Second only to Alzheimer’s disease, Idiopathic Parkinson’s Disease (IPD) is one of the most common neurodegenerative disorders. Despite its prevalence, approximately 5 to 10% of patients with IPD are misdiagnosed, and conversely, up to 20% of patients diagnosed with IPD reveal alternative diagnoses upon autopsy, such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, Ad type pathology, and cerebrovascular disease.
Improving Accuracy with MDS-PD
It has been suggested that an accuracy of 90% is the best that can be achieved with clinical assessment and existing Parkinson’s disease diagnostic criteria, such as the UK PD Society Brain Bank criteria. In an effort to improve on this and increase diagnostic specificity, the Movement Disorders Society (MDS) recently published Clinical Diagnostic Criteria for Parkinson’s disease (MDS-PD), which reflects more recent understanding of IPD.
Increasing Recognition to Non-Motor Manifestations
Designed specifically for use in clinical research, but also as a general guide to clinical diagnosis of IPD consequent to Lewy body pathology1, the updated Parkinson’s disease diagnostic criteria gives increasing recognition to non-motor manifestations (motor abnormalities remain central). As with previous diagnostic criteria, the MDS-PD criteria utilize a two-step process for diagnoses. First, parkinsonism, defined as bradykinesia in combination with either rest tremor, rigidity or both, is required. However, this definition of parkinsonism fails to take into consideration a loss of postural reflexes, flexed posture, and freezing phenomenon.
Step 2: Exclusion Criteria
Having established that the patient has parkinsonism, the MDS-PDs created supportive and absolute exclusion criteria, as well as a red flag list that is applied to determine whether or not the patient meets criteria for IPD as the cause of their parkinsonism. There are two levels of certainty, including clinically established PD, defined as parkinsonism with at least two supportive criteria, absence of absolute exclusion criteria and no red flags, and clinically probable PD, defined as parkinsonism with no absolute exclusion criteria and presence of red flag counterbalanced by supportive criteria.
Supportive criteria include clear and dramatic beneficial response to dopaminergic therapy, presence of levodopa induced dyskinesia, rest tremor of limb, and either olfactory loss or cardiac sympathetic denervation documented by metaiodobenzylguanilidne scintigraphy. Two of the four supportive criteria are treatment response-related taken from step three of the UK Brain Bank Criteria, making diagnosis of IPD in early stage of disease as difficult as it was before the emergence of the MDS-PD criteria.
Implications of MDS-PD for Parkinson’s Clinical Trials
What’s more, MDS-PD criteria neglect the insidious unilateral onset progressing to bilateral, as well as a role of structural neuroimaging to rule out other basal ganglia disorders. In practice, an early IPD patient with no resting tremor can be still easily misdiagnosed using the MDS-PD criteria. Therefore, diagnostic accuracy varies considerably according to disease duration (lower on first visit than after longer follow-up), the expertise of the physician, and evolution of the understanding of IPD.2
Urgent Need for PD Researchers
This is problematic as the early and accurate diagnosis of IPD is a priority in Parkinson’s disease drug clinical trials and creates an urgent need for researchers to successfully move forward in the development of valid and reliable biomarkers that accurately reflect both the presence and status of disease.
A Positive Outlook for Early Stage IPD Diagnosis
Despite the shortcomings, I am sure that the MDS-PD criteria will stimulate new research into earlier stages of IPD, with the ultimate goal of designing Parkinson’s clinical trials to test intervention for disease prevention in at-risk individuals.
For further information or to discuss this subject further, please contact Worldwide Clinical Trials.
Postuma RB, Berg D, Ster M et al. MDS Clinical Diagnostic Criteria for Parkinson’s Disease. Movement Disorders 2015;30:1591-1599.
Hughes AJ, Daniel SE, Lees AJ. Improved accuracy of clinical diagnosis of Lewy body Parkinson’s disease. Neurology 2001;57:1497-1499