Respiratory symptoms are common in stiff person syndrome spectrum disorders and are associated with number of body regions involved.

BACKGROUND AND PURPOSE: Stiff person syndrome (SPS) spectrum disorders (SPSSD) cause spasms and rigidity throughout different body regions and can be associated with apnea and acute respiratory failure. There are limited data on the prevalence and predictors of respiratory symptoms with spasms (RSwS) in SPSSD. We sought to characterize the spirometry patterns and the frequency and predictors of RSwS in a large SPSSD cohort. METHODS: Participants were recruited from the Johns Hopkins SPS Center between 1997 and 2021, as part of an ongoing, longitudinal observational study. Medical records were reviewed to assess demographics and clinical characteristics. Data were analyzed using descriptive statistics and multivariable logistic regression models. RESULTS: One-hundred ninety-nine participants (mean age = 53.4 ± 13.6 years, median time to diagnosis = 36 [IQR 66] months, 74.9% women, 69.8% White, 62.8% classic SPS phenotype) were included in final analyses; 35.2% of participants reported RSwS, of whom 24.3% underwent spirometry as part of routine clinical care. Obstructive (23.5%) and restrictive (23.5%) patterns were most commonly observed in those with SPSSD. An increasing number of body regions involved predicted the presence of RSwS (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.50-2.53); those with ≥5 body regions involved (vs. ≤4) had higher odds (OR = 6.19, 95% CI = 2.81-13.62) of experiencing RSwS in adjusted models. Two patients died from SPSSD-associated respiratory compromise. CONCLUSIONS: RSwS are common in SPSSD and may be predicted by an increasing number of body regions involved by SPSSD. Close clinical monitoring and having a low threshold to obtain spirometry should be considered in people with SPSSD.

Socioeconomic disparity is associated with faster retinal neurodegeneration in multiple sclerosis.

Disease course in multiple sclerosis is notably heterogeneous, and few prognostic indicators have been consistently associated with multiple sclerosis severity. In the general population, socioeconomic disparity is associated with multimorbidity and may contribute to worse disease outcomes in multiple sclerosis. Herein, we assessed whether indicators of socioeconomic status are associated with disease progression in patients with multiple sclerosis using highly sensitive imaging tools such as optical coherence tomography, and determined whether differential multiple sclerosis management or comorbidity mediate any observed socioeconomic status-associated effects. We included 789 participants with longitudinal optical coherence tomography and low contrast letter acuity (at 1.25 and 2.5%) in whom neighbourhood- (derived via nine-digit postal codes) and participant-level socioeconomic status indicators were available ≤10 years of multiple sclerosis symptom onset. Sensitivity analyses included participants with socioeconomic status indicators available ≤3years of symptom onset (n = 552). Neighbourhood-level indicators included state and national area deprivation indices, median household income and the Agency for Healthcare Research and Quality (AHRQ) Socioeconomic Status Index. Participant-level indicators included education level. Biannual optical coherence tomography scans were segmented to quantify thickness of the composite macular ganglion cell+inner plexiform (GCIPL) layer. We assessed the association between socioeconomic status indicators and GCIPL atrophy or low contrast letter acuity loss using mixed models adjusting for demographic (including race and ethnicity) and disease-related characteristics. We also assessed socioeconomic status indicators in relation to multiple sclerosis therapy changes and comorbidity risk using survival analysis. More disadvantaged neighbourhood-level and patient-level socioeconomic status indicators were associated with faster retinal atrophy. Differences in rate of GCIPL atrophy for individuals in the top quartile (most disadvantaged) relative to the bottom quartile (least) for state area deprivation indices were -0.12 µm/year faster [95% confidence interval (CI): -0.19, -0.04; P = 0.003], for national area deprivation indices were -0.08 µm/year faster (95% CI: -0.15, -0.005; P = 0.02), for household income were -0.11 µm/year faster (95% CI: -0.19, -0.03; P = 0.008), for AHRQ Socioeconomic Status Index were -0.12 µm/year faster (95% CI: -0.19, -0.04) and for education level were -0.17 µm/year faster (95% CI: -0.26, -0.08; P = 0.0002). Similar associations were observed for socioeconomic status indicators and low contrast letter acuity loss. Lower socioeconomic status was associated with higher risk of incident comorbidity during follow-up. Low socioeconomic status individuals had faster rates of therapy escalation, suggesting the association between socioeconomic status and GCIPL atrophy may not be explained by differential contemporaneous multiple sclerosis therapy management. In conclusion, socioeconomic disparity is associated with faster retinal neurodegeneration in multiple sclerosis. As low socioeconomic status was associated with a higher risk of incident comorbidities that may adversely affect multiple sclerosis outcomes, comorbidity prevention may mitigate some of the unfavourable socioeconomic status-associated consequences.

Depression in multiple sclerosis across the adult lifespan.

OBJECTIVES: The objective of this study is to examine the burden of depressive symptoms across the adult age span in people with multiple sclerosis (MS) and test if the relationship between depressive symptoms and MS characteristics vary across age groups. METHODS: In analyses of the MS Partners Advancing Technology and Health Solutions (MS PATHS) network of adults with MS, we compared the prevalence of depression in MS PATHS with non-MS controls across age and evaluated for effect modification by age in the association between depressive symptoms and clinical and neuroperformance measures via multivariable-adjusted regression models. RESULTS: In total, 13,821 individuals with MS were included. The prevalence of depression was higher in MS versus non-MS controls, but was similar between men/women across age. The association between depression and processing speed (PST; p for interaction = 0.009) or walking speed (p for interaction = 0.04) varied by age. For example, younger depressed individuals had 0.45 standard deviation (SD) (95% confidence interval (CI) = -0.62, -0.29) worse PST Z-scores versus non-depressed younger participants, whereas older depressed individuals had 0.20 SD (95% CI = -0.32, -0.08) worse PST Z-scores versus non-depressed older participants. CONCLUSION: Depressive symptoms and age should be considered when interpreting measures of walking speed and cognitive function; these findings may have implications for analyses of neuroperformance change.

Recurrent Optic Neuritis and Perineuritis Followed by an Unexpected Discovery: From the National Multiple Sclerosis Society Case Conference Proceedings.

We describe a woman with a history of relapsing acute optic neuritis and perineuritis. Testing failed to confirm a specific diagnosis; hence, she was diagnosed with seronegative neuromyelitis optica spectrum disorder and treated with the immunotherapy rituximab, later in conjunction with mycophenolate mofetil. She achieved a durable remission for 9 years until she presented with paresthesia affecting her left fifth digit, right proximal thigh, and left foot, while also reporting a 25-pound weight loss over the prior 3 months. New imaging demonstrated a longitudinally extensive and enhancing optic nerve, in conjunction with multifocal enhancing lesions within the spinal cord, in a skip-like distribution. The differential diagnosis is discussed.

Cognitive and Mood Profiles Among Patients With Stiff Person Syndrome Spectrum Disorders.

An emerging body of evidence suggests that changes in cognitive and emotional function are common aspects of stiff person spectrum disorders (SPSD). We sought to examine the pattern of cognitive impairment and psychiatric symptoms in SPSD. Methods: A retrospective review of medical records was conducted for patients seen at the Johns Hopkins Stiff Person Syndrome (SPS) center from 1997 to January 1st, 2020. Individuals who had received formal cognitive testing as part of routine clinical care for patient-reported cognitive changes were included. Demographics, prevalence of cognitive impairment, psychoactive medication use, and clinically significant psychiatric symptoms were described. Results: Out of 205 patients screened, 20 completed cognitive testing (75% female, mean age 47.4 years). The most common domains of impairment were verbal learning and recall memory (n = 14, 70%), verbal fluency (n = 10, 50%), processing speed (n = 8, 40%), and attention (n = 8, 40%). 9/11 patients assessed for depression reported clinically significant symptoms, and 4/9 patients assessed for anxiety reported clinically significant symptoms. Conclusions: Screening for cognitive impairment in SPSD should utilize testing that assesses verbal learning and recall, phonemic verbal fluency, attention, and processing speed. Moreover, it is important to evaluate for co-existing depression and anxiety symptoms, as these are common in SPSD.

The impact of socioeconomic status on mental health and health-seeking behavior across race and ethnicity in a large multiple sclerosis cohort.

BACKGROUND: Psychiatric symptoms are common in multiple sclerosis (MS) and may contribute to worse MS outcomes. Previous studies suggest the burden of symptoms may vary by race, ethnicity and socioeconomic status (SES). Our objective was to expand upon this previous work and explore the associations between SES, race, and ethnicity, as predictors of psychiatric symptoms, mental health attitudes, and health-seeking behavior in patients with MS. METHODS: Persons with MS answered a national web-based survey including demographic characteristics (including race, ethnicity and measures of SES), mental health attitudes, the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Modified Fatigue Impact Scale 5-item version (MFIS-5), and the Alcohol Use Disorders Identification Test (AUDIT). The survey also queried mental health availability and perceptions of care. We measured neighborhood-level SES (nSES) of each participant using the Agency for Healthcare Research and Quality (AHRQ) index that was calculated from 5-digit postal codes. Other indicators of participant-level SES included education level and self-reported household income. We assessed the association between race, ethnicity, and neighborhood/participant-level SES indicators and affective symptom burden using generalized linear models that were adjusted for age, sex, and MS characteristics. RESULTS: 2095 participants answered the survey (mean AHRQ index 54.6 ± 5.4, age 51.3 ± 12.2 years, 7% Black/African American, 5.4% Hispanic/Latino, and 81.8% female). Those in the lowest quartile of nSES (most disadvantaged) were more likely to be either Black/African American or Hispanic/Latino as compared to those in highest quartile (least disadvantaged). Those in the lowest quartile of nSES had higher mean MFIS-5 (1.02 points; 95% CI: 0.39, 1.43), PHQ-9 (1.24 points; 95% CI: 0.49, 1.98), and GAD-7 (0.69 points; 95% CI: -0.01, 1.38) scores relative to those in the highest quartile. Of those who consumed alcohol (n = 1489), participants in the lowest AHRQ quartile had lower mean AUDIT scores (-0.73 points; 95% CI: -1.18, -0.29) as compared to those in higher quartiles. Race and ethnicity were not associated with self-reported psychiatric symptom burden in this cohort. SES was also associated with self-reported improvement of symptoms after receiving mental health care. A higher proportion of Black/African American (44.1% vs 30.2%, p = 0.003) and Hispanic/Latino (49.1% vs 30.6%, p<0.001) participants were more likely to report they would "definitely go" receive mental health care if services were co-located with their MS care as compared to white and Non-Hispanic/Latino participants, respectively. CONCLUSION: Higher SES was associated with a lower burden of psychiatric symptoms and with a higher likelihood of self-reported symptom recovery after receiving mental health treatment. Attitudes regarding mental health care delivery in MS varied according to racial and ethnic background. Future longitudinal studies in more diverse populations should assess whether co-location of mental health services with MS care helps to reduce the gap between access and need of mental health care in MS.

Perceptions and Preferences Regarding Multiple Sclerosis Research Among Racial and Ethnic Groups.

BACKGROUND: For unclear reasons, minorities have been historically underrepresented in multiple sclerosis (MS) clinical trials. We hypothesized that different perceptions and preferences about research participation among racial and ethnic groups contribute to this imbalance. METHODS: Members of the MS Minority Research Engagement Partnership Network developed a Web-based survey in English and Spanish on research impressions, concerns, and preferences regarding study attributes among people with MS. Invitations to take the survey were distributed by network members and partner organizations. RESULTS: We included 2599 participants with MS (2111 White, 215 African American; 188 Hispanic). Consistently disliked study attributes included potential harms to health and confusing study information. Compared with White and non-Hispanic participants, respectively, African American (odds ratio [OR] = 2.05, P ≤ .001) and Hispanic (OR = 1.79, P = .003) participants were more concerned about being used by the research team. Hispanic participants were more concerned about research participation carrying risks to their legal status (OR = 1.70, P = .001). Hispanic (OR = 3.18, P ≤ .001) and African American (OR = 5.51, P ≤ .001) participants were more likely to prefer for the study to benefit their own racial/ethnic group. A top concern across all groups was not being fully informed about the research. CONCLUSIONS: We found strong support for research across racial and ethnic groups; however, minority groups have specific concerns regarding mistrust, receiving poor-quality care, unemployment, health insurance, and legal status. Investigators wanting to recruit a diverse study population are advised to show how they have addressed these concerns and to communicate how the research will advance the science and literature and result in better care and/or other benefits to underrepresented communities.

Safety and preliminary efficacy of intranasal insulin for cognitive impairment in Parkinson disease and multiple system atrophy: A double-blinded placebo-controlled pilot study.

Parkinson disease (PD) is associated with cognitive impairment. We aimed to determine the effects of intranasal insulin (INI) on cognition and motor performance in PD. This was a proof of concept, randomized, double-blinded, placebo-controlled trial evaluating the effects of 40 international units (IU) of insulin or saline once daily for four weeks on cognitive and functional performance. Of 16 subjects enrolled, eight in the INI group and six in the placebo group completed verbal fluency (FAS), Unified Parkinson Disease Scale (UPDRS), and modified Hoehn and Yahr scale (HY, PD severity) at baseline and post-treatment and were included in the analyses. After treatment, the INI group had a better total FAS score (p = 0.02) (41 ± 8.2 vs. 30.8 ± 7.1, mean ±SD, p = 0.02) compared to the placebo group. The INI group also had improved HY (p = 0.04) and UPDRS-Motor (Part III) (p = 0.02) scores when compared to baseline. One INI treated patient with multiple system atrophy (MSA) remained stable and did not show disease progression. The placebo group had no change. INI administration was well tolerated and there were no hypoglycemic episodes or serious study related adverse events or medications interactions. INI is safe in PD and MSA patients and may provide clinically relevant functional improvement. Larger studies are warranted to determine the INI effect in treatment of cognitive and motor impairment in Parkinson disease. Trial Registration: ClinicalTrial.gov NCT02064166.

Lower cerebral vasoreactivity as a predictor of gait speed decline in type 2 diabetes mellitus.

Gait speed is an indicator of overall functional health and is correlated with survival in older adults. We prospectively evaluated the long-term association between cerebral vasoreactivity and gait speed during normal walking (NW) and dual-task walking (DTW) in older adults with and without type 2 diabetes mellitus (T2DM). 40 participants (aged 67.3 ± 8.8 years, 20 with T2DM) completed a 2-year prospective study consisting of MRI, blood sampling, and gait assessments. The whole brain vasoreactivity was quantified using continuous arterial spin labeling MRI. Gait speed during DTW was assessed by subtracting serial sevens. Dual-task cost was calculated as the percent change in gait speed from NW to DTW. In the entire cohort, higher glycemic profiles were associated with a slower gait speed. In the diabetic group, lower vasoreactivity was associated with a slower gait speed during NW ([Formula: see text] = 0.30, p = 0.019) and DTW ([Formula: see text] = 0.35, p = 0.01) and a higher dual-task cost ([Formula: see text] = 0.69, p = 0.009) at 2-year follow-up. The participants with T2DM and lower cerebral vasoreactivity had a greater decrease in gait speed during NW and DTW after the 2-year follow-up ([Formula: see text] = 0.17, p = 0.04 and [Formula: see text] = 0.28, p = 0.03, respectively). Longer diabetes duration was associated with a higher dual-task cost ([Formula: see text] = 0.19, p = 0.04) and a greater decrease in gait speed during NW ([Formula: see text] = 0.17, p = 0.02). These findings indicate that in older adults with type 2 diabetes, gait performance is highly dependent on the integrity of cerebrovascular regulation.