Chronic Neuroleptic‐Induced Parkinsonism Examined With Positron Emission Tomography

Abstract

BackgroundNeuroleptic drug‐induced parkinsonism (NIP) is a leading cause of parkinsonism, particularly in aging. Based on abnormal dopamine transporter scan results, individuals displaying chronic NIP are often diagnosed with Lewy‐body Parkinson's disease (PD), but this assumption needs further substantiation.ObjectiveTo quantitate the profile of striatal dopaminergic nerve terminal density in NIP relative to PD.MethodsWe used the positron emission tomography ligand [11C](+)‐dihydrotetrabenazine targeting vesicular monoamine transporter type 2 (VMAT2) binding sites and collected various clinical parameters (motor ratings, olfaction, polysomnography to document rapid eye movement sleep muscle activity, quantitative sensory testing for pain thresholds) possibly predicting binding results in patients older than age 50 living with schizophrenia spectrum disorders under long‐term stable antipsychotic drug treatment, with (N = 11) or without (N = 11) chart documention of chronic NIP, and compared them to healthy volunteers (N = 11) and others medicated for PD (N = 12).ResultsStriatal VMAT2 binding was dichotomous in the NIP group between those with spared (N = 5) or low (N = 6) PD‐like values. Striatal binding reduction in the low VMAT2‐NIP group was asymmetric without the gradient of maximal involvement in the posterior putamen typical of PD. Anosmia was the only nonmotor parameter measured matching the abnormal striatal VMAT2 binding status.ConclusionThese preliminary observations suggest that striatal VMAT2 binding is abnormal in a fraction of chronic NIP cases and differs in spatial distribution from PD. The possibility of a drug‐induced axonopathy and resultant synaptopathy, as well as the evolution of the binding deficit, warrant further longitudinal studies in a large cohort. © 2020 International Parkinson and Movement Disorder Society

Recognition and Management of Antipsychotic-Induced Parkinsonism in Older Adults: A Narrative Review

“…Patient-related factors are organic brain damage, learning disability, dementia, IPD, hypertension, organic personality disorder, schizophrenia, mania, depression or anxiety, HIV infection, non-European ancestry, and presence of HLA-B44 [3,31,33,[47][48][49]; whilst drug-related causes are high potency APs, higher dosage of APs, and long-term exposure to APs [3,33]. The diagnosis of DIP has also been reported to triple the lifetime risk of developing IPD [50,51], whilst the relative risk of developing IPD was found in one study to be of 24.3 (CI 95%) [52].…”

“…Motor features of DIP have been reported to be similar to those of IPD [7,8,51,[72][73][74][75], presenting in a more symmetrical way, with an upper limb predominance [76], and with less axial impairment [6] compared to IPD. In keeping with this, a PET study of DaT in AIP [77] showed that symmetrical parkinsonism was more frequent in patients with normal uptake in the striatal DaTs.…”

“…An alternative imaging method to DaT scan is the study of the vesicular monoamine transporter type 2 (VMAT2), using PET and the radioligand [11C](+)-dihydrotetrabenazine which binds to this transporter molecule. This imaging modality has been suggested as an alternative to DaT scan, as the VMAT2 is less modulated by drugs that affect dopaminergic transmission in the brain [51]. In a study using PET to measure binding to VMAT2 in patients with schizophrenia with chronic AIP, patients with schizophrenia without AIP, normal controls, and patients with IPD, observed that in the group with AIP there was a dichotomous striatal binding to VMAT2, with a spared binding subgroup, and a low binding one [51].…”

Drug-induced parkinsonism: what should a psychiatrist know?

“…The hyperkinetic symptoms observed in DIP, such as oromandibular dyskinesia, may be also explained by the prolonged blockage of dopaminergic receptors; but in this case, the dyskinesia is due to the compensatory hypersensitivity they develop 24 . Other implicated mechanisms include type 2 vesicular monoamine transporter 2 blockage and the modification of calcium channels at the presynaptic terminal 25 .…”

“…Amantadine and anticholinergics, including biperiden, benztropine, or trihexyphenidyl, have been used for the control of symptoms but they lack strong evidence to support their use 25,44 .…”