PISA Syndrome-Orthopedic manifestation of a neurological disease?
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Abstract
Pleurothotonus, commonly known as Pisa Syndrome (PS), is a rare neurological disorder characterized by lateral bending of the trunk with a tendency to lean to one side. This is typically mobile and resolves in supine position. It often presents as an incapacitating symptom of underlying neurodegenerative conditions like Parkinson’s disease, alzheimer’s disease, multisystem atrophy, dementia with Lewy bodies, progressive supranuclear palsy and even subacute sclerosing panencephalitis. It is known to be associated with neuroleptics, dopaminergic agents, valproic acid and lithium. PS is also seen in neurosurgical disorders like subdural hematoma, normotensive hydrocephalus, or as a late complication of pallidotomy in patients with PD. It can present either as an acute emergency or can develop gradually over time.PS tend to happen in coronal plane and can be controlled and managed if diagnosed in early stage. However, a chronic form known as “camptocormia” occurs often in a combined fashion with anteroposterior flexion which can improve to some extent, remain stable or even get worse. Pathophysiologic mechanism is not completely understood. This review will discuss all the updated literatures published in PS in terms of prevalence, pathophysiology, clinical manifestation, and treatment modalities.
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Barone P, Santangelo G, Amboni M, Pellecchia MT, Vitale C. Pisa syndrome in Parkinson's disease and parkinsonism: clinical features, pathophysiology, and treatment. Lancet Neurol. 2016; 15: 1063–1074. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27571158
Geroin C, Squintani G, Morini A, Donato F, Smania N, et al. Pisa syndrome in Parkinson's disease: electromyographic quantification of paraspinal and non-paraspinal muscle activity. Funct Neurol. 2017; 32: 143–151. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29042003
Tinazzi M, Fasano A, Geroin C. Pisa syndrome in Parkinson disease: An observational multicenter Italian study.Neurology.2015; 85: 1769–1779. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26491088
Ekbom K, Lindholm H, Ljungberg L. New dystonic syndrome associated with butyrophenone therapy. Z Neurol. 1972; 202: 94–103. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/4115928
Marsili L, Bologna M, Kojovic M, Berardelli A, Espay AJ, et al. Dystonia in atypical parkinsonian disorders. Parkinsonism Relat Disord. 2019; 66: 25–33. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31443953
Woo KA, Yoo D, Ki CS, Lee JY. Spontaneous Pisa syndrome in a patient with early-ons, et al. zheimer's disease. Neurol Sci. 2019.
Shinfuku M, Nakajima S, Uchida H, Watanabe K, Kocha H, et al. Pisa syndrome caused by an acetylcholinesterase inhibitor in a patient with dementia with Lewy bodies. Psychiatry Clin Neurosci. 2011; 65: 299. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21507139
Salazar Z, Tschopp L, Calandra C, Micheli F. Pisa syndrome and parkinsonism secondary to valproic acid in Huntington's disease. Mov Disord. 2008; 23: 2430–2431. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18823027
Solla P, Cannas A, Congia S, Floris G, Aste R, et al. Levodopa/carbidopa/entacapone-induced acute Pisa syndrome in a Parkinson's disease patient. J Neurol Sci. 2008; 275: 154–156. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18814889
Pandey S, Tomar LR, Tater P. Pisa Syndrome in a Child With Subacute Sclerosing Panencephalitis. JAMA Neurol. 2018; 75: 255–256. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29297046
Suzuki T, Matsuzaka H. Drug-induced Pisa syndrome (pleurothotonus): epidemiology and management. CNS Drugs.2002; 16: 165–174. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11888337
Todisco M, Pozzi NG, Zangaglia R, Minafra B, Servello D, et al. Pisa syndrome in Idiopathic Normal Pressure Hydrocephalus. Parkinsonism Relat Disord. 2019; 66: 40–44. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31300263
Leon-Sarmiento FE, Pradilla G, Del Rosario Zambrano M. Primary and Reversible Pisa Syndrome in Juvenile Normal Pressure Hydrocephalus. Acta Neuropsychiatr. 2013; 25: 57–60. PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686565/
Marchione P, Spallone A, Valente M, Giannone C, De Angelis F, Meco G. Reversible Pisa syndrome associated to subdural haematoma: case-report. BMC Neurol. 2014; 14: 149. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25123109
van deWarrenburg BP, Bhatia KP, Quinn NP. Pisa syndrome after unilateral pallidotomy in Parkinson's disease: an unrecognised, delayed adverse event? J Neurol Neurosurg Psychiatry. 2007; 78: 329–330. PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2117655/
Bhattacharya KF, Giannakikou I, Munroe N, Chaudhuri KR. Primary anticholinergic-responsive Pisa syndrome. Mov Disord. 2000; 15: 1285–1287. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11104229
Doherty KM, van de Warrenburg BP, Peralta MC, Moriyama LS, Azulay JP, et al. Postural deformities in Parkinson’s disease. Lancet Neurol. 2011; 10: 538-549. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21514890
Yassa R, Nastase C, Cvejic J, Laberge G. The Pisa syndrome (or pleurothotonus): prevalence in a psychogeriatric population. Biol Psychiatry. 1991; 29: 942–945. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/1675591
Stübner S, Padberg F, Grohmann R, et al. Pisa syndrome (pleurothotonus): report of a multicenter drug safety surveillance project. J Clin Psychiatry. 2000; 61: 569–574. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10982199
Zannas AS, Okuno Y, Doraiswamy PM. Cholinesterase inhibitors and Pisa syndrome: a pharmacovigilance study. Pharmacotherapy. 2014; 34: 272–278. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24127392
Bonanni L, Thomas A, Varanese S, Scorrano V, Onofrj M. Botulinum toxin treatment of lateral axial dystonia in Parkinsonism. Mov Disord. 2007; 22: 2097–2103. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17685467
Ashour R, Jankovic J. Joint and skeletal deformities in Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Mov Disord. 2006; 21: 1856–1863. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16941460
Baik JS, Kim JY, Park JH, Han SW, Park JH, et al. Scoliosis in patients with Parkinson's disease. J Clin Neurol. 2009; 5: 91–94. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19587816
Grimes JD, Hassan MN, Trent G, Halle D, Armstrong GW. Clinical and radiographic features of scoliosis in Parkinson's disease. Adv Neurol. 1987; 45: 353–355. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/3825710
Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord. 2015; 30: 1591–1601. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26474316
Vitale C, Falco F, Trojano L, Erro R, Moccia M, et al. Neuropsychological correlates of Pisa syndrome in patients with Parkinson's disease. Acta Neurol Scand. 2016; 134: 101–107. https://www.ncbi.nlm.nih.gov/pubmed/26427765
Huh YE, Kim K, Chung WH, Youn J, Kim S, et al. Pisa Syndrome in Parkinson's Disease: Pathogenic Roles of Verticality Perception Deficits. Sci Rep. 2018; 8: 1804. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29379091
Castrioto A, Piscicelli C, Perennou D, Krack P, Debu B. The pathogenesis of Pisa syndrome in Parkinson’s disease. Mov Disord.2014; 29: 1100-1107. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24909134
Tinazzi M, Geroin C, Gandolfi M, Smania N, Tamburin S, et al. Pisa syndrome in Parkinson's disease: An integrated approach from pathophysiology to management. Mov Disord. 2016; 31: 1785–1795. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27779784
Vorovenci RJ, Biundo R, Antonini A. Therapy-resistant symptoms in Parkinson's disease. J Neural Transm (Vienna). 2016; 123: 19–30. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26410626
Villarejo A, Camacho A, García-Ramos R, Moreno T, Penas M, et al. Cholinergic-dopaminergic imbalance in Pisa syndrome. Clin Neuropharmacol. 2003; 26: 119–121. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12782913
Spanaki C, Zafeiris S, Plaitakis A. Levodopa-aggravated lateral flexion of the neck and trunk as a delayed phenomenon of unilateral pallidotomy.Mov Disord. 2010; 25: 655–656. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20131399
Vitale C, Marcelli V, Furia T, Santangelo G, Cozzolino A, et al. Vestibular impairment and adaptive postural imbalance in parkinsonian patients with lateral trunk flexion. Mov Disord. 2011; 26: 1458–1463. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21465552
Tinazzi M, Juergenson I, Squintani G, Vattemi G, Montemezzi S, et al. Pisa syndrome in Parkinson’s disease: an electrophysiological and imaging study.J Neurol. 2013; 260: 2138–2148. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23695587
Tassorelli C, Furnari A, Buscone S, Alfonsi E, Pacchetti C, et al. Pisa syndrome in Parkinson’s disease: clinical, electromyographic, and radiological characterization.Mov Disord. 2012; 27: 227–235. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21997192
Frazzitta G, Balbi P, Gotti F, Maestri R, Sabetta A, et al. Pisa syndrome in Parkinson’s disease: electromyographic aspects and implication for rehabilitation. Parkinsons Dis. 2015; 2015: 437190. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26682083
Doherty KM, Davagnanam I, Molloy S, Silveira-Moriyama L, Lees AJ. Pisa syndrome in Parkinson’s disease: a mobile or fixed deformity? J Neurol Neurosurg Psychiatry. 2013; 84: 1400–1403. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23532719
Hozumi I, Piao YS, Inuzuka T, Matsuyama Z, Yamada Y, et al. Marked asymmetry of putaminal pathology in an MSA-P patient with Pisa syndrome. Mov Disord. 2004; 19: 470–472. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15077247
Solla P, Grau-Rivera O, Gelpi E, Marrosu F, Martí MJ. Pisa syndrome in a patient with pathologically confirmed Parkinson's disease. Neuropathol Appl Neurobiol. 2016; 42: 654–658. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26999006
PubMed: Vrtovec T, Pernus F, Likar B. A review of methods for quantitative evaluation of spinal curvature. Eur Spine J. 2009; 18: 593–607. https://www.ncbi.nlm.nih.gov/pubmed/19247697
Vrtovec T, Pernus F, Likar B. A review of methods for quantitative evaluation of axial vertebral rotation. Eur Spine J. 2009; 18: 1079–1090. PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2899509/
Cannas A, Solla P, Floris G, Tacconi P, Serra A, et al. Reversible Pisa syndrome in patients with Parkinson’s disease on dopaminergic therapy. J Neurol. 2009; 256: 390–395. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19319462
Miletić V, Radić B, Relja M. Acute pisa syndrome as a neurological emergency. J Neuropsychiatry Clin Neurosci. 2015; 27: e159–e160. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25923868
Yokochi F. Lateral flexion in Parkinson's disease and Pisa syndrome. J Neurol. 2006; 253 Suppl 7: VII17–VII20. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17131222
Stübner S, Padberg F, Grohmann R, Hampel H, Hollweg M, et al. Pisa syndrome (pleurothotonus): report of a multicenter drug safety surveillance project. J Clin Psychiatry. 2000; 61: 569–574. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10982199
Suzuki T, Koizumi J, Moroji T, Sakuma K, Hori M, et al. Clinical characteristics of the Pisa syndrome. Acta Psychiatr Scand. 1990; 82: 454–457.
Praharaj SK, Arora M. Pisa syndrome: acute and tardive forms. South Med J. 2007; 100: 853–854.
Martin JP. Curvature of the spine in post-encephalitic parkinsonism. J Neurol Neurosurg Psychiatry. 1965; 28: 395–400. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/5838474
Geroin C, Gandolfi M, Bruno V, Smania N, Tinazzi M. Integrated Approach for Pain Management in Parkinson Disease. Curr Neurol Neurosci Rep. 2016; 16: 28. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26879763
Di Matteo A, Fasano A, Squintani G, Ricciardi L, Bovi T, et al. Lateral trunk flexion in Parkinson's disease: EMG features disclose two different underlying pathophysiological mechanisms. J Neurol. 2011; 258: 740–745. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21079986
Geroin C, Smania N, Schena F, Dimitrova E, Verzini E, et al. Does the Pisa syndrome affect postural control, balance, and gait in patients with Parkinson's disease? An observational cross-sectional study. Parkinsonism Relat Disord. 2015; 21: 736–741. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25940999
Saifee TA, Edwards MJ. Tardive movement disorders: a practical approach. Pract Neurol. 2011; 11: 341–348.
Schwab FJ, Smith VA, Biserni M, Gamez L, Farcy JP, et al. Adult scoliosis: a quantitative radiographic and clinical analysis. Spine (Phila Pa 1976). 2002; 27: 387–392. PubMed: https://pubmed.ncbi.nlm.nih.gov/11840105
El-Hawary R, Chukwunyerenwa C. Update on evaluation and treatment of scoliosis. Pediatr Clin North Am. 2014; 61: 1223–1241. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25439021
Wunderlich S, Csoti I, Reiners K, Günthner-Lengsfeld T, Schneider C, et al. Camptocormia in Parkinson's disease mimicked by focal myositis of the paraspinal muscles. Mov Disord. 2002; 17: 598–600. https://www.ncbi.nlm.nih.gov/pubmed/12112214
Abboud H, Sivaraman I, Ontaneda D, Tavee J. Camptocormia and Pisa syndrome as manifestations of acute myasthenia gravis exacerbation. J Neurol Sci. 2015; 359: 8–10. https://www.ncbi.nlm.nih.gov/pubmed/26671078
Doherty KM, Silveira-Moriyama L, Giladi N, Bhatia KP, Parton M, et al. Camptocormia: don’t forget muscle disease in the movement disorder clinic. J Neurol. 2012; 259: 1752–1754. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22349871
Kim JS, Park JW, Chung SW, Kim YI, Kim HT, et al. Pisa syndrome as a motor complication of Parkinson's disease. Parkinsonism Relat Disord. 2007; 13: 126–128. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16731022
Arora M, Praharaj SK, Sarkar S. Clozapine effective in olanzapine-induced Pisa syndrome. Ann Pharmacother. 2006; 40: 2273–2275. PubMed: https://pubmed.ncbi.nlm.nih.gov/17132806/
Kurtz G, Kapfhammer HP, Peuker B. Pisa syndrome in clozapine therapy [in German]. Nervenarzt. 1993; 64: 742–746. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/8278016
Michel SF, Arias Carrión O, Correa TE, Alejandro PL, Micheli F. Pisa Syndrome. Clin Neuropharmacol. 2015; 38: 135–140. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26166239
Walder A, Greil W, Baumann P. Drug-induced Pisa syndrome under quetiapine. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33: 1286–1287. https://www.ncbi.nlm.nih.gov/pubmed/19646500
Kwak YT, Han IW, Baik J, Koo MS. Relation between cholinesterase inhibitor and Pisa syndrome. Lancet. 2000; 355: 2222. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10881902
Srivanitchapoom P, Hallett M. Camptocormia in Parkinson's disease: definition, epidemiology, pathogenesis and treatment modalities. J Neurol Neurosurg Psychiatry. 2016; 87: 75–85. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25896683
Zannas AS, Okuno Y, Doraiswamy PM. Cholinesterase inhibitors and Pisa syndrome: a pharmacovigilance study. Pharmacotherapy. 2014; 34: 272–278. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24127392
Suzuki T, Matsuzaka H. Drug-induced Pisa syndrome (pleurothotonus): epidemiology and management. CNS Drugs. 2002; 16: 165–174. https://www.ncbi.nlm.nih.gov/pubmed/11888337
Jankovic J. Botulinum toxin in clinical practice. J Neurol Neurosurg Psychiatry. 2004; 75: 951–957. PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1739107/
Tassorelli C, De Icco R, Alfonsi E, Bartolo M, Serrao M, et al. Botulinum toxin type A potentiates the effect of neuromotor rehabilitation of Pisa syndrome in Parkinson disease: a placebo controlled study. Parkinsonism Relat Disord. 2014; 20: 1140–1144. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25175601
Dupeyron A, Viollet E, Coroian F, Gagnard C, Renard D, et al. Botulinum Toxin-A for treatment of Pisa syndrome: A new target muscle. Parkinsonism Relat Disord. 2015; 21: 669–670. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25899457
Santamato A, Ranieri M, Panza F, Zoccolella S, Frisardi V, et al. Botulinum toxin type A and a rehabilitation program in the treatment of Pisa syndrome in Parkinson's disease. J Neurol. 2010; 257: 139–141. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19763384
Upadhyaya CD, Starr PA, Mummaneni PV. Spinal deformity and Parkinson disease: a treatment algorithm. Neurosurg Focus. 2010; 28: E5. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20196652
Capecci M, Serpicelli C, Fiorentini L, Censi G, Ferretti M, et al. Postural rehabilitation and Kinesio taping for axial postural disorders in Parkinson's disease. Arch Phys Med Rehabil. 2014; 95: 1067–1075. https://www.ncbi.nlm.nih.gov/pubmed/24508531
Bartolo M, Serrao M, Tassorelli C, Don R, Ranavolo A, et al. Four-week trunk-specific rehabilitation treatment improves lateral trunk flexion in Parkinson's disease. Mov Disord. 2010; 25: 325–331. https://www.ncbi.nlm.nih.gov/pubmed/20131386
Kataoka H, Ikeda M, Horikawa H, Ueno S. Reversible lateral trunk flexion treated with a rehabilitation program in a patient with Parkinson's disease. Parkinsonism Relat Disord. 2013; 19: 494–497. https://www.ncbi.nlm.nih.gov/pubmed/23274084
Visser JE, Allum JH, Carpenter MG, Esselink RA, Speelman JD, et al. Subthalamic nucleus stimulation and levodopa-resistant postural instability in Parkinson's disease. J Neurol. 2008; 255: 205–210. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18274810
Stefani A, Lozano AM, Peppe A, Stanzione P, Galati S, et al. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease. Brain. 2007; 130: 1596–1607. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17251240
Shih LC, Vanderhorst VG, Lozano AM, Hamani C, Moro E. Improvement of pisa syndrome with contralateral pedunculopontine stimulation. Mov Disord. 2013; 28: 555–556. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23389993
Ricciardi L, Piano C, Bentivoglio AR, Fasano A. Long-term effects of pedunculopontine nucleus stimulation for Pisa syndrome. Parkinsonism Relat Disord. 2014; 20: 1445–1446. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25455696
Ha Y, Oh JK, Smith JS, Ailon T, Fehlings MG, et al. Impact of Movement Disorders on Management of Spinal Deformity in the Elderly. Neurosurgery. 2015; 77 Suppl 4: S173–S185. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26378355
Suzuki T, Hori T, Baba A, Abe S, Shiraishi H, et al. Effectiveness of anticholinergics and neuroleptic dose reduction on neuroleptic-induced pleurothotonus (the Pisa syndrome). J Clin Psychopharmacol. 1999; 19: 277–280. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10350039
Fasano A, Di Matteo A, Vitale C, Squintani G, Ferigo L, et al. Reversible Pisa syndrome in patients with Parkinson's disease on rasagiline therapy. Mov Disord. 2011; 26: 2578–2580. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22170277
Artusi CA, Montanaro E, Tuttobene S, Romagnolo A, Zibetti M, et al. Pisa Syndrome in Parkinson's Disease Is Associated With Specific Cognitive Alterations. Front Neurol. 2019; 10: 577. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31214112
Fujioka S, Yoshida R, Nose K, Hayashi Y, Mishima T, et al. A new therapeutic strategy with istradefylline for postural deformities in Parkinson's disease. Neurol Neurochir Pol. 2019; 53: 291‐295. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31441493