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

Background: A consensus conference on multiple system atrophy (MSA) in 1998 established criteria for diagnosis that have been accepted widely. Since then, clinical, laboratory, neuropathologic, and imaging studies have advanced the field, requiring a fresh evaluation of diagnostic criteria. We held a second consensus conference in 2007 and present the results here.Methods: Experts in the clinical, neuropathologic, and imaging aspects of MSA were invited to participate in a 2-day consensus conference. Participants were divided into five groups, consisting of specialists in the parkinsonian, cerebellar, autonomic, neuropathologic, and imaging aspects of the disorder. Each group independently wrote diagnostic criteria for its area of expertise in advance of the meeting. These criteria were discussed and reconciled during the meeting using consensus methodology.Results: The new criteria retain the diagnostic categories of MSA with predominant parkinsonism and MSA with predominant cerebellar ataxia to designate the predominant motor features and also retain the designations of definite, probable, and possible MSA. Definite MSA requires neuropathologic demonstration of CNS alpha-synuclein-positive glial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebellar structures. Probable MSA requires a sporadic, progressive adult-onset disorder including rigorously defined autonomic failure and poorly levodopa-responsive parkinsonism or cerebellar ataxia. Possible MSA requires a sporadic, progressive adult-onset disease including parkinsonism or cerebellar ataxia and at least one feature suggesting autonomic dysfunction plus one other feature that may be a clinical or a neuroimaging abnormality.Conclusions: These new criteria have simplified the previous criteria, have incorporated current knowledge, and are expected to enhance future assessments of the disease.

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Second consensus statement on the diagnosis of multiple system atrophy

Mini Mental State

ContextPostmenopausal women have a greater risk than men of developing Alzheimer
disease, but studies of the effects of estrogen therapy on Alzheimer disease
have been inconsistent. On July 8, 2002, the study drugs, estrogen plus progestin,
in the Women's Health Initiative (WHI) trial were discontinued because of
certain increased health risks in women receiving combined hormone therapy.ObjectiveTo evaluate the effect of estrogen plus progestin on the incidence of
dementia and mild cognitive impairment compared with placebo.Design, Setting, and ParticipantsThe Women's Health Initiative Memory Study (WHIMS), a randomized, double-blind,
placebo-controlled clinical trial, began enrolling participants from the Women's
Health Initiative (WHI) estrogen plus progestin trial in May 1996. Of the
4894 eligible participants of the WHI study, 4532 (92.6%) postmenopausal women
free of probable dementia, aged 65 years or older, and recruited from 39 of
40 WHI clinical centers were enrolled in the WHIMS.InterventionParticipants received either 1 daily tablet of 0.625 mg of conjugated
equine estrogen plus 2.5 mg of medroxyprogesterone acetate (n = 2229), or
a matching placebo (n = 2303).Main Outcome MeasuresIncidence of probable dementia (primary outcome) and mild cognitive
impairment (secondary outcome) were identified through a structured clinical
assessment.ResultsThe mean (SD) time between the date of randomization into WHI and the
last Modified Mini-Mental State Examination (3MSE) for all WHIMS participants
was 4.05 (1.19) years. Overall, 61 women were diagnosed with probable dementia,
40 (66%) in the estrogen plus progestin group compared with 21 (34%) in the
placebo group. The hazard ratio (HR) for probable dementia was 2.05 (95% confidence
interval [CI], 1.21-3.48; 45 vs 22 per 10 000 person-years; P = .01). This increased risk would result in an additional 23 cases
of dementia per 10 000 women per year. Alzheimer disease was the most
common classification of dementia in both study groups. Treatment effects
on mild cognitive impairment did not differ between groups (HR, 1.07; 95%
CI, 0.74-1.55; 63 vs 59 cases per 10 000 person-years; P = .72).ConclusionsEstrogen plus progestin therapy increased the risk for probable dementia
in postmenopausal women aged 65 years or older. In addition, estrogen plus
progestin therapy did not prevent mild cognitive impairment in these women.
These findings, coupled with previously reported WHI data, support the conclusion
that the risks of estrogen plus progestin outweigh the benefits.

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Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial.

. The neuropatho -logical diagnosis of PD requires the pres-ence of Lewy body degeneration with cell loss in the substantia nigra leading to stri-atal dopamine deficiency. The pathology of PD, however, is much more widespread, involving a multitude of brain areas beyond the nigrostriatal dopamine system, many of which are not primarily involved in motor control including brain stem nuclei such as the locus coeruleus, raphe nuclei, dorsal vagal nucleus and other ponto-medullary cell groups, the bulbus and tractus olfacto -rius and piriform cortex, large parts of the limbic and neocortex, the diencephalon, thalamus and also extend to the peripheral autonomic nervous system

Nonmotor symptoms in Parkinson's

Substantia nigra hypoechogenicity in Friedreich ataxia

The purpose of this study was to investigate the monoamine transporter status of dopamine, serotonin and norepinephrine throughout the brain in spinocerebellar ataxia type 2 (SCA2). To this end, nine patients were studied with [123I]β-CIT SPECT. Data were compared with ten age-matched healthy control subjects and ten patients with young-onset Parkinson’s disease (YOPD), matched for age. Parametric SPECT images of the specific-to-non-displaceable equilibrium partition coefficient (V
 3″), which is proportional to the receptor density (B
 max), were generated. In order to objectively localise focal changes in β-CIT uptake throughout the brain volume without having to make an a priori hypothesis as to their location, statistical parametric mapping (SPM) was applied to SPECT images. Data clusters revealed by SPM, showing significant differences in V
 3″ values between groups, were transformed onto the individual V
 3″ image to obtain mean regional uptake values. Both SCA2 and YOPD patients showed significant decreases in striatal [123I]β-CIT SPECT uptake when compared with controls. However, in SCA2 patients, additional reductions in caudate/anterior putamen, midbrain and pons [123I]β-CIT uptake were localised with SPM. Voxel-wise analysis of [123I]β-CIT SPECT revealed more widespread decline of monoamine transporter availability in SCA2 than in YOPD, reflecting differences in the underlying pathology. We suggest that the quantification of midbrain and pons [123I]β-CIT signal is likely to improve the diagnostic accuracy in patients presenting with clinical features of both SCA2 and YOPD at initial investigation.

Topography of cerebral monoamine transporter availability in families with SCA2 mutations: a voxel-wise [123I]beta-CIT SPECT analysis.

We read the article by Chen et al.1 that reported hyposmia as a risk factor for incident Parkinson disease (PD) in the ABC Health Study with interest. While, in the short term, this association had been established in other cohorts,2,3 Chen et al. could show that smell loss is associated with incident PD beyond 5 years of follow-up. This is an important detail, as the identification of PD risk cohorts heavily relies on the temporal course of the markers in relation to the development of defining motor symptoms.4 We sought to replicate the findings of Chen et al. in the cohort of the prospective population-based Bruneck Study of the 2005 assessment (n = 539 without PD or secondary parkinsonism; median age 67.2 [25th–75th percentile; 61.4–76.2] years; 290 females).5 Participants underwent the 12-item Sniffin' Sticks test at baseline. Cases of incident PD were identified by in-person examination after 5 and 10 years using the United Kingdom Parkinson's Disease Society Brain Bank criteria (11 and 9 cases, respectively).5 The relative risk for hyposmic participants to develop PD was 2.99 (95% confidence interval 0.89–10.06) over the first 5 years, 4.06 (1.03–15.91) over the second 5 years, and 3.60 (1.48–8.78) over the entire follow-up (4.54 [1.25–16.51] in men and 2.79 [0.78–9.96] in women), corroborating the observations of Chen et al.

Reader response: Olfaction and incident Parkinson disease in US white and black older adults.

The efficacy of deep brain stimulation (DBS) to treat medically intractable motor complications in advanced Parkinson’s disease (PD) has been established in multiple randomized controlled long-term trials of 6 months duration or longer. These have revealed consistent findings of markedly reduced motor complications and improved quality of life (QoL) as compared with best medical management in advanced PD patients with a mean duration of levodopa treatment usually above 10 years, such that current medical practice is to reserve DBS for those PD subjects with a prolonged history of intractable response oscillations and dyskinesias. 1,2 Recently, Schuepbach et al. 3 investigated the effect of DBS on QoL in PD patients with significantly shorter disease duration and a history of motor complications from Ldopa of 3 years. Their EARLYSTIM trial randomized 251 patients to either DBS plus medical therapy or medical therapy alone demonstrating significant improved QoL, motor disability, activities of daily living, and L-dopa‐induced motor complications in the DBS-treated patients versus those on best medical therapy alone after 2 years of follow-up. The authors suggested to consider earlier use of DBS than is currently reflected by clinical practice and to potentially opt for surgical treatment in patients within the first 3 years after the onset of motor complications. An accompanying editorial to this publication, however, cautioned that the investigated population in the EARLYSTIM trial might only represent a small fraction of PD patients, 4 possibly less than 10%. The authors themselves point out that their study population might not be 100% representative for the general PD population to explain the usually high rate of suicide and suicide attempts during the trial. We sought to better define the percentage of PD patients seen in a tertiary movement disorders center of the type recruited and participating in EARLYSTIM for whom the current trial results might prompt a change in the timing of DBS. For this purpose we retrospectively applied the main inclusion and exclusion criteria of EARLYSTIM to all PD patients seen at the movement disorders center at the Department of Neurology of the Medical University Inns

Klaus Seppi

Papers

Nonmotor symptoms in Parkinson's

Substantia nigra hypoechogenicity in Friedreich ataxia

Topography of cerebral monoamine transporter availability in families with SCA2 mutations: a voxel-wise [123I]beta-CIT SPECT analysis.

Reader response: Olfaction and incident Parkinson disease in US white and black older adults.

Relevance of EARLYSTIM in a tertiary movement disorders center