Spontaneous Pisa syndrome in a patient with early-onset Alzheimer’s disease

Abstract

Dear Editor-in-Chief, Pisa syndrome refers to an involuntary and reversible lateral deviation of the trunk and is typically defined as a bending degree greater than 10° or 15° [1, 2]. The syndrome was first described as an adverse effect of neuroleptics and has subsequently been described in Parkinson’s disease, atypical parkinsonism, and other neurodegenerative disorders [1, 3]. A few cases, mostly drug-induced, have been reported in Alzheimer’s disease (AD) [4]. Herein, we report a case of early-onset AD (EOAD) with spontaneous Pisa syndrome and posterior cortical symptoms. A 53-year-old female was admitted for cognitive impairment and lateral truncal bending. She exhibited a tonic flexion to the left aggravated by standing or walking, consistent with Pisa syndrome (Fig. 1a). The bending had developed insidiously 2 years before and persisted with only minor fluctuations. The caregivers simultaneously noticed a progressive memory decline, which they had not recognized before, and a few months later, a short-stepped gait. She started levodopa at another hospital, but posture and gait continued to worsen. She had previously been in good health besides hypertension. Her parents and her mother’s siblings had no remarkable medical history. History of other relatives was unavailable. She scored a 4 on the Mini-Mental Status Examination and 5 on the Montreal Cognitive Assessment. Poor comprehension and behavioral perseveration complicated testing. Optic ataxia, dressing, and constructional apraxia were prominent. Parkinsonian symptoms were observed, including generalized bradykinesia and decreased arm swings. There was no sign of autonomic dysfunction, spontaneous visual hallucination, fluctuating cognition, or dream enactment behavior. Magnetic resonance imaging (MRI) of the brain demonstrated prominent medial temporal atrophy with widespread cortical atrophy. [F]-fluorodeoxyglucose positron emission tomography (PET) showed posterior-dominant hypometabolism involving the parieto-occipital, posterior temporal, and posterior cingulate cortices. The amyloid PET scan was strongly positive with diffuse cortical [F]-florbetaben binding, supporting a diagnosis of AD (Fig. 1b–d). We screened 31 genes linked to dementia risk (Online Resource). A variant of uncertain significance (VUS) w a s f o u n d i n e x o n 6 o f t h e A P P g e n e (NM_000484.3(APP):c.694G>A;p.(Glu232Lys), heterozygous). We reduced the patient’s levodopa and started donepezil for management of AD. Truncal bending was modestly improved until the last follow-up. Cognitive symptoms showed mild subjective improvement. The mechanism of Pisa syndrome has yet to be elucidated, but a dopaminergic-cholinergic imbalance is suggested to be a factor [1]. Alterations of the sensorimotor integrating pathways and musculoskeletal system have been implicated in Parkinsonism [2, 5]. In AD, druginduced Pisa cases have been reported, mostly after the use of acetylcholinesterase inhibitors (AChEI), implying that abruptly induced cholinergic excess may produce Pisa syndrome in cholinergically depleted AD [4]. To our knowledge, just one case of spontaneous Pisa syndrome has been reported in clinically diagnosed AD [6]. In our patient, a strongly positive amyloid PET scan supported AD. Unresponsiveness to levodopa and improvement of Pisa by reducing levodopa and adding acetylcholinesterase inhibitor were the unique features. Besides drug-induced cholinergic surge, a discrete Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10072-019-04160-3) contains supplementary material, which is available to authorized users.