Pallidal Deep Brain Stimulation in a Parkinsonian Patient with Late-Life Dementia: Sustained Benefit in Motor Symptoms but Not in Functional Disability

Pallidal surgery is now well established in the treatment of motor symptoms in Parkinson’s disease (PD) [1]. Experience with pallidal surgery for atypical parkinsonian disorders, however, is limited so far. We report on a 75-year-old right-handed man with an 18-year history of parkinsonism, presenting with unilateral right-hand rest tremor, followed by left-sided tremor and by akinesia, which responded to levodopa. After gradual disease progression, pallidal deep brain stimulation was indicated for the treatment of disabling motor fluctuations and severe dyskinesia. His general preoperative condition was unremarkable, and he scored 22 of 30 points on the Mini Mental State Examination (MMSE) with short-term memory impairment. At the time of surgery, the patient took a daily dose of 1,200 mg of regular levodopa-carbidopa and 20 mg of paroxetine. There was no other medication; in particular, the patient did not take anticholinergics. Off drug he presented with hypophonia, hypomimia and rest tremor, rigidity and bradykinesia more pronounced on the right side. He had considerable difficulties rising from a chair, disturbed postural stability and a severe gait disorder with start hesitations, occasional freezing and festination, but he did not require assistance (table 1). MRI showed moderate cortical atrophy and widening of the ventricular system. A monopolar electrode (Medtronic SP 5535-300) was positioned into the left internal segment of the globus pallidus [2]. A marked improvement of the right-sided symptoms including postural instability was noted in the early postoperative period (table 1). There were no adverse effects. In the postoperative follow-up period, the dosage of levodopa-carbidopa remained unchanged and there was no other change in medication. At the 1-year follow-up, the patient’s family reported marked fluctuations in cognitive function. The previous functional gain was lost, although there was still a significant motor improvement (table 1). Most remarkably, there was a global cognitive deterioration with disorientation in time and place, gross impairment of immediate and distant recall and severe apraxia. Since the cause for the rapid mental deterioration was unclear, the implantable pulse generator was switched off for 9 weeks. While this resulted in worsening of motor function, the patient’s mental status was unchanged. Relatives reported on well-formed visual hallucinations, which were not related to medication, for example, threatening wild animals. He presented fluctuating cognition with pronounced variations in attention and alertness. During a stay at our inpatient department for observation, his status changed from drowsy and disoriented to alert. MMSE scores varied from 8 to 16 within 3 days. In addition, transient loss of consciousness was observed. He had ideomotor and ideational apraxia. Regardless whether the implantable pulse generator was on or off, similar poor findings on neuropsychological assessments using criteria of the Consortium to Establish a Registry for Alzheimer’s Disease [3] were documented. Single-photon emission computed tomography (SPECT) studies with 99mTc-ethylcysteinate dimer both during stimulation on and off showed a parieto-temporo-occipital hypoperfusion defect resembling a horseshoe pattern defect. 123I-ßcarboxymethoxy-3ß-(4-iodophenyl)tropane SPECT showed decreased striatal dopamine transporter density, which was more pronounced on the left. The presence of progressive dementia in PD patients is a source of ongoing nosological controversy. While the preoperative course of the disease with an 18-year history of parkinsonism, sustained benefit to levodopa and only late-course moderate cognitive impairment is consistent with a diagnosis of idiopathic PD, the course over the past 18 months suggests the coexistence or the transition into another parkinsonian syndrome. According to operational criteria recently