Abnormal venous postural control: multiple sclerosis-specific change related to gray matter pathology or age-related neurodegenerative phenomena?

BACKGROUND: Autonomic nervous system dysfunction has been previously observed in multiple sclerosis (MS) patients. OBJECTIVE: To assess associations between magnetic resonance imaging-detected neuroinflammatory and neurodegenerative pathology and postural venous flow changes indicative of autonomic nervous system function. METHODS: We used a standardized 3T magnetic resonance imaging protocol to scan 138 patients with MS and 49 healthy controls. Lesion volume and brain volumes were assessed. The cerebral venous flow (CVF) was examined by color-Doppler sonography in supine and upright positions and the difference was calculated as ΔCVF. Based on ΔCVF, subjects were split into absolute or quartile groups. Student's t test, χ2-test, and analysis of covariance adjusted for age and sex were used accordingly. Benjamini-Hochberg procedure corrected the p-values for multiple comparisons. RESULTS: No differences were found between healthy controls and patients with MS in both supine and upright Doppler-derived CVF, nor in prevalence of abnormal postural venous control. Patients with absolute negative ΔCVF had higher disability scores (p = 0.013), lower gray matter (p = 0.039) and cortical (p = 0.044) volumes. The negative ΔCVF MS group also showed numerically worse bladder/bowel function when compared to the positive ΔCVF (2.3 vs. 1.5, p = 0.052). Similarly, the lowest quartile ΔCVF MS group had higher T1-lesion volumes (p = 0.033), T2-lesion volumes (p = 0.032), and lower deep gray matter (p = 0.043) and thalamus (p = 0.033) volumes when compared to those with higher ΔCVF quartiles. CONCLUSION: No difference in postural venous outflow between patients with MS and healthy controls was found. However, when the abnormal ΔCVF is present within the MS population, it may be associated with more inflammatory and neurodegenerative pathology. Further studies should explore whether the orthostatic venous changes are an aging or an MS-related phenomenon and if the etiology is due to impaired autonomic nervous system functioning.

Decrease in Secondary Neck Vessels in Multiple Sclerosis: A 5-year Longitudinal Magnetic Resonance Angiography Study.

BACKGROUND: Studies have previously shown greater arterial and venous extracranial vascular changes in persons with multiple sclerosis (PwMS) when compared to healthy controls (HCs). OBJECTIVES: To determine the change in the number and size of secondary neck vessels in PwMS and HCs over a 5-year follow-up period. METHODS: Both at baseline and follow-up, 83 PwMS and 25 HCs underwent magnetic resonance angiography (MRA) imaging and analysis. The number and cross-sectional area (CSA) of all secondary neck vessels (excluding the common/internal carotid, vertebral artery, and internal jugular vein) measured at levels from C2-T1 were determined by semi-automated edge detection/ contouring software. The longitudinal change in the number and CSA of the secondary neck vessels from the PwMS and HCs were analyzed by non-parametric Wilcoxon repeated measure. Benjamini-Hochberg procedure adjusted for false discovery rate (FDR). RESULTS: For over 5 years, PwMS demonstrated a consistent longitudinal decrease in both the number of secondary neck vessels (Z-change between -3.3 and -5.4, q=0.001) and their CSA (Zchange between -2.9 and -5.2, q=0.004). On the contrary, the HCs did not demonstrate a significant longitudinal change in secondary neck vessels over the follow-up period. Due to the longitudinal decrease, the PwMS showed a lower number of secondary neck vessels when compared to HCs measured at follow-up (p<0.029, except for C4 with trending p=0.071). The PwMS changes were also corroborated within each MS phenotype. CONCLUSION: PwMS demonstrate a significant mid-term decrease in the number and the size of the secondary neck vessels. The clinical relevance of these findings and the effect on intracranial blood flow are currently unknown.

Vascular aspects of multiple sclerosis: emphasis on perfusion and cardiovascular comorbidities.

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. Over the last two decades, more favorable MS long-term outcomes have contributed toward increase in prevalence of the aged MS population. Emergence of age-associated pathology, such as cardiovascular diseases, may interact with the MS pathophysiology and further contribute to disease progression. Areas covered: This review summarizes the cardiovascular involvement in MS pathology, its disease activity, and progression. The cardiovascular health, the presence of various cardiovascular diseases, and their effect on MS cognitive performance are further explored. In similar fashion, the emerging evidence of a higher incidence of extracranial arterial pathology and its association with brain MS pathology are discussed. Finally, the authors outline the methodologies behind specific perfusion magnetic resonance imaging (MRI) and ultrasound Doppler techniques, which allow measurement of disease-specific and age-specific vascular changes in the aging population and MS patients. Expert opinion: Cardiovascular pathology significantly contributes to worse clinical and MRI-derived disease outcomes in MS. Global and regional cerebral hypoperfusion may be associated with poorer physical and cognitive performance. Prevention, improved detection, and treatment of the cardiovascular-based pathology may improve the overall long-term health of MS patients.