Factors Associated with Cognitive Impairment in Patients with Persisting Sequelae of COVID-19.

OBJECTIVE: Quantify cognitive deficits in patients with postacute sequelae of COVID-19 (PASC) and identify key variables related to cognitive impairment in PASC. METHOD: Patients with polymerase chain reaction-confirmed COVID-19 underwent a comprehensive neuropsychological evaluation. The comparison group included patients without neurological disorders determined by the neuropsychologist to be cognitively intact. Cognitive impairment was defined as impairment (Composite T ≤35) in 1 of 6 cognitive domains. The PASC group was split into impaired or intact based on the above criteria. Multivariable logistic regression models assessed predictors including demographics, COVID-19 severity, clinical characteristics, and mood. RESULTS: There were 210 patients with PASC, predominantly female (73.3%, P < .001), without other demographic differences when compared with 369 normal controls. Patients with PASC were more likely to have cognitive impairment (odds ratio 3.61; 95% confidence interval, 2.36-5.54; P < .001) compared with controls, with significantly lower scores in domains of memory, language, processing speed, visuospatial function, executive function (P < .001), and higher depressive (P = .004) and anxiety symptoms (P = .003). Patients with PASC who demonstrated cognitive impairment (n = 93) had higher body mass index compared with those with PASC without cognitive impairment (n = 117), without differences in other predictors. CONCLUSION: Patients with PASC are almost 4 times more likely to evidence cognitive dysfunction compared with normal controls. Forty-four percent of patients with PASC demonstrated cognitive deficits about 7 months from infection. Estimated premorbid intelligence significantly correlated with impairment. Higher body mass index was the only metric shown to differentiate those with PASC and cognitive impairment from those with PASC who were cognitively intact.

Polygenic burden and its association with baseline cognitive function and postoperative cognitive outcome in temporal lobe epilepsy.

OBJECTIVE: Demographic and disease factors are associated with cognitive deficits and postoperative cognitive declines in adults with pharmacoresistant temporal lobe epilepsy (TLE), but the role of genetic factors in cognition in TLE is not well understood. Polygenic scores (PGS) for neurological and neuropsychiatric disorders and IQ have been associated with cognition in patient and healthy populations. In this exploratory study, we examined the relationship between PGS for Alzheimer's disease (AD), depression, and IQ and cognitive outcomes in adults with TLE. METHODS: 202 adults with pharmacoresistant TLE had genotyping and completed neuropsychological evaluations as part of a presurgical work-up. A subset (n = 116) underwent temporal lobe resection and returned for postoperative cognitive testing. Logistic regression was used to determine if PGS for AD, depression, and IQ predicted baseline domain-specific cognitive function and cognitive phenotypes as well as postoperative language and memory decline. RESULTS: No significant findings survived correction for multiple comparisons. Prior to correction, higher PGS for AD and depression (i.e., increased genetic risk for the disorder), but lower PGS for IQ (i.e., decreased genetic likelihood of high IQ) appeared possibly associated with baseline cognitive impairment in TLE. In comparison, higher PGS for AD and IQ appeared as possible risk factors for cognitive decline following temporal lobectomy, while the possible relationship between PGS for depression and post-operative cognitive outcome was mixed. SIGNIFICANCE: We did not observe any relationships of large effect between PGS and cognitive function or postsurgical outcome; however, results highlight several promising trends in the data that warrant future investigation in larger samples better powered to detect small genetic effects.

Predicting disability and mortality in CV2/CRMP5-IgG associated paraneoplastic neurologic disorders.

BACKGROUND: We aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response-mediator protein 5 (CRMP5)-IgG paraneoplastic neurologic disorders (PND). METHODS: This is a retrospective study of patients with CV2/CRMP5-IgG PND evaluated between 2002-2022. We examined the association of clinical variables (including age, clinical phenotype [autoimmune encephalopathy, myelopathy, polyneuropathy/radiculopathy, MG, cerebellar ataxia, chorea, optic neuropathy], cancer) with three clinical outcomes (wheelchair dependence, modified Rankin Scale [mRS], mortality) using univariate logistic regression and Cox proportional hazards modeling. Kaplan-Meier estimates were used to determine the probability of survival. RESULTS: Twenty-seven patients (56% female) with CV2/CRMP5-IgG PND were identified with a median follow-up of 54 months (IQR = 11-102). An underlying tumor was identified in 15 patients (56%) including small cell lung cancer (SCLC) (8, [53%]), thymoma (4, [27%]), and other histologies (3, [20%]). At last follow-up, 10 patients (37%) needed a wheelchair for mobility and this outcome was associated with myelopathy (HR = 7.57, 95% CI = 1.87-30.64, P = 0.005). Moderate-severe mRS = 3-5 was associated with CNS involvement (encephalopathy, myelopathy, or cerebellar ataxia) (OR = 7.00, 95% CI = 1.18-41.36, P = 0.032). The probability of survival 4 years after symptom onset was 66%. Among cancer subtypes, SCLC (HR = 18.18, 95% CI = 3.55-93.04, P < 0.001) was significantly associated with mortality, while thymoma was not. INTERPRETATION: In this retrospective longitudinal study of CV2/CRMP5-IgG PND, patients with CNS involvement, particularly myelopathy, had higher probability of disability. SCLC was the main determinant of survival in this population.

Characteristics and Attendance of Patients Eligible for the PASS Clinic: A Transition of Care Model After Acute Symptomatic Seizures.

Background and Objectives: Most acute symptomatic seizure (ASyS) patients stay on antiseizure medications (ASM) long-term, despite low epilepsy development risk. The Post-Acute Symptomatic Seizure (PASS) clinic is a transition of care model for ASyS patients who individualize ASM management with the goal of a safe deprescription. We evaluated patients discharged on ASMs after a witnessed or suspected ASyS to analyze their PASS clinic visit attendance and its predictors. Methods: A single-center, retrospective cohort study of adults without epilepsy who were discharged from January 1, 2019, to September 30, 2019, on first-time ASMs due to witnessed or suspected ASyS (PASS clinic-eligible). We fit a cause-specific Cox proportional hazards model to analyze factors associated with PASS clinic attendance, which depends on survival in this patient population that has a high early postdischarge mortality (a competing risk). We checked for multicollinearity and the assumption of proportional hazards. Results: Among 307 PASS clinic-eligible patients, 95 (30.9%) attended the clinic and 136 (44.3%) died during a median follow-up of 14 months (interquartile range = 2-34). ASyS occurred in 60.2% (convulsive 47%; electrographic 26.7%) of patients. ASMs were continued in the absence of ASyS or epileptiform abnormalities (EAs) in 27% of patients. Multivariable analysis revealed that the presence of EAs (HR = 1.69, 95% CI 1.10-2.59), PASS clinic appointments provided before discharge (HR = 3.39, 95% CI 2.15-5.33), and less frequently noted ASyS etiologies such as autoimmune encephalitis (HR = 2.03, 95% CI 1.07-3.86) were associated with an increased clinic attendance rate. Medicare/Medicaid insurance (HR = 0.43, 95% CI 0.24-0.78, p = 0.005) and the presence of progressive brain injury (i.e., tumors; HR = 0.55, 95% CI 0.32-0.95, p = 0.032) were associated with reduced rate of PASS clinic attendance. Discussion: Our real-world data highlight the need for appropriate postdischarge follow-up of ASyS patients, which can be fulfilled by the PASS clinic model. Modest PASS clinic attendance can be significantly improved by adhering to a structured discharge planning process whereby appointments are provided before discharge. Future research comparing patient outcomes, specifically safe ASM discontinuation in a PASS clinic model to routine clinical care, is needed.

Treatment outcomes for ARUBA-eligible brain arteriovenous malformations: a comparison of real-world data from the NVQI-QOD AVM registry with the ARUBA trial.

BACKGROUND: Significant controversy exists about the management of unruptured cerebral arteriovenous malformations (AVMs). Results from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) suggested that intervention increases the risk of stroke/death compared with medical management. However, numerous study limitations raised concerns about the trial's generalizability. OBJECTIVE: To assess the rate of stroke/death and functional outcomes in ARUBA-eligible patients from a multicenter database, the Neurovascular Quality Initiative-Quality Outcomes Database (NVQI-QOD). METHODS: We performed a retrospective analysis of prospectively collected data of ARUBA-eligible patients who underwent intervention at 18 participating centers. The primary endpoint was stroke/death from any cause. Secondary endpoints included neurologic, systemic, radiographic, and functional outcomes. RESULTS: 173 ARUBA-eligible patients underwent intervention with median follow-up of 269 (25-722.5) days. Seventy-five patients received microsurgery±embolization, 37 received radiosurgery, and 61 received embolization. Baseline demographics, risk factors, and general AVM characteristics were similar between groups. A total of 15 (8.7%) patients experienced stroke/death with no significant difference in primary outcome between treatment modalities. Microsurgery±embolization was more likely to achieve AVM obliteration (P<0.001). Kaplan-Meier survival curves demonstrated no difference in overall death/stroke outcomes between the different treatment modalities' 5-year period (P=0.087). Additionally, when compared with the ARUBA interventional arm, our patients were significantly less likely to experience death/stroke (8.7% vs 30.7%; P<0.001) and functional impairment (mRS score ≥2 25.4% vs 46.2%; P<0.01). CONCLUSION: Our results suggest that intervention for unruptured brain AVMs at comprehensive stroke centers across the United States is safe.

Longitudinal Disability, Cognitive Impairment, and Mood Symptoms in Patients With Anti-NMDA Receptor Encephalitis.

BACKGROUND AND OBJECTIVES: Longitudinal outcomes in anti-NMDA receptor encephalitis (anti-NMDARe) are still not fully understood and may not be adequately captured with the modified Rankin Scale (mRS), often the sole reported outcome. We aim to characterize longitudinal outcomes in anti-NMDARe using multiple outcome measures. METHODS: This single-center, retrospective, observational study examined outcome measures (mRS and Clinical Assessment Scale in Autoimmune Encephalitis [CASE]) in adults with NMDA receptor-IgG in CSF at short- and long-term follow-ups using linear and logistic regression modeling. Patients with evaluations for cognitive impairment (Montreal Cognitive Assessment/Mini-Mental State Examination), depression (Patient Health Questionnaire-9), and anxiety (General Anxiety Disorder-7) >6 months from symptom onset were correlated with final CASE scores. RESULTS: Thirty-eight patients (76% female, median disease onset age = 28 years, range = 1-75 years) were included. The majority received first-line immunosuppressants (97%) at a median of 3.9 weeks (interquartile range [IQR] = 2.1-9.7) from symptom onset and 68% received second-line therapies. At baseline, median/mean mRS and CASE were 4 (IQR = 3-5) and 12.9 (SD = 7.2), respectively. At short-term follow-up (median = 10 weeks, IQR = 6-17), factors associated with higher CASE and mRS included dysautonomia, coma/lethargy, seizures/status epilepticus, and intensive care unit admission (p < 0.05). At long-term follow-up (median = 70 weeks, IQR = 51-174), median/mean mRS and CASE were 2 (IQR = 1-3) and 4.4 (SD = 4.2), respectively. Only weakness at symptom onset predicted higher mRS scores (odds ratio = 5.6, 95% confidence interval 1.02-30.9, p = 0.047). Despite both mRS and CASE improving from baseline (p < 0.001), only 9 patients (31%) returned to their premorbid function. Among patients with cognitive and mood evaluations >6 months from onset, moderate-severe cognitive impairment (42%), depression (28%), and anxiety (30%) were frequent. Cognitive and depression measures were associated with final CASE subscores (including memory, language, weakness, and psychiatric). DISCUSSION: Multiple clinical factors influenced short-term outcomes, but only onset weakness influenced long-term mRS, highlighting that mRS is predominantly affected by global motor function. Although mRS and CASE improved over time for most patients, these outcome measures did not capture the full extent of long-term functional impairment in terms of mood, cognition, and the ability to return to premorbid function. This emphasizes the need for increased utilization of more nuanced cognitive and mood outcome measures.

Influence of psychological factors on the relationship between subjective and objective memory in adults with pharmacoresistant temporal lobe epilepsy.

PURPOSE: Many adults with temporal lobe epilepsy (TLE) report subjective cognitive impairment; however, prior studies have shown a discrepancy between these subjective complaints and objective cognitive deficits on neuropsychological measures. Mood disorders/symptoms are also common in TLE and have been linked to greater subjective cognitive difficulties. To further understand these relationships, this retrospective study sought to determine if symptoms of depression and anxiety moderate or mediate the relationship between subjective cognitive impairment and objective cognitive performance in adults with TLE. METHOD: Participants were 345 adults (mean age = 40.7; 55 % female) with pharmacoresistant TLE who completed self-report screening measures of depression, anxiety, and subjective cognitive function along with objective memory measures as part of a pre-surgical clinical neuropsychological evaluation. A series of linear regression analyses was conducted to examine the potential moderating and mediating effects of mood on the relationship between subjective and objective memory function after adjusting for relevant covariates. RESULTS: Consistent with existing literature, self-reported depression and anxiety symptoms were significantly correlated with subjective memory difficulties across all scales (all p < .001). Subjective memory impairment was also significantly correlated with objective memory performance on neuropsychological measures, albeit with small effect sizes (estimate range 0.04-0.20). Contrary to our hypothesis, depression and anxiety did not moderate or mediate the relationship between subjective memory complaints and objective memory performance. CONCLUSIONS: While symptoms of depression and anxiety were associated with subjective memory ability in this cohort of adults with TLE, this study suggests that mood symptoms do not fully explain the relationship between subjective and objective memory function, likely reflecting the complex and multifactorial relationships among these variables. Nevertheless, our results highlight the importance of screening for depression and anxiety symptoms and assessing patients' subjective memory complaints as part of a neuropsychological evaluation as each of these factors tap into a different aspect of the patient functioning.

Sleep-Disordered Breathing, Hypoxia, and Pulmonary Physiologic Influences in Atrial Fibrillation.

Background We leverage a large clinical cohort to elucidate sleep-disordered breathing and sleep-related hypoxia in incident atrial fibrillation (AF) development given the yet unclear contributions of sleep-related hypoxia and pulmonary physiology in sleep-disordered breathing and AF. Methods and Results Patients who underwent sleep studies at Cleveland Clinic January 2, 2000, to December 30, 2015, comprised this retrospective cohort. Cox proportional hazards models were used to examine apnea hypopnea index, percentage time oxygen saturation <90%, minimum and mean oxygen saturation, and maximum end-tidal carbon dioxide on incident AF adjusted for age, sex, race, body mass index, cardiopulmonary disease and risk factors, antiarrhythmic medications, and positive airway pressure. Those with spirometry were additionally adjusted for forced expiratory volume in 1 second, forced vital capacity, and forced expiratory volume in 1 second/forced vital capacity. This cohort (n=42 057) was 50.7±14.1 years, 51.3% men, 74.1% White individuals, had median body mass index 33.2 kg/m2, and 1947 (4.6%) developed AF over 5 years. A 10-unit apnea hypopnea index increase was associated with 2% higher AF risk (hazard ratio [HR], 1.02 [95% CI, 1.00-1.03]). A 10-unit increase in percentage time oxygen saturation <90% and 10-unit decreases in mean and minimum oxygen saturation were associated with 6% (HR, 1.06 [95% CI, 1.04-1.08]), 30% (HR, 1.30 [95% CI, 1.18-1.42]), and 9% (HR, 1.09 [95% CI, 1.03-1.15]) higher AF risk, respectively. After adjustment for spirometry (n=9683 with available data), only hypoxia remained significantly associated with incident AF, although all coefficients were stable. Conclusions Sleep-related hypoxia was associated with incident AF in this clinical cohort, consistent across 3 measures of hypoxia, persistent after adjustment for pulmonary physiologic impairment. Findings identify a strong role for sleep-related hypoxia in AF development without pulmonary physiologic interdependence.

The relationship between mood and anxiety and cognitive phenotypes in adults with pharmacoresistant temporal lobe epilepsy.

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) are often at a high risk for cognitive and psychiatric comorbidities. Several cognitive phenotypes have been identified in TLE, but it is unclear how phenotypes relate to psychiatric comorbidities, such as anxiety and depression. This observational study investigated the relationship between cognitive phenotypes and psychiatric symptomatology in TLE. METHODS: A total of 826 adults (age = 40.3, 55% female) with pharmacoresistant TLE completed a neuropsychological evaluation that included at least two measures from five cognitive domains to derive International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) cognitive phenotypes (i.e., intact, single-domain impairment, bi-domain impairment, generalized impairment). Participants also completed screening measures for depression and anxiety. Psychiatric history and medication data were extracted from electronic health records. Multivariable proportional odds logistic regression models examined the relationship between IC-CoDE phenotypes and psychiatric variables after controlling for relevant covariates. RESULTS: Patients with elevated depressive symptoms had a greater odds of demonstrating increasingly worse cognitive phenotypes than patients without significant depressive symptomatology (odds ratio [OR] = 1.123-1.993, all corrected p's < .05). Number of psychotropic (OR = 1.584, p < .05) and anti-seizure medications (OR = 1.507, p < .001), use of anti-seizure medications with mood-worsening effects (OR = 1.748, p = .005), and history of a psychiatric diagnosis (OR = 1.928, p < .05) also increased the odds of a more severe cognitive phenotype, while anxiety symptoms were unrelated. SIGNIFICANCE: This study demonstrates that psychiatric factors are not only associated with function in specific cognitive domains but also with the pattern and extent of deficits across cognitive domains. Results suggest that depressive symptoms and medications are strongly related to cognitive phenotype in adults with TLE and support the inclusion of these factors as diagnostic modifiers for cognitive phenotypes in future work. Longitudinal studies that incorporate neuroimaging findings are warranted to further our understanding of the complex relationships between cognition, mood, and seizures and to determine whether non-pharmacologic treatment of mood symptoms alters cognitive phenotype.

The Roles Between Gratitude, Perceived Stress, and Quality of Life Among Patients with Multiple Sclerosis.

Dispositional gratitude has been negatively associated with perceived stress (PS) and positively associated with higher well-being in both general and chronically ill people. Attempts to understand the relationship between gratitude and aspects of quality of life (QOL) have been documented; however, there is limited research on determining the potential mediating effect of PS on gratitude and QOL factors in individuals with Multiple Sclerosis (MS). In this cross-sectional study, participant demographics, dispositional gratitude, PS, and QOL factors were collected online via self-report measures from a sample of 68 participants diagnosed with MS. Results indicated that both dispositional gratitude and PS were associated with aspects of QOL and that PS was found to partially and indirectly account for the relationship between gratitude and improved QOL. Findings are consistent with existing research conducted with non-chronically ill samples. Clarifying relationships between PS and dispositional factors in MS is necessary to inform future interventions aimed at maintaining and enhancing an individual's QOL.

Race, economic status, and disparities in the receipt of benzodiazepine prescriptions in a large primary care sample.

OBJECTIVE: To evaluate the relationship between race, economic status, and patient characteristics with benzodiazepine prescribing in an urban and suburban primary care context. METHOD: This retrospective study used data from a previously described cohort of patients seen in a large Ohio healthcare system's primary care clinics from 2019 to 2020. Associations and interactions between race, economic status (using median income of patient ZIP code as a proxy), patient characteristics, and prescription of benzodiazepines were assessed using multivariable logistic regression. RESULTS: 455,537 patients had 1,643,473 primary care visits, and 5.8% of patients were prescribed a benzodiazepine. White patients were prescribed benzodiazepines more often than Multiracial/Multicultural, African American and Asian American patients (6.5%, 3.8%, 2.7% and 2.0% respectively). Patients from lower income ZIP codes were less likely to receive a prescription. Interaction effects were observed between race, patient economic status, gender, insurance status, and diagnoses (general anxiety disorder, insomnia, and panic disorder). The largest prescribing disparities by race were among patients with these three diagnoses. The largest disparity in prescription by income was seen in African American patients. CONCLUSION: African American, Multicultural/Multiracial and Asian American patients were less likely than White patients to receive benzodiazepine prescriptions. Middle and lower-income patients are particularly susceptible to this prescribing disparity.

Prescribing of Z-Drugs With and Without Opioid Coprescribing to Primary Care Patients in a Large Health Care System From 2019-2020.

Objective: This study aimed to characterize Z-drug prescribing with and without opioid coprescribing pre- and post-COVID-19 lockdown in the primary care clinics of a large health care system.Methods: A retrospective, cross-sectional study was conducted that measured the prevalence of Z-drug prescribing with and without opioids for adults aged ≥ 18 years that were seen in the primary care clinics of a large health care system in 2019 and 2020. The pre-COVID time period was defined as March 24, 2019-December 31, 2019, and the post-lockdown time period was defined as March 24, 2020-December 31, 2020.Results: Among 455,537 adult patients, 6,743 (1.48%) were prescribed a Z-drug during the study period. In addition, 1,064 (0.2%) were coprescribed a Z-drug and an opioid at least once, constituting 15.78% of patients receiving a Z-drug prescription. There was no change in the rate of Z-drug prescription post-lockdown (odds ratio [OR] = 0.978, 95% confidence interval [CI] = 0.942-1.010, P = .233), though odds of coprescribing decreased (OR = 0.883, 95% CI = 0.789-0.988, P = .031). Important correlates of receiving a Z-drug prescription during the study period were older age, White race, and diagnosis of opioid use disorder. Older age and a diagnosis of opioid use disorder were also associated with coprescribing. Receiving a de novo Z-drug prescription post-lockdown was associated with increased age, White race, and diagnosis of bipolar disorder, generalized anxiety disorder, and insomnia.Conclusions: Rates of Z-drug prescribing were unchanged post-lockdown, while rates of Z-drug with opioid coprescribing decreased. Some patient populations vulnerable to Z-drug adverse effects were at heightened risk of Z-drug prescription, while racial disparities in Z-drug prescribing were observed.

Utilities Estimated from PROMIS Scales for Cost-Effectiveness Analyses in Stroke.

BACKGROUND: The EQ-5D and Health Utilities Index Mark 3 (HUI-3) are preference-based measures used in cost-effectiveness studies. The Patient Reported Outcomes Measurement Information System (PROMIS) Preference scoring system (PROPr) is a new preference-based measure. In addition, algorithms were previously developed to map PROMIS Global Health (PROMIS-GH) items to HUI-3 using linear equating (HUILE) and 3-level EQ-5D using linear (EQ5DLE). We sought to evaluate and compare estimated utilities based on PROPr and PROMIS-GH in adult stroke survivors. METHODS: We performed a retrospective cohort study of adults diagnosed with 1 of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage seen in an outpatient clinic between 2015 and 2019. Patients completed PROMIS scales and other measures. We computed a modified version of PROPr (mPROPr) and compared the distributional characteristics and correlations with stroke outcomes for mPROPr, HUILE, and EQ5DLE. RESULTS: T toal of 4,159 stroke survivors (average age 62.7 ± 14.7 y, 48.4% female, 77.6% ischemic stroke) were included. Mean utility estimates for mPROPr, EQ5DLE, and HUILE were 0.333 ± 0.244, 0.739 ± 0.201, and 0.544 ± 0.301, respectively. Correlations between the modified Rankin Scale and each of mPROPr and HUILE were both -0.48 and -0.43 for EQ5DLE. Regression analyses indicated that mPROPr scores may be too low for stroke patients in good health and that EQ5DLE scores may be too high for stroke patients in poor health. CONCLUSIONS: All 3 PROMIS-based utilities were associated with measures of stroke disability and severity, but the distributions of utilities were very different. Our study highlights the problem cost-effectiveness researchers face of valuing health states with certainty. For researchers using utilities estimated from PROMIS scales, our study indicates that mapping PROMIS-GH item scores to HUI-3 via linear equating may be most appropriate in stroke patients. HIGHLIGHTS: A new preference-based measure has been developed from the Patient Reported Outcomes Measurement Information System (PROMIS), known as the PROMIS-Preference (PROPr) scoring system, and published equations mapping PROMIS Global Health (PROMIS-GH) items to the Health Utilities Index Mark 3 (HUI-3) and EQ-5D-3L are available for use in cost-effectiveness studies.Our study provides distributional characteristics and comparisons of utilities estimated using a modified version of PROPr and equations mapping PROMIS-GH items to EQ-5D-3L and HUI-3 in a sample of stroke survivors.The results of our study show large differences in the distributions of utilities estimated using the different health state measures, and these differences highlight the ongoing difficulty researchers face in valuing health states with certainty.

Clinical characteristics and patient-reported outcomes of chronic and episodic migraine patients at a US tertiary headache center: A retrospective observational study.

OBJECTIVE: To describe differences in clinical and demographic characteristics between patients with episodic migraine (EM) or chronic migraine (CM) and determine the effect of migraine subtype on patient-reported outcome measures (PROM). BACKGROUND: Prior studies have characterized migraine in the general population. While this provides a basis for our understanding of migraine, we have less insight into the characteristics, comorbidities, and outcomes of migraine patients who present to subspecialty headache clinics. These patients represent a subset of the population that bears the greatest burden of migraine disability and are more representative of migraine patients who seek medical care. Valuable insights can be gained from a better understanding of CM and EM in this population. METHODS: We conducted a retrospective observational cohort study of patients with CM or EM seen in the Cleveland Clinic Headache Center between January 2012 and June 2017. Demographics, clinical characteristics, and patient-reported outcome measures (3-Level European Quality of Life 5-Dimension [EQ-5D-3L], Headache Impact Test-6 [HIT-6], Patient Health Questionnaire-9 [PHQ-9]) were compared between groups. RESULTS: Eleven thousand thirty-seven patients who had 29,032 visits were included. More CM patients reported being on disability 517/3652 (14.2%) than EM patients 249/4881 (5.1%) and had significantly worse mean HIT-6 (67.3 ± 7.4 vs. 63.1 ± 7.4, p < 0.001) and median [interquartile range] EQ-5D-3L (0.77 [0.44-0.82] vs. 0.83 [0.77-1.00], p < 0.001), and PHQ-9 (10 [6-16] vs. 5 [2-10], p < 0.001). CONCLUSIONS: There are multiple differences in demographic characteristics and comorbid conditions between patients with CM and EM. After adjustment for these factors, CM patients had higher PHQ-9 scores, lower quality of life scores, greater disability, and greater work restrictions/unemployment.

Emergency department utilization among patients who receive outpatient specialty care for headache: A retrospective cohort study analysis.

OBJECTIVES: To compare clinical characteristics among outpatient headache clinic patients who do and do not self-report visiting the emergency department for headache. BACKGROUND: Headache is the fourth most common reason for emergency department visits, compromising 1%-3% of visits. Limited data exist about patients who are seen in an outpatient headache clinic but still opt to frequent the emergency department. Clinical characteristics may differ between patients who self-report emergency department use and those who do not. Understanding these differences may help identify which patients are at greatest risk for emergency department overutilization. METHODS: This observational cohort study included adults treated at the Cleveland Clinic Headache Center between October 12, 2015 and September 11, 2019, who completed self-reported questionnaires. Associations between self-reported emergency department utilization and demographics, clinical characteristics, and patient-reported outcome measures (PROMs: Headache Impact Test [HIT-6], headache days per month, current headache/face pain, Patient Health Questionnaire-9 [PHQ-9], Patient-Reported Outcomes Measurement Information System [PROMIS] Global Health [GH]) were evaluated. RESULTS: Of the 10,073 patients (mean age 44.7 ± 14.9, 78.1% [7872/10,073] female, 80.3% [8087/10,073] White patients) included in the study, 34.5% (3478/10,073) reported visiting the emergency department at least once during the study period. Characteristics significantly associated with self-reported emergency department utilization included younger age (odds ratio = 0.81 [95% CI = 0.78-0.85] per decade), Black patients (vs. White patients) (1.47 [1.26-1.71]), Medicaid (vs. private insurance) (1.50 [1.29-1.74]), and worse area deprivation index (1.04 [1.02-1.07]). Additionally, worse PROMs were associated with greater odds of emergency department utilization: higher (worse) HIT-6 (1.35 [1.30-1.41] per 5-point increase), higher (worse) PHQ-9 (1.14 [1.09-1.20] per 5-point increase), and lower (worse) PROMIS-GH Physical Health T-scores (0.93 [0.88-0.97]) per 5-point increase. CONCLUSION: Our study identified several characteristics associated with self-reported emergency department utilization for headache. Worse PROM scores may be helpful in identifying which patients are at greater risk for utilizing the emergency department.

Examining degenerative disease adjacent to lumbosacral transitional vertebrae: a retrospective cohort study.

OBJECTIVE: Bertolotti syndrome is a clinical diagnosis given to patients with low-back pain arising from a lumbosacral transitional vertebra (LSTV). While biomechanical studies have demonstrated abnormal torques and range of motion occurring at and above this type of LSTV, the long-term effects of these biomechanical changes on the LSTV adjacent segments are not well understood. This study examined degenerative changes at segments superjacent to the LSTV in patients with Bertolotti syndrome. METHODS: This study involved a retrospective comparison of patients between 2010 and 2020 with an LSTV and chronic back pain (Bertolotti syndrome) and control patients with chronic back pain with no LSTV. The presence of an LSTV was confirmed on imaging, and the caudal-most mobile segment above the LSTV was assessed for degenerative changes. Degenerative changes were assessed by grading the intervertebral disc, facets, degree of spinal stenosis, and spondylolisthesis using well documented grading systems. All computations were performed in R, version 4.1.0. All tests were two-sided, and p values < 0.05 was considered statistically significant. Separate logistic regression analyses were run with the associated dependent variables for each aim, with age at MRI and sex included as covariates. Odds ratios and 95% confidence intervals were computed. RESULTS: A total of 172 patients were included, 101 with Bertolotti syndrome and 71 controls. Control patients consisted of patients with low-back pain but no diagnosis of Bertolotti syndrome or an LSTV. Fifty-six Bertolotti (55.4%) and 27 control (38.0%) patients were female, (p = 0.03). After adjusting for age at MRI and sex, Bertolotti patients had pelvic incidence (PI) that was 9.83° greater than control patients (95% CI 5.15°-14.50°, p < 0.001). Sacral slope was not significantly different between the Bertolotti and control groups (beta estimate 3.10°, 95% CI -1.07° to 7.27°; p = 0.14). Bertolotti patients had 2.69 times higher odds of having a high disc grade at L4-5 (3-4 vs 0-2), compared with control patients (OR 2.69, 95% CI 1.28-5.90; p = 0.01). There were no significant differences between Bertolotti patients and controls for spondylolisthesis, facet grade, or spinal stenosis grade. CONCLUSIONS: Patients with Bertolotti syndrome had a significantly higher PI and were more likely to have adjacent-segment disease (ASD; L4-5) compared with control patients. However, after controlling for age and sex, PI and ASD did not appear to have a significant association within the cohort of Bertolotti patients. The altered biomechanics and kinematics in this condition may be a causative factor in this degeneration, although proof of causation is not possible in this study. This association may warrant closer follow-up protocols for patients being treated for Bertolotti syndrome, but further prospective studies are needed to establish if radiographic parameters can serve as an indicator for biomechanical alterations in vivo.

The impact of stigma on perceived quality of life and experience of anxiety and depression in individuals diagnosed with MS.

BACKGROUND: Stigma experienced by persons living with multiple sclerosis (PwMS) is underrepresented in the literature. Discovering how the experience of stigma impacts quality of life and mood symptoms in PwMS may guide future care considerations with the goal of improving overall quality of life. METHODS: A retrospective review of data from the Quality of Life in Neurological Disorders (Neuro-QoL) set of measures and PROMIS Global Health (PROMIS-GH) scale was conducted. Multivariable linear regression was used to assess relationships between baseline (first visit) Neuro-QoL Stigma, Anxiety, Depression, and PROMIS-GH. Mediation analyses examined whether mood symptoms mediated the relationship between stigma and quality of life (PROMIS-GH). RESULTS: 6,760 patients (mean age 60.2 ± 8.9 years, 27.7% male, 74.2% white) were included. Neuro-QoL Stigma was significantly related to PROMIS-GH Physical Health (beta=-0.390, 95% CI [-0.411, -0.368]; p < 0.001) and PROMIS-GH Mental Health (beta=-0.595, 95% CI [-0.624, -0.566]; p < 0.001). Neuro-QoL Stigma was also significantly related to Neuro-QoL Anxiety (beta=0.721, 95% CI [0.696, 0.746]; p < 0.001) and Neuro-QoL Depression (beta=0.673, 95% CI [0.654, 0.693]; p < 0.001). Mediation analyses revealed that both Neuro-QoL Anxiety and Depression partially mediated the relationship between Neuro-QoL Stigma and PROMIS-GH Physical and Mental Health. CONCLUSION: Results demonstrate stigma is associated with decreased quality of life in both physical and mental health domains in PwMS. Stigma was also associated with more significant symptoms of anxiety and depression. Finally, anxiety and depression play a mediating role in the relationship between stigma and both physical and mental health in PwMS. Therefore, tailoring interventions to effectively reduce symptoms of anxiety and depression in PwMS may be warranted, as it will likely improve overall quality of life and reduce negative impacts of stigma.

An Analysis of Benzodiazepine Prescribing to Primary Care Patients in a Large Healthcare System from 2019-2020.

We sought to quantify benzodiazepine prescribing by primary care providers from 2019 to 2020 and identify correlates of prescribing. We hypothesized prescribing would increase post-COVID-19 lockdown. We conducted a retrospective cohort study of adult patients with primary care visits in 2019 or 2020 in a large Ohio healthcare system. Demographics, diagnosis codes, and receipt of benzodiazepine prescriptions were collected. Using multivariable logistic regression, we examined factors associated with benzodiazepine prescription receipt during the whole study period and post-lockdown. 455,537 adult patients had 1,643,473 visits. Benzodiazepines were prescribed in 3.2% (53,049/1,643,473) of visits. Effect sizes for positive associations with benzodiazepine prescription were largest for anxiety disorders. For negative associations, they were largest for Black patients and patients with cocaine use disorder. Benzodiazepine prescribing was positively associated with multiple groups having contraindications, though effect sizes were small. Contrary to our hypothesis, odds of receiving a prescription were 8.8% lower post-lockdown. Benzodiazepine prescribing rates in our system compared favorably to national rates. Year over year odds of receiving a prescription were slightly lower post-lockdown. Racial disparities were present and deserve further study. Strategies to reduce benzodiazepine prescribing to patients with anxiety may yield the largest reductions for benzodiazepine prescribing in primary care settings.

Quality of life after epilepsy surgery: How domain-specific cognitive changes impact QOL within the context of seizure outcome.

PURPOSE: Neurosurgery is an effective treatment option for pharmacoresistant epilepsy. Although post-surgical seizure freedom is considered the primary goal of epilepsy surgery, other factors that impact Quality of Life (QOL) are also important to consider, including post-surgical cognitive changes. This study aimed to examine the impact of post-surgical cognitive changes on QOL in the context of seizure outcomes. METHODS: Participants were 196 adults with focal epilepsy who underwent either frontal (n = 27) or temporal (n = 169) lobe resection. Each participant completed pre- and post-surgical neuropsychological evaluations, and cognitive composites were constructed for the following domains: language, attention/processing speed, memory, executive function, and visuospatial skill. The Quality of Life in Epilepsy (QOLIE-10) questionnaire was used to assess QOL. Seizure outcome was determined by seizure status six months post-surgery. RESULTS: Eighty-one percent of patients were seizure-free post-surgery and generally reported improved QOL. While a significant portion of patient's demonstrated declines in language and verbal memory following surgery, only a decline in verbal memory was associated with worse QOL; however, this relationship was no longer significant after controlling for seizure outcome. Instead, reduced post-surgical QOL was primarily observed in those who experienced both seizure recurrence and a decline in executive function. Notably, depression was a significant covariate in all of the models. CONCLUSIONS: The findings from this study improve our ability to counsel patients about the trade-off between cognitive decline and seizure remittance in the greater context of overall QOL. Reassuringly, it appears that QOL is improved regardless of cognitive changes when patients have good seizure outcomes. However, for those that experience a "double hit" (i.e., cognitive decline without seizure remission), post-surgical QOL may be reduced. Changes in depression also appear to play a crucial role in QOL outcomes.

The Effect of Cervical and Lumbar Decompression Surgery for Spinal Stenosis on Erectile Dysfunction.

STUDY DESIGN: Observational study. OBJECTIVES: To evaluate the prevalence of erectile dysfunction and evaluate the effects of decompressive surgery on erectile dysfunction in cervical spinal stenosis and lumbar canal stenosis patients. METHODS: This observational, prospective analysis enrolled patients aged 18-80 with cervical spinal stenosis and/or lumbar canal stenosis that underwent respective decompressive surgery. The IIEF-5 questionnaire was administered preoperatively, and at 6- and 12-months postoperatively to assess erectile dysfunction severity. The EPIC database was queried to determine any postoperative complications and document prominent erectile dysfunction risk factors. RESULTS: Of 79 patients included in the analysis, 42 (53.2%) completed the IIEF-5 at 6 months, and 62 (78.5%) completed it at 12 months. Eighteen had cervical stenosis only, 54 had lumbar stenosis only, and 7 had both. 72% (18/25) of cervical stenosis patients and 83.6% (51/61) of lumbar stenosis patients had erectile dysfunction preoperatively according to IIEF-5 responses. The average preoperative IIEF-5 score indicated significant presence of erectile dysfunction for both the cervical and lumbar stenosis groups. No significant differences were identified in IIEF-5 score deltas from pre- to both postoperative periods. The presence of erectile dysfunction in both the cervical and lumbar stenosis groups was not significantly associated with the presence of any documented risk factors. CONCLUSIONS: Our results suggest no significant improvement in overall erectile function postoperatively for patients with preoperative erectile dysfunction. This is important to address during patient counseling for decompression surgery candidates with cervical spinal stenosis and/or lumbar canal stenosis to manage expectations.