Therapeutic approaches to cholinergic deficiency in Lewy body diseases.

Introduction: Cortical cholinergic denervation resulting from degeneration of the nucleus basalis of Meynert (NBM) is a primary contributor to cognitive impairment and neuropsychiatric symptoms in the Lewy body diseases Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB). Considering the morbidity associated with cognitive impairment and neuropsychiatric symptoms in these diseases, it is important to investigate all potential therapies to improve these symptoms.Areas covered: The authors review the current landscape of pharmacological and surgical therapies for mitigating the cortical cholinergic deficiency in PD, PDD, and DLB.Expert opinion: The cholinesterase inhibitors rivastigmine, donepezil, and galantamine are currently the primary pharmacological treatments available to improve cognition and associated neuropsychiatric symptoms in Lewy body diseases. Other possible pharmacological strategies include increasing acetylcholine release with 5-HT4 agonists or directly stimulating cholinergic receptors with muscarinic and nicotinic agonists. The side effect profile of muscarinic agonists is a deterrent to their future study, but 5-HT4 and nicotinic agonists deserve further investigation. Targeting the basal forebrain with either deep brain stimulation (DBS)- or cell-based therapies is another strategy to mitigate cortical cholinergic deficiency. Before NBM DBS studies continue, it will be important to resolve issues related to targeting, stimulation pattern, and duration.

Choreo-ballistic movement after thalamotomy in a patient with Lewy body dementia.

Thalamotomy is an established treatment for medically refractory tremor. Major complications of thalamotomy include cognitive disturbance, paralysis, dysphagia, sensory loss, and speech disturbance. Hemiballism is a rare complication after thalamotomy. We herein present a 74-year-old female patient who developed choreo-ballistic movement after thalamotomy. She was diagnosed with Lewy body dementia at the age of 70 years and exhibited worsening bilateral hand tremor. Her tremor was severe and pharmacoresistant. Left thalamotomy was planned with the trajectory passing through the ventralis intermedius (VIM) nucleus to the posterior subthalamic area (PSA). The right VIM nucleus and PSA were both coagulated with one trajectory, resulting in the immediate amelioration of right hand tremor. However, four days after surgery, choreo-ballistic movement appeared in the right leg and persisted for six months. Furthermore, tremor recurred after one month. Postoperative MRI showed a small coagulated lesion in the subthalamic nucleus. Although choreo-ballistic movement is a rare complication, it needs to be considered, particularly in patients in which the inferior border of the VIM nucleus is targeted.