Reversible Pisa Syndrome in Parkinson’s Disease During Treatment With Pergolide A Case Report To the Editor: The term Pisa syndrome (or pleu- rothotonus) refers to a dystonic syn- drome characterized by tonic lateral flexion accompanied by slight rotation of the trunk in the sagittal plane, with a postural disturbance resembling the leaning tower of Pisa. This type of dys- tonia was described by Ekbom et al 1 in 1972 as a side effect of prolonged expo- sure to neuroleptic medications in three elderly women taking methylperone and/or haloperidol. Subsequently, devel- opment of Pisa syndrome has also been reported in patients receiving other drugs, in those with neurodegenerative diseases, or in idiopathic cases. 2,3 We report the development of reversible Pisa syndrome in a patient with Parkinson’s disease (PD) during treatment with pergolide. A 56-year-old man with a 3-year history of PD and a good response to dopaminergic therapy, periodically observed in our Movement Disorders Center, developed a peculiar postural dis- turbance. Neurologic examination showed a persistent truncal dystonia of the cervical to lumbar musculature, with tonic lateral flexion of the trunk to the right side, slightly rotated backward and worsening with walking. These features fit the description of the Pisa syndrome. The patient was receiving pergolide (1 mg thrice daily) for 4 months and levodopa–benserazide (100/25 mg/day), and was not taking drugs such as antidepressants, antipsychotic and anti- emetic medications, or other treatments potentially responsible for dystonic re- actions. Laboratory findings were nor- mal. Brain MRI did not reveal any focal lesion or other abnormalities in the basal ganglia. First, levodopa–benserazide was switched with levodopa–carbidopa with- out improvement. Thirteen months later pergolide was stopped without switching to another dopamine agonist. Three months after pergolide withdrawal, the patient presented a complete resolution of Pisa syndrome. Although axial dystonia in PD patients has been documented by pre- vious reports, 4 a recent article by Villarejo et al 5 notes that Pisa syndrome has never been described in PD. To our knowledge, this is the first case report of reversible Pisa syndrome in an idiopathic PD patient not taking cholinesterase inhibitors. With regard to its correlation with pergolide treatment, we cannot exclude that this agent might facilitate onset of the postural disorder, even if a certain verdict cannot be expressed. Indeed, pergolide is an ergot derivative dopamine agonist, but like other ergot alkaloids has serotonergic and adrenergic properties. 6 For example, 5-hydroxytryptamine-2B (5-HT2B) receptor activation by pergo- lide has been involved in restrictive car- diac valvulopathies. 7 Nondopaminergic effects of pergolide at the level of serotonergic/adrenergic receptors might have played a pathogenic role in our patient, suggesting that a dysfunction of these systems may be implicated in the development of this axial dystonia. 2 Furthermore, if the onset of Pisa syndrome in a PD patient could reinforce previous hypothesis about a dopaminer- gic–cholinergic imbalance, 5 the possible action of pergolide makes more compli- cated the solution of the problem. In fact, the underlying pathophysiologic mecha- nisms probably involved in the develop- ment of Pisa syndrome are much more complex than oversimplified models have suggested thus far. Antonino Cannas, MD* Paolo Solla, MD* Gianluca Floris, MD* Giuseppe Borghero, MD* Paolo Tacconi, MD* Andrea Spissu, MD† From the *Department of Neurology University of Cagliari †Department of Neurology General Hospital ‘‘San Michele’’ Cagliari, Italy REFERENCES 1. Ekbom K, Lindholm H, Ljundberg L. New dystonic syndrome associated with butyrophe- none therapy. Z Neurol. 1972;202:94–103. 2. Suzuki T, Matsuzaka H. Drug-induced Pisa syndrome (pleurothotonus): epidemiology and management. CNS Drugs. 2002;16:165–174. 3. Vanacore N, Suzzareddu G, Maggini M, et al. Pisa syndrome in a cohort of Alzheimer’s disease patients. Acta Neurol Scand. 2005;111: 199–201. 4. Inzelberg R, Hattori N, Nisipeanu P, et al. Camptocormia, axial dystonia, and parkinson- ism: phenotypic heterogeneity of a parkin mutation. Neurology . 2003;60:1393–1394. 5. Villarejo A, Camacho A, Garcia–Ramos R, et al. Cholinergic–dopaminergic imbalance in Pisa syndrome. Clin Neuropharmacol. 2003;26: 119–121. 6. Millan MJ, Maiofiss L, Cussac D, et al. Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther. 2002;303: 791–804. 7. Jahnichen S, Horowski R, Pertz HH. Agonism at 5-HT2B receptors is not a class effect of the ergolines. Eur J Pharmacol. 2005;513: 225–228. 252 Clin Neuropharmacol  Volume 28, Number 5, September - October 2005