Gray matter atrophy underlies PD subtypes

By Eleanor McDermid, Senior medwireNews Reporter

Patients with the postural instability gait difficulty (PIGD) subtype of Parkinson's disease (PD) have marked gray matter (GM) atrophy relative to those with the tremor dominant subtype, shows research.

On magnetic resonance imaging, the overall percentage of whole-brain GM was similar in 30 patients with the PIGD subtype and in 29 with the tremor dominant subtype, report Jeffrey Hausdorff (Tel-Aviv Sourasky Medical Center, Israel) and colleagues.

"This similarity suggests that any GM differences between the PD subtypes are attributable to site-specific tissue changes and not general brain GM atrophy," they write in Neurology.

Voxel-based morphometry (VBM) analysis revealed reduced GM in all the major lobes and some subcortical areas of patients with PIGD versus tremor-dominant PD. On region-of-interest analysis, the team found that PIGD scores worsened with decreasing GM volumes in areas involved in motor control. These included the pre-supplementary motor area (SMA), which Hausdorff et al say is involved in motor initiation and planning, and is activated before the onset of movement.

"The difficulties with the initiation of movement that are often present among patients with PIGD may be related to atrophy in this region," they suggest.

Furthermore, GM volume in the pre-SMA was positively associated with functional connectivity; in other words, patients with GM atrophy had reduced functional connectivity in this area.

The association between GM volume and PIGD score was also seen for the SMA proper and the postcentral gyrus, as well as the primary motor area, the latter finding suggesting an underlying cause for the gait difficulties in the PIGD group, measured as decreased postural control in the pull test.

PIGD scores were also associated with GM volumes in multiple subcortical motor areas, and in the cerebellum declive and culmen. "This finding is consistent with the hypothesis that the cerebellum plays an important role in gait, by regulating posture and balance and by adjusting the feedforward control of locomotor output through error-feedback learning," say the researchers.

Patients' PIGD scores also increased in line with decreased GM volume in the inferior frontal gyrus; conversely, lower GM volume in this area was associated with fewer tremor symptoms.

"The present findings indicate that relatively widespread GM atrophy is apparently a characteristic feature of a distinct subset of patients with PD," Hausdorff et al conclude. But they caution that the study design does not shed light on the association between GM atrophy and disease progression.

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