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Parkinsonism and Related Disorders 19 (2013) 772–773

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Parkinsonism and Related Disorders

journal homepage: www.elsevier .com/locate/parkreldis

Letter to the Editor

Does 123I-MIBG scintigraphy really assist the diagnosisof Parkinson’s disease?q,qq

Keywords:Parkinson’s diseaseMIBGCardiac sympathetic system

q Institution where work was performed: UniversityItaly.qq Funding received for this work from any organiz

1353-8020/$ – see front matter � 2013 Elsevier Ltd.http://dx.doi.org/10.1016/j.parkreldis.2013.04.015

Whenones (1–

To the Editor

Several studies in the last decade have focused on the use of123I-metaiodobenzylguanidine (MIBG) scintigraphy for Lewy bodydisorders (LBD) [1]. A recent systematic meta-analysis suggestedhigh sensitivity and specificity (up to 90%) with this techniquefor differentiating Parkinson’s disease (PD) from other neurode-generative forms of parkinsonism, through both early and delayedimaging phases [2]. Nevertheless, a surprising variability betweenstudies emerges, being sensitivity 79–100% and specificity 84–89%[1,3]. In Orimo et al., for instance, specificity by the delayed H/Mratio was 80.2% in PD patients (stages 1/2) defined in that studyas “early” [2]. In addition, few investigations were based on unbi-ased enrollment of PD consecutive patients, irrespective of theirmotor and non-motor clinical profile. A correct understanding ofpotentials and pitfalls of 123I-MIBG scintigraphy is critical wheninterpreting PD pathogenesis. An unequivocal early cardiacinvolvement would confirm the caudorostral ascending patternof Lewy pathologies as inferred by Braak and colleagues, indicatingfurther PD as a multisystem disorder not confined to the nigro-striatal dopamine deficiency.

Here we extend at 2 years follow-up the observations started on53 PD patients, compared with a control group of age-matchedhealthy volunteers (n ¼ 18) [4]. As we moved to an ideal Specificityof 100% the Sensitivity of the test was only 41.51%. When a Speci-ficity of 90% was considered, Sensitivity slightly increased to47.17% (Area under the ROC curve 0.7278; 95% CI; P ¼ 0.0028,Fig. 1). Utilizing a cut-off ¼ 1.635 for delayed images (consistentwith a Specificity of 90% as above) only 25 patients (47%) met thecriteria for a positive scan.

We are currently expanding the analysis in a larger number ofpatients, [n¼ 92, fromHoehn & Yahr (H&Y) stage 1–4]. In particular,35.8% (n ¼ 33) of the patients actually being examined are H&Ystage 1 and 20.6% (n ¼ 19) are stage 1.5. We noticed that the major-ity of the negative I-MIBG belong to stage 1 and 1.5 since using thecut-off mentioned above (w1.6) only about 44% of these patientsmeet the criteria for a positive scan (n ¼ 23).

Hospital “Tor Vergata”, Rome,

ation: none.

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comparing advanced H&Y stages (2–4) with the early1.5) a specificity level of 90% and a sensitivity of 52% is

obtained for values of 1.34 in delayed images, suggesting that acut-off of 1.3 in H/M ratio could help in discriminating patientsat early stages (Area under the ROC curve 0.7429; 95% CI;P ¼ 0.0024).

This seems to question the supposed lack of linear relationshipbetween 123I-MIBG cardiac uptake and motor disease severity (asdetectable by UPDRS score [1]). Moreover, in our population, thepresence or absence of a positive 123I-MIBG scan did not correlatewith the degree of therapy responsiveness (almost none is exhib-iting a significant decline of levodopa response in >6 monthsfollow-up); nor correlated with a specific clinical pattern(tremor-dominant versus rigid-akinetic or mixed forms), at oddswith our initial observations based on the 53 patients samplewhere differences in 123I-MIBG uptake in different clinical pheno-types was investigated by means of Mann–Whitney test [4].Consistent with the ample variability of 123I-MIBG impairment isthe variety of autonomic involvement as observed in PD patients[5]. For example, orthostatic hypotension, in our series, may corre-late with 123I-MIBG only in a subset of advanced cases. All together,our observations imply that 123I-MIBG may be a PD marker fordiagnostic integration in the advanced stages of the disease,much less applicable, in contrast to what inferred [2], as a diag-nostic aid in the early phases.

Fig. 1. ROC curve of delayed H/M ratio of 53 PD patients compared to a control groupof 18 healthy subjects. At a Specificity of 90% only 47% of the PD patients met thecriteria of a positive scan (see text).

Letter to the Editor / Parkinsonism and Related Disorders 19 (2013) 772–773 773

References

[1] Spiegel J. Diagnostic and pathophysiological impact of myocardial MIBG scintig-raphy in Parkinson’ disease. Parkinson’s Dis 2010:1–6.

[2] Orimo S, Suzuki M, Inaba A, Mizusawa H. 123I-MIBG myocardial scintigraphy fordifferentiating Parkinson’s disease from other neurodegerative parkinsonism: asystematic review and meta-analysis. Parkinsonism Relat Disord 2012;18:494–500.

[3] Treglia G, Stefanelli A, Cason E, Cocciolillo F, Di Giuda D, Giordano A. Diag-nostic performance of iodine-123-metaiodobenzylguanidine scintigraphy indifferential diagnosis between Parkinson’s disease and multiple-systen atro-phy. A systematic review and a meta-analysis. Clin Neurol Neurosurg2011;113:823–9.

[4] Chiaravalloti A, Stefani A, Tavolozza M, Pierantozzi M, Di Biagio D, Olivola E,et al. Different patterns of cardiac sympathetic denervation in tremor-typecompared to akinetic-rigid-type Parkinson’s disease: molecular imaging with123I-MIBG. Mol Med Rep 2012;6:1337–42.

[5] Oka H, Chizuko Toyoda C, Yogo M, Mochio S. Olfactory dysfunction andcardiovascular dysautonomia in Parkinson’s disease. J Neurol 2010;257:969–76.

Agostino ChiaravallotiDepartment of Biopathology and Diagnostic Imaging,

University Hospital “Tor Vergata”, Rome, Italy

Alessandro Stefani*IRCCS Fondazione S. Lucia, Rome, Italy

Department of System Medicine, Movement Disorder Center,University “Tor Vergata”, Rome, Italy

Mariangela PierantozziIRCCS Fondazione S. Lucia, Rome, Italy

Paolo StanzioneIRCCS Fondazione S. Lucia, Rome, Italy

Department of System Medicine, Movement Disorder Center,University “Tor Vergata”, Rome, Italy

Orazio SchillaciDepartment of Biopathology and Diagnostic Imaging, University

Hospital “Tor Vergata”, Rome, Italy

IRCCS Neuromed of Pozzilli, Italy

* Corresponding author. Fondazione Policlinico Tor Vergata, VialeOxford, 00173 Rome, Italy. Tel.: þ39 06 20903113; fax: þ39 06

20903118.E-mail address: stefani@uniroma2.it (A. Stefani)

8 January 2013