Long term follow-up in advanced Parkinson’s disease treated with DBS of the subthalamic nucleus

Volontè, Maria Antonietta; Clarizio, Giacomo; Galantucci, Sebastiano; Scamarcia, Pietro Giuseppe; Cardamone, Rosalinda; Barzaghi, Lina Raffaella; Falautano, Monica; Mortini, Pietro; Comı, Gıancarlo; Filippi, Massimo

doi:10.1007/s00415-021-10430-y

Cited by 18 publications

(24 citation statements)

References 33 publications

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“…[ 17 ] For example, DBS shows no long‐lasting effect on axial symptoms, e.g., freezing of gait and negatively impacts cognitive and neuropsychiatric symptoms. [ 18 , 19 ] Importantly palliative therapies do not solve the issue of neuronal loss and the long‐term prognosis. Consequently, cell replacement therapy for PD has been recently reevaluated as a potential cure for PD, [ 20 ] leading to recent trials aimed at improved grafting procedures, [ 21 ] and to pave the way for stem‐cell based transplantation in humans.…”

Section: Introductionmentioning

confidence: 99%

Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: A Longitudinal Study in a Macaque Model of Parkinson's Disease

et al. 2022

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Parkinson's disease (PD) evolves over an extended and variable period in humans; years prior to the onset of classical motor symptoms, sleep and biological rhythm disorders develop, significantly impacting the quality-of-life of patients. Circadian-rhythm disorders are accompanied by mild cognitive deficits that progressively worsen with disease progression and can constitute a severe burden for patients at later stages. The gold-standard 6-methyl-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) macaque model of PD recapitulates the progression of motor and nonmotor symptoms over contracted periods of time. Here, this multidisciplinary/multiparametric study follows, in five animals, the steady progression of motor and nonmotor symptoms and describes their reversal following grafts of neural precursors in diverse functional domains of the basal ganglia. Results show unprecedented recovery from cognitive symptoms in addition to a strong clinical motor recuperation. Both motor and cognitive recovery and partial circadian rhythm recovery correlate with the degree of graft integration, and in a subset of animals, with in vivo levels of striatal dopaminergic innervation and function. The present study provides empirical evidence that integration of neural precursors following transplantation efficiently restores function at multiple levels in parkinsonian nonhuman primates and, given interindividuality of disease progression and recovery, underlines the importance of longitudinal multidisciplinary assessments in view of clinical translation.

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Section: Introductionmentioning

confidence: 99%

Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: A Longitudinal Study in a Macaque Model of Parkinson's Disease

et al. 2022

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“…These suggest that STN‐DBS induced improvements of cardinal motor symptoms (tremor>rigidity>bradykinesia) 29 are sustained in the long‐term with reductions from baseline in off medication scores of 30%–50%. Effects on levodopa‐induced motor complications also persist in the long‐term with improvements of 60%–70% and are accompanied by dose reductions of dopaminergic medications in the order of 40%–60% compared with the preoperative state 25,26,28‐30,32,33 . Nevertheless, improvements of motor scores become blunted with increasing duration of follow‐up (Fig.…”

Section: Long‐term Impact Of Dbs On Motor Symptoms and Quality Of Lifementioning

confidence: 97%

“…Effects on levodopa-induced motor complications also persist in the long-term with improvements of 60%-70% and are accompanied by dose reductions of dopaminergic medications in the order of 40%-60% compared with the preoperative state. 25,26,[28][29][30]32,33 Nevertheless, improvements of motor scores become blunted with increasing duration of follow-up (Fig. 1) and on medication motor scores generally decline below baseline levels by year 5.…”

Section: Long-term Impact Of Dbs On Motor Symptoms and Quality Of Lifementioning

confidence: 98%

“…24 These findings are consistent with those from multiple observational long-term studies reporting sustained effects on motor outcomes of STN-DBS over periods of 8-16 years. [25][26][27][28][29][30][31][32][33] Figure 1 shows changes of outcome measures of those studies that reported follow-up results at 5 years and at 8-11 years in comparison to preoperative baseline motor functioning. These suggest that STN-DBS induced improvements of cardinal motor symptoms (tremor>rigidity>bradykinesia) 29 are sustained in the long-term with reductions from baseline in off medication scores of 30%-50%.…”

Section: Long-term Impact Of Dbs On Motor Symptoms and Quality Of Lifementioning

confidence: 99%

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How Does Deep Brain Stimulation Change the Course of Parkinson's Disease?

et al. 2022

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A robust body of evidence from randomized controlled trials has established the efficacy of deep brain stimulation (DBS) in reducing off time and dyskinesias in levodopa‐treated patients with Parkinson's disease (PD). These effects go along with improvements in on period motor function, activities of daily living, and quality of life. In addition, subthalamic DBS is effective in controlling drug‐refractory PD tremor. Here, we review the available data from long‐term observational and controlled follow‐up studies in DBS‐treated patients to re‐examine the persistence of motor and quality of life benefits and evaluate the effects on disease progression, major disability milestones, and survival. Although there is consistent evidence from observational follow‐up studies in DBS‐treated patients over 5–10 years and beyond showing sustained improvement of motor control, the long‐term impact of DBS on overall progression of disability in PD is less clear. Whether DBS reduces or delays the development of later motor and non‐motor disability milestones in comparison to best medical management strategies is difficult to answer by uncontrolled observational follow‐up, but there are signals from controlled long‐term observational studies suggesting that subthalamic DBS may delay some of the late‐stage disability milestones including psychosis, falls, and institutionalization, and also slightly prolongs survival compared with matched medically managed patients. These observations could be attributable to the sustained improvements in motor function and reduction in medication‐induced side effects, whereas there is no clinical evidence of direct effects of DBS on the underlying disease progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

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“…For example, DBS shows no long-lasting effect on axial symptoms e.g. freezing of gait and negatively impacts cognitive and neuropsychiatric symptoms [9, 10]. Importantly palliative therapies do not solve the issue of neuronal loss and the long-term prognosis.…”

Section: Introductionmentioning

confidence: 99%

Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: a Longitudinal Study in a Macaque Model of Parkinson’s Disease

Wianny

Dzahini

Fifel

et al. 2020

Preprint

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Cognitive deficits as well as disorders of sleep and biological rhythms constitute non-motor symptoms that significantly impact quality of life in Parkinson′s disease patients. Few studies have evaluated the impact of cell replacement therapy on such non-motor symptoms. We used a multidisciplinary approach to assess the therapeutic potential of bilateral grafts of neural stem cells in a macaque model of Parkinson′s disease on both motor and non-motor markers of functional recovery. Grafts led to varying degrees of functional recovery while sham experiments did not. Motor and cognitive but not circadian rhythm recovery correlated with the degree of graft integration into the host environment and dopaminergic function. Transplantation of neural stem cells thus restore function at multiple levels in the parkinsonian monkeys.

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Long term follow-up in advanced Parkinson’s disease treated with DBS of the subthalamic nucleus

Cited by 18 publications

References 33 publications

Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: A Longitudinal Study in a Macaque Model of Parkinson's Disease

Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: A Longitudinal Study in a Macaque Model of Parkinson's Disease

How Does Deep Brain Stimulation Change the Course of Parkinson's Disease?

Induced Cognitive Impairments Reversed by Grafts of Neural Precursors: a Longitudinal Study in a Macaque Model of Parkinson’s Disease

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