Background: The diagnosis of different parkinsonian syndromes and the ability to predict long-term drug efficacy constitute important clinical issues. Design: Motor responses to the acute administration of levodopa and apomorphine were analyzed in a series of 134 parkinsonian patients, including 83 patients with a clinical diagnosis of idiopathic Parkinson’s disease (PD), 28 patients with multiple-system atrophy (MSA), 6 with progressive supranuclear palsy, and 17 with an unclassified parkinsonian syndrome. Methods: The patients received oral levodopa/carbidopa (250/25 mg) and subcutaneous apomorphine (1.5, 3 and 4.5 mg). Clinical variations of the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score were evaluated 1 h following levodopa administration or 20 min following apomorphine. The motor improvement produced by each acute challenge was matched with the clinical diagnosis and with the response to chronic levodopa treatment. The diagnosis was verified by repeated clinical assessments or by autopsy in 2 cases. A receiver operating characteristics curve was plotted comparing PD vs. non-PD, PD vs. MSA and chronic responders vs. nonresponders. Cutoff threshold improvement was defined as the value closest to the crossing point for 80% sensitivity and 80% specificity, corresponding to the best trade-off for a predictive evaluation. Results: UPDRS motor score improvement was on average higher in PD than in non-PD patients (levodopa: 29.8 vs. 12.2%; apomorphine 1.5 mg: 27.1 vs. 10.5%; apomorphine 3 mg: 27.7 vs. 9.7%; apomorphine 4.5 mg: 28.8 vs. 11.8%; p < 0.01 with Student’s t test). When PD patients were compared to non-PD patients, levodopa challenge had the best diagnostic accuracy with a threshold improvement of 16%. Apomorphine had the best diagnostic accuracy with a threshold improvement of 13.5% for 1.5 mg, 13% for 3 mg, and 16% for 4.5 mg. This meant that patients improving at least 16% in all tests had the highest probability of having PD. When PD patients were compared to MSA patients, levodopa acute challenge had the best diagnostic accuracy with a threshold improvement of 17%. Apomorphine had the best diagnostic accuracy with an improvement of 13% for 1.5 mg, 15% for 3 mg, and 18% for 4.5 mg. This meant that patients improving at least 18% in all tests had the highest probability of having PD rather than MSA. When patients who responded to chronic levodopa treatment were compared to those who did not, acute challenge with levodopa had the best predictive accuracy with a threshold improvement of 14.5%. Apomorphine had the best predictive accuracy with an improvement of 13% for 1.5 mg, and 14% for 3 and 4.5 mg. This meant that patients improving at least 14.5% in all tests had the highest probability of responding to chronic treatment. Conclusion: A good agreement was found between acute challenges with levodopa/carbidopa and apomorphine, and the use of both improved the reliability of the test. Different threshold improvements after acute challenges would support a diagnosis of PD or the exclusion of MSA, and would have a predictive value for subsequent response to chronic levodopa therapy.

1.
Hughes AJ, Ben-Shlomo Y, Daniel SE, Lees AJ: What features improve the accuracy of clinical diagnosis in Parkinson’s disease? A clinicopathologic study. Neurology 1992;42:1142–1146.
2.
Rajput AH, Rozdilsky B, Rajput A, Ang L: Levodopa efficacy and pathological basis of Parkinson syndrome. Clin Neuropharmacol 1990;13:553–558.
3.
Quinn N: Multiple system atrophy; in Marsden CD, Fahn S (eds): Movement Disorders 3. London, Butterworth-Heinemann, 1994, pp 262–281.
4.
Albanese A, Colosimo C, Bentivoglio AR, Fenici R, Melillo G, Tonali P: Multiple system atrophy presenting as parkinsonism: Clinical features and diagnostic criteria. J Neurol Neurosurg Psychiatry 1995;59:144–151.
5.
Albanese A, Ghika J: Acute challenge with apomorphine predicts the response to dopamine agonists in multiple system atrophy. Neurology 1998;50:A366.
6.
Hughes AJ, Lees AJ, Stern GM: Apomorphine test to predict dopaminergic responsiveness in parkinsonian syndromes. Lancet 1990;336:32–34.
7.
Colosimo C, Merello M, Albanese A: Clinical usefulness of apomorphine in movement disorders. Clin Neuropharmacol 1994;17:243–259.
8.
Gasser T, Schwarz J, Arnold G, Trenkwalder C, Oertel WH: Apomorphine test for dopaminergic responsiveness in patients with previously untreated Parkinson’s disease. Arch Neurol 1992;49:1131–1134.
9.
Langston JW, Widner H, Goetz CG, Brooks D, Fahn S, Freeman T, Watts R: Core assessment program for intracerebral transplantations (CAPIT). Mov Disord 1992;7:2–13.
10.
Gibb WR, Lees AJ: The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 1988;51:745–752.
11.
Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, Goetz CG, Golbe LI, Grafman J, Growdon JH, Hallett M, Jankovic J, Quinn NP, Tolosa E, Zee DS: Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): Report of the NINDS-SPSP international workshop. Neurology 1996;47:1–9.
12.
Daniel SE: The neuropathology and neurochemistry of multiple system atrophy; in Bannister R, Mathias CJ (eds): Autonomic Failure. A textbook of clinical disorders of the autonomic nervous system. Oxford, Oxford University Press, 1992, pp 564–585.
13.
Forno LS: Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 1996;55:259–272.
14.
Metz CE: Basic Principles of ROC analysis. Semin Nucl Med 1978;8:283–289.
15.
Rybicki BA, Johnson CC, Gorell JM: Demographic differences in referral rates to neurologists of patients with suspected Parkinson’s disease: Implications for case-control study design. Neuroepidemiology 1995;14:72–81.
16.
Hughes AJ, Lees AJ, Stern GM: Apomorphine in the diagnosis and treatment of parkinsonian tremor. Clin Neuropharmacol 1990;13:312–317.
17.
Hughes AJ, Lees AJ, Stern GM: Challenge tests to predict the dopaminergic response in untreated Parkinson’s disease. Neurology 1991;41:1723–1725.
18.
Sage JI, Miller DC, Golbe LI, Walters A, Duvoisin RC: Clinically atypical expression of pathologically typical Lewy-body parkinsonism. Clin Neuropharmacol 1990;13:36–47.
19.
van Laar T, Jansen EN, Essink AW, Neef C, Oosterloo S, Roos RA: A double-blind study of the efficacy of apomorphine and its assessment in ‘off’-periods in Parkinson’s disease. Clin Neurol Neurosurg 1993;95:231–235.
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