Purpose of Review:There is no consensus or standardized framework to characterize disease activity in CNS neurosarcoidosis, and the existing literature is highly heterogeneous. Here, we aimed to aggregate all longitudinal monitoring metrics in neurosarcoidosis through a systematic review. The review protocol is registered in PROSPERO (ID:533857). Articles were included if they incorporated at least 1 longitudinal monitoring or outcome metric relevant to neurosarcoidosis disease activity. In addition, we aimed to establish an evidence-based clinical framework for characterizing, monitoring, and communicating neurosarcoidosis disease activity, applicable to both clinical care and research. Recent Findings:Of 387 articles initially identified, 67 met the inclusion criteria. Most studies focused on metrics within a single domain (clinical, imaging, or laboratory) or analyzed multiple domains independently. Often, the definitions were not formally outlined. Only 11 studies included a multidomain monitoring metric. Our proposed framework integrates 3 critical domains for assessing the neurosarcoidosis disease activity: (1) clinical, (2) imaging, and (3) laboratory and supports a standardized characterization of the disease, especially when domain results are discordant. The overarching goal in defining the elements of each domain was to prioritize specificity in attributing activity to neurosarcoidosis while minimizing the risk of misattribution. Each domain includes criteria for 4 categories of disease status: "improved," "stable," "worsened," or "resolved." The overall disease status of activity or inactivity is then determined by reconciling the independent domains into a summary disease activity assessment, communicated with additional clinical context, including immune treatment status and neuroanatomic localization. Sustained clinical stability of persistent neurologic symptoms or signs in the absence of MRI or CSF activity is considered in the summary assessment to reflect inactive disease with sustained neurologic deficits. Summary:A systematic review highlighted substantial heterogeneity in how CNS neurosarcoidosis disease activity is measured, with many studies lacking formal definitions and often reporting activity only within isolated domains. This proposed framework integrates multiple domains to comprehensively characterize CNS neurosarcoidosis disease activity. With further validation, this approach has the potential to standardize research practices and improve clinical reasoning and communication.

Introduction Sarcoidosis-associated small fiber neuropathy (S-SFN) is frequently associated with chronic pain and poor quality of life. Tocilizumab is an anti-IL-6 receptor monoclonal antibody used to treat rheumatological conditions; however, its utility in S-SFN remains uncertain. This study aims to describe the clinical outcomes of three patients with S-SFN treated with tocilizumab. Methods A retrospective chart review was conducted for three patients with S-SFN who were treated with tocilizumab at the Neurosarcoidosis Center at Johns Hopkins Hospital between 2014 and 2024. Demographic and clinical data were extracted and described. IRB approved the patient's chart review. Results Patient 1: 54-year-old male with S-SFN causing severe refractory neuropathic pain and dysautonomia. No response shown to methotrexate and infliximab. Intolerance to IVIG due to aseptic meningitis. Subcutaneous tocilizumab was initiated at 162 mg every 7 days with improved pain. Patient 2: 67-year-old female with S-SFN causing paresthesia and numbness in extremities and dysautonomia. Adalimumab was discontinued after anti-adalimumab antibody development; IVIG was suspended after superior mesenteric artery thrombosis. Subcutaneous tocilizumab was initiated at 162 mg every 14 days, improving numbness, neuropathic and gastrointestinal symptoms. Patient 3: 61-year-old female with S-SFN causing neuropathic pain and dysautonomia. No response to corticosteroids, TNF-alpha inhibitors, mycophenolate, and methotrexate. Tocilizumab was initiated at 162 mg every 7 days, improving systemic symptoms, gastrointestinal dysmotility, and neuropathic pain. Conclusion Tocilizumab may improve pain, gastrointestinal, and sensory symptoms in patients with S-SFN refractory to standard sarcoidosis immunosuppressive therapies. IL-6 may play a role in the underlying pathophysiology of S-SFN.

To establish a comprehensive research protocol for clinical assessment of patients with neurosarcoidosis (NS) to precisely characterize clinical phenotypes, pathogenic mechanisms, and biomarkers in a longitudinal observational cohort study.

OBJECTIVE:The optimal treatment for neurosarcoidosis myelitis is uncertain. We characterize incident neurosarcoidosis myelitis and assess treatment response by MRI and clinical scales. METHODS:Incident probable or definite neurosarcoidosis myelitis in adults was retrospectively identified from 13 academic medical centers. Cases were analyzed by initial treatment. The primary outcome was T1 post-contrast gadolinium enhancement resolution at 6 months post-treatment. Secondary outcomes were changes in modified Rankin scale (mRS) and Expanded Disability Status Scale (EDSS) from nadir to final follow-up. RESULTS:Two hundred two patients were identified (median diagnosis age: 47 years (IQR 39-55); male: female 1.3:1). Median nadir mRS and EDSS were 2 (IQR 2-3) and 4 (IQR 2.5-6). At initial treatment, 129 (63.9%) received prolonged corticosteroids ≥ 4 weeks (group A1), 36 (17.8%) received corticosteroids < 4 weeks (B1), 21 (10.4%) received corticosteroids plus sarcoidosis-directed immunosuppressant (E), and 16 (7.9%) received corticosteroids plus non-sarcoidosis-directed agents (F). In 167 cases with sufficient imaging, there were no significant differences in contrast enhancement resolution at 6 months (A1 27/106 (25.5%), B1 9/28 (32.1%), E 5/19 (26.3%), F 5/14 (35.7%); Fisher's exact p = 0.76). There were no significant differences in changes in mRS or EDSS among treatment groups (Kruskal-Wallis p = 0.69 and 0.63, respectively) after median follow-up of 46.5 months (IQR 18-91.3). INTERPRETATION:Different initial immunosuppression strategies did not correlate with MRI contrast enhancement resolution at 6 months or clinical scales (mRS, EDSS). However, conclusions are limited by retrospective design, imbalanced cohorts, and insensitivity of binary MRI outcomes and available clinical scales for treatment response in neurosarcoidosis.

Sarcoidosis is a systemic disease characterized by marked clinical equipoise regarding optimal methods for disease diagnosis, monitoring, and treatment. As a result of these challenges, patients with sarcoidosis face substantial delays in care and have reported psychological distress from the uncertainty they face throughout their care journeys. In complex diseases with multisystemic involvement, multidisciplinary care models can help provide diagnostic clarity and streamline care. Although experts and guidelines in the field advocate for multidisciplinary care to improve clinical management of sarcoidosis, limited primary literature describes implementation of these care models in sarcoidosis. In this review, we outline best practices and common challenges associated with establishing a multidisciplinary care team for sarcoidosis. We describe the development of the Johns Hopkins Sarcoidosis Center (JHSC) multidisciplinary team as well as the formation of the Johns Hopkins Sarcoidosis patient advisory board, which helps inform the team's goals and initiatives. Finally, we review the broader literature on multidisciplinary care models in sarcoidosis and interstitial lung disease, identifying areas for further study.

Sarcoidosis is an immune-mediated multisystem granulomatous disorder. Neurosarcoidosis (NS) accounts for 5% to 35% of cases. The diagnostic evaluation of NS can be a clinical challenge. Gadolinium-enhanced magnetic resonance imaging (MRI) is the gold standard to evaluate central nervous system NS. In almost all cases treatment is warranted. Although glucocorticoids remain the first-line therapy in patients with sarcoidosis, in NS timely initiation of second- or third-line treatment is strongly recommended. Of these, tumor necrosis factor-alpha inhibitors are the most promising. However, the treatment itself may be responsible for/associated with developing neurologic symptoms mimicking NS. Thus, it is important to consider the possibility of drug-induced neurologic symptoms in sarcoidosis.

Background: Sarcoidosis is a systemic disease characterized by granulomatous inflammation. Cardiac involvement is associated with increased morbidity. However, differences in clinical characteristics and outcomes based on initial sarcoidosis organ manifestation in patients with cardiac sarcoidosis (CS) have not been described. Methods: A retrospective cohort of 252 patients with CS at an urban, quaternary medical center was studied. Presentation, treatment and outcomes of de novo CS and prior ECS groups were compared. Survival free of primary composite outcome (left ventricular assist device implantation, orthotopic heart transplantation (OHT), or death) was assessed. Results: There were 124 de novo CS patients and 128 with prior ECS at time of CS diagnosis. De novo CS patients were younger at CS diagnosis (p = 0.020). De novo CS patients had a more advanced cardiac presentation: lower left ventricular ejection fraction (LVEF) (p < 0.001), more frequent sustained ventricular arrhythmias (VA) (p = 0.001), and complete heart block (p = 0.001). During follow-up, new VA (p < 0.001), ventricular tachycardia ablation (p < 0.001), and OHT (p = 0.003) were more common in the de novo CS group. Outcome free survival was significantly shorter for de novo CS patients (p = 0.005), with increased hazard of primary composite outcome (p = 0.034) and development of new VA (p = 0.027) when compared to ECS patients. Overall mortality was similar between groups. Conclusion: Patients presenting with CS as their first recognized organ manifestation of sarcoidosis have an increased risk of adverse cardiac outcomes as compared to those with a prior history of ECS. Improved awareness and diagnosis of CS is warranted for earlier recognition.

Neurosarcoidosis affects 5-26% of patients with systemic sarcoidosis and can be the first or only manifestation of the disease. Neurosarcoidosis can affect any part of the nervous system with heterogeneous clinical manifestations and imaging appearances that overlap with many infectious, inflammatory, and neoplastic disorders, making its diagnosis challenging. In the absence of a reliable biomarker to confirm neurosarcoidosis, the diagnosis is based on identifying a compatible clinical and imaging profile and identifying pathological evidence of non-caseating granulomas by biopsy of other organs or, if needed, in the nervous system, with the exclusion of other causes of granulomatous disease and possible neuroinfectious and neuroinflammatory disorder mimics. This review focuses on the clinical features of neurosarcoidosis with an emphasis on the recognition of the main presentation phenotypes and the initial diagnostic approach and differential diagnosis of neurosarcoidosis.

Facial palsy is a common neurologic concern and is the most common cranial neuropathy. The facial nerve contains motor, parasympathetic, and special sensory functions. The most common form of facial palsy is idiopathic (Bell's palsy). A classic presentation requires no further diagnostic measures, and generally improves with a course of corticosteroid and antiviral therapy. If the presentation is atypical, or concerning features are present, additional studies such as brain imaging and cerebrospinal fluid analysis may be indicated. Many conditions may present with facial weakness, either in isolation or with other neurologic signs (e.g., multiple cranial neuropathies). The most important ones to recognize include infections (Ramsay-Hunt syndrome associated with herpes zoster oticus, Lyme neuroborreliosis, and complications of otitis media and mastoiditis), inflammatory (demyelination, sarcoidosis, Miller-Fisher variant of Guillain-Barré syndrome), and neoplastic. No matter the cause, individuals may be at risk for corneal injury, and, if so, should have appropriate eye protection. Synkinesis may be a bothersome residual phenomenon in some individuals, but it has a variety of treatment options including neuromuscular re-education and rehabilitation, botulinum toxin chemodenervation, and surgical intervention.

Background:People with autoimmune or inflammatory conditions who take immunomodulatory/suppressive medications may have a higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. Objective:Assess whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterize pandemic-associated changes to care. Design:Longitudinal registry study. Participants:4666 individuals with autoimmune or inflammatory conditions followed by specialists in neurology, rheumatology, cardiology, pulmonology or gastroenterology at Johns Hopkins. Measurements:Periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. Results:A total of 265 (5.6%) developed COVID-19 over 9 months of follow-up (April-December 2020). Patient characteristics (age, race, comorbidity, medication exposure) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in multivariable models incorporating behavior and other potential confounders (OR: 1.43; 95%CI: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95%CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95%CI: 1.24, 2.28), and chronic kidney disease (OR: 1.76; 95%CI: 1.04, 2.97) were each associated with higher odds of COVID-19. Pandemic-related disruption to care was common. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions. Individuals experiencing changes to employment or income were at highest odds of care disruption. Limitations:Results may not be generalizable to all patients with autoimmune or inflammatory conditions. Information was self-reported. Conclusions:Exposure to glucocorticoids may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.

Abstract Background People with autoimmune or inflammatory conditions taking immunomodulatory/suppressive medications may have higher risk of novel coronavirus disease 2019 (COVID-19). Chronic disease care has also changed for many patients, with uncertain downstream consequences. Methods We included participants with autoimmune or inflammatory conditions followed by specialists at Johns Hopkins. Participants completed periodic surveys querying comorbidities, disease-modifying medications, exposures, COVID-19 testing and outcomes, social behaviors, and disruptions to healthcare. We assessed whether COVID-19 risk is higher among those on immunomodulating or suppressive agents and characterized pandemic-associated changes to care and mental health. Results In total, 265 (5.6%) developed COVID-19 over 9 months of follow-up (April–December 2020). Patient characteristics (age, race, comorbidity, medications) were associated with differences in social distancing behaviors during the pandemic. Glucocorticoid exposure was associated with higher odds of COVID-19 in models incorporating behavior and other potential confounders (odds ratio [OR]: 1.43; 95% confidence interval [CI]: 1.08, 1.89). Other medication classes were not associated with COVID-19 risk. Diabetes (OR: 1.72; 95% CI: 1.08, 2.73), cardiovascular disease (OR: 1.68; 95% CI: 1.24, 2.28), and kidney disease (OR: 1.76; 95% CI: 1.04, 2.97) were associated with higher odds of COVID-19. Of the 2156 reporting pre-pandemic utilization of infusion, mental health or rehabilitative services, 975 (45.2%) reported disruptions therein, which disproportionately affected individuals experiencing changes to employment or income. Conclusions Glucocorticoid exposure may increase risk of COVID-19 in people with autoimmune or inflammatory conditions. Disruption to healthcare and related services was common. Those with pandemic-related reduced income may be most vulnerable to care disruptions.

Abstract Neurosarcoidosis (NS) is an often severe, destructive manifestation with a likely under-reported prevalence of 5 to 15% of sarcoidosis cases, and in its active phase demands timely treatment intervention. Clinical signs and symptoms of NS are variable and wide-ranging, depending on anatomical involvement. Cranial nerve dysfunction, cerebrospinal parenchymal disease, aseptic meningitis, and leptomeningeal disease are the most commonly recognized manifestations. However, non-organ-specific potentially neurologically driven symptoms, such as fatigue, cognitive dysfunction, and small fiber neuropathy, appear frequently. Heterogeneous clinical presentations and absence of any single conclusive test or biomarker render NS, and sarcoidosis itself, a challenging definitive diagnosis. Clinical suspicion of NS warrants a thorough systemic and neurologic evaluation hopefully resulting in supportive extraneural physical exam and/or tissue findings. Treatment targets the severity of the manifestation, with careful discernment of whether NS reflects active potentially reversible inflammatory granulomatous disease versus inactive postinflammatory damage whereby functional impairment is unlikely to be pharmacologically responsive. Non-organ-specific symptoms are poorly understood, challenging in deciphering reversibility and often identified too late to respond to conventional immunosuppressive/pharmacological treatment. Physical therapy, coping strategies, and stress reduction may benefit patients with all disease activity levels of NS. This publication provides an approach to screening, diagnosis, disease activity discernment, and pharmacological as well as nonpharmacological treatment interventions to reduce disability and protect health-related quality of life in NS.