Brain metabolic alterations herald falls in patients with Parkinson’s disease

Isaias, Ioannis U.; Brumberg, Joachim; Pozzi, Nicoló Gabriele; Palmisano, Chiara; Canessa, Andrea; Marotta, Giorgio; Volkmann, Jens; Pezzoli, Gianni

doi:10.1002/acn3.51013

Cited by 12 publications

(8 citation statements)

References 25 publications

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“…These findings corroborate and prefigure prior cross-sectional work in freezers showing increased coupling across cortico-subcortical limbic circuitry at rest 56 , and reduced coupling within the cognitive control networks at rest 56 , 57 and during freezing episodes 58 , 59 . Our findings thereby add to the body of literature indicating that persons with PD increasingly rely on non-motor circuits 60 , 61 in order to overcome reduced processing in the depleted sensorimotor circuits, and that over time, altered processing in these compensatory circuits predisposes them for gait breakdown and the onset of FOG. As a result of this increasing reliance on the limbic and associative circuitry, plastic changes may occur in the coupled medial thalamic nuclei, giving rise to the morphological differences seen here.…”

Section: Discussionsupporting

confidence: 57%

Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease

DʼCruz

Vervoort

Chalavi

et al. 2021

npj Parkinsons Dis.

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The onset of freezing of gait (FOG) in Parkinson’s disease (PD) is a critical milestone, marked by a higher risk of falls and reduced quality of life. FOG is associated with alterations in subcortical neural circuits, yet no study has assessed whether subcortical morphology can predict the onset of clinical FOG. In this prospective multimodal neuroimaging cohort study, we performed vertex-based analysis of grey matter morphology in fifty-seven individuals with PD at study entry and two years later. We also explored the behavioral correlates and resting-state functional connectivity related to these local volume differences. At study entry, we found that freezers (N = 12) and persons who developed FOG during the course of the study (converters) (N = 9) showed local inflations in bilateral thalamus in contrast to persons who did not (non-converters) (N = 36). Longitudinally, converters (N = 7) also showed local inflation in the left thalamus, as compared to non-converters (N = 36). A model including sex, daily levodopa equivalent dose, and local thalamic inflation predicted conversion with good accuracy (AUC: 0.87, sensitivity: 88.9%, specificity: 77.8%). Exploratory analyses showed that local thalamic inflations were associated with larger medial thalamic sub-nuclei volumes and better cognitive performance. Resting-state analyses further revealed that converters had stronger thalamo-cortical coupling with limbic and cognitive regions pre-conversion, with a marked reduction in coupling over the two years. Finally, validation using the PPMI cohort suggested FOG-specific non-linear evolution of thalamic local volume. These findings provide markers of, and deeper insights into conversion to FOG, which may foster earlier intervention and better mobility for persons with PD.

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Section: Discussionsupporting

confidence: 57%

Thalamic morphology predicts the onset of freezing of gait in Parkinson’s disease

DʼCruz

Vervoort

Chalavi

et al. 2021

npj Parkinsons Dis.

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“…The efficacy of an online compensatory role of the cerebellum [ 70 , 78 ] is suggested in our study by the relatively preserved SCoM temporal movement sequencing [ 79 ], which could have also prevented the appearance of any gait freezing episode during our acquisitions. Relative timing of segmental movements was also described as unaltered in patients with PD by Rosin and colleagues (1997), further suggesting a compensatory rather than detrimental role of the cerebellum in Parkinsonian patients with FOG and balance disturbances [ 60 , 78 , 80 ]. Of relevance, the high variability in the SCoM movement onsets might have prevented us from detecting differences across groups.…”

Section: Discussionmentioning

confidence: 98%

Gait Initiation Impairment in Patients with Parkinson’s Disease and Freezing of Gait

et al. 2022

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Freezing of gait (FOG) is a sudden episodic inability to produce effective stepping despite the intention to walk. It typically occurs during gait initiation (GI) or modulation and may lead to falls. We studied the anticipatory postural adjustments (imbalance, unloading, and stepping phase) at GI in 23 patients with Parkinson’s disease (PD) and FOG (PDF), 20 patients with PD and no previous history of FOG (PDNF), and 23 healthy controls (HCs). Patients performed the task when off dopaminergic medications. The center of pressure (CoP) displacement and velocity during imbalance showed significant impairment in both PDNF and PDF, more prominent in the latter patients. Several measurements were specifically impaired in PDF patients, especially the CoP displacement along the anteroposterior axis during unloading. The pattern of segmental center of mass (SCoM) movements did not show differences between groups. The standing postural profile preceding GI did not correlate with outcome measurements. We have shown impaired motor programming at GI in Parkinsonian patients. The more prominent deterioration of unloading in PDF patients might suggest impaired processing and integration of somatosensory information subserving GI. The unaltered temporal movement sequencing of SCoM might indicate some compensatory cerebellar mechanisms triggering time-locked models of body mechanics in PD.

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“…Scans were spatially normalized to a [18F]FDG PET template in the standardized Montreal Neurological Institute (MNI) space (16 iterations, non-linear transformation and trilinear interpolation) and then smoothed with a 10-mm isotropic Gaussian filter to account for subtle variations in anatomic structures and to increase the signal-to-noise ratio. A second group of 12 age- and gender-matched HC, different from the healthy subjects recruited for the biomechanical assessment and previously acquired using the same PET protocol, served as the control group for the molecular imaging comparison ( Isaias et al, 2020 ). Paired t -test applied to voxel-wise comparisons was used to recognize significant differences between PSP patients and controls.…”

Section: Methodsmentioning

confidence: 99%