> Falls occur mainly during posture changes, in particular during a half-turn, or while performing activities that require a double task demand (cognitive or motor).11 The more the second task is difficult, the more the balance control is altered and fall risk increased
> Usually, FOG is improved by visual (e.g. marks on the ground) or auditory cueing (rhythmic sounds). Paradoxically, running, cycling or climbing stairs are performed more easily than usual gait. Generally, freezing is defined as an abrupt difficulty in starting or continuing rhythmic and repetitive movements
> A hyperactivation has also been found in PD patients in the cerebellum, a structure known to be crucial for motor coordination and balance control.57 This hyperactivation was interpreted as a strategy of the central nervous system to compensate for the defective function of the basal ganglia and brainstem but could also be causative. Thus, unraveling the role of cerebellar dysfunction in gait and balance deficits in PD may represent a major challenge for the future.
In a Phase 2 clinical trial, lixisenatide was found to have beneficial effects on Parkinson’s disease progression. This suggests that lixisenatide may have neuroprotective effects in the substantia nigra, potentially slowing down the neurodegeneration associated with Parkinson’s disease.
However, it’s important to note that while these findings are promising, further research and clinical trials are needed to fully understand the effects of lixisenatide on the substantia nigra and its potential as a treatment for Parkinson’s disease. < grok reply
Lixisenatide
Trial of Lixisenatide in Early Parkinson’s Disease
exenatide
Multisensory mechanisms of gait and balance in Parkinson’s disease: an integrative review
> the three dominant theoretical angles present in the field (Zhang et al., 2020).
“ Inverse effectiveness” theories suggest that older adults depend more on multisensory integration for the maintenance of balance because of age-related deterioration in individual sensory modalities.
“Attentional control deficit” theory attempts to explain the costliness of dual-task on gait and balance stability by suggesting that attentional resources that would otherwise be allocated to multisensory integration are diverted to the dual-task, leading to impairments in balance.
Lastly, “larger time window of integration” theories suggest that multisensory integration depends on the binding of information within discrete temporal windows. With peripheral sensory deficits, such as those encountered in aging, these timeframes extend. This extension results in an amalgamation of incongruent multisensory information, ultimately disrupting the processing associated with maintaining balance. These theories need not be mutually exclusive, but none of them seem to emphasize the specific roles of individual sensory modalities.
> Most intriguing, this constellation of doorway-related gait impairments emerges early in the progression of PD, being present several years before the diagnosis
> Failure of visual processing due to attentional misallocation towards the doorway stimulus prevents the acquisition of sufficient evidence about footholds 1.5–2 seconds into the future, which leads to a freezing event.
> Galvanic vestibular stimulation (GVS) is being actively pursued as a non-invasive treatment for postural instability and gait difficulty symptoms in PD
> PD freezers in medication OFF state were also recently shown to exhibit a profound difficulty with balance on unstable support surfaces in association with longer critical time intervals (Roytman et al., 2023)
> Lastly, recent findings demonstrate that suppression of the right hemispheric cortical cholinergic system in PD patients by high anti-cholinergic burden profoundly affects their ability to effectively integrate visual and vestibular cues for balance on an unstable support surface in medication OFF state (Roytman et al., 2023
Normal and pathological gait: what we learn from Parkinson’s disease
> However the most impairing gait disruptions are related with balance deficit and FOG episodes that tend to become resistant to levodopa, thus suggesting the involvement of extra-nigral lesions.1
> “Since these gait and balance deficits are resistant to dopaminergic drugs, their occurrence could be related to the development of extra-dopaminergic lesions in PD patients”
Axial symptoms predict mortality in patients with Parkinson disease and subthalamic stimulation