0001). In addition, approval has been granted from the Administration of Radioactive Substances Advisory Committee. The results of this trial will be disseminated through publication in scientific journals and presentation at national and international conferences, and a lay summary will be available on our website.Trial registration numbersISRCTN14616801 and EudraCT- 2018-003089-14.


1997 ◽  
Vol 2 (3) ◽  
pp. E13 ◽  
Author(s):  
Ronald F. Young ◽  
Anne Shumway-Cook ◽  
Sandra S. Vermeulen ◽  
Peter Grimm ◽  
John Blasko ◽  
...  

Fifty-five patients underwent radiosurgical placement of lesions either in the thalamus (27 patients) or globus pallidus (28 patients) for treatment of movement disorders. Patients were evaluated pre- and postoperatively by a team of observers skilled in the assessment of gait and movement disorders who were blinded to the procedure performed. They were not associated with the surgical team and concomitantly and blindly also assessed a group of 11 control patients with Parkinson's disease who did not undergo any surgical procedures. All stereotactic lesions were made with the Leksell gamma unit using the 4-mm secondary collimator helmet and a single isocenter with dose maximums from 120 to 160 Gy. Clinical follow-up evaluation indicated that 88% of patients who underwent thalamotomy became tremor free or nearly tremor free. Statistically significant improvements in performance were noted in the independent assessments of Unified Parkinson's Disease Rating Scale (UPDRS) scores in the patients undergoing thalamotomy. Eighty-five and seven-tenths percent of patients undergoing pallidotomy who had exhibited levodopa-induced dyskinesias had total or near-total relief of that symptom. Clinical assessment indicated improvement of bradykinesia and rigidity in 64.3% of patients who underwent pallidotomy. Independent blinded assessments did not reveal statistically significant improvements in Hoehn and Yahr scores or UPDRS scores. On the other hand, 64.7% of patients showed improvements in subscores of the UPDRS, including activities of daily living (58%), total contralateral score (58%), and contralateral motor scores (47%). Ipsilateral total UPDRS and ipsilateral motor scores were both improved in 59% of patients. One (1.8%) of 55 patients experienced a homonymous hemianopsia 9 months after pallidotomy due to an unexpectedly large lesion. No other complications of any kind were seen. Follow-up neuroimaging confirmed correct lesion location in all patients, with a mean maximum deviation from the planned target of 1 mm in the vertical axis. Measurements of lesions at regular interals on postoperative magnetic resonance images demonstrated considerable variability in lesion volumes. The safety and efficacy of functional lesions made with the gamma knife appear to be similar to those made with the assistance of electrophysiological guidance with open functional stereotactic procedures. Functional lesions may be made safely and accurately using gamma knife radiosurgical techniques. The efficacy is equivalent to that reported for open techniques that use radiofrequency lesioning methods with electrophysiological guidance. Complications are very infrequent with the radiosurgical method. The use of functional radiosurgical lesioning to treat movement disorders is particularly attractive in older patients and those with major systemic diseases or coagulopathies; its use in the general movement disorder population seems reasonable as well.


2021 ◽  
pp. 1-16
Author(s):  
Michael Bartl ◽  
Mohammed Dakna ◽  
Sebastian Schade ◽  
Tamara Wicke ◽  
Elisabeth Lang ◽  
...  

Background: The MDS-Unified Parkinson’s disease (PD) Rating Scale (MDS-UPDRS) is the most used scale in clinical trials. Little is known about the predictive potential of its single items. Objective: To systematically dissect MDS-UPDRS to predict PD progression. Methods: 574 de novo PD patients and 305 healthy controls were investigated at baseline (BL) in the single-center DeNoPa (6-year follow-up) and multi-center PPMI (8-year follow-up) cohorts. We calculated cumulative link mixed models of single MDS-UPDRS items for odds ratios (OR) for class change within the scale. Models were adjusted for age, sex, time, and levodopa equivalent daily dose. Annual change and progression of the square roots of the MDS-UDPRS subscores and Total Score were estimated by linear mixed modeling. Results: Baseline demographics revealed more common tremor dominant subtype in DeNoPa and postural instability and gait disorders-subtype and multiethnicity in PPMI. Subscore progression estimates were higher in PPMI but showed similar slopes and progression in both cohorts. Increased ORs for faster progression were found from BL subscores I and II (activities of daily living; ADL) most marked for subscore III (rigidity of neck/lower extremities, agility of the legs, gait, hands, and global spontaneity of movements). Tremor items showed low ORs/negative values. Conclusion: Higher scores at baseline for ADL, freezing, and rigidity were predictors of faster deterioration in both cohorts. Precision and predictability of the MDS-UPDRS were higher in the single-center setting, indicating the need for rigorous training and/or video documentation to improve its use in multi-center cohorts, for example, clinical trials.


2020 ◽  
Author(s):  
Mahmut Atum ◽  
Bekir Enes Demiryurek

Abstract Background: The study aims to investigate the relationship between the progression of idiopathic Parkinson's disease (IPD) and retinal morphology. Methods: The study was carried out with 23 patients diagnosed with early-stage IPD (phases 1 and 2 of the Hoehn and Yahr scale) and 30 age-matched healthy controls. All patients were followed up at least two years, with 6-month intervals (initial, 6th month, 12th month, 18th month, and 24th month), and detailed neurological and ophthalmic examinations were performed at each follow-up. Unified Parkinson's Disease Rating Scale part III (UPDRS Part III) scores, Hoehn and Yahr (H&Y) scores, best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness were analyzed at each visit. Results: The average age of the IPD and control groups was 43.96 ± 4.88 years, 44.53 ± 0.83 years, respectively. The mean duration of the disease in the IPD group was 7.48 ± 5.10 months at the start of the study (range 0-16). There was no statistically significant difference in BCVA and IOP values between the two groups during the two-year follow-up period (p> 0.05, p> 0.05, respectively). Average and superior quadrant RNFL thicknesses were statistically different between the two groups at 24 months and there was no significant difference between other visits (p = 0.025, p=0.034, p> 0.05, respectively). There was no statistically significant difference in CMT between the two groups during the follow-up period (p> 0.05). Conclusion: Average and superior quadrant RNFL thicknesses were significantly thinning with the progression of IPD.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ka-Kit Chua ◽  
Adrian Wong ◽  
Kam-Wa Chan ◽  
Yin-Kei Lau ◽  
Zhao-Xiang Bian ◽  
...  

Nonmotor symptoms (NMS) of Parkinson’s disease (PD) have devastating impacts on both patients and their caregivers. Jiawei-Liujunzi Tang (JLT) has been used to treat some NMS of PD based on the Chinese medicine theory since Qing dynasty. Here we report a double-blind, randomized, placebo-controlled, add-on clinical trial aiming at evaluating the efficacy and safety of the JLT in treating NMS in PD patients. We randomly assigned 111 patients with idiopathic PD to receive either JLT or placebo for 32 weeks. Outcome measures were baseline to week 32 changes in Movement Disorder Society-Sponsored Revision of Unified PD Rating Scale (MDS-UPDRS) Parts I–IV and in NMS assessment scale for PD (NMSS). We observed improvements in the NMSS total score (p=0.019), mood/cognition (p=0.005), and reduction in hallucinations (p=0.024). In addition, post hoc analysis showed a significant reduction in constipation (p<0.001). However, there was no evidence of improvement in MDS-UPDRS Part I total score (p=0.216) at week 32. Adverse events (AEs) were mild and comparable between the two groups. In conclusion, long-term administration of JLT is well tolerated and shows significant benefits in improving NMS including mood, cognition, and constipation.


2013 ◽  
Vol 16 (7) ◽  
pp. 1529-1537 ◽  
Author(s):  
Lina Zhang ◽  
Zhiqin Zhang ◽  
Yangmei Chen ◽  
Xinyue Qin ◽  
Huadong Zhou ◽  
...  

Abstract Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable – mean adjusted total daily off time – decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.


2015 ◽  
Vol 86 (11) ◽  
pp. e4.86-e4
Author(s):  
Hannah Goddard ◽  
Angus Macleod ◽  
Carl Counsell

BackgroundIdiopathic Parkinson's disease (PD) is a common, disabling, neurodegenerative disorder. The overall co-morbidity burden associated with PD is unclear, but may be important to adjust for when predicting prognosis or comparing cases and controls.Aims ▸ To determine how best to assess overall co-morbidity in PD▸ To compare PD co-morbidity burden to that of age- and sex-matched controlsMethodsData from an incident, community-based cohort of 205 patients with PD and 148 age-, sex- and GP-matched controls (the PINE study) were used. The intra- and inter-rater reliability and mortality predictive ability of three co-morbidity scales (the Charlson Co-Morbidity Index, the Cumulative Illness Rating Scale and a disease count) were evaluated. The co-morbidity burden of cases and controls was compared at baseline and over 5 years of follow-up.Results and conclusionsThe Charlson Co-Morbidity Index was more reliable for use in PD and was the only scale that was independently predictive of mortality (hazard ratio=1.20, [95% CI 1.07–1.34]). There was no significant difference between cases and controls at baseline (p=0.20). Charlson Co-Morbidity Index scores increased over time. This increase was greater in patients with PD than controls and greater in patients and controls who died earlier.


Neurosurgery ◽  
2006 ◽  
Vol 59 (5) ◽  
pp. E1140-E1140 ◽  
Author(s):  
Francesco Vergani ◽  
Andrea Landi ◽  
Angelo Antonini ◽  
Erik P. Sganzerla

Abstract OBJECTIVE Subthalamic (Stn) deep brain stimulation (DBS) is a valid surgical therapy for the treatment of severe Parkinson's disease. In recent years, StnDBS has been proposed for patients who previously received other surgical treatments, such as thalamotomy and pallidotomy. Nonetheless, there is no consensus about the indications of DBS in patients who previously underwent surgery. To the best of our knowledge this is the first reported case of a patient treated with DBS after previous thalamotomy and adrenal grafting. CLINICAL PRESENTATION A 62-year-old man with a long history (more than 30 yr) of Parkinson's disease received unilateral thalamotomy and autologous adrenal graft on two independent occasions. Thalamotomy led to a significant improvement, although limited to the control of contralateral tremor. The autologous adrenal graft was of no benefit. For the subsequent occurrence of L-dopa related dyskinesias and severe “off” periods, the patient was referred to our center for StnDBS. INTERVENTION The patient underwent bilateral StnDBS, obtaining a satisfactory improvement of rigidity and bradykinesia on both sides. The 1-year follow-up evaluation showed a 46% improvement in the Unified Parkinson's Disease Rating Scale motor section, along with a noticeable reduction in antiparkinsonian therapy (81%). CONCLUSION This case is consistent with previous reports from the literature, suggesting that StnDBS is feasible and safe, even in patients who previously received other surgical treatments for Parkinson's disease, such as thalamotomy or cell grafting.


2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Howard E. Gendelman ◽  
Yuning Zhang ◽  
Pamela Santamaria ◽  
Katherine E. Olson ◽  
Charles R. Schutt ◽  
...  

Abstract A potential therapeutic role for immune transformation in Parkinson’s disease evolves from more than a decade of animal investigations demonstrating regulatory T cell (Treg) nigrostriatal neuroprotection. To bridge these results to human disease, we conducted a randomized, placebo-controlled double-blind phase 1 trial with a well-studied immune modulator, sargramostim (granulocyte-macrophage colony-stimulating factor). We enrolled 17 age-matched non-Parkinsonian subjects as non-treated controls and 20 Parkinson’s disease patients. Both Parkinson’s disease patients and controls were monitored for 2 months for baseline profiling. Parkinson’s disease patients were then randomized into two equal groups to self-administer placebo (saline) or sargramostim subcutaneously at 6 μg/kg/day for 56 days. Adverse events for the sargramostim and placebo groups were 100% (10/10) and 80% (8/10), respectively. These included injection site reactions, increased total white cell counts, and upper extremity bone pain. One urticarial and one vasculitis reaction were found to be drug and benzyl alcohol related, respectively. An additional patient with a history of cerebrovascular disease suffered a stroke on study. Unified Parkinson’s disease rating scale, Part III scores in the sargramostim group showed modest improvement after 6 and 8 weeks of treatment when compared with placebo. This paralleled improved magnetoencephalography-recorded cortical motor activities and Treg numbers and function compared with pretreated Parkinson’s disease patients and non-Parkinsonian controls. Peripheral Treg transformation was linked to serum tryptophan metabolites, including L-kynurenine, quinolinic acid, and serotonin. These data offer a potential paradigm shift in modulating immune responses for potential therapeutic gain for Parkinson’s disease. Confirmation of these early study results requires larger numbers of enrolled patients and further clinical investigation.


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