A Case of Tizanidine Withdrawal Syndrome: Features and Management in the Emergency Department.

Anxiety medications, muscle relaxants, and sleeping pills have the potential to cause complications, side effects, and withdrawal symptoms if not prescribed and managed appropriately. Tizanidine, a short-acting muscle relaxant, acts on central alpha-2-adrenergic receptors to reduce spasticity. However, abrupt withdrawal of tizanidine can lead to symptoms such as hypertension, reflex tachycardia, hypertonicity, and anxiety as a result of high adrenergic activity. Few cases have been reported on tizanidine withdrawal syndrome. Here, we are presenting a rare occurrence of tizanidine withdrawal syndrome in a patient presenting to the emergency department with vomiting, generalized tremor, dysthermia, hypertension, and tachycardia. We discuss the management approach used to stabilize the patient and successfully control the symptoms by reintroducing a low therapeutic dose of tizanidine.

The Mysterious Association Between Atrial Fibrillation and Cancer: A Literature Review.

Atrial fibrillation (AF) is a prevalent cardiac dysrhythmia, particularly affecting older adults, with its prevalence rising due to the aging population. AF is linked to several adverse outcomes, including embolic stroke, heart failure, and cancer. The association between AF and cancer is intricate and not yet fully understood. Studies suggest that the rise in cancer survivorship, along with cancer treatments, may contribute to an increased incidence of AF among cancer patients. This literature review was conducted using various databases to explore the relationship between AF and cancer. Studies from 2002 to 2022 were included, focusing on the adult population. Independent authors evaluated and validated the studies, ensuring rigorous methodology. The connection between AF and cancer appears multifaceted. There is evidence of increased cancer incidence within the first few months following an AF diagnosis, with potential shared risk factors like age, obesity, and smoking. Medications used to treat AF, notably amiodarone, were associated with increased cancer risk. Colon cancer risk might be linked to anticoagulation-induced gastrointestinal bleeding. It remains uncertain whether AF diagnosis leads to early cancer detection or if cancer itself contributes to AF development. The complex interplay between AF and cancer involves shared risk factors, potential medication-related influences, and unclear causal directions. The intricacies of this relationship warrant further research to clarify the underlying mechanisms and potential interactions. A comprehensive meta-analysis could provide more insights into this intriguing association and guide future clinical interventions.

The Role of Automated External Defibrillator Use in the Out-of-Hospital Cardiac Arrest Survival Rate and Outcome: A Systematic Review.

Out-of-hospital cardiac arrest (OHCA) remains a significant cause of death. The chance of survival significantly increases when immediate defibrillation with an on-site automated external defibrillator (AED) is available. Our aim is to systematically evaluate the impact of public access defibrillators (PAD) on the outcomes of outpatient cardiac arrest. We conducted a systematic review of the data from global studies on the role of bystander and emergency medical service (EMS) interventions, primarily focusing on the usage of AEDs, during OHCA events. The results highlight the critical significance of PADs in improving survival outcomes in OHCA settings. The majority of OHCA incidents occurred in private residences, but public spaces such as schools and airports had better outcomes, likely due to AED accessibility and trained individuals. Placing AEDs in public areas, especially high-risk zones, can boost survival chances. Timely defibrillation, particularly by bystanders, correlated with better survival and neurological conditions. The review emphasizes the importance of widespread cardiopulmonary resuscitation (CPR) and AED training, strategic AED placement, and continuous monitoring of interventions and outcomes to enhance survival rates and neurological recovery after OHCAs. This systematic review showed that bystander interventions, including CPR and AED usage, significantly increased the survival rate. Overall, immediate response and accessibility to AEDs in public areas can significantly improve outcomes in OHCA events.

Exploring Methylene Blue and Its Derivatives in Alzheimer's Treatment: A Comprehensive Review of Randomized Control Trials.

Methylene blue (MB) and its compounds are investigated for their potential benefits in the management of Alzheimer's disease (AD). AD is a widely seen neuropathological disorder characterized by the gradual decline of cognitive abilities, ultimately leading to the development of severe dementia. It is anticipated that there will be a significant increase in the prevalence of AD due to the aging population. Histopathologically, AD is distinguished by the presence of intracellular tangles of neurofibrillary tissues (NFTs) and extracellular amyloid plaques within the brain. MB is a thiophenazine dye with FDA approval for treating several illnesses. Its ease in crossing the blood-brain barrier and potential therapeutic use in central nervous system diseases have increased interest in its application for treating AD. The literature review includes randomized clinical trials investigating MB's potential benefits in treating AD. The findings of the studies indicate that the administration of MB has demonstrated enhancements in cognitive function, reductions in the accumulation of plaques containing beta-amyloid, improvements in memory and cognitive function in animal subjects, and possesses antioxidant properties that can mitigate oxidative stress and inflammation within the brain. This review evaluates the modern and latest research on the application of MB for treating AD.

A Combination Therapy in a Rare Case of Adult-Onset Autoimmune Enteropathy.

Autoimmune enteropathy (AIE) is a differential diagnosis of incurable chronic diarrhea, malnutrition, and weight loss. This type of diarrhea is associated with protein enteropathy that usually affects the small intestine. The diagnosis of AIE is based on chronic diarrhea, malabsorption, specific histological result, antibodies against enterocytes, and excluding similar conditions. In this case, a 28-year-old female presented with diarrhea, lower limb edema, weight loss, and electrolyte imbalances. Endoscopic examination demonstrated duodenal villous atrophy, while duodenal biopsies revealed villous blunting, scattered intraepithelial lymphocytes, and crypt hyperplasia in the lamina propria. The patient was treated with immunosuppressive treatment including methylprednisolone and azathioprine, achieving clinical remission.

Varicella-Zoster Virus Myocarditis: Early Clinical Diagnosis and Outcome.

Varicella-zoster virus (VZV) is a viral infection that causes chickenpox and shingles. Although it is usually self-limiting, it can lead to severe complications, especially in pediatric and immunocompromised patients. VZV was first discovered as a cause of myocarditis in 1953. In this review article, we aim to investigate the early clinical diagnosis of myocarditis in VZV infections and the efficacy of the VZV vaccine in preventing myocarditis. The literature search was done using PubMed, Google Scholar, and Sci-Hub databases. A high VZV mortality rate was noted among adults, infants, and immunocompromised patients. The early diagnosis and treatment of VZV myocarditis can reduce mortality.

Does Vitamin D Have a Role in Diabetes?

Vitamin D, a fat-soluble vitamin, acts in the calcium and phosphorus metabolism in its active form (1,25-dihydroxy vitamin D). It may help prevent and treat autoimmune diseases, including diabetes mellitus. Diabetes has become a significant global health issue with a rising incidence and prevalence. A recent focus has been on vitamin D supplementation as part of efforts to discover novel ways to prevent and treat diabetes. Most evidence points to the vitamin D receptors (VDRS) gene in both types of diabetes. The main objective of this study is to analyze how vitamin D affects both type 1 and type 2 diabetes. In this literature review, we searched the PubMed and Google Scholar databases to collect related articles from 13 papers of different study designs. We found a significant association between vitamin D deficiency and type 1 and type 2 diabetes development. It has been shown that vitamin D supplements have a promising effect in reducing glycated hemoglobin (HbA1c) in patients with type 1 diabetes, with no significant impact on the incidence or improvement of type 2 diabetes. Patients with diabetes and people at high risk of diabetes need the appropriate amount of vitamin D; therefore, regular testing and vitamin D supplementation are advised for the management and prevention of diabetes. Additional randomized studies with bigger sample sizes and longer-term trials are required to fully explore the benefits of vitamin D supplementation in patients with type 1 and type 2 diabetes.

Isotretinoin-Induced Inflammatory Bowel Disease: Is There a Real Association?

Inflammatory bowel disease (IBD) is an autoimmune inflammatory disorder that affects the gastrointestinal system with an annual increase in incidence and prevalence worldwide. While the precise cause behind IBD remains obscured, certain genetic susceptibilities, in addition to environmental factors, may trigger the stimulation of the immunoinflammatory system against the gastrointestinal system, eventually resulting in IBD. Furthermore, certain medications have been proposed to increase the risk of developing IBD, such as isotretinoin. IBD has been reported during the post-marketing phase of isotretinoin. Subsequently, IBD development was added as a potential gastrointestinal adverse effect of isotretinoin. This review article aims to evaluate the possible association between isotretinoin exposure and the development of inflammatory bowel disease. We enrolled 32 relevant studies, including case reports, case-control, and cohort studies. The results were critically analyzed and reviewed by independent authors to answer the research question and achieve the primary endpoint.

Brain Health: Attitudes towards Technology Adoption in Older Adults.

(1) Background: There is increasing scholarly support for the notion that properly implemented and used, technology can be of substantial benefit for older adults. Use of technology has been associated with improved self-rating of health and fewer chronic conditions. Use of technology such as handheld devices by older adults has the potential to improve engagement and promote cognitive and physical health. However, although, literature suggests some willingness by older adults to use technology, simultaneously there are reports of a more cautious attitude to its adoption. Our objective was to determine the opinions towards information technologies, with special reference to brain health, in healthy older adults either fully retired or still working in some capacity including older adult workers and retired adults living in an independent elderly living community. We were especially interested in further our understanding of factors that may play a role in technology adoption and its relevance to addressing health related issues in this population; (2) Methods: Two focus groups were conducted in an inner-city community. Participants were older adults with an interest in their general health and prevention of cognitive decline. They were asked to discuss their perceptions of and preferences for the use of technology. Transcripts were coded for thematic analysis; (3) Results: Seven common themes emerged from the focus group interviews: physical health, cognitive health, social engagement, organizing information, desire to learn new technology, advancing technology, and privacy/security; and (4) Conclusions: This study suggests that in order to promote the use of technology in older adults, one needs to consider wider contextual issues, not only device design per se, but the older adult's rationale for using technology and their socio-ecological context.

MRI characteristics of familial and sporadic multiple sclerosis patients.

PURPOSE: To investigate the MRI characteristics in a large cohort of multiple sclerosis (MS) patients with and without a family history of MS. METHODS: Enrolled in this prospective study were 758 consecutive MS patients (mean age 46.2 ± 10.1 years, disease duration 13.6 ± 9.2 years and EDSS 3.4 ± 2.1), of whom 477 had relapsing-remitting, 222 secondary-progressive, and 30 primary-progressive disease courses and 29 had clinically isolated syndrome. One hundred and ninety-six patients (25.9%) had a positive family history of MS. Patients were assessed using measurements of lesions, brain atrophy, magnetization transfer ratio (MTR) and diffusion-weighted imaging. RESULTS: The familial MS group had greater T1-lesion volume (p=0.009) and a trend for lower MTR of T1-lesion volume (p=0.047) than the sporadic MS group. No clinical differences were found between familial versus sporadic group, or by a degree of affected relative subgroups. CONCLUSIONS: While familial MS was associated with more severe T1-lesion volume and its MTR characteristics, there were no clinical status differences between familial and sporadic MS patients. Therefore, a better understanding of the genetic and/or epigenetic influences causing these differences can advance the understanding and management of MS.

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.

Extent of cerebellum, subcortical and cortical atrophy in patients with MS: a case-control study.

Cortical and subcortical atrophy occurs in multiple sclerosis (MS) and relates to clinical outcomes. FreeSurfer, a voxel-based automated software for brain reconstruction was used to investigate the extent of subcortical and cortical atrophy in 71 MS and 17 clinically isolated syndrome (CIS) patients, and 38 normal controls (NC), and to relate group differences to disease type and severity. Segmentation was performed on 3D SPGR T1-weighted MRI 1.5T images. Region-specific subcortical tissue volumes were calculated in mm(3) and cortical thickness in mm. Logistic regression and general linear model analyses, adjusted for age and intracranial volume, examined differences between NC, MS and CIS patients and disease subtypes. The MS group was characterized by significantly lower volumes of thalamus (left and right p<0.0001), left inferior lateral ventricle, third ventricle (p<0.0001), ventral diencephalon, pallidum and putamen bilaterally, as well as of right accumbens and brainstem with corresponding bilateral increase in volumes of lateral ventricles (p<0.01). Focal cortical atrophy areas in the thalamus, inferior parietal lobule of left hemisphere and in right precuneus were also significant in the MS sample. Versus CIS patients, RR or progressive MS patients showed significantly lower volumes of subcortical regions and cortical thinning. Hippocampal atrophy appeared only in advanced disease stages. Cerebellum WM volumes were significantly lower in MS and CIS patients vs. NC. Subcortical and cortical atrophy correlated with higher disability as measured by EDSS. This study confirmed selective deep gray matter atrophy (mostly thalamic), revealed cerebellum WM atrophy from the earliest clinical stages, and showed that cortical thinning advances with disease progression.

Use of perfusion- and diffusion-weighted imaging in differential diagnosis of acute and chronic ischemic stroke and multiple sclerosis.

OBJECTIVE: To investigate differences in lesions and surrounding normal appearing white matter (NAWM) by perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) in patients with acute and chronic ischemic stroke and multiple sclerosis (MS). METHODS: Study subjects included 45 MS patients, 22 patients with acute ischemic stroke and 20 patients with chronic ischemic stroke. All subjects underwent T2-weighted imaging (WI), flair attenuated inversion recovery (FLAIR), DWI and dynamic contrast enhanced PWI. Apparent diffusion coefficient (ADC) and mean transit time (MTT) maps were generated and values were calculated in the acute and chronic ischemic and demyelinating lesions, and in NAWM for distances of 5, 10 and 15 mm. Fifty-three acute ischemic and 33 acute demyelinating lesions, and 775 chronic ischemic and 998 chronic demyelinating lesions, were examined. Univariate, multivariate and data mining analyses were used to examine the feasibility of a prediction model between different lesion types. Correctly and incorrectly classified lesions, true positive (TP), false positive (FP) and precision rates were calculated. RESULTS: Patients with acute ischemic lesions presented more prolonged mean MTT values in lesions (p=0.002) and surrounding NAWM for distances of 5, 10 and 15 mm (all p<0.0001) than those with acute demyelinating lesions. In multinomial logistic regression analysis, 65 of 86 acute lesions were correctly classified (75.6%). The TP rates were 81.1% for acute ischemic lesions and 66.7% for acute demyelinating lesions. The FP rates were 33.3% for acute ischemic and 18.9% for acute demyelinating lesions. The precision was 79.6% for classification of acute ischemic lesions and 68.8% for prediction of acute demyelinating lesions. The logistic model tree decision algorithm revealed that prolonged MTT of surrounding NAWM for a distance of 15 mm (> or =7459.2 ms) was the best classifier of acute ischemic versus acute demyelinating lesions. Patients with chronic ischemic lesions presented higher mean ADC (p<0.0001) and prolonged MTT (p=0.013) in lesions, and in surrounding NAWM for distances of 5, 10 and 15 mm (all p<0.0001), compared to the patients with chronic demyelinating lesions. Data mining analyses did not show reliable predictability for correctly discerning between chronic ischemic and chronic demyelinating lesions. The precision was 56.7% for classification of chronic ischemic and 58.9% for prediction of chronic demyelinating lesions. DISCUSSION: We found prolonged MTT values in lesions and surrounding NAWM of patients with acute and chronic ischemic stroke when compared to MS patients. The use of PWI is a promising tool for differential diagnosis between acute ischemic and acute demyelinating lesions. The results of this study contribute to a better understanding of the extent of hemodynamic abnormalities in lesions and surrounding NAWM in patients with MS.

Application of hidden Markov random field approach for quantification of perfusion/diffusion mismatch in acute ischemic stroke.

The perfusion/diffusion 'mismatch model' in acute ischemic stroke provides the potential to more accurately understand the consequences of thrombolytic therapy on an individual patient basis. Few methods exist to quantify mismatch extent (ischemic penumbra) and none have shown a robust ability to predict infarcted tissue outcome. Hidden Markov random field (HMRF) approaches have been used successfully in many other applications. The aim of the study was to develop a method for rapid and reliable identification and quantification of perfusion/diffusion mismatch using an HMRF approach. An HMRF model was used in combination with automated contralateral identification to segment normal tissue from non-infarcted tissue with perfusion abnormality. The infarct was used as a seed point to initialize segmentation, along with the contralateral mirror tissue. The two seeds were then allowed to compete for ownership of all unclassified tissue. In addition, a novel method was presented for quantifying tissue salvageability by weighting the volume with the degree of hypoperfusion, allowing the penumbra voxels to contribute unequal potential damage estimates. Simulated and in vivo datasets were processed and compared with results from a conventional thresholding approach. Both simulated and in vivo experiments demonstrated a dramatic improvement in accuracy with the proposed technique. For the simulated dataset, the mean absolute error decreased from 171.9% with conventional thresholding to 2.9% for the delay-weighted HMRF approach. For the in vivo dataset, the mean absolute error decreased from 564.6% for thresholding to 34.2% for the delay-weighted HMRF approach. The described method represents a significant improvement over thresholding techniques.

Cortical atrophy and personality in multiple sclerosis.

Although the cognitive disorder of multiple sclerosis (MS) is well characterized, little is known about personality changes that may occur in this disease. There are reliable personality tests available for research in neurological disease, based on the well-known Five Factor Model. Preliminary research suggests that cognitively impaired MS patients exhibit elevation in Neuroticism, and diminution in Extraversion, Agreeableness, and Conscientiousness, as do patients with Alzheimer's disease. We predicted that these characteristics would be associated with lower neocortical volume. We studied 44 patients using brain MRI and the NEO Five-Factor Inventory. Regression models controlling for T2 lesion volume, depression, and cognitive dysfunction revealed significant correlation between cortical atrophy and reduction in Extraversion and Conscientiousness. Discrepancies between patient- and informant-reports were found, and overreporting of high Openness and Conscientiousness among patients was associated with lower neocortical volume. A final regression model accounting for depression, cognitive function, and personality accounted for 38% of the variance in neocortical volume. These findings suggest that cortical atrophy in MS is associated with adverse impact on personality, although longitudinal research is needed to test this hypothesis.

Preservation of gray matter volume in multiple sclerosis patients with the Met allele of the rs6265 (Val66Met) SNP of brain-derived neurotrophic factor.

To investigate the association of the rs6265 (Val66Met) single nucleotide polymorphism (SNP) of brain-derived neurotrophic factor (BDNF) with brain morphometry and functional status as measured by quantitative magnetic resonance imaging (MRI) and neurocognitive testing in multiple sclerosis (MS) patients. BDNF is released by neurons and by immune cells in MS brain. The rs6265 SNP variation of BDNF causes substitution of valine (Val) for methionine (Met) and interferes with activity-dependent BDNF secretion. A total of 209 treated MS patients (161 females; 48 males) underwent clinical brain MRI and were genotyped for the BDNF rs6265 Val66Met SNP. A subset of 108 patients had neurocognitive testing for processing speed, memory and executive function. The MRI measurements included T2 and T1-lesion volume (LV); normalized brain volume measures of whole brain (WB) volume, white and gray matter volume (NWMV and NGMV) and the diffusion-weighted imaging measure of WB mean parenchyma diffusivity (MPD). The Met66 allele status was positively associated with NGMV (P = 0.015, standardized beta = 0.15) and negatively associated with T2-LV (P = 0.041, standardized beta = -0.14). There were no significant associations between Met66 allele status and T1-LV, NWMV or MPD. On the Paced Serial Addition Test (PASAT), a trend (P = 0.057) favoring the Met66 allele group was observed. There were no significant associations between Met66 allele status and other neurocognitive measures. The BDNF Met66 allele is associated with lower damage as evidenced by measurement of NGMV and T2-LV in MS patients.

Immune cell BDNF secretion is associated with white matter volume in multiple sclerosis.

PURPOSE: To investigate the relationship between immune cell secretion of brain-derived neurotrophic factor (BDNF) with clinical and MRI variables in multiple sclerosis (MS) patients. BACKGROUND: BDNF exerts beneficial effects on neuronal growth and repair and is secreted by both neurons and immune cells. Consequently, it may mediate the crosstalk between the immune system and CNS in autoimmune diseases such as MS. METHODS: Fifty-two relapsing MS patients (41 females, age: 48.8+/-6.6 years, disease duration: 12.7+/-8.4 years) were enrolled. Clinical and MRI measurements (including, T1-, T2- and contrast-enhancing (CE) lesion volumes (LVs); normalized measures of whole brain, white matter (WM) and gray matter (GM) volumes; diffusion weighted imaging measure of mean whole brain (WB) parenchyma diffusivity and magnetization transfer ratio (MTR) measures were obtained. RESULTS: Immune cell BDNF secretion after anti-CD3 plus anti-CD28 stimulation was positively associated with increased CE-LV (p=0.026). The MTR of CE-LV and normal-appearing (NA) WM (NAWM) were negatively associated with immune cell BDNF secretion after anti-CD3 plus anti-CD28 stimulation. Immune cell BDNF secretion after anti-CD3 plus anti-CD28 was positively associated with higher WM volume (p=0.027). Immune cell BDNF secretion after anti-CD3 plus anti-CD28 stimulation was decreased with increasing disease duration (p=0.031). The BDNF secretion was independent of the BDNF Val66Met (dBSNP ID: rs6265) SNP genotype. CONCLUSIONS: Immune cell BDNF secretion is associated with the sites of higher inflammatory activity as evidenced by CE lesions and may represent an important factor associated with the WM volume of patients with MS.

Independent contributions of cortical gray matter atrophy and ventricle enlargement for predicting neuropsychological impairment in multiple sclerosis.

The primary goal of this study was to investigate associations between regional gray matter (GM) atrophy and neuropsychological function in multiple sclerosis (MS), while accounting for the influence of central brain atrophy (i.e. third ventricle enlargement). Using a cross-sectional design, we studied 59 MS patients with brain MRI and neuropsychological testing. Regional gray matter fractions (rGMFs) were calculated from MRI images for 11 homologous brain areas using the semiautomatic brain region extraction (SABRE) technique. Neuropsychological testing followed consensus panel guidelines and included tests emphasizing episodic memory, working memory and processing speed. The analytic approach was stepwise linear regression, with forward selection and p<0.05 threshold for significance. Consistent with previous research, there were significant correlations between third ventricle width and neuropsychological tests. Stepwise linear regression analyses controlling for third ventricle width retained rGMFs obtained from specific regions within the prefrontal cortex. Left frontal atrophy was associated with tests emphasizing auditory/verbal memory. Right frontal atrophy was associated with impairment in visual episodic and working memory. For the first time, we show an independent relationship between cortical atrophy and cognitive impairment after accounting for the effects of central atrophy.

Interferon inhibitory activity in patients with multiple sclerosis.

BACKGROUND: Interferon inhibitory activity (IIA) is a logical candidate for explaining neutralizing antibody-negative partial responsiveness to interferon beta in multiple sclerosis (MS), but its role has not been evaluated. OBJECTIVE: To investigate the role of IIA and soluble interferon-alpha/beta receptor (sIFNR) in determining response of patients with MS to interferon beta therapy. DESIGN: Parallel-group, open-label study. SETTING: Baird Multiple Sclerosis Center, Buffalo, NY. Patients Blood was obtained before and 24 hours after injection of interferon beta-1a from 38 anti-interferon beta neutralizing antibody-negative patients with relapsing-remitting MS and 16 untreated healthy controls. On the basis of clinical parameters of response to interferon beta therapy, the patients were divided into stable or good-responder (n = 20) and active or partial-responder (n = 18) groups. MAIN OUTCOME MEASURES: Quantitative analyses of magnetic resonance imaging were obtained; the IIA and sIFNR levels were measured using bioassay and enzyme-linked immunosorbent assay, respectively. RESULTS: The IIA and sIFNR levels were elevated in MS patients compared with controls (P<.001). The IIA levels were higher in active or partial responders compared with stable or good responders (P<.001); the sIFNR levels were not different between groups. The Extended Disability Status Score and T2 lesion volumes were higher in the active or partial-responder group compared with the stable or good-responder group. Interferon beta-1a did not have short-term effects on the IIA and sIFNR levels. In univariate general linear model and stepwise regression analyses, IIA levels were associated with T2 lesion volume. CONCLUSION: The levels of IIA are associated with increased MS disease activity and with responsiveness to interferon beta therapy in anti-interferon beta neutralizing antibody-negative MS patients.

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.