Department of Neuropsychiatry, Japanese Red Cross Ashikaga Hospital, 49-1 Yobe, Ashikaga, Tochigi, Japan.
Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan.
BMC Neurol. 2020 May 13;20(1):183. doi: 10.1186/s12883-020-01769-2.
Pisa syndrome (PS) is characterized by an abnormally sustained posture, with flexion of the body and head to one side and slight rotation of the trunk. Although PS most commonly arises as an adverse effect of antipsychotic drugs, choline-esterase inhibitors (ChEIs) are also sometimes known to induce PS. Despite the fact that the precise mechanism remains unclear, cholinergic-dopaminergic imbalance has been considered as a possible pathophysiologic mechanism underlying the genesis of PS.
We hereby report the case of a 60-year-old woman with Alzheimer's disease who presented with the signs of PS after her treatment was switched to galantamine, a type of ChEI, even though she had received donepezil, another type of ChEI, for 5 years without any complications. To the best of our knowledge, this is the first report of PS associated with treatment switch from one to another type of ChEI. Galantamine, but not other ChEIs, can enhance striatal dopamine release through allosteric modulation of the nicotinic acetylcholine receptor, and has weaker muscarinic effects than donepezil. Therefore, we propose two novel hypotheses to explain the development of PS, as follows; galantamine, which enhances dopamine release, can induce imbalance of dopamine levels in the striatum of patients with dementia, resulting in PS, and the weaker muscarinic effects of the drug could be one of the factors predisposing to the development of PS.
The present case suggests that treatment with galantamine is associated with a higher risk of development of PS than that with other ChEIs, such as donepezil, despite the pharmacological profile of galantamine as a dopamine modulator. Also, this report provides novel insight into another plausible mechanism underlying the development of PS, besides cholinergic-dopaminergic imbalance, namely, dopamine imbalance in the striatum with muscarinic-nicotinic imbalance.
Pisa 综合征（PS）的特征是姿势异常持久，身体和头部向一侧弯曲，轻微旋转。尽管 PS 最常见于抗精神病药物的不良反应，但胆碱酯酶抑制剂（ChEIs）有时也会引起 PS。尽管确切的机制尚不清楚，但胆碱能-多巴胺能失衡被认为是 PS 发生的一种可能的病理生理机制。
我们在此报告一例 60 岁女性阿尔茨海默病患者，在改用另一种 ChEI 加兰他敏后出现 PS 迹象，尽管她已经使用另一种 ChEI 多奈哌齐治疗了 5 年，没有任何并发症。据我们所知，这是首例与从一种 ChEI 转换为另一种 ChEI 治疗相关的 PS 病例。加兰他敏而非其他 ChEIs 通过变构调节烟碱型乙酰胆碱受体增强纹状体多巴胺释放，且与多奈哌齐相比其毒蕈碱作用较弱。因此，我们提出了两个新假说来解释 PS 的发生机制，如下：加兰他敏增强多巴胺释放，可能导致痴呆患者纹状体多巴胺水平失衡，从而引发 PS，而药物较弱的毒蕈碱作用可能是易患 PS 的因素之一。
尽管加兰他敏作为多巴胺调节剂具有药理学特征，但与其他 ChEI（如多奈哌齐）相比，加兰他敏治疗与 PS 发生风险增加相关。此外，本报告为除了胆碱能-多巴胺能失衡之外，PS 发生的另一种可能机制，即纹状体多巴胺失衡与毒蕈碱-烟碱失衡，提供了新的见解。
