Structural findings in the basal ganglia in genetically determined and idiopathic Parkinson's disease

Abstract

A bilateral compensatory increase of basal ganglia (BG) gray matter value (GMV) was recently demonstrated in asymptomatic Parkin mutation carriers, who likely have an increased risk to develop Parkinson's disease (PD). We hypothesized BG morphological changes in symptomatic Parkin mutation carriers (sPARKIN-MC) and idiopathic PD patients (iPD) after the occurrence of PD symptoms, reflecting the breakdown of compensatory mechanisms. Nine sPAR-KIN-MC, 14 iPD, and 24 controls were studied clinically and with voxel-based morphometry. Analysis of variance revealed mainly BG decrease of GMV in sPARKIN-MC and to a lesser extent in iPD. However, a slight increase in GMV was also found in the right globus pallidus externus in sPARKIN-MC and in the right putamen in iPD. This may reflect a structural correlate of functional compensation that can only partially be maintained when nigrostriatal neurodegeneration becomes manifest. Simple regression analyses with the UPDRS-III and disease duration score revealed a distinct more bilateral linear decrease of BG GMV in sPARKIN-MC than in iPD that may correspond to previous findings showing a symmetric reduction in putaminal 18 F-DOPA-uptake and bilateral manifestation of symptoms in sPARKIN-MC. In symptomatic PD, BG are subject to a progressive atrophy, which gradually increases with disease severity and duration.

Cerebral pathological and compensatory mechanisms in the premotor phase of leucine-rich repeat kinase 2 parkinsonism

“…L = left; PPC = posterior parietal cortex; R = right; V2 = visual area 2. indicates that asymptomatic LRRK2-G2019S mutation carriers have a functional impairment in the striatum. Furthermore, in contrast to the structural alterations seen in the ventrolateral striatum of patients with idiopathic Parkinson's disease and nonmanifesting carriers of parkin and PINK1 mutations (Buhmann et al, 2005;Binkofski et al, 2007;Reetz et al, 2009), the striatal impairment in asymptomatic LRRK2 carriers arose in the caudate nucleus. Third, asymptomatic LRRK2-G2019S mutation carriers had increased imagery-related activity in the right dorsal premotor cortex.…”

Grey matter abnormality in autism spectrum disorder: an activation likelihood estimation meta-analysis study

“…For example, the amygdalae show a decrease in GM volume whereas other monosynaptically connected structures such as the temporal pole, caudate head or orbitofrontal cortex show an increase in GM volume. A compensatory function may be involved as, similarly, in asymptomatic Parkinson's disease mutation carriers, where a bilateral compensatory increase in basal ganglia GM has been demonstrated, or in patients with schizophrenia treated with conventional antipsychotics (but not atypical drugs), where a compensatory caudate volume increase was observed 45 46. In ASD, GM volume increases in several structures may reflect an effort to balance a functional decrease in another related structure.…”

Neuropathology of Parkinson’s Disease

“…In early stages of PD, overactivation in the basal ganglia is suggested to compensate for the dopaminergic defect in the striatal motor circuit [ 272 ]. The increase in striatal neuronal activity with decreased excitation of D1-bearing neurons leads to reduced activity of the "direct" pathway, whereas reduced inhibition of D2-bearing striatal neurons results in decreased activity in striatopallidal (GPe) projections (see Fig.…”