الفهرس 
Chapter (1): Vascular pathophysiological basis in Multiple SclerosisOnly 14 pages are availabe for public view
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Abstract
• Cerebral blood flow will be maintained near the desired set point values by autonomic and neurocardiogenic system with regulation of vascular, neuronal and humoral mechanisms after changing from supine to upright position.
• TCCD is a non-invasive ultrasound procedure to evaluate the changes in CBFV. Evaluation of the reduction in CBFV by TCCD, after changing from supine to upright position, may provide information about cerebral autoregulation.
• Cerebrovascular reactivity synthetizes the compensatory ability of cerebral vasculature to adequate blood flow and preserve perfusion through the vasodilatation of arterioles in response to vasoactive stimuli.
• The pathophysiology of hemodynamic impairment in MS patients is reasonably multifactorial and, at least partly, secondary to the downstream effects of the neuro-inflammatory cascades. The changes of endothelial cells induced by inflammatory cytokines and oxidative stress compromise chemoreception and control of vascular tone.
• The chronically high levels of vasoactive mediators like nitric oxide can sustain vasodilation, desensitize smooth muscle, induce vascular habituation and, hence, prevent small vessels to further dilate when vasoactive triggers occur.
• Our study built up the “vasculo-neuronal-inflammatory” model of MS, which recognizes the neurovascular unit dysfunction and interplay between inflammatory and vascular changes as key players in the pathophysiology of the disease.
• Indeed, the impairment of cerebral blood flow regulation can promote a state of tissue hypoxia and, in turn, perpetuate the brain injury by favoring demyelination and neuronal loss. It is also worth to notice that vascular risk factors and comorbidities that negatively influence the cerebrovascular integrity correlate with increased lesion burden, brain atrophy and faster disability progression.
• Cerebrovascular hemodynamic insufficiency in MS may have clinical implications. The impairment of vasomotor response can be the functional substrate that joins with structural damage and contributes to MS symptomatology.
• The main findings of this study were the decrease in CVR observed in patients affected by MS in comparison to healthy controls and the relationship between BHI values and disease status, being the progressive phenotype associated with a greater impairment in cerebral hemodynamics than the RR form.
• Widespread decrease in perfusion in normal-appearing white matter, has been documented using contrast-enhanced MRI in MS patients compared to control individuals and associated with neurologic impairment and disability.
• These findings also suggested a continuum of reduction in tissue perfusion, beginning in the white matter and spreading to other structures with the disease progression.
• Dysregulation of the autonomic nervous system may present with various clinical symptoms in MS patients that reduce quality of life. Prevalent and clinically relevant autonomic disturbances include neurogenic lower urinary tract dysfunction, symptoms of cardiovascular and gastrointestinal dysregulation as well as sudomotor and pupillomotor dysfunction. These disturbances constitute a clinical challenge to the physician due to variability of clinical presentation and inconsistent data on diagnosis and treatment. Furthermore, the mechanisms whereby autonomic disturbances are mediated in MS are not fully elucidated.
• Ninety percent of MS patients had symptoms related with autonomic dysfunction. Orthostatic dizziness, vasosecretory motor symptoms and bladder problems were those most commonly reported.
• Parasympathetic dysfunction was closely related to the progression of disability in patients with MS. In contrast, sympathetic dysfunction was associated to the clinical activity of MS. This is in line with previous observations suggesting that the autonomic nervous system may be intimately linked with the disordered immune regulation in MS.