Patterns of levodopa response in Parkinson's disease: a clinico-pathological study

Kempster, Peter; Williams, David R.; Selikhova, Marianna; Holton, Janice L.; Révész, Tamás; Lees, Andrew J.

doi:10.1093/brain/awm142

Cited by 171 publications

(131 citation statements)

References 30 publications

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“…Indeed, patients with PD who develop disabling levodopa-induced motor fluctuations tend to have experienced a stronger therapeutic response than those without motor complications. 261 In a community-based study, motor complications were also found to be associated with the use of high doses of levodopa. 262 Indeed, it is generally felt that severe dyskinesias are less prevalent today compared with a decade ago, because of the tendency to use lower doses of levodopa.…”

Section: 242mentioning

confidence: 99%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

741

653

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Parkinson disease (PD) is an age-related neurodegenerative disorder that affects as many as 1-2% of persons aged 60 years and older. With the aging of the population, the frequency of PD is expected to increase dramatically in the coming decades. Current therapy is largely based on a dopamine replacement strategy, primarily using the dopamine precursor levodopa. However, chronic treatment is associated with the development of motor complications, and the disease is inexorably progressive. Further, advancing disease is associated with the emergence of features such as freezing, falling, and dementia which are not adequately controlled with dopaminergic therapies. Indeed, it is now appreciated that these nondopaminergic features are common and the major source of disability for patients with advanced disease. Many different therapeutic agents and treatment strategies have been evaluated over the past several years to try and address these unmet medical needs, and many promising approaches are currently being tested in the laboratory and in the clinic. As a result, there are now many new therapies and strategic approaches available for the treatment of the different stages of PD, with which the treating physician must be familiar in order to provide patients with optimal care. This monograph provides an overview of the management of PD patients, with an emphasis on pathophysiology, and the results of recent clinical trials. It is intended to provide physicians with an understanding of the different treatment options that are available for managing the different stages of the disease and the scientific rationale of the different approaches. 1 PD is the second most common neurodegenerative disorder, with an average age at onset of about 60 years. An estimated 5 million people throughout the world have PD, with 1 million individuals each in the United States and in Europe with the disorder. PD affects approximately 0.3% of the population and 1% to 2% of those older than 60 years.2 With the aging of the population and the substantial increase in the number of at-risk individuals older than 60 years, it is anticipated that the prevalence of PD will increase dramatically in the coming decades.

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Section: 242mentioning

confidence: 99%

The scientific and clinical basis for the treatment of Parkinson disease (2009)

Olanow¹,

Stern²,

Sethi³

2009

Neurology

741

653

View full text Add to dashboard Cite

show abstract

“…However, development of PDD is associated with a strong increase in mortality (33). In fact, the mean time span between onset of dementia and death appears to be only about 2-4 y (33,34). Compared with PD, APSs are characterized by the early presence of additional debilitating symptoms and a more rapid progression to death (10).…”

Section: Treatment and Prognosismentioning

confidence: 99%

¹⁸F-FDG PET in Parkinsonism: Differential Diagnosis and Evaluation of Cognitive Impairment

et al. 2017

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Learning Objectives: On successful completion of this activity, participants should be able to (1) describe the clinical demand and rationale for differential diagnosis in parkinsonism, (2) recognize and differentiate the disease-specific patterns of regional glucose metabolism associated with Parkinson disease and the different atypical parkinsonian syndromes, and (3) identify regional metabolic changes that predict cognitive decline in Parkinson disease.Financial Disclosure: Dr. Meyer receives support from GE and Piramal for a research study outside the present topic. The authors of this article have indicated no other relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNMMI is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNMMI designates each JNM continuing education article for a maximum of 2.0 AMA PRA category 1 credits. Physicians should claim only credit commensurate with the extent of their participation in the activity. For CE credit, SAM, and other credit types, participants can access this activity through the SNMMI website (http://www.snmmilearningcenter.org) through December 2020.Accurate differential diagnosis of parkinsonism is of paramount therapeutic and prognostic importance. In addition, with the development of invasive therapies and novel disease-specific therapies, strategies for patient enrichment in trial populations are of growing importance. Imaging disease-specific patterns of regional glucose metabolism with PET and 18 F-FDG allows for a highly accurate distinction between Parkinson disease (PD) and atypical parkinsonian syndromes, including multiple-system atrophy, progressive supranuclear palsy, and corticobasal degeneration. On the basis of a preliminary metaanalysis of currently available studies with inclusion of multiple disease groups, we estimated that the diagnostic sensitivity and specificity for visual PET readings supported by voxel-based statistical analyses for diagnosis of atypical parkinsonian syndromes are 91.4% and 90.6%, respectively. The diagnostic specificity of 18 F-FDG PET for diagnosing multiple-system atrophy, progressive supranuclear palsy, and corticobasal degeneration was consistently shown to be high (.90%), whereas sensitivity was more variable (.75%). It is increasingly acknowledged that cognitive impairment represents a major challenge in PD, with mild cognitive impairment being a prodromal stage of PD with dementia (PDD). In line with clinical and neuropsychologic studies, recent PET studies demonstrated that posterior cortical dysfunction in nondemented PD patients precedes cognitive decline and the development of PDD by several years. Taken together, the current literature underscores the utility of 18 F-FDG PET for diagnostic evaluation of parkinsonism and the promising role of 18 F-FDG PET for assessment and risk stratification of cognitive impairment in PD.

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“…PD is a late-onset disease that is likely to have evolved over several decades, and end-stage pathology will inevitably be associated with widespread neuronal degeneration and microglia activation. The age at death of individuals suffering from PD is in their mid-70s (Kempster et al 2007); importantly, this is an aged nervous system with well-documented evidence that microglia are progressing toward a more activated phenotype (Perry et al 1993;DiPatre and Gelman 1997). The microglia in the diseased brain are also likely to be influenced by systemic disease that may have existed some time before death, and the cause of death will also have an impact.…”

Section: Microglia and Macrophagesmentioning

confidence: 99%

Innate Inflammation in Parkinson's Disease

Perry

2012

Cold Spring Harbor Perspectives in Medicine

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The resident macrophages of the brain-the microglia-are morphologically activated during the progression of Parkinson's disease. Observational studies in human postmortem material and studies in animal models seek to define the contribution that this innate immune response might make to the pathogenesis and rate of progression of Parkinson's disease. We review here some of the key conceptual issues that need to be considered when performing these studies. We highlight the fact that most postmortem studies have not given due consideration to common comorbidities present in patients with Parkinson's disease and also the limitations of attempting to extrapolate from animal models to a chronic progressive neurodegenerative disease in humans that lasts for many years.

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Patterns of levodopa response in Parkinson's disease: a clinico-pathological study

Cited by 171 publications

References 30 publications

The scientific and clinical basis for the treatment of Parkinson disease (2009)

The scientific and clinical basis for the treatment of Parkinson disease (2009)

¹⁸F-FDG PET in Parkinsonism: Differential Diagnosis and Evaluation of Cognitive Impairment

Innate Inflammation in Parkinson's Disease

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Patterns of levodopa response in Parkinson's disease: a clinico-pathological study

Cited by 171 publications

References 30 publications

The scientific and clinical basis for the treatment of Parkinson disease (2009)

The scientific and clinical basis for the treatment of Parkinson disease (2009)

18F-FDG PET in Parkinsonism: Differential Diagnosis and Evaluation of Cognitive Impairment

Innate Inflammation in Parkinson's Disease

Contact Info

Product

Resources

About

¹⁸F-FDG PET in Parkinsonism: Differential Diagnosis and Evaluation of Cognitive Impairment