BACKGROUND AND PURPOSE: Parkinson's disease (PD) and multiple-system atrophy of the parkinsonian type (MSA-P) are progressive neurodegenerative disorders that in addition to dysfunction of the motor system also present with features of dysautonomia, frequently manifesting as orthostatic hypotension (OH). The pathophysiology of OH has been proposed to differ between these two disorders. This study investigated the spontaneous and cardiovagal baroreflex sensitivity (BRS) in Parkinson's disease patients with orthostatic hypotension (PD(OH)) and multiple system atrophy of Parkinsonian type with orthostatic hypotension in an attempt to differentiate the two disorders. METHODS: Two methods were used for determining the BRS: a spontaneous method (spontaneous BRS) and the reflexive baroreflex gain (cardiovagal BRS) from phases II and IV of the Valsalva maneuver (VM) in PD(OH) and MSA-P(OH). RESULTS: The spontaneous BRS (5.04±0.66 ms/mm Hg vs. 4.78±0.64 ms/mm Hg, p=0.54) and the cardiovagal BRS from phase II of the VM (0.96±0.75 ms/mm Hg vs. 1.34±1.51 ms/mm Hg, p=0.76) did not differ between PD(OH) and MSA-P(OH), but the cardiovagal BRS from phase IV of the VM (0.03±0.07 ms/mm Hg vs. 2.86±2.39 ms/mm Hg, p=0.004) was significantly lower in PD(OH). CONCLUSIONS: The cardiovagal BRS from phase IV of the VM has potential for differentiating PD(OH) and MSA-P(OH), indicating a difference in the pathophysiological mechanisms underlying the autonomic dysfunction in the two disorders.
Atrophy* ; Baroreflex* ; Humans ; Hypotension, Orthostatic ; Multiple System Atrophy ; Neurodegenerative Diseases ; Parkinson Disease* ; Primary Dysautonomias ; Reflex ; Valsalva Maneuver

Background & Objective: Transthyretin (TTR) has been associated with spinocerebellar ataxia (SCA) by several independent case reports. Coexistence of TTR and SCA mutations, overlapping clinical symptoms as well as altered levels of TTR in SCA patients suggest a correlation between TTR and SCA. To our knowledge, no large cohort based study has been attempted to examine the association of SCA with polymorphism in TTR gene. Here, we chose to investigate TTR variations in SCA patients (n=266) and controls (n=192) of North Indian ethnicity. Methods: We sequenced the exons including exon-intron boundaries of TTR gene in 55 patients and 55 controls. We observed four variations which were further genotyped by single base extension method (SNaPshot) in a larger cohort (SCA patients n=211 and controls n=137). Results: A novel synonymous variation c.372 C>G in exon 4 was detected in heterozygous condition in one control sample. We found nominal association for rs1800458 (Gly6Ser), with SCA (p-value < 0.05) which did not remain after Bonferroni correction for multiple tests. Pairwise linkage disequilibrium (LD) analysis revealed no LD between studied SNPs. Further, we employed two-marker sliding window analysis and observed a weak association of haplotype AT of rs1800458 and rs1667251 with SCA patients (p-value <0.05) which was not retained after Bonferroni correction. Conclusion: Our data suggests no association of genetic variations of TTR in SCA pathology.