Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson's disease

It will be interesting to see whether this leads to better prognostication...

Eur J Nucl Med Mol Imaging. 2014 May 28. [Epub ahead of print]

Kaasinen V, Kinos M, Joutsa J, Seppänen M, Noponen T.

PURPOSE:

Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor.

METHODS:

[123I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates.

RESULTS:

Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p < 0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen.

CONCLUSION:

The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor.

Prodromal symptoms and early detection of Parkinson's disease in general practice: a nested case-control study

Fam Pract. 2014 May 28. pii: cmu025. [Epub ahead of print]

Plouvier AO, Hameleers RJ, van den Heuvel EA, Bor HH, Olde Hartman TC, Bloem BR, van Weel C, Lagro-Janssen AL.

BACKGROUND:

Timely diagnosis of Parkinson's disease (PD), facilitating early intervention, depends largely on the GP's awareness of early symptomatology. For general practice, it is unknown which prodromal symptoms (symptoms preceding the typical motor symptoms of PD) demand the GP's alertness.

OBJECTIVE:

To assess prodromal symptoms that should alert the GP to the possibility of PD in primary care patients.

METHODS:

A nested case-control study was carried out in a population of approximately 12000 patients registered in the Continuous Morbidity Registration database affiliated with the University of Nijmegen in the Netherlands. The database pools subject data from four primary care practices. The subjects comprised all 86 patients diagnosed with PD between 1972 and 2007, and 78 controls, matched by sex, age, socioeconomic status and primary care practice. The primary measures of outcome were the prodromal symptoms presenting in the two years prior to the diagnosis of PD. The number (and type) of referrals and diagnostic tests were also assessed.

RESULTS:

In the two-year period prior to diagnosis, PD patients more often presented with functional somatic symptoms, constipation, hyperhidrosis and sleep disorders than controls. Patients also more frequently experienced more than one prodromal symptom and were more often referred within the primary care team or to a medical specialist.

CONCLUSIONS:

Prodromal symptoms of PD are encountered in general practice. GPs should be alert when patients present with multiple prodromal symptoms in a two-year period, especially considering the benefits of early intervention, and the future possibilities for disease-modifying therapy.

[¹²³I]FP-CIT SPECT (DaTSCAN) may be a useful tool to differentiate between Parkinson's disease and vascular or drug-induced parkinsonisms: a meta-analysis.

Eur J Neurol. 2014 Apr 30. doi: 10.1111/ene.12444. [Epub ahead of print]

Brigo F, Matinella A, Erro R, Tinazzi M.

Abstract

BACKGROUND AND PURPOSE:

Differentiating idiopathic Parkinson's disease from secondary parkinsonian syndromes is crucial since their management and prognosis differ considerably. Functional imaging of the dopaminergic pathway by means of [¹²³I]FP-CIT SPECT (DaTSCAN) might be useful in this regard, but its role is still controversial. The accuracy of DaTSCAN in the differential diagnosis between Parkinson's disease and vascular or drug-induced parkinsonism was therefore systematically reviewed.

METHODS:

MEDLINE and CENTRAL were searched for studies aiming to determine accuracy measures (sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios) of DaTSCAN in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism.

RESULTS:

Five studies were included. Pooled accuracy measures in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism were relatively high, with sensitivity and specificity values above 85% and 80%, respectively.

CONCLUSIONS:

DaTSCAN might accurately differentiate between early Parkinson's disease and secondary parkinsonian conditions, namely vascular or drug-induced, in patients with clinically unclear parkinsonism. However, all the studies reviewed here show several methodological limits, which prevent definitive conclusions on the role of DaTSCAN being drawn in this context. Further studies are needed to confirm our results and definitely evaluate the utility of DaTSCAN in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism.

Bradykinesia-Akinesia Incoordination Test: Validating an Online Keyboard Test of Upper Limb Function

Our new paper on the validation of the BRAIN test which we use in PREDICT-PD for remote assessment of upper limb speed and accuracy...

PLoS One. 2014 Apr 29;9(4):e96260. doi: 10.1371/journal.pone.0096260. eCollection 2014.

Noyce AJ, Nagy A, Acharya S, Hadavi S, Bestwick JP, Fearnley J, Lees AJ, Giovannoni G.

Abstract

BACKGROUND:

The Bradykinesia Akinesia Incoordination (BRAIN) test is a computer keyboard-tapping task that was developed for use in assessing the effect of symptomatic treatment on motor function in Parkinson's disease (PD). An online version has now been designed for use in a wider clinical context and the research setting.

METHODS:

Validation of the online BRAIN test was undertaken in 58 patients with Parkinson's disease (PD) and 93 age-matched, non-neurological controls. Kinesia scores (KS30, number of key taps in 30 seconds), akinesia times (AT30, mean dwell time on each key in milliseconds), incoordination scores (IS30, variance of travelling time between key presses) and dysmetria scores (DS30, accuracy of key presses) were compared between groups. These parameters were correlated against total motor scores and sub-scores from the Unified Parkinson's Disease Rating Scale (UPDRS).

RESULTS:

Mean KS30, AT30 and IS30 were significantly different between PD patients and controls (p≤0.0001). Sensitivity for 85% specificity was 50% for KS30, 40% for AT30 and 29% for IS30. KS30, AT30 and IS30 correlated significantly with UPDRS total motor scores (r = -0.53, r = 0.27 and r = 0.28 respectively) and motor UPDRS sub-scores. The reliability of KS30, AT30 and DS30 was good on repeated testing.

CONCLUSIONS:

The BRAIN test is a reliable, convenient test of upper limb motor function that can be used routinely in the outpatient clinic, at home and in clinical trials. In addition, it can be used as an objective longitudinal measurement of emerging motor dysfunction for the prediction of PD in at-risk cohorts.