A prospective cohort study of vitamin D in optic neuritis recovery.

BACKGROUND: Vitamin D sufficiency is associated with better inflammatory outcomes in multiple sclerosis (MS). We hypothesize that it is also associated with better long-term neurodegenerative measures. OBJECTIVES: To show that vitamin D sufficient patients (25-hydroxy vitamin D (25(OH)D) > 80 nmol/L) have better optical coherence tomography (OCT) neuroaxonal measures of ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL) thickness after optic neuritis. METHODS: In this prospective cohort study, acute optic neuritis patients underwent OCT and serum 25(OH)D assessments at baseline and at month 6, with comparisons between vitamin D sufficient and insufficient patients, and men and women. Potential confounding variables were evaluated. RESULTS: Of 49 enrolled, 36 had complete, analyzable data. At baseline, vitamin D insufficiency was associated with greater RNFL thickness (134.3 vs. 95.2 µm; p = 0.003) in affected eyes. At month 6, insufficient patients had greater GCL thinning (GCL inter-eye difference: 14.2 vs. 4.0 µm, p = 0.008). Men had greater RNFL and GCL thinning than women (GCL: 61.2 vs. 69.6 µm, p = 0.036). CONCLUSION: Acutely, in optic neuritis, RNFL thickness is increased with vitamin D insufficiency. Chronically, neuronal, and possibly axonal loss are associated with vitamin D insufficiency and male gender, suggesting vitamin D and female gender may confer neuroprotection in optic neuritis, and possibly, central nervous system (CNS) inflammatory disease.

Skewness of Fractional Anisotropy Detects Decreased White Matter Integrity Resulting From Acute Optic Neuritis.

PURPOSE: Diffusion tensor imaging (DTI) has demonstrated optic nerve damage associated with optic neuritis (ON); however, the usefulness of mean fractional anisotropy (FA) specifically is varied in the literature. We wished to determine whether histogram analysis of FA better detects ON damage than mean FA. METHODS: The ON patients (n = 24) underwent DTI within 1 month of symptoms and then 6 months later (n = 21). Twelve control subjects participated in one session. Mean FA and axial (AD), radial (RD), and mean (MD) diffusivities were compared between ON and fellow eyes, control eyes, and sessions. Values were sorted into bins, and coefficients of skewness of FA, AD, RD, and MD were compared between ON and fellow eyes, control eyes, and sessions. RESULTS: Mean AD, RD, and MD of ON eyes were significantly reduced compared with fellow eyes (P < 0.04) within 1 month of symptoms, but did not differ at 6 months. Mean AD and RD of ON eyes were significantly lower than control eyes (P < 0.05). No differences were observed for mean FA. The coefficient of skewness of FA was significantly different between ON eyes and fellow eyes (P = 0.03) and control eyes (P = 0.04) within 1 month of symptoms, but did not differ at 6 months. No differences were observed for AD, RD, and MD. CONCLUSIONS: Skewness of FA can detect white matter damage associated with ON and its recovery, which may further inform us of how DTI can measure white matter injury and repair.

MRI texture heterogeneity in the optic nerve predicts visual recovery after acute optic neuritis.

PURPOSE: To test the feasibility of using multi-scale MRI texture analysis to assess optic nerve pathology and to investigate how visual recovery relates to the severity of acute tissue damage in the optic nerve in patients after optic neuritis (ON). MATERIALS AND METHODS: We recruited 25 patients with acute ON. Retinal nerve fiber layer (RNFL) thickness; MRI lesion length and enhancement; optic nerve area ratio; and multi-scale MRI texture analysis, a measure of structural integrity, were used to assess tissue damage at baseline, and at 6 and 12 months. The recovery in vision was defined as the functional outcome. Eight healthy subjects were imaged for control. RESULTS: We identified 25 lesions in the affected eyes (9 enhanced) and 5 in the clinically non-affected eyes (none enhanced). At baseline, we found that RNFL values were 20% thicker and lesion texture 14% more heterogeneous in the affected eyes than in the non-affected eyes, and lesion texture ratio of affected to non-affected eyes was greater in patients than in controls. In the affected eyes, visual acuity recovered significantly over 6 (18/23 patients) and 12 months (18/21 patients) when RNFL thickness and optic nerve area ratio decreased over time. Texture heterogeneity in the standard MRI of acute optic nerve lesions was the only measure that predicted functional recovery after ON. CONCLUSIONS: Tissue heterogeneity may be a potential measure of functional outcome in ON patients and advanced analysis of the texture in standard MRI could provide insights into mechanisms of injury and recovery in patients with similar disorders.

Validity of the diagnostic criteria for chronic cerebrospinal venous insufficiency and association with multiple sclerosis.

BACKGROUND: The chronic cerebrospinal venous insufficiency theory proposes that altered cerebral venous hemodynamics play a role in the pathophysiology of multiple sclerosis. We aimed to explore the validity of this hypothesis by assessing the diagnostic criteria for chronic cerebrospinal venous insufficiency in persons with and without multiple sclerosis. METHODS: We compared the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls using extracranial Doppler ultrasonography and gadolinium-enhanced magnetic resonance venography. Interpreting radiologists were blinded to the clinical status of participants. RESULTS: We enrolled 120 patients with multiple sclerosis and 60 healthy controls. High proportions of both patients (67/115 [58%]) and controls (38/60 [63%]) met 1 or more of the proposed ultrasound criteria for diagnosis of chronic cerebrospinal venous insufficiency (p = 0.6). A minority of patients (23/115 [20%]) and controls (6/60 [10%]) fulfilled 2 or more of the proposed criteria (p = 0.1). There were no differences between patients and controls in the prevalence of each individual ultrasound criterion. Similarly, there were no differences in intracranial or extracranial venous patency between groups, as measured by magnetic resonance venography. INTERPRETATION: We detected no differences in the proportion of venous outflow abnormalities between patients with multiple sclerosis and healthy controls. Moreover, our study revealed significant methodologic concerns regarding the proposed diagnostic criteria for chronic cerebrospinal venous insufficiency that challenge their validity.

Sex-specific differences in retinal nerve fiber layer thinning after acute optic neuritis.

OBJECTIVE: The primary objective of this study was to explore the potential influence of gender on recovery from optic neuritis (ON) by determining whether differences in retinal nerve fiber layer (RNFL) thickness can be detected between men and women 6 months after an ON event. METHODS: In this prospective cohort study, 39 men and 105 women with acute ON underwent repeat visual and optical coherence tomography (OCT) testing. The main outcome measures were change in RNFL measurements for male and female patients 6 months after ON. RESULTS: Men were older (mean age = 39 years) than women (35 years) (p = 0.05) in this study, and more men (62%) than women (41%) had a diagnosis of relapsing-remitting multiple sclerosis (MS) (p = 0.02). Because age and MS subtype were 2 significant covariates, both variables were controlled for in multiple regression analyses. Other covariates controlled for in the multivariate regression included disease duration (years), use of disease-modifying therapy (yes/no), and use of high-dose corticosteroids for acute ON (yes/no). After 6 months, mean RNFL values were lower in men (74 µm) than women (91 µm) (p < 0.001). Men showed more apparent change in RNFL thickness in their ON eyes from baseline to 6 months after ON than women (p = 0.003). CONCLUSIONS: There may be differences in recovery between men and women after ON, which can be difficult to detect with conventional visual testing. Our findings raise interesting questions about the potential influence of gender in MS, which may be explored in future studies.