Biomedical subjects

R Rudick

Publications and source records attributed to R Rudick.

11 recordsLinked to original sources

PubMed2003

Pattern reversal visual evoked potentials as a measure of visual pathway pathology in multiple sclerosis.

BACKGROUND: Pattern reversal visual evoked potentials (PRVEPs) have a well-documented role in diagnosis of multiple sclerosis (MS), but their value as a visual function surrogate remains controversial. METHODS: We evaluated PRVEP in 37 patients with MS who were participating in a long-term follow-up study following a phase III trial of interferon beta-1a (Avonex). Patients were examined to determine the Kurtzke Extended Disability Status Score (EDSS), multiple sclerosis functional composite (MSFC), contrast letter acuity (CLA), and had cranial MRI scans to determine whole brain atrophy (BPF). PRVEP was evaluated for P100 latency, amplitude, and waveform morphology. Two summary scores were created: for Score A, abnormal latencies, morphologies, and amplitudes of each individual eye were added; for Score B, abnormal latencies, morphologies, and amplitude ratio between eyes was determined. Sixteen patients in this group also had PRVEP at the time they enrolled in the clinical trial, eight years previously. RESULTS: At the follow-up exam, over 75% of patients had abnormal PVEP parameters while visual acuity (VA) was abnormal only in 59%. Increased PRVEP latency over the eight-year period correlated with deterioration assessed by EDSS (P = 0.006), BPF (P = 0.0001), and MSFC (P = 0.0041). Score A was significantly correlated with EDSS, BPF, CLA, cognitive function, and quality of life assessed with the Sickness Impact profile. No correlation was seen with the MSFC. CONCLUSIONS: The results indicate that PRVEP measures MS-related pathology, and can provide not only diagnostic but also prognostic information during evaluation of MS patients.

Evoked Potentials, Visual↗

PubMed2001

Relationship between serum levels of IL-10, MRI activity and interferon beta-1a therapy in patients with relapsing remitting MS.

BACKGROUND: The purposes of this study were to: (1) compare monthly serum IL-10 in patients with relapsing remitting (RR) multiple sclerosis (MS) and healthy controls, (2) determine the relationship between IL-10 and MRI activity and (3) determine the effect of interferon beta-1a (IFNB-1a) treatment on IL-10 levels. RESULTS: Median serum IL-10 levels were lower in untreated RRMS (185.5 pg/ml) compared to controls (438.5 pg/ml) (P=0.19). Serum levels of IL-10 did not appear to predict the appearance of new gadolinium-enhancing (Gd+) lesions concurrently or 1 month thereafter. However, IL-10 levels were more likely to be elevated the month during which Gd+ lesions resolved (OR=3.14, P=0.01). Median IL-10 levels were lower during IFNB-1a treatment (P=0.01). CONCLUSIONS: These observations suggest a relationship between serum IL-10 levels and resolution of abnormal vascular permeability in new lesions.

Adolescent↗

PubMed2000

Extended observations on MS patients treated with IM interferon-beta1a (Avonex): implications for modern MS trials and therapeutics.

Extended observations of the pivotal phase III clinical trial of interferon-beta1a (IFNbeta1a; Avonex, Biogen) in relapsing MS patients revealed that: (1) active treatment significantly slowed the accumulation of physical disability over time, reduced clinical exacerbations and MRI brain lesions; (2) clinical efficacy did not depend on disability endpoints; (3) active treatment benefited multiple MRI measures of brain lesions; (4) cerebral atrophy occurred over 2 years in relatively mildly disabled patients; and (5) Avonex could slow the development of atrophy after the first year of treatment. Data from this study were recently used to design a new outcome measure for MS clinical trials (the Multiple Sclerosis Functional Composite), and was also the basis for two ongoing studies of IFNbeta1a: one in patients with monosymptomatic onset of MS and the other in secondary progressive MS.

Adjuvants, Immunologic↗

PubMed2000

Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients.

Axonal degeneration has been proposed as a cause of irreversible neurological disability in multiple sclerosis (MS) patients. The purpose of this study was to quantify axonal loss in spinal cord lesions from 5 paralyzed (Expanded Disability Status Scale score > or =7.5) MS patients and to determine if axonal number or volume correlated with levels of the neuronal marker N-acetyl aspartate (NAA). Axonal loss in MS lesions ranged from 45 to 84% and averaged 68%. NAA levels were significantly reduced (>50%) in cross sections of spinal cords containing MS lesions. Reduced NAA correlated with reduced axonal numbers within lesion areas. In addition, NAA levels per axonal volume were significantly reduced in demyelinated axons (42%) and in myelinated axons in normal-appearing white matter (30%). The data support axonal loss as a major cause of irreversible neurological disability in paralyzed MS patients and indicate that reduced NAA as measured by magnetic resonance spectroscopy can reflect axonal loss and reduced NAA levels in demyelinated and myelinated axons.

Adult↗

PubMed1999

Axonal pathology in multiple sclerosis: relationship to neurologic disability.

In this review, data is summarized supporting the hypothesis that axonal loss is a major pathologic process responsible for irreversible neurologic disability in patients with multiple sclerosis. Pathologic studies implicate inflammatory demyelination as a principal cause of axonal transection and subsequent axonal degeneration. Axonal degeneration caused by chronic demyelination in the absence of active inflammation may also contribute to progressive disability in the later stages of the disease. Studies using magnetic resonance spectroscopy suggest that axonal loss begins at the onset of the disease, and studies using magnetic resonance imaging have documented brain atrophy in the earliest stages of multiple sclerosis. Brain atrophy increases during the relapsing-remitting disease stage without concurrent disability progression. This suggests that compensatory mechanisms maintain neurologic function, despite progressive brain tissue loss during the early stages of the disease. Beyond a threshold, however, further axonal loss leads to continuously progressive neurologic disability. We hypothesize that the rate and extent of axonal loss during relapsing-remitting multiple sclerosis determines when a patient enters the secondary progressive stage of the disease. This view of disease pathogenesis has several important implications. First, surrogate markers of axonal loss are needed to monitor the disease process for patient care and for clinical trials. We propose brain parenchymal fraction, a precise measure of whole-brain atrophy, as an attractive candidate for this purpose. Second, disease-modifying therapy should be used early in multiple sclerosis patients, before extensive axonal loss has occurred. Third, neuroprotective drugs should be tested in combination with anti-inflammatory drugs in multiple sclerosis patients. Finally, studies of the time course of axonal loss, and its mechanisms are critical for effective therapeutic intervention.

Axons↗

PubMed1998

Axonal transection in the lesions of multiple sclerosis.

BACKGROUND: Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system and is the most common cause of neurologic disability in young adults. Despite antiinflammatory or immunosuppressive therapy, most patients have progressive neurologic deterioration that may reflect axonal loss. We conducted pathological studies of brain tissues to define the changes in axons in patients with multiple sclerosis. METHODS: Brain tissue was obtained at autopsy from 11 patients with multiple sclerosis and 4 subjects without brain disease. Fourteen active multiple-sclerosis lesions, 33 chronic active lesions, and samples of normal-appearing white matter were examined for demyelination, inflammation, and axonal pathologic changes by immunohistochemistry and confocal microscopy. Axonal transection, identified by the presence of terminal axonal ovoids, was detected in all 47 lesions and quantified in 18 lesions. RESULTS: Transected axons were a consistent feature of the lesions of multiple sclerosis, and their frequency was related to the degree of inflammation within the lesion. The number of transected axons per cubic millimeter of tissue averaged 11,236 in active lesions, 3138 at the hypocellular edges of chronic active lesions, 875 in the hypocellular centers of chronic active lesions, and less than 1 in normal-appearing white matter from the control brains. CONCLUSIONS: Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease.

Adolescent↗

PubMed1997

Recommendations from the National Multiple Sclerosis Society Clinical Outcomes Assessment Task Force.

This article provides recommendations from the National Multiple Sclerosis Society's Clinical Outcomes Assessment Task Force. The Task Force was appointed in 1994 and charged with recommendending improved approaches for clinical outcomes assessment in future controlled clinical trials. The recommendations herein follow extensive deliberation and data analysis during 2.5 years. General principles and desirable measurement attributes were used to assess alternative measurement techniques and clinical scales. On the basis of the analysis of existing multiple sclerosis (MS) data sets, a new measurement approach is proposed. The approach is based on quantitative functional composites that consist of simple quantitative measures from the major clinical dimensions of MS combined into a single score. Quantitative functional composites are likely to provide improved precision and sensitivity in future MS clinical trials. Studies necessary to further refine quantitative functional composites as useful MS clinical trial outcomes are delineated.

Clinical Trials as Topic↗

PubMed1996

Clinical outcomes assessment in multiple sclerosis.

This article represents initial deliberation of an international task force appointed by the US National Multiple Sclerosis Society to develop recommendations for optimal clinical assessment tools for multiple sclerosis clinical trials. Presented within this article are the key issues identified by the task force during its initial year of deliberation. These include the precise purpose for a clinical assessment tool, the clinical dimensions to be measured in a multidimensional outcome measure, desirable attributes of an optimal clinical outcome measure, the complexities of multidimensional outcome measures, the relative merits of categorical clinical ratings and quantitative functional assessments, and a number of other important design issues that relate to the use of a multidimensional outcome measure. An action plan for analysis of existing data is summarized, as are the plans for more detailed recommendations from the task force.

Clinical Trials as Topic↗

PubMed1988

Pregnancy and multiple sclerosis.

MS is an unpredictable, potentially disabling condition that occurs most commonly in women of reproductive age. The decision to have a baby after this diagnosis is a difficult and very personal one. Each couple considering a family deserves preconception counseling with accurate information and support to facilitate an informed decision. Consistently, studies have found that pregnancy is a period of safety from worsening of MS but that exacerbation occurs at two to three times the expected rate after delivery. Gestational history does not seem to affect the ultimate prognosis of the disease. The decision to bear children then seems to depend first on the desire of the woman to have a family. Additional issues to consider for a woman with MS considering pregnancy are current physical impairment and support available from father, family, and friends. There is considerable evidence that some protective factor exists during pregnancy to cause the disease to be less active. Presumably, this is a soluble factor or factors that suppress the cellular immune system. This is of great potential scientific interest, since it may contribute to our understanding of MS and potentially lead to newer avenues of research and treatment.

Adult↗

PubMed1986

Pregnancy and multiple sclerosis.

Retrospective studies strongly suggest that pregnancy is an example of a naturally occurring human condition that consistently and predictably affects the course of multiple sclerosis (MS). Pregnancy seems to be associated with clinical MS stability or improvement, while the postpartum period seems to be one of high risk for clinical flares of the disease symptoms. Similarly, pregnancy protects animals from developing experimental allergic encephalomyelitis. Immune system changes in pregnancy and MS are reviewed, as they may be involved in the observed clinical effects of pregnancy on MS. Important questions of the patient with MS in the childbearing age group are addressed.

Abnormalities, Drug-Induced↗

PubMed1981

Ocular bobbing in encephalitis.

Abnormal eye movements described as ocular bobbing are most often encountered in the setting of pontine vascular disease. This report deals wih the onset and course of ocular bobbing in a young woman who had encephalitis confirmed by biopsy. Unusual eye movements developed during progressive deterioration of brain and brain stem function which led to coma. The eye movements occurred spontaneously and could also be triggered by cutaneous stimulation of the face, head, extremities, and auditory canals. The patient recovered fully over a period of several months.

Adult↗