Faculty Bibliography

BACKGROUND: Multiple system atrophy (MSA) is a rare, adult-onset, rapidly progressive fatal synucleinopathy that primarily affects oligodendroglial cells in the brain. Patients with MSA only rarely have visual complaints, but recent studies of the retina using optical coherence tomography (OCT) showed atrophy of the peripapillary retinal nerve fiber layer (RNFL) and to a lesser extent the macular ganglion cell layer (GCL) complex. METHODS: We performed a literature review and meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines for studies published before January 2017, identified through PubMed and Google Scholar databases, which reported OCT-related outcomes in patients with MSA and controls. A random-effects model was constructed. RESULTS: The meta-analysis search strategy yielded 15 articles of which 7 met the inclusion criteria. The pooled difference in the average thickness of the RNFL was -5.48 mum (95% CI, -6.23 to -4.73; p < 0.0001), indicating significant thinning in patients with MSA. The pooled results showed significant thinning in all the specific RNFL quadrants, except in the temporal RNFL quadrant, where the thickness in MSA and controls was similar [pooled difference of 1.11 microm (95% CI, -4.03 to 6.26; p = 0.67)]. This pattern of retinal damage suggests that MSA patients have preferential loss of retinal ganglion cells projecting to the magnocellular pathway (M-cells), which are mainly located in the peripheral retina and are not essential for visual acuity. Visual acuity, on the other hand, relies mostly on macular ganglion cells projecting to the parvocellular pathway (P-cells) through the temporal portion of the RNFL, which are relatively spared in MSA patients. CONCLUSION: The retinal damage in patients with MSA differs from that observed in patients with Parkinson disease (PD). Patients with MSA have more relative preservation of temporal sector of the RNFL and less severe atrophy of the macular GCL complex. We hypothesize that in patients with MSA there is predominant damage of large myelinated optic nerve axons like those originating from the M-cells. These large axons may require higher support from oligodendrocytes. Conversely, in patients with PD, P-cells might be more affected.

Study Objectives: Sudden unexpected death during sleep (SUDS) is the most common cause of death in patients with familial dysautonomia, an autosomal recessive disease characterized by sensory and autonomic dysfunction. It remains unknown what causes SUDS in these patients and who is at highest risk. We tested the hypothesis that SUDS in FD is linked to sleep-disordered breathing. Methods: We retrospectively identified patients with familial dysautonomia who died suddenly and unexpectedly during sleep and had undergone polysomnography within the 18-month period prior to death. For each case, we sampled one age-matched surviving subject with familial dysautonomia that had also undergone polysomnography within the 18-month period prior to study. Data on polysomnography, EKG, ambulatory blood pressure monitoring, arterial blood gases, blood count, and metabolic panel were analyzed. Results: Thirty-two deceased cases and 31 surviving controls were included. Autopsy was available in 6 cases. Compared with controls, subjects with SUDS were more likely to be receiving treatment with fludrocortisone (odds ratio; 95% confidence interval) (OR 29.7; 4.1-213.4), have untreated obstructive sleep apnea (OR 17.4; 1.5-193) and plasma potassium levels < 4 mEq/L (OR 19.5; 2.36-161), but less likely to use non-invasive ventilation at night (OR 0.19; 0.06-0.61). Conclusions: Initiation of non-invasive ventilation when required, and discontinuation of fludrocortisone treatment may reduce the high incidence rate of SUDS in patients with familial dysautonomia. Our findings contribute to the understanding of the link between autonomic, cardiovascular, and respiratory risk factors in sudden unexpected death during sleep.

BACKGROUND: Droxidopa, a prodrug of norepinephrine, was approved for treatment of neurogenic orthostatic hypotension (nOH) due to primary autonomic disorders based on 3 randomized double-blind studies. We performed safety and efficacy analyses of this pooled dataset (n = 460). METHODS: Efficacy was assessed using Orthostatic Hypotension Questionnaire (OHQ) scores (composite and individual items). Safety and tolerability were also examined. RESULTS: Droxidopa improved virtually all nOH symptom scores compared with placebo, significantly reducing OHQ composite score (-2.68 +/- 2.20 vs -1.82 +/- 2.34 units; P < 0.001), dizziness/lightheadedness score (-3.0 +/- 2.9 vs -1.8 +/- 3.1 units; P < 0.001), and 3 of 5 other symptom assessments (visual disturbances, weakness, and fatigue [P