A graduate medical education (GME) quality improvement curriculum leads to improved knowledge and participation in high quality improvement projects by trainees.

BACKGROUND: There is increased awareness about the need for quality improvement (QI) education for trainees within clinical training programs. However, formal integration of a QI curriculum into graduate medical education (GME) remains a work-in-progress. We describe the creation and implementation of a novel, virtual QI curriculum complemented by virtual-based workshops. OBJECTIVE: To determine the impact of a GME QI curriculum on 1) trainee QI knowledge; 2) Quality of QI projects. METHODS: The GME Quality Improvement curriculum was transitioned to an optional formal curriculum in 2020. It is led by three faculty with expertise in QI training and education. The team developed four, web-based learning modules that focused on fundamental QI concepts. These modules are completed monthly and are paired with virtual workshops that facilitate applying learned QI concepts to project development. We evaluated the effectiveness of the curriculum by assessing participants' performance on knowledge-based quizzes before and after each online module. We used IBM SPSS (version 28), to conduct a two-sided paired samples t-test, comparing each post-session test scores with their corresponding pre-session scores. The alpha, or statistical threshold significance threshold, was 0.05. Additionally, two independent judges with expertise in QI evaluated the quality of the projects presented at the annual QI showcase using a standardized scoring rubric. The poster evaluation forms included 8 questions, rated on a scale from 1 to 5. Projects were graded into 4 quartiles (poor, fair, good, excellent). RESULTS: In the knowledge assessment quiz, the difference between the mean pre- and post-session quiz scores was statistically significant (p < 0.01). The average score of the quality of the projects presented at the annual showcase was 31, in the fourth quartile which was graded as "excellent" quality. CONCLUSION: A GME-led QI curriculum was effective in improving knowledge of QI concepts and producing high-quality scholarly projects.

Improved Accuracy/Completeness of EHR Race/Ethnicity Data: A Requisite Step to Address Disparities in Care.

Accurate and complete racial/ethnic data in the electronic health record are a requisite step to addressing disparities in neurologic care, and at local, regional, and national levels. The current data pertaining to the patients' race and ethnicity contained in the electronic health record are inadequate. This article outlines recommendations at the individual practice and electronic health record vendor level to improve documentation of race and ethnicity.

Bruton's Tyrosine Kinase Inhibitors: The Next Frontier of B-Cell-Targeted Therapies for Cancer, Autoimmune Disorders, and Multiple Sclerosis.

Bruton's tyrosine kinase (BTK) is an important protein belonging to the tyrosine kinase family that plays a key role in the intracellular signaling and proliferation, migration, and survival of normal and malignant B-lymphocytes and myeloid cells. Understanding the role of BTK in the B-cell signaling pathway has led to the development of BTK inhibitors (BTKi) as effective therapies for malignancies of myeloid origin and exploration as a promising therapeutic option for other cancers. Given its central function in B-cell receptor signaling, inhibition of BTK is an attractive approach for the treatment of a wide variety of autoimmune diseases that involve aberrant B-cell function including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). Here, we review the role of BTK in different cell signaling pathways, the development of BTKi in B-cell malignancies, and their emerging role in the treatment of MS and other autoimmune disorders.

Clinical and Neuroimaging Manifestations of Erdheim-Chester Disease: A Review.

Erdheim-Chester disease (ECD) is a rare disorder characterized by accumulation of non-Langerhans cell histiocytes in multiple organs. The clinical manifestations are protean and vary from asymptomatic focal disease to potentially fatal multisystem disorder. The commonest presentation is symmetric osterosclerotic lesions of lower extremity long bones; other organs, including cardiovascular, nervous, and endocrine system may be affected. Central nervous system involvement can occur in up to 50% cases and is associated with poor prognosis. The disease pathogenesis involves organ involvement secondary to histiocytic infiltration and systemic inflammation driven by Th1 cytokine activation. The recent discovery of activating mutations in proto-oncogene B-rapidly accelerated fibrosarcoma (BRAF) V600E and other genes involved in mitogen-activated protein kinase (MAPK) pathways has led to redefinition of ECD as a myeloid neoplastic disorder. The diagnosis requires histochemical and molecular analysis of histiocytes in tissue biopsies in patients with compatible clinical and imaging features. The treatment options include interferon-alpha, anakinra, and immunosuppressive therapies. Better understanding of disease pathogenesis has led to development of novel targeted and effective therapies including BRAF and MEK inhibitors. The rarity of the disease and variable clinical features and course often results in diagnostic errors and delays. Rare primary neurological presentation can occur mimicking CNS inflammatory, neoplastic, or demyelinating disorders. We report an unusual case of ECD presenting with progressive encephalopathy and ataxia along with multifocal brainstem and cerebellar lesions. A comprehensive review of clinical and neuroimaging features and immunohistochemical and molecular characteristic of ECD are presented along with review of neuroimaging findings in two previously reported cases.

Causes and Predictors of 30-Day Readmission in Elderly Patients With Delirium.

OBJECTIVE: To study 30-day readmission (30-DR) rate and predictors for readmission among elderly patients with delirium. METHODS: This was a retrospective observational cohort study of patients aged ≥65 years with discharge diagnosis of delirium identified from the Nationwide Readmission Database using common International Classification of Diseases, Ninth Revision, and Clinical Modification codes linked to delirium diagnosis. Multivariate logistic regression analyses were performed adjusting for stratified cluster design to identify patient/system-specific factors associated with 30-DR. RESULTS: Overall, the 30-DR rate was 17% (7,140 of 42,655 weighted index admissions). The common causes of readmission were systemic diseases (43%), infections (27%), and neurologic diseases (18%). Compared with initial hospitalization, readmission costs were higher ($11,442 vs $10,350, p < 0.0001) with a longer length of stay (6.6 vs 6.1 days, p < 0.0001). Independent predictors of readmission included discharge against medical advice (odds ratio [OR] 1.8, p < 0.0034), length of stay (OR 1.3, p < 0.0001), and chronic systemic diseases (anemia, OR 2.4, p < 0.0001, chronic renal failure OR 1.4, p < 0.0001, congestive heart failure OR 1.3, p < 0.0001, lung disease OR 1.2, p < 0.0004, and liver disease OR 1.2, p < 0.03). Private insurance was associated with a lower risk of readmission (OR 0.78, p < 0.02). CONCLUSIONS: The main predictors of readmission were chronic systemic diseases and discharge against medical advice. These data may help design directed clinical care pathways to optimize medical management and postdischarge care to reduce readmission rates.

Contemporary Neuroscience Core Curriculum for Medical Schools.

Medical students need to understand core neuroscience principles as a foundation for their required clinical experiences in neurology. In fact, they need a solid neuroscience foundation for their clinical experiences in all other medical disciplines also, because the nervous system plays such a critical role in the function of every organ system. Due to the rapid pace of neuroscience discoveries, it is unrealistic to expect students to master the entire field. It is also unnecessary, as students can expect to have ready access to electronic reference sources no matter where they practice. In the pre-clerkship phase of medical school, the focus should be on providing students with the foundational knowledge to use those resources effectively and interpret them correctly. This article describes an organizational framework for teaching the essential neuroscience background needed by all physicians. This is particularly germane at a time when many medical schools are re-assessing traditional practices and instituting curricular changes such as competency-based approaches, earlier clinical immersion, and increased emphasis on active learning. This article reviews factors that should be considered when developing the pre-clerkship neuroscience curriculum, including goals and objectives for the curriculum, the general topics to include, teaching and assessment methodology, who should direct the course, and the areas of expertise of faculty who might be enlisted as teachers or content experts. These guidelines were developed by a work group of experienced educators appointed by the Undergraduate Education Subcommittee (UES) of the American Academy of Neurology (AAN). They were then successively reviewed, edited, and approved by the entire UES, the AAN Education Committee, and the AAN Board of Directors.

Thirty-day readmissions in multiple sclerosis: An age and gender-based US national retrospective analysis.

BACKGROUND: Hospital readmission rate is an important indicator of the quality of care, healthcare economic burden, and post-discharge care. Multiple sclerosis (MS) is a potentially progressive neurological disease predominantly affecting young women. The natural history of the disease involves intermittent relapses and/or accrued baseline disability overtime especially in older patients contributing to frequent hospitalizations. The readmission metrics for patients with MS have not been studied. OBJECTIVE: To estimate nationwide 30-day readmission (30-DR) rate among patients hospitalized with MS and to study the predictors of readmission based on age and gender. METHODS: This was a retrospective observational cohort study of patients hospitalized with primary discharge diagnosis of MS using 2013 Nationwide Readmission Database (NRD). The cases were identified by ICD 9-CM code (340) linked to MS diagnosis. We used patient unique identifiers 'NRD visit link' to identify MS index hospitalizations and readmissions. Age (<40 vs. >40 years) and gender-based analyses were performed using multivariable logistic regression adjusting co-variables to identify the patient/system-specific factors associated with 30-DR. RESULTS: The overall 30-day readmission rate (30-DRR) was 10.2%. No gender difference was seen in the readmission rates (men 10.7% vs. women 10.1%, p = 0.56); higher readmission rates were observed in older patients (11.2% vs. 8.8%; p = 0.0055). However, readmission cost was higher in younger age group (≈ $ 12,586 vs. ≈$ 11,827; p = 0.62) and among women (≈$ 12,217 vs. ≈$ 11,746; p = 0.75). The common causes of 30-DR were MS exacerbation (42.5%), sepsis (13.7%) and respiratory complications (7.3%). The predictors of higher 30-DRR in younger patients were diabetes (OR 1.87, p = 0.02), intravenous immunoglobulin (IVIG) use (OR 3.64, p = 0.016), and discharge to a nursing facility (OR 1.66, p = 0.03), whereas in older age group, higher Charlson-Deyo Comorbidity Index (CCI) (OR 1.15, p = 0.0057), and plasma exchange (PLEX) (OR 2.38, p = 0.03) were predictive of higher readmission rate. The longer length of stay (LOS) during index admission (OR 1.81, p = 0.03) in men and higher CCI (OR 1.15, p = 0.007) and intravenous immunoglobulin (IVIG) use (OR 2.27, p = 0.04) in women increased the odds of readmission. CONCLUSION: The overall 30-day readmission rate among patients following hospitalization for MS was 10.2%. The readmission rate was higher in older (>40 years) patients. The common causes of readmission were MS exacerbation, respiratory complications, and sepsis. A higher systemic disease burden, longer length of stay, and treatment with IVIG and PLEX were associated with higher risk of readmission. The readmissions were associated with higher cost of care and longer LOS compared to index admissions highlighting the economic impact of readmissions. Future strategies to lower the risk of readmissions in patients with MS should focus on optimal management of medical co-morbidities and infections.

Clinical and MRI correlates of autoreactive antibodies in multiple sclerosis patients.

BACKGROUND: Autoreactive antibodies (ARAB) occur more frequently in patients with multiple sclerosis (MS) than in general population and the presence of these antibodies often causes uncertainty regarding the disease course, response to therapy and the diagnosis of MS. METHODS: Retrospective analyses of the ARAB, clinical and MRI data of a consecutive patient cohort of MS and clinically isolated syndrome (CIS) patients were conducted. The patients were evaluated for an extensive panel that included various subtypes of antiphospholipid antibody (APLA) including anti-phosphatidylethanolamine (APE), anti-phosphatidylserine (APS), anti-beta-2-glycoprotein-1 (ABGP), anti-cardiolipin (ACA), and several other ARAB such as antinuclear antibody (ANA), anti-neutrophilic cytoplasmic antibodies (ANCA), anti-thyroid peroxidase antibodies (ATA), anti-SS-A, and anti-SS-B antibodies. Quantitative MRI analysis was performed in a subgroup of MS patients measuring T2-lesion volume (LV), T1 black hole LV and brain parenchymal fraction (BPF). RESULTS: A total of 137 patients (mean age 44.7, 84% female) with either MS (n=111; age: mean 46.5+/-S.D. 10.3 years; disease duration: mean 13.0+/-S.D. 10.4 years; EDSS: mean 3.2+/-S.D. 1.9) or CIS (n=26; age: mean 37.7+/-S.D. 7.8 years; disease duration: mean 1.3+/-S.D. 1.1 years; EDSS: mean 1.0+/-S.D. 0.7) were enrolled. Among MS patients, 82 were RRMS, 26 SPMS, and 3 had PPMS. Seventy-seven (69%) of MS patients showed presence of one or more ARAB. The proportion of MS patients with APLA was 55% (61 patients); IgM subtype was most frequent. Co-occurrence of ACA and APE was more frequent in SPMS as compared to RRMS (15.4% vs. 1.2%, p=0.012). The proportion of CIS patients with ARAB was 75% with IgM subtype being the most frequent. However, the ARAB in majority of CIS patients (9 out of 14, 64%) were transient on repeated testing. In a subgroup of 62 MS patients, quantitative MRI analysis showed significantly higher T2-LV in patients with positive APLA (15.1 ml for APLA positive vs. 6.75 ml for APLA negative) after correcting for the disease duration (p=0.048). The patients with ATA also had significantly higher T2-LV after correction for disease duration (19.0 ml vs.8.5, p=0.044). CONCLUSIONS: ARAB were present in more than two thirds of MS and CIS patients although most of APLA in CIS were transient. The presence of APLA in MS patients was associated with higher T2-LV.

Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis.

BACKGROUND: Cognitive dysfunction is common in multiple sclerosis (MS). Correlations are reported between atrophy and neuropsychological test results. OBJECTIVE: To determine if neocortical volume would supplant or supplement third ventricular width and other magnetic resonance imaging measures when predicting neuropsychological impairment. DESIGN: Cross-sectional study. SETTING: University MS clinic. PARTICIPANTS: Seventy-seven patients with relapsing-remitting MS, 42 patients with secondary progressive MS, and 27 healthy control subjects. MAIN OUTCOME MEASURES: Brain atrophy and lesion burden measures were obtained in all patients. A subset of 82 patients and all controls underwent neuropsychological testing. RESULTS: Patients with secondary progressive MS had more atrophy than patients with relapsing-remitting MS and controls. Neocortical volume was significantly correlated with all neuropsychological measures, with r values ranging from 0.29 to 0.58. Third ventricular width was retained in most stepwise regression analyses predicting cognitive impairment in patients with MS and distinguishing secondary progressive from relapsing-remitting courses of MS. CONCLUSIONS: We confirm an association between neocortical volume and multiple cognitive domains in MS, although neocortical volume did not explain significantly more variance than other magnetic resonance imaging measures. Of the magnetic resonance imaging variables studied, third ventricular width was retained in most regression models.

An update on immunopathogenesis, diagnosis, and treatment of multiple sclerosis.

BACKGROUND: Multiple sclerosis is an acquired demyelinating disease of the central nervous system. It is the second most common cause of disability in adults in United States after head trauma. DISCUSSION: The etiology of MS is probably multifactorial, related to genetic, environmental, and several other factors. The pathogenesis is not fully understood but is believed to involve T-cell-mediated inflammation directed against myelin and other related proteins with a possible role for B cells. The McDonald criteria have been proposed and revised over the years to guide the diagnosis of MS and are based on clinical presentation and magnetic resonance imaging (MRI) of the brain and spinal cord to establish dissemination in time and space. The treatment of MS includes disease modification with immunomodulator drugs and symptom management to address the specific symptoms such as fatigue, spasticity, and pain. CONCLUSION: An update on etiology, pathogenesis, diagnosis, and immunomodulatory treatment of MS is presented.

Computed tomography angiographic correlates of early computed tomography signs in acute ischemic stroke.

BACKGROUND AND PURPOSE: Early computed tomography (CT) signs of stroke signify major arterial occlusion. CT angiogram (CTA) is useful in detecting major arterial occlusion and may help triaging patients for intra-arterial thrombolysis. The correlation between the early signs of stroke and arterial occlusion on CTA was studied. METHODS: Consecutive patients with suspected acute anterior circulation ischemic stroke presenting within 6 hours of symptom onset underwent noncontrast CT of the head followed by CTA. The scans were later reviewed for evidence of early signs of stroke on CT scan and intracranial arterial occlusion on CTA. RESULTS: Sixteen of 65 patients had arterial occlusion on CTA; 12 (75%) of these showed the early CT signs of stroke. All the early signs except M2 "dot" sign significantly correlated with middle cerebral artery (MCA) occlusion on CTA. Hyperdense MCA sign was the only independent predictor of a MCA occlusion. CONCLUSION: In a small sample, early CT signs of stroke strongly correlated with arterial occlusion, with hyperdense MCA sign being the most predictive of a MCA occlusion.

Leucine-rich glioma-inactivated protein 1 antibody encephalitis: A case report.

OBJECTIVE: To describe a case of leucine-rich glioma-inactivated protein 1 (LGI1) antibody-associated encephalitis. METHODS: The clinical and ancillary data and brain MRIs were gathered retrospectively by chart review. Relevant literature on similar cases was also reviewed. RESULTS: The diagnosis of LGI1 antibody-associated autoimmune encephalitis was based on the typical clinical presentation of seizures, psychiatric symptoms, and memory loss as well as negative diagnostic testing for cancer; the diagnosis was confirmed by positive LGI1 antibody. The patient responded favorably to treatment with IV immunoglobulin and continues to do well. CONCLUSION: LGI1 antibody-associated encephalitis has increasingly been recognized as a primary autoimmune disorder with good prognosis and response to treatment.

Glatiramer acetate recovers microscopic tissue damage in patients with multiple sclerosis. A case-control diffusion imaging study.

Traditional magnetic resonance imaging (MRI) techniques have contributed to the management of multiple sclerosis (MS) but are limited in their ability to detect neuronal damage. Advanced MRI metrics provide assessment of microscopic neuronal changes; however, few studies have examined the effects of MS therapies on these measures. This prospective, open-label, observational study evaluated the effect of subcutaneous glatiramer acetate (GA) 20mg/day on the 1- and 2-year changes in diffusion-weighted imaging (DWI) measures in patients with relapsing-remitting (RR) MS and in age- and sex-matched healthy controls (HC). Inclusion criteria were age 18-65, RR disease course, expanded disability status scale (EDSS) score ≤5.5 and disease duration<20 years. MS patients and HC underwent 1.5T MRI scans and clinical examinations at baseline and at 1- and 2-year follow-up. Nineteen RRMS patients and 16 HC completed the 1-year follow-up and 16 MS patients and 13 HC the 2-year follow-up of the study. In MS patients, treatment with GA promoted recovery of DWI mean parenchymal diffusivity (MPD) at year 1 (-7.1%, p=0.007) and at year 2 (-10.1%, p=0.028). The recovery of DWI MPD was significantly higher in MS patients compared to HC at year 1 (p=0.01) and year 2 (p<0.001). GA promoted recovery of DWI entropy at 2 years (-1.2%, p=0.018). No significant DWI MPD and entropy changes were observed in HC over the follow-up. No significant deterioration in magnetization transfer ratio occurred over the follow-up in MS patients and HC. Patients on GA and HC did not develop significant global or regional atrophy over 2 years. GA significantly improved microscopic tissue damage in the brain, as measured by DWI over the 1- and 2-year follow-up.

MRI characteristics of patients with antiphospholipid syndrome and multiple sclerosis.

MRI findings of primary anti-phospholipid antibody syndrome (PAPLS) are difficult to distinguish from those of multiple sclerosis (MS). Only a few previous studies have compared conventional and non-conventional MRI findings in MS and PAPLS patients. In addition, MRI differences between anti-phospholipid antibody (APLA) positive (+) and APLA negative (-) MS patients have not been reported. Therefore, the aim of this study was to investigate the differences in MRI measures among patients with PAPLS, MS and normal control (NC) subjects. We also explored non-conventional MRI measures in APLA+ and APLA- MS patients. Forty-nine (49) consecutive MS patients among whom 39 had relapsing-remitting (RR) and 10 secondary-progressive (SP) disease course, 30 patients with PAPLS and 49 NC were enrolled. Twenty-eight (28) MS patients were APLA+. MRI measures of T1- and T2-lesion volumes (LV) and brain atrophy, including fractions of whole brain (BPF), gray matter (GMF) and white matter (WMF), were evaluated. The magnetization transfer ratio (MTR) of T2- and T1-LVs and different normal-appearing brain tissue (NABT) compartments as well as diffusion-weighted imaging of whole brain mean parenchyma diffusivity (MPD) were obtained. MS patients differed significantly from NC in all MRI measures. PAPLS patients differed from NC in their T2-LV, in MTR measures and in MPD. When MS patients were compared to PAPLS patients, they showed significantly higher T2- and T1-LVs and T2-LV MTR, lower BPF and GMF and higher MPD. APLA+ RR and SPMS (all APLA+) patients showed significantly higher T2-LV, lower GMF, lower normal-appearing gray matter MTR and higher MPD when compared to APLA- patients. The results indicate that brain abnormalities can be detected in PAPLS patients with non-conventional MRI. MRI reveals more profound injury in patients with MS versus PAPLS. APLA mediates heterogeneous cerebral pathology that remains to be further investigated.

Validity of the Wisconsin Card Sorting and Delis-Kaplan Executive Function System (DKEFS) Sorting Tests in multiple sclerosis.

Multiple sclerosis (MS) is a disease of the central nervous system that causes cognitive impairment with a frequency of roughly 50%. While processing speed and memory defects are most commonly observed, a substantial number of patients also have deficiency in higher executive ability. Two tests, the Wisconsin Card Sorting Test (WCST) and the Sorting Test from the Delis-Kaplan Executive Function System (DKEFS), have been recommended for evaluation of neuropsychological impairment in MS. We investigated the validity of these tests in 111 MS patients and 46 age- and education-matched controls. MS patients performed more poorly on both measures, but only the DKEFS discriminated the groups after controlling for depression. Both tests were modestly or strongly correlated with MRI indices of brain atrophy or lesion burden and discriminated between employed and disabled patients. While both tests appear to have good validity in the MS population, the availability of alternative forms makes the DKEFS an attractive alternative to the WCST, as was suggested by a consensus panel.

Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS).

Cognitive impairment occurs in roughly 50% of patients with multiple sclerosis (MS). It is well known that processing speed and episodic memory deficits are the most common neuropsychological (NP) sequelae in this illness. Consensus has emerged about the specific tests that prove most helpful for routine monitoring of MS associated cognitive impairment. The purpose of this study was to examine the validity of the Minimal Assessment of Cognitive Function in MS (MACFIMS), a recommended battery based on the findings of an international conference held in 2001. We tested 291 MS patients and 56 healthy controls. Frequencies of impairment paralleled those reported in previous work for both individual cognitive domains and general impairment. All tests were impaired in the MS group, and distinguished relapsing-remitting (RR) from secondary progressive (SP) course. Principle components analysis showed a distinct episodic memory component. Most of the MACFIMS tests discriminated disabled from employed patients. However, in regression models accounting for all NP tests, those emphasizing verbal memory and executive function were most predictive of vocational status. We conclude that the MACFIMS is a valid approach to routine NP assessment of MS patients. Future work is planned to determine its psychometric properties in a longitudinal study.

Interferon-beta modulates bone-associated cytokines and osteoclast precursor activity in multiple sclerosis patients.

PURPOSE: Multiple sclerosis (MS) patients have a high risk of low bone density. The purpose of this study was to examine the molecular mechanisms potentially capable of modulating bone homeostasis in response to interferon-beta-1a (IFN-beta-1a) treatment and the focus was the bone-modulating system comprised of receptor activator of nuclear factor-kappaB (RANK), its ligand RANKL and its decoy receptor, osteoprotegerin (OPG). METHODS: In this open-label pharmacodynamic study, peripheral blood was obtained from relapsing-remitting MS patients just prior to and at multiple time points after intramuscular injection of 30 microg IFN-beta-1a. Samples were analysed for RANKL, tumour necrosis factor related apoptosis-inducing ligand (TRAIL), OPG and macrophage inflammatory protein-1 alpha/beta expression. Osteoclast precursor differentiation from peripheral blood cells of MS patients in the presence of exogenously added IFN-beta-1a was also assessed. Additionally, the changes in plasma levels of osteocalcin and the C-telopeptides after 1 year of treatment were measured as surrogate markers of bone formation and degradation, respectively. RESULTS: IFN-beta-1a treatment modulated RANKL and OPG in a selective, time-dependent manner. The levels of OPG protein decreased 25% at the 8-h time point, then increased 43% at the 24-h time point. The levels of free RANKL reached a maximum at the 8-h time point. Increases in the levels of macrophage inflammatory protein-1beta (MIP-1beta), a chemokine that increases osteolysis, were observed. The levels of the bone formation marker, osteocalcin, were lower in MS patients compared to controls and increased after one year of treatment. Ex vivo treatment of peripheral blood lymphocytes with IFN-beta resulted in a marked reduction of osteoclast-like cells in the presence of RANKL and macrophage colony stimulating factor. CONCLUSIONS: IFN-beta treatment induces complex, specific and time-dependent changes in multiple proteins and mRNAs related to bone homeostasis in MS patients.