Background

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a devastating neurological disorder of particular importance to the U.S. Military because it is highly disabling, often rapidly causing complete or partial blindness and/or paralysis. NMOSD can permanently disqualify a service-member from continued duty, leading not only to personal disability for the member, but degraded capability for the Force.

Objectives

The objective of this study is to define the epidemiology of NMOSD among U.S. Military Active Duty Service Members (ADSM). Specifically, we aimed to understand the prevalence, demographics, disease subtypes (seropositive (SP), seronegative (SN), anti-MOG), and disease associations among ADSM diagnosed with NMOSD between 2004 and 2019.

Methods

A U.S. Military Health Systems database (MHS Mart, M2) was searched for outpatient clinic encounters that listed ICD9 (341.0) and ICD10 (G36.0) codes for NMOSD between 2004 and 2019. ADSM with at least one encounter listing an ICD9 or ICD10 code for NMOSD were included in the study. Relevant information was then abstracted systematically from clinical electronic medical records systems (AHLTA, HAIMS, JLV). A clinical database was generated. Data was analyzed using standard statistical methods. This project was reviewed and approved by the Walter Reed National Military Medical Center IRB and the University of Utah/SLC VA IRB.

Results

118 patients were identified. Forty Seven (48) met 2015 criteria for NMOSD. Of these, 28 were women. There were 34 SP, 10 SN, and 4 anti-MOG patients. The average age at time of disease onset was 36 years for women, and 40 years for men. Age of onset by serostatus was 40 years for SP, and 32 years for SN patients. Distribution by race was as follows: Black: 25, Caucasian: 16, Other or Unknown: 4, Hispanic: 2, Asian / Pacific Islander: 1. SP patients presented with longitudinally extensive transverse myelitis (LETM) (15), optic neuritis (ON) (11), area postrema syndrome (4), or multifocal symptoms (3). SN patients presented with LETM (5), ON (2), or multifocal symptoms (2). Co-existing autoimmunity was seen in 19 SP patients and 1 SN patient. The most common co-existing autoimmune disease was Sjogren Syndrome (7). The incidence of NMOSD in the US Military ranged from 0 – 0.7 cases per 100,000 ADSM for the period in question.

Conclusions

This study clarifies the epidemiology of NMOSD within the US Military during the years 2004-2019. It demonstrates disease burden based on race and gender and confirms an association of co-existing autoimmunity among patients with SP NMOSD. Further research assessing pre-symptomatic sera for AQP4-IgG from the Department of Defense Serum Repository in this cohort will hopefully shed further light on this disease.

Background

Patients with neuromyelitis optica spectrum disorder (NMOSD) can experience repeated relapses and increased neurologic disability, such as pain. However, little is known about the impact of relapses on pain and subsequent pain medication use in patients with NMOSD.

Objectives

A retrospective, observational, cohort analysis was conducted to examine pain medication use in patients with NMOSD.

Methods

Patients with anti-aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD in the University of Utah Health Care System were identified. Electronic data, including patient-level treatments/therapies, medications, health status, and physician notes, were extracted from the Enterprise Data Warehouse and confirmed via chart review by Neurology and Pharmacotherapy faculty members.

Results

Forty-seven patients with AQP4+ NMOSD were included in the analysis. The average age at diagnosis was 46 years; 75% were female, and 70% were white. At the initial presentation of disease, 25 (53%) patients had optic neuritis, 15 (32%) had transverse myelitis, and 7 (15%) had a mixed or unknown presentation. The mean follow-up time was 4 years (standard deviation 3.64 years). During the follow-up period, 14 of 47 patients experienced 26 provider-documented relapses.

Overall, pain medication was used by 45 (95.7%) of 47 patients with AQP4+ NMOSD. A higher proportion of relapsing patients used pain medication than nonrelapsing patients: opioid analgesics (79% vs 58%), non-narcotic analgesics (93% vs 43%), anticonvulsants (86% vs 46%), and musculoskeletal therapy agents (71% vs 46%). Furthermore, among the relapsing patients with AQP4+ NMOSD, pain medication use increased within 90 days of the relapse when compared with the prerelapse use of pain medications: opioids analgesics (27% vs 12%), non-narcotic analgesics (39% vs 12%), anticonvulsants (35% vs 27%), and musculoskeletal therapy agents (39% vs 23%).

Conclusions

In this study, more patients with AQP4+ NMOSD who experienced relapses used pain medication than nonrelapsing patients. In addition, the increase in pain medication use within 90 days following a relapse suggests that pain is associated with relapse activity in patients with NMOSD. Treatment strategies that reduce relapses should be considered for all patients with NMOSD, not only to reduce traditional measures of neurological disability, but also to reduce the burden of pain and accompanying use of relapse-related pain medication.

Background

Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing disease predominately affecting the optic nerves and spinal cord. Patients with NMOSD may experience visual and neurological deficits that can lead to blindness and paralysis. However, little is reported about the cumulative impact of relapses on visual acuity and recovery.

Objectives

A retrospective, observational cohort analysis was conducted to assess the impact of relapses on visual acuity and neurological disability in patients with anti-aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD.

Methods

Patients with AQP4+ NMOSD in the University of Utah healthcare system were identified. Electronic data (health status, physician notes, AQP4+ status, NMOSD diagnosis, and other key patient data) were extracted from the Enterprise Data Warehouse and confirmed via medical chart reviews.

Results

The analysis included 47 patients with AQP4+ NMOSD (mean age at diagnosis: 46 years; female: 75%, white: 70%; median [minimum, maximum] follow-up time: 3.6 [0.0, 11.4] years). At enrollment, 25 patients (53%) had optic neuritis, 15 (32%) had transverse myelitis, and 7 (15%) had a mixed or unknown presentation. Of the 47 patients, 14 experienced a total of 26 relapses, and 33 did not relapse.

Baseline visual acuity was assessed in a subset of symptomatic patients. Data were available for 9 relapsing and 23 nonrelapsing patients. At baseline, 28% of patients had bad eyesight (20/150-no light perception). From baseline to last follow-up, the proportion of patients with bad eyesight increased from 21% to 29% in relapsing patients and decreased from 30% to 24% in nonrelapsing patients.

Neurological disability was assessed via the modified Rankin Scale (mRS). Pre-enrollment mean (standard deviation [SD]) mRS values were similar in relapsing (1.50 [1.22]) and nonrelapsing patients (1.42 [1.39]). At the last visit, the mean (SD) mRS value in relapsing patients was 3.43 (1.79), which was 1.49-fold higher than the mean mRS value in nonrelapsing patients.

Conclusions

In this cohort of patients with AQP4+ NMOSD, the proportion of relapsing patients with bad eyesight increased over time, but the proportion of nonrelapsing patients with bad eyesight decreased. Per the mRS, relapsing patients also experienced increased neurological disability when compared with nonrelapsing patients. Treatment strategies that reduce the risk of relapse should be considered to prevent progression of these deficits in patients with NMOSD.

Background

Glutamic acid decarboxylase (GAD-65) and glycine receptor (GlyR) autoimmunity includes a wide range of clinical phenomena including stiff-person syndrome and epilepsy. Both GAD and GlyR interact with the retina. Optical coherence tomography (OCT) has previously been used in a variety of other neurological disorders to establish baseline characteristics and monitor disease course. This presents a noninvasive opportunity to evaluate for a biomarker that may assist with treatment of these rare but debilitating disorders.

Objectives

To provide a description of the retinal nerve fiber layer (RNFL) in patients with GAD-65 and GlyR neurological autoimmunity.

Methods

OCT measures of RNFL were studied in patients with GAD-65 and GlyR neurological autoimmunity and compared to that of 148 healthy control eyes and 472 eyes from patients with multiple sclerosis.

Results

The 15 patients were mostly female, in keeping with reported female preponderance in these conditions. We report initial post-diagnosis mean RNFL thickness and standard deviations, by sector, for the whole group, as compared with respective controls and patients with multiple sclerosis. Multiple sectors showed RNFL thinning, most apparent in the anti-GAD-65 group.

Conclusions

This study provides insight into baseline post-diagnosis RNFL thickness in a group with GAD-65 and GlyR autoimmunity, two conditions which may produce varied symptoms. While limited by sample size, RNFL thinning was most evident in the anti-GAD-65 group, and to a lesser extent, in the anti-GlyR group. This provides a baseline characterization and suggests that future studies should be done to determine the utility of OCT as a biomarker for these conditions.

Background

Patients with neuromyelitis optica spectrum disorder (NMOSD) can experience repeated relapses and increased neurologic disability, such as pain. However, little is known about the impact of relapses on pain and subsequent pain medication use in patients with NMOSD.

Objectives

A retrospective, observational, cohort analysis was conducted to examine pain medication use in patients with NMOSD.

Methods

Patients with anti-aquaporin-4 immunoglobulin G-positive (AQP4+) NMOSD in the University of Utah Health Care System were identified. Electronic data, including patient-level treatments/therapies, medications, health status, and physician notes, were extracted from the Enterprise Data Warehouse and confirmed via chart review by Neurology and Pharmacotherapy faculty members.

Results

Forty-seven patients with AQP4+ NMOSD were included in the analysis. The average age at diagnosis was 46 years; 75% were female, and 70% were white. At the initial presentation of disease, 25 (53%) patients had optic neuritis, 15 (32%) had transverse myelitis, and 7 (15%) had a mixed or unknown presentation. The mean follow-up time was 4 years (standard deviation 3.64 years). During the follow-up period, 14 of 47 patients experienced 26 provider-documented relapses.

Overall, pain medication was used by 45 (95.7%) of 47 patients with AQP4+ NMOSD. A higher proportion of relapsing patients used pain medication than nonrelapsing patients: opioid analgesics (79% vs 58%), non-narcotic analgesics (93% vs 43%), anticonvulsants (86% vs 46%), and musculoskeletal therapy agents (71% vs 46%). Furthermore, among the relapsing patients with AQP4+ NMOSD, pain medication use increased within 90 days of the relapse when compared with the prerelapse use of pain medications: opioids analgesics (27% vs 12%), non-narcotic analgesics (39% vs 12%), anticonvulsants (35% vs 27%), and musculoskeletal therapy agents (39% vs 23%).

Conclusions

In this study, more patients with AQP4+ NMOSD who experienced relapses used pain medication than nonrelapsing patients. In addition, the increase in pain medication use within 90 days following a relapse suggests that pain is associated with relapse activity in patients with NMOSD. Treatment strategies that reduce relapses should be considered for all patients with NMOSD, not only to reduce traditional measures of neurological disability, but also to reduce the burden of pain and accompanying use of relapse-related pain medication.