Objective: Parkinson’s disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. Methods: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included “Parkinson’s disease”, “diagnosis” and “signs and symptoms”. Results: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. Conclusions: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

https://jnnp.bmj.com/content/jnnp/79/4/368.full.pdf

Parkinson’s disease: clinical features and diagnosis

Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease.

This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances.

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MDS clinical diagnostic criteria for Parkinson's disease

Interpretation of clinical trials comparing different drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications. To address this problem, conversion factors have been calculated for antiparkinsonian drugs that yield a total daily levodopa equivalent dose (LED). LED estimates vary, so we undertook a systematic review of studies reporting LEDs to provide standardized formulae. Electronic database and hand searching of references identified 56 primary reports of LED estimates. Data were extracted and the mean and modal LEDs calculated. This yielded a standardized LED for each drug, providing a useful tool to express dose intensity of different antiparkinsonian drug regimens on a single scale. Using these conversion formulae to report LEDs would improve the consistency of reporting and assist the interpretation of clinical trials comparing different PD medications.

Systematic review of levodopa dose equivalency reporting in Parkinson's disease

Objective: To devise a short bedside cognitive and behavioral battery to assess frontal lobe functions. Methods: The designed battery consists of six subtests exploring the following: conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. It takes approximately 10 minutes to administer. The authors studied 42 normal subjects and 121 patients with various degrees of frontal lobe dysfunction (PD, n = 24; multiple system atrophy, n = 6; corticobasal degeneration, n = 21; progressive supranuclear palsy, n = 47; frontotemporal dementia, n = 23). Results: The Frontal Assessment Battery scores correlated with the Mattis Dementia Rating Scale scores (rho = 0.82, p p p p Conclusion: The Frontal Assessment Battery is easy to administer at bedside and is sensitive to frontal lobe dysfunction.

The FAB A frontal assessment battery at bedside

Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.

https://jnnp.bmj.com/content/jnnp/55/3/181.full.pdf

Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

Many authorities have drawn attention to the difficulties in clinically distinguishing Parkinson's disease (PD) from other parkinsonian syndromes. We assessed the clinical features of 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic PD according to their pathologic findings. Seventy-six percent of these cases were confirmed to have PD. By using selected criteria (asymmetrical onset, no atypical features, and no possible etiology for another parkinsonian syndrome) the proportion of true PD cases identified was increased to 93%, but 32% of pathologically confirmed cases were rejected on this basis. These observations suggest that studies based on consultant diagnosis of PD, using standard diagnostic criteria, will include cases other than PD, thus distorting results from clinical trials and epidemiologic studies. The strict use of additional criteria can reduce misdiagnosis but at the cost of excluding genuine PD cases.

What features improve the accuracy of clinical diagnosis in Parkinson's disease A clinicopathologic study

We have reviewed the clinical and pathological diagnoses of 143 cases of parkinsonism seen by neurologists associated with the movement disorders service at The National Hospital for Neurology and Neurosurgery in London who came to neuropathological examination at the United Kingdom Parkinson's Disease Society Brain Research Centre, over a 10-year period between 1990 and the end of 1999. Seventy-three (47 male, 26 female) cases were diagnosed as having idiopathic Parkinson's disease (IPD) and 70 (42 male, 28 female) as having another parkinsonian syndrome. The positive predictive value of the clinical diagnosis for the whole group was 85.3%, with 122 cases correctly clinically diagnosed. The positive predictive value of the clinical diagnosis of IPD was extremely high, at 98.6% (72 out of 73), while for the other parkinsonian syndromes it was 71.4% (50 out of 70). The positive predictive values of a clinical diagnosis of multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) were 85.7 (30 out of 35) and 80% (16 out of 20), respectively. The sensitivity for IPD was 91.1%, due to seven false-negative cases, with 72 of the 79 pathologically established cases being diagnosed in life. For MSA, the sensitivity was 88.2% (30 out of 34), and for PSP it was 84.2% (16 out of 19). The diagnostic accuracy for IPD, MSA and PSP was higher than most previous prospective clinicopathological series and studies using the retrospective application of clinical diagnostic criteria. The seven false-negative cases of IPD suggest a broader clinical picture of disease than previously thought acceptable. This study implies that neurologists with particular expertise in the field of movement disorders may be using a method of pattern recognition for diagnosis which goes beyond that inherent in any formal set of diagnostic criteria.

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The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service

The clinical details of 100 cases of histologically confirmed Parkinson's disease were examined and correlated with pathologic findings. Age at disease onset (mean, 62.4 years), disease duration (mean, 13.1 years), and age at death (mean, 75.5 years) were similar to those in previous smaller series. Asymmetric, tremulous onset was most common, although 23% of patients had no rest tremor. Motor fluctuations and dyskinesias occurred in 60% of levodopa-treated patients. All patients had clinical parkinsonism; however, 12 had atypical clinical features of Parkinson's disease, including severe early dementia, fluctuating confusional states, no response to levodopa, and early marked autonomic disturbance. Neuropathologic examination found coexistent Alzheimer-type change in 17 cases and striatal abnormality--mainly vascular--in 34 cases. Cortical Lewy bodies were present in all cases, but only four satisfied proposed criteria for diffuse Lewy body disease. Dementia occurred in 44% of cases; 29% had Alzheimer's disease, 10% had numerous cortical Lewy bodies, and 6% had a possible vascular cause; in 55% no definite pathologic cause was found. Nigral cell loss correlated with disease duration and severity. Although the general pattern of disease conformed to traditional descriptions, the findings broaden the present clinical and pathologic spectrum of Parkinson's disease.

A clinicopathologic study of 100 cases of Parkinson's disease.

The authors studied the accuracy of clinical diagnosis of idiopathic PD (IPD) in 100 consecutive clinically diagnosed cases that came to neuropathological examination. Ninety fulfilled pathologic criteria for IPD. Ten were misdiagnosed: multiple system atrophy (six), progressive supranuclear palsy (two), post-encephalitic parkinsonism (one), and vascular parkinsonism (one). Assessment of the clinical features suggests that an accuracy of 90% may be the highest that can be expected using current diagnostic criteria.

Susan E. Daniel

Papers

Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

What features improve the accuracy of clinical diagnosis in Parkinson's disease A clinicopathologic study

The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service

A clinicopathologic study of 100 cases of Parkinson's disease.

Improved accuracy of clinical diagnosis of Lewy body Parkinson's disease.