Thalamic cholinergic innervation and postural sensory integration function in Parkinson's disease.

The pathophysiology of postural instability in Parkinson's disease remains poorly understood. Normal postural function depends in part on the ability of the postural control system to integrate visual, proprioceptive, and vestibular sensory information. Degeneration of cholinergic neurons in the brainstem pedunculopontine nucleus complex and their thalamic efferent terminals has been implicated in postural control deficits in Parkinson's disease. Our aim was to investigate the relationship of cholinergic terminal loss in thalamus and cortex, and nigrostriatal dopaminergic denervation, on postural sensory integration function in Parkinson's disease. We studied 124 subjects with Parkinson's disease (32 female/92 male; 65.5 ± 7.4 years old; 6.0 ± 4.2 years motor disease duration; modified Hoehn and Yahr mean stage 2.4 ± 0.5) and 25 control subjects (10 female/15 male, 66.8 ± 10.1 years old). All subjects underwent (11)C-dihydrotetrabenazine vesicular monoaminergic transporter type 2 and (11)C-methylpiperidin-4-yl propionate acetylcholinesterase positron emission tomography and the sensory organization test balance platform protocol. Measures of dopaminergic and cholinergic terminal integrity were obtained, i.e. striatal vesicular monoaminergic transporter type 2 binding (distribution volume ratio) and thalamic and cortical acetylcholinesterase hydrolysis rate per minute (k3), respectively. Total centre of pressure excursion (speed), a measure of total sway, and sway variability were determined for individual sensory organization test conditions. Based on normative data, principal component analysis was performed to reduce postural sensory organization functions to robust factors for regression analysis with the dopaminergic and cholinergic terminal data. Factor analysis demonstrated two factors with eigenvalues >2 that explained 52.2% of the variance, mainly reflecting postural sway during sensory organization test Conditions 1-3 and 5, respectively. Regression analysis of the Conditions 1-3 postural sway-related factor [R(2)adj = 0.123, F(5,109) = 4.2, P = 0.002] showed that decreased thalamic cholinergic innervation was associated with increased centre of pressure sway speed (ß = -0.389, t = -3.4, P = 0.001) while controlling for covariate effects of cognitive capacity and parkinsonian motor impairments. There was no significant effect of cortical cholinergic terminal deficits or striatal dopaminergic terminal deficits. This effect could only be found for the subjects with Parkinson's disease. We conclude that postural sensory integration function of subjects with Parkinson's disease is modulated by pedunculopontine nucleus-thalamic but not cortical cholinergic innervation. Impaired integrity of pedunculopontine nucleus cholinergic neurons and their thalamic efferents play a role in postural control in patients with Parkinson's disease, possibly by participating in integration of multimodal sensory input information.

Effectiveness of Active Therapy-Based Training to Improve the Balance in Patients with Fibromyalgia: A Systematic Review with Meta-Analysis.

Balance impairment is a frequent disorder in patients with fibromyalgia (FMS), increasing the risk of falls and decreasing physical function and quality of life. In recent years, the use of active therapy-based training (ATBT) has increased, with the aim of improving balance in women with FMS. Our study aimed to assess the effect of ATBT to improve different balance outcomes in subjects with FMS. A systematic review with meta-analysis was carried out. We searched PubMed Medline, SCOPUS, Web of Science, CINAHL, and PEDro (Physiotherapy Evidence Database) databases up to September 2020. We included randomized controlled trials (RCT) that assessed the balance in patients with FMS after ATBT and compared to other treatments or no intervention. In a random-effects model, the standardized mean difference (SMD) was used to calculate the effect size. Ten studies were included in the review providing data from 546 FMS patients with a mean age of 52.41 ± 2.90 years old (98% females). Our results showed a medium effect favors ATBT with respect to other therapies for monopedal static balance (SMD = 0.571; 95% CI = 0.305, 0.836; p < 0.001), dynamic balance (SMD = 0.618; 95% CI = 0.348, 0.888; p < 0.001), and functional balance (SMD = 0.409; 95% CI = 0.044, 0.774; p = 0.028). No statistically significant differences were found for balance on unstable support. The present meta-analysis showed moderate-quality evidence of a medium effect of ATBT to improve dynamic and functional balance and low-quality evidence of a medium effect to improve monopedal static balance with respect to other therapies or no intervention.