A single-arm, open-label pilot study of neuroimaging, behavioral, and peripheral inflammatory correlates of mindfulness-based stress reduction in multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these "silent" symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of systemic inflammatory biology. To address these issues, we conducted a prospective, observational pilot study to investigate the psychological, biological, and neuroarchitecture changes associated with a mindfulness-based stress reduction (MBSR) program in MS. The overarching hypothesis was that MBSR modulates systemic and central nervous system inflammation via top-down neurocognitive control over forebrain limbic areas responsible for the neurobiological stress response. 23 patients were enrolled in MBSR and assessed pre/post-program with structural 3 T MRI, behavioral measures, hair cortisol, and blood measures of peripheral inflammation, as indexed by the Conserved Transcriptional Response to Adversity (CTRA) profile. MBSR was associated with improvements across a variety of behavioral outcomes, as well as on-study enlargement of the head of the right hippocampus. The CTRA analyses revealed that greater inflammatory gene expression was related to worse patient-reported anxiety, depression, stress, and loneliness, in addition to lower eudaimonic well-being. Hair cortisol did not significantly change from pre- to post-MBSR. These results support the use of MBSR in MS and elucidate inflammatory mechanisms related to key patient-reported outcomes in this population.

Chemotherapy-associated hemorrhagic posterior reversible encephalopathy syndrome (PRES) with considerations for circle of Willis variants on cerebral blood flow and autoregulation: A case report.

RATIONALE: Hodgkin lymphoma, a lymphatic system cancer, is treated by chemotherapy, radiation therapy, and hematopoietic stem cell transplantation. Posterior reversible encephalopathy syndrome (PRES) is a rare neurotoxic effect associated with several drugs and systemic conditions. This case study emphasizes the potential risks of intensive chemotherapy regimens and postulates the impact of the circle of Willis variants on the heterogeneity of hemispheric lesions in PRES. PATIENT CONCERNS: A 42-year-old woman diagnosed with stage IIA nodular sclerosing Hodgkin lymphoma and chronic thrombocytopenia presented after 6 years of initial diagnosis and 4 years post-haploidentical transplant. She underwent planned chemotherapy with ifosfamide, carboplatin, and etoposide. DIAGNOSES: She developed an alteration in her mental status. A computerized tomography scan and angiogram of the head and neck revealed findings consistent with PRES and a left fetal-type posterior cerebral artery with an aplastic A1 segment of the left anterior cerebral artery. One hour later she was found comatose with clinical sequelae of an uncal herniation. INTERVENTIONS: Subsequent events led to emergent intubation, and administration of 23.4% hypertonic saline. A repeat computerized tomography scan showed a right intraparenchymal hemorrhage with fluid-fluid levels measuring up to 4.7 cm, bilateral subarachnoid hemorrhage, right uncal herniation, and 15 mm of leftward midline shift. She emergently underwent a right decompressive hemi-craniectomy. OUTCOMES: An magnetic resonance imaging of the brain demonstrated bilateral cytotoxic edema involving the parieto-occipital lobes. Despite interventions, the patient's neurological condition deteriorated, leading to a declaration of brain death on the 8th day. LESSONS: This case underscores the importance of recognizing the severe neurological complications, including PRES, associated with chemotherapeutic treatments in Hodgkin lymphoma. PRES may also be exacerbated by coagulopathies such as thrombocytopenia in this case. The circle of Willis variants may influence cerebral blood flow, autoregulation, and other factors of hemodynamics, leading to increased susceptibility to both radiographic lesion burden and the worst clinical outcomes.

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.

A real-world cohort analysis of alemtuzumab outcomes in relapsing multiple sclerosis.

Multiple sclerosis (MS) is a chronic and progressive neurological disease characterized by recurrent episodes of inflammatory demyelination of the brain and spinal cord. Alemtuzumab has been previously shown in large phase III trials to be an effective therapy in reducing MS clinical flares as well as new radiological activity and atrophy rates. The purpose of this study was to examine real-world effectiveness and safety data from a large cohort of people treated with alemtuzumab at an academic medical center, including those who failed B-cell depletion therapy. Over an average of 2.6 years follow-up, there were small but significant improvements in neurological disability scores, and a 61% rate of the composite "No Evidence of Disease Activity" (NEDA-3) outcome at 2-year follow-up. There were no substantial safety issues encountered in our review; rates of adverse events were similar or below those reported in Phase III trials. We compare and contrast our results to other available real-world data using alemtuzumab in multiple sclerosis.

A Novel Tool to Improve Shared Decision Making and Adherence in Multiple Sclerosis: Development and Preliminary Testing.

Background. Most people with multiple sclerosis (MS) want to be involved in medical decision making about disease-modifying therapies (DMTs), but new approaches are needed to overcome barriers to participation. Objectives. We sought to develop a shared decision-making (SDM) tool for MS DMTs, evaluate patient and provider responses to the tool, and address challenges encountered during development to guide a future trial. Methods. We created a patient-centered design process informed by image theory to develop the MS-SUPPORT SDM tool. Development included semistructured interviews and alpha and beta testing with MS patients and providers. Beta testing assessed dissemination and clinical integration strategies, decision-making processes, communication, and adherence. Patients evaluated the tool before and after a clinic visit. Results. MS-SUPPORT combines self-assessment with tailored feedback to help patients identify their treatment goals and preferences, correct misperceptions, frame decisions, and promote adherence. MS-SUPPORT generates a personal summary of their responses that patients can share with their provider to facilitate communication. Alpha testing (14 patients) identified areas needing improvement, resulting in reorganization and shortening of the tool. MS-SUPPORT was highly rated in beta testing (15 patients, 4 providers) on patient-provider communication, patient preparation, adherence, and other endpoints. Dissemination through both patient and provider networks appeared feasible. All patient testers wanted to share the summary report with their provider, but only 60% did. Limitations. Small sample size, no comparison group. Conclusions. The development process resulted in a patient-centered SDM tool for MS that may facilitate patient involvement in decision making, help providers understand their patients' preferences, and improve adherence, though further testing is needed. Beta testing in real-world conditions was critical to prepare the tool for future testing and inform the design of future studies.

Whose Preferences Matter? A Patient-Centered Approach for Eliciting Treatment Goals.

BACKGROUND: Patients facing a high-stakes clinical decision are often confronted with an overwhelming array of options. High-quality decisions about treatment should reflect patients' preferences as well as their clinical characteristics. Preference-assessment instruments typically focus on pre-selected clinical outcomes and attributes chosen by the investigator. OBJECTIVE: We sought to develop a patient-centered approach to elicit and compare the treatment goals of patients with multiple sclerosis (MS) and healthcare providers (HCPs). METHODS: We conducted five nominal group technique (NGT) meetings to elicit and prioritize treatment goals from patients and HCPs. Five to nine participants in each group responded silently to one question about their treatment goals. Responses were shared, consolidated, and ranked to develop a prioritized list for each group. The ranked lists were combined. Goals were rated and sorted into categories. Multidimensional scaling and hierarchical cluster analysis were used to derive a visual representation, or cognitive map, of the data and to identify conceptual clusters, reflecting how frequently items were sorted into the same category. RESULTS: Five NGT groups yielded 34 unique patient-generated treatment goals and 31 unique HCP-generated goals. There were differences between patients and HCPs in the goals generated and how they were clustered. Patients' goals tended to focus on the impact of specific symptoms on their day-to-day lives, whereas providers' goals focused on slowing down the course of disease progression. CONCLUSIONS: Differences between the treatment goals of patients and HCPs underscore the limitations of using HCP- or investigator-identified goals. This new adaptation of cognitive mapping is a patient-centered approach that can be used to generate and organize the outcomes and attributes for values clarification exercises while minimizing investigator bias and maximizing relevance to patients.

The varieties of psychosis in multiple sclerosis: A systematic review of cases.

OBJECTIVES: Multiple Sclerosis (MS) is known to be associated with a wide range of psychiatric symptoms, particularly with affective disorders. However, a link to psychotic disorders has not been fully established. METHODS: A systematic review of the PubMed/MEDLINE database was performed to identify cases of MS presenting with psychotic symptoms. Variables analyzed included patient demographics, clinical presentation, imaging characteristics and treatment. RESULTS: Ninety-one cases were identified. The mean age was 34.4, and there was a female predominance. The majority of patients did not have a prior history of MS or psychiatric disease. The majority of cases could be classified as having either Psychotic Disorders or Mood Disorders with psychotic features. Most patients received some type of antipsychotic therapy, with variable success. At least 26 patients were treated with corticosteroids in the acute phase of their psychotic symptoms, and the majority responded favorably. Imaging data was available for 50 patients. Of these, 60% had predominantly fronto-temporal lesions, and most had contrast enhancing lesions. CONCLUSIONS: MS can present with a variety of psychotic symptoms. The presence of enhancing lesions and steroid-responsiveness suggests these could be characterized as flares.