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Biomedical subjects

Fred D Lublin

Publications and source records attributed to Fred D Lublin.

9 recordsLinked to original sources
PubMed2024

Polygenic liability for anxiety in association with comorbid anxiety in multiple sclerosis.

OBJECTIVE: Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2-item scale polygenic score with anxiety in MS. METHODS: Using a case-control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview-diagnosed, and lifetime self-report physician-diagnosed. The polygenic score was computed for current anxiety symptoms using summary statistics from a previous genome-wide association study and was tested using regression. RESULTS: A total of 71,343 individuals of European genetic ancestry were used: Canada (n = 334; 212 MS), UK Biobank (n = 70,431; 1,390 MS), and the USA (n = 578 MS). Meta-analyses identified that in MS, each 1-SD increase in the polygenic score was associated with ~50% increased odds of comorbid moderate anxious symptoms compared to those with less than moderate anxious symptoms (OR: 1.47, 95% CI: 1.09-1.99). We found a similar direction of effects in the other measures. MS had a similar anxiety genetic burden compared to people with anxiety as the index disease. INTERPRETATION: Higher genetic burden for anxiety was associated with significantly increased odds of moderate anxious symptoms in MS of European genetic ancestry which did not differ from those with anxiety and no comorbid immune disease. This study suggests a genetic basis for anxiety in MS.

Humans↗
PubMed2004

Longitudinal analyses of the effects of neutralizing antibodies on interferon beta-1b in relapsing-remitting multiple sclerosis.

We have analysed data on exacerbation rates, Expanded Disability Status Scale (EDSS) scores, and lesion burdens using the results of two neutralizing antibody (NAB) assays (CPE and MxA) from the pivotal relapsing-remitting multiple sclerosis (MS) trial of interferon beta-1b (IFNB) with a longitudinal approach, where the influence of NABs in individual patients is assessed by comparing responses during NAB-positive and NAB-negative periods. There are apparent influences on exacerbation rate related to dose of IFNB, titer level, and duration of positivity. With the MxA assay, exacerbation rates after switching to NAB-positive status are estimated to be 28% higher [95% confidence interval (CI): (-15%, 92%)] and -2% higher [95% CI: (-21%, 21%)] on the low- and high-dose IFNB arms, respectively. When compared with all NAB-negative periods, exacerbation rates during NAB-positive periods are estimated to be 29% higher [95% CI: (0%, 67%)] and 18% higher [95% CI: (0%, 40%)] on the low- and high-dose IFNB arms, respectively. When NAB-positive patients again become NAB-negative, no evidence of increased exacerbation rates could then be demonstrated. More detailed exploratory analyses indicate that the effects are most evident in the approximately 20% of patients developing high titers. In these patients, the influence of NABs may be self-limited, as titers often diminish or NABs become undetectable with time.

Adjuvants, Immunologic↗
PubMed2003

Effect of relapses on development of residual deficit in multiple sclerosis.

OBJECTIVE: To determine the percentage of patients with residual deficits following multiple sclerosis (MS) exacerbations and the magnitude of those deficits using a database of pooled placebo patients from clinical trials. METHODS: A database of patients assigned to the placebo group in several randomized clinical trials was queried to determine those patients with Expanded Disability Status Scale (EDSS) and Scripps Neurologic Rating Scale assessments prior to, at the time of, and after an acute exacerbation of MS. The extent of deficit present at these time points was compared to determine the acute effect of exacerbations and the degree of persistent disability. RESULTS: Forty-two percent of patients had residual deficit of at least 0.5 and 28% had residual of >or=1.0 EDSS units, at an average of 64 days after an exacerbation. The results were reproduced across subsequent exacerbations and were sustained over time. The subgroup of patients with measurable change in EDSS during the exacerbation had more extensive residual impairment on the follow-up visits. Similar results were seen when the Scripps score was examined. CONCLUSION: MS exacerbations produce a measurable and sustained effect on disability.

Adolescent↗
PubMed2003

Magnetic resonance imaging of meningoradiculomyelitis in early disseminated Lyme disease.

Lyme disease, a multisystem illness caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. There are 3 clinical stages of Lyme disease: early localized, early disseminated, and late persistent disease. Neuroborreliosis, infection of the nervous system by B. burgdorferi, may occur during early disseminated or late persistent disease. Spinal cord involvement in early disseminated disease is extremely rare. In patients with early disseminated neuroborreliosis, treatment with antibiotics often leads to rapid recovery and may prevent further complications of Lyme disease. The authors present the clinical and radiographic findings, both before and after treatment, in a patient with meningoradiculomyelitis due to early disseminated Lyme disease.

Adult↗
PubMed2002

The diagnosis of multiple sclerosis.

Multiple sclerosis is a clinical diagnosis and as such requires the integration of historical information with neurological examination and relevant laboratory and paraclinical tools, such as magnetic resonance imaging. A recent revision of the diagnostic guidelines for multiple sclerosis has been published that formalizes the use of magnetic resonance imaging information along with the clinical picture. These new guidelines should provide for the earlier and easier diagnosis of multiple sclerosis, useful for both clinical trials and neurological practice.

Central Nervous System↗
PubMed2002

Quantitative functional MR imaging of the visual cortex at 1.5 T as a function of luminance contrast in healthy volunteers and patients with multiple sclerosis.

BACKGROUND AND PURPOSE: In patients with multiple sclerosis (MS), a few preliminary functional MR (fMR) imaging studies of the visual cortex reveal information about magnitude differences between healthy individuals and patients with MS at only a single luminance level. We therefore investigated whether varying luminance contrast levels can help uncover subtle changes in fMR imaging characteristics of the visual cortex in healthy volunteers and patients with MS. METHODS: Blood oxygenation level-dependent fMR imaging signal changes in the primary visual cortex were examined as a function of luminance contrast at 1.5 T in 10 healthy volunteers and nine patients with MS. Ten axial sections through the calcarine fissure were obtained with an echo-planar T2*-weighted imaging sequence (4000/54/1 [TR/TE/excitation]; field of view, 220 mm; voxel size, 1.72 x 1.72 x 5 mm). The imaging series consisted of an alternating 20-second rest epoch (black screen) with a 20-second activation epoch (flickering checkerboard) repeated six times. Each imaging series used a graded increase of eight luminance contrast levels. A paired t test between rest and activation images was used to analyze significant (P <.001) contiguous voxels in the region of interest (primary visual cortex). RESULTS: A progressive increase in fMR imaging activation across all luminance contrast levels in healthy controls and patients with MS was shown. The patients with MS had a significantly lower magnitude in the number of fMR imaging activated voxels at all luminance contrast levels (P <.001). A statistically significant increase in fMR imaging activation (activation threshold) was seen at the second luminance contrast level in controls and at the seventh level in patients with MS. CONCLUSION: Quantifiable changes in blood oxygenation level-dependent signal and a progressive increase in activated voxels within the primary visual cortex with increasing luminance contrast were demonstrated at 1.5 T in controls. The patients with MS showed a significant decrease in the number of activated voxels and an increase in activation threshold compared with healthy controls.

Adult↗
PubMedDate not supplied

Immunotherapy of multiple sclerosis--current practice and future directions.

Over the past decade, multiple sclerosis (MS) has become a treatable neurological disease. This paper reviews the therapies that have been studied to treat MS and discusses various treatment approaches on the horizon. Immunosuppressive and immunomodulatory therapies have been shown to alter the long-term course of MS. Therapies are currently available for relapsing-remitting, secondary progressive, and progressive relapsing disease. Although effective, these therapies have a modest impact on reduction in relapse rate and slowing of disease progression. Much work is needed to improve upon this modest effect and hopefully obtain a cure.

Adjuvants, Immunologic↗