This case report describes a 68‐year‐old woman, residing in a residential care center, with progressive dementia because of Alzheimer's disease (AD) since 5 years. Prescription medication consisted of escitalopram, memantine, and donepezil, the latter was started 5 years ago. The staff noted the acute development of lateroflexion of the trunk to the right while walking as well as while sitting (Video 1). The patient did not experience pain or discomfort, and the posture could be passively corrected to the normal position. The disorder of posture was completely alleviated while in supine position. The remainder of the physical and neurological examination was unremarkable. Because of the strict COVID‐19 lockdown measures at the time, a telemedicine consult was set up with the neurologist to discuss the phenomenology and treatment. It was decided to stop donepezil for a trial period, which resulted in a gradual normalization of the posture in the following few weeks. Six months after donepezil cessation, the posture remains normal (Video 1).
Video 1.
The first video segment shows a lateroflexion of the trunk to the right while standing and walking (Pisa syndrome). The second video segment shows resolution of the posture disorder after cessation of the cholinesterase inhibitor donepezil.
Pisa syndrome (PS), or pleurothotonus, is defined as a sustained lateral flexion of the trunk, which almost completely normalizes in supine position or by passive mobilization.1 PS often occurs in the setting of a neurodegenerative disorder such as Parkinson's disease (PD), multiple system atrophy, Lewy body dementia, or AD. Pathophysiologically, the evidence points to a central mechanism involving basal ganglia–brainstem dysfunction and abnormal integration of sensory information.2 This central dysfunction is linked to a dopaminergic–cholinergic imbalance, explaining why in PD, PS can both be seen as an off‐medication state, as well as a consequence of dopamine‐enhancing drugs such as dopamine agonists. This dopaminergic–cholinergic hypothesis also explains why drug‐induced PS can occur both under treatment with dopamine receptor blockers and cholinesterase inhibitors (galantamine, rivastigmine, and donepezil).3, 4 The cholinergic involvement is further exemplified by a case of idiopathic PS with successful resolution of the postural disorder after treatment with anticholinergics, and with recurrence of symptoms on withdrawal of anticholinergic drugs.5 Cholinergic neurons involved in postural control are present in the striatum and the pedunculopontine nucleus. An input asymmetry to the latter region could explain trunk muscle tone imbalance and could also explain the posture normalization while supine because of the decrease of the antigravity extensor muscle tone.2 Interestingly, the majority of PD patients with PS exhibit a postural deviation toward the clinically least affected side, and, therefore, the side of the most affected striatum.2 Hypothetically in this case, the progressive neurodegeneration of AD could gradually increase an asymmetric imbalance already amplified by donepezil.
This case highlights the importance of recognizing PS early and the need to be aware of its potential reversibility in the subacute phase preventing evolution to a chronic irreversible state. This case emphasizes PS as a potential adverse effect of cholinesterase inhibitors, a class of medication that is increasingly prescribed in the aging population. Discontinuation of a potentially offending agent should be performed first, even if the medication onset was multiple years ago, before attempting more intrusive options such as botulinum toxin injections.1
Author Roles
(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Review and Critique.
A.B.: 1A, 1B, 1C, 3A
L.L.: 1B, 1C, 3A
P.S.: 1B, 1C, 3B
Disclosures
Ethical Compliance Statement
The authors confirm that the approval of an institutional review board was not required for this work. Written informed consent from the patient's legal representative was obtained for publication of this work including the video material. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflicts of Interest
No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.
Financial Disclosures for the Previous 12 Months
A.B. is funded by a PhD fellowship grant from the Research Foundation Flanders (FWO Vlaanderen). P.S. is a senior clinical researcher funded by the FWO Vlaanderen.
Relevant disclosures and conflicts of interest are listed at the end of this article.
References
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