The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD).
The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.
Our findings suggest that cognitively intact older men compared with women have higher resilience to pathophysiological processes of Alzheimer's disease.
Improvement in all 3 subscale scores of the Toronto Western Spasmodic Torticollis Rating Scale with bilateral GPi deep brain stimulation seems to be the rule. Refinement of stimulation parameters might have a significant impact on the cost/benefit ratio of the treatment. The dissociation of improvement in posture severity and pain provides tangible evidence of the complex nature of cervical dystonia and offers interesting insight into the complex functional organization of the GPi.
A syringopleural shunt should, in our view, be the syrinx diversion procedure of choice. More series of institutional experiences with a homogeneous approach would be helpful to verify this recommendation.
Two relatively elderly male patients (61 and 78 years) suffered moderately severe trauma to the head 1 and 3 years, respectively, prior to presentation with progressive quadriparesis and neck pain. Investigations revealed retroodontoid ligamentous hypertrophy and subtle mobile atlantoaxial dislocation. Following atlantoaxial fixation, both patients showed remarkable and sustained neurological improvement. These cases provide further evidence that retroodontoid ligamentous hypertrophic mass lesion could be secondary to instability of the atlantoaxial region.
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