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Biomedical subjects

D E Goodkin

Publications and source records attributed to D E Goodkin.

At least 19 recordsLinked to original sources
PubMed1992

Low-dose (7.5 mg) oral methotrexate for chronic progressive multiple sclerosis. Design of a randomized, placebo-controlled trial with sample size benefits from a composite outcome variable including preliminary data on toxicity.

OBJECTIVE: To present a detailed description of (1) the study design of this ongoing trial, (2) advantages of using a composite outcome variable instead of multiple individual outcome measures, (3) treatment group characteristics at baseline, and (4) observed short-term methotrexate (MTX) toxicity. DESIGN: Randomized, double-masked, placebo-controlled intervention study. SETTING: Referral-based outpatient multidisciplinary multiple sclerosis (MS) clinic. PATIENTS: Participation offered to all clinically definite chronic progressive multiple sclerosis (CPMS) patients attending clinic ages 21 to 60, disease duration > 1 year, Expanded Disability Status Scale (EDSS) score 3.0 to 6.5 (ambulatory with moderate disability). Patients first stratified by EDSS 3.0 to 5.5 and 6.0 to 6.5, then randomized to MTX or placebo treatment. INTERVENTION: Weekly oral low-dose (7.5 mg) MTX or identical-appearing placebo for 2 years followed by a 1-year observation period. MAIN OUTCOME MEASURES: Sample size calculations undertaken prior to enrolling patients based upon a composite outcome variable consisting of designated change in any of the following functional measures: (1) EDSS, (2) Ambulation Index (AI), (3) Box and Block Test (BBT), and (4) 9-Hole Peg Test (9HPT). RESULTS: (1) Treatment group characteristics were comparable at baseline, (2) no patient has been withdrawn for adverse effects or lost to follow-up, (3) no significant short-term MTX toxicity has been observed. CONCLUSIONS: (1) The use of a composite outcome measure in the design of MS clinical trials is a promising alternative to multiple individual outcome measures that are relatively insensitive to detecting clinical change, (2) low-dose oral weekly MTX does not appear to be associated with significant short-term toxicity in CPMS. Conclusions regarding therapeutic efficacy of MTX in MS must await completion of this clinical trial.

Adult↗
PubMed1992

Magnetic resonance imaging lesion enlargement in multiple sclerosis. Disease-related activity, chance occurrence, or measurement artifact?

Magnetic resonance imaging (MRI) may demonstrate disease activity in a number of ways in patients with multiple sclerosis. Newly appearing MRI lesions, gadolinium-enhancing lesions, and enlargement of preexisting lesions are frequently taken as evidence of disease activity. Furthermore, serial MRI studies have been stated to be more sensitive than repeated neurologic examinations in detecting disease activity. We assessed the validity of using lesion enlargement as a measure of disease activity by repeatedly measuring the area of all MRI lesions in four patients with multiple sclerosis. The size-frequency distribution in all patients was similar, with 80% of the lesions measuring less than 0.67 cm2. The median coefficient of variation for three successive lesion measurements was inversely related to lesion area, ranging from 22.6% for the more common smaller lesions (less than 0.67 cm2) to 12.1% for larger lesions. Based on these coefficients of variation, a change in a particular lesion exceeding 45.2% for a baseline lesion smaller than 0.67 cm2 and 24.2% for a baseline lesion greater than or equal to 0.67 cm2 should be required to exclude a change due to measurement variability. It remains necessary to determine the number of lesions that must change when multiple lesions are present in the baseline MRI to reliably exclude chance occurrence when establishing MRI-evident disease activity. Guidelines for determining these criteria are presented, as are the limitations inherent in the statistical model employed to make these determinations.

Humans↗
PubMed1992

Inter- and intrarater scoring agreement using grades 1.0 to 3.5 of the Kurtzke Expanded Disability Status Scale (EDSS). Multiple Sclerosis Collaborative Research Group.

We determined inter- and intrarater Kurtzke Expanded Disability Status Scale (EDSS) scoring agreement for four trained examining physicians who evaluated 10 clinically stable multiple sclerosis patients. These patients had previously been determined to have EDSS scores of 1.0 to 3.5 and were scheduled to participate in a funded clinical trial of intramuscular recombinant interferon-beta. Intrarater reliability was greater than interrater reliability for scoring the EDSS and all of its component functional systems scores (FSS). Specifically, individual examiners were able to reproduce three serial examination scores on the same patient on the same day (intrarater agreement) within 1.0 EDSS or 2.0 individual FSS points. Reproducible scoring across examiners (interrater agreement), however, could only be accomplished within 1.5 EDSS or 3.0 individual FSS points. Additionally, the interrater scoring variability in our patients is greater than that previously reported for patients with higher EDSS scores. We conclude that clinical trials that employ the EDSS as an outcome measure of treatment efficacy should include inter- and intrarater agreement data for all examining physicians. Most importantly, studies using a single examining physician to evaluate individual patients throughout the course of a clinical trial will require less change in the EDSS to reliably measure disease activity than will studies using more than one examining physician to evaluate individual patients throughout the trial.

Adult↗
PubMed1991

Overview of azathioprine treatment in multiple sclerosis.

The efficacy of azathioprine in the treatment of multiple sclerosis was assessed by meta-analysis of the results of all published blind, randomised, controlled trials. 793 patients were enrolled in 5 double-blind and 2 single-blind studies. After 1 year of treatment, the increase in Kurtzke disability status score was no different in treated and control groups, but at 2 years there was a small difference (-0.22; 95% confidence interval [CI] -0.43, 0.003) in favour of azathioprine treatment; this difference was sustained, but not increased, after 3 years. The probability of freedom from any relapse during 1, 2, and 3 years' treatment was significantly greater in the azathioprine-treated group (relative odds over 3 years 1.97; 95% Cl 1.27, 3.04), but it is debatable whether the slight clinical benefits of azathioprine outweigh its side-effects.

Azathioprine↗
PubMed1991

Diagnostic criteria for multiple sclerosis research involving multiply affected families.

Existing diagnostic criteria for multiple sclerosis present significant limitations when assessing multiplex families for three reasons: (1) restricting age of onset to 10 to 50 years is likely to exclude 10% of patients known to have a later onset, (2) diagnoses based on subjective information can potentially result in a false-positive diagnosis, and (3) including progressive myelopathies occurring within families, particularly when highly symmetrical, may result in the improper inclusion of genetically determined neurological diseases such as familial spastic paraparesis. The validity of any molecular genetic approach for determining disease susceptibility critically depends on diagnostic accuracy. We present adapted diagnostic criteria that address each of these diagnostic pitfalls unique to multiplex multiple sclerosis family research.

Family↗
PubMed1991

The efficacy of azathioprine in relapsing-remitting multiple sclerosis.

We randomized 59 patients with relapsing-remitting multiple sclerosis to receive azathioprine (AZA) 3.0 mg/kg daily or placebo in a double-masked therapeutic trial. Analysis of data for predetermined primary outcome measures demonstrated a significant difference favoring AZA for observed mean exacerbation rate after 2 years of therapy and time to deterioration in both Ambulation Index and Kurtzke Expanded Disability Status Scale score. This study confirms a modest therapeutic benefit for azathioprine previously reported by other investigators.

Adolescent↗
PubMed1991

EDSS reliability.

Explore the source record for details and available documents.

Disability Evaluation↗
PubMed1990

Screening for cognitive impairment in multiple sclerosis. An evaluation of the Mini-Mental State Examination.

The usefulness of the Mini-Mental State Examination (MMSE) as a screening test for identifying cognitive impairment in patients with multiple sclerosis (MS) has been questioned because many patients who score above the suggested cutoff score of 24 exhibit severe focal or global cognitive deficits. We reevaluated the usefulness of the MMSE by studying 85 patients with clinically definite MS who also received an extensive battery of neuropsychological tests. Although scores on the MMSE were negatively correlated with the number of neuropsychological tests on which patients with MS displayed impairment, the MMSE was not sufficiently sensitive to identify precisely defined dementia in these patients. The MMSE was nonetheless a useful predictor of focal cognitive impairment, particularly in relapsing-remitting patients with relatively minor physical disabilities. Additional analyses suggested strategies for minor modifications of the MMSE that may improve its sensitivity and specificity for identifying dementia while preserving its major advantages as a screening examination: brevity and ease of administration and scoring.

Adult↗
PubMed1990

Clinical and demographic predictors of cognitive performance in multiple sclerosis. Do diagnostic type, disease duration, and disability matter?

Patients with chronic progressive multiple sclerosis often perform more poorly on cognitive tasks than do patients with the relapsing-remitting form of this disease. Whether these differences reflect an independent influence of disease type on cognitive performance is uncertain. We used multiple regression techniques to determine how well performance on a number of tasks done poorly by groups of patients with multiple sclerosis could be predicted by disease type and its confounds: age, disease duration, and disability status as well as other demographic variables. Disease types were assigned longitudinally, based on serial neurological examinations at 6-month intervals over a minimum of 2 years. None of the demographic or clinical variables predicted cognitive performance with more than minimal accuracy. These findings fail to provide support for the assertion that disease type is an important independent determinant of cognitive impairment in multiple sclerosis.

Adult↗
PubMed1989

Seasonal variation of multiple sclerosis exacerbations in North Dakota.

A prospective study of the relationship between exacerbations and season in 336 patients with clinically definite multiple sclerosis showed a significant monthly variation as well as a seasonal pattern of exacerbations. The data obtained are compared with earlier studies that have used varying methodologies. The results continue to support the hypothesis that undefined environmental factors influence the course of multiple sclerosis.

Adolescent↗
PubMed1989

Exacerbation rates and adherence to disease type in a prospectively followed-up population with multiple sclerosis. Implications for clinical trials.

Two hundred fifty-four patients with definite multiple sclerosis were followed up prospectively for 1 to 5 years (mean, 2.6 years). None of the patients received immunosuppressive medication. Yearly exacerbation rates and each patient's adherence to initial disease type were determined. Disease type was defined at entry and prospectively each subsequent year as stable, relapsing remitting stable, relapsing remitting progressive, or chronic progressive. Exacerbation rates determined prospectively did not decline significantly during 3 years of follow-up, even if patients were stratified by disease duration. Adherence to the initially assigned disease type was highly variable. When followed up for 2 years, 30% of patients with chronic progressive disease had conditions become stable, 32% of patients with stable disease had conditions become chronic progressive, 20% of patients with relapsing remitting disease had conditions become stable, and 20% of patients with relapsing remitting disease had conditions become chronic progressive. Patients with stable or relapsing remitting stable disease switched to one of the progressive categories as frequently (44%) as patients with progressive disease stabilized (46%). Progression of disease measured by changes in Kurtzke Expanded Disability Status Scores did not differ between the different disease types. The results challenge dogma regarding the natural history of exacerbation rates and the assumption that we can reliably assign patients to a specific disease type. The findings have important implications for understanding the natural history of multiple sclerosis and designing clinical trials.

Clinical Trials as Topic↗
PubMed1989

Cognitive disturbances in patients with relapsing remitting multiple sclerosis.

The performance of 42 patients with relapsing remitting (RR) multiple sclerosis was compared with that of 24 age-, education-, and gender-matched control subjects on a battery of neuropsychological tests known from previous studies to be sensitive to the impairments of patients with chronic progressive (CP) multiple sclerosis. Like CP patients, RR patients exhibited deficits on tests of information-processing speed, verbal fluency, and problem solving, and on recall measures of anterograde and remote memory. Although a few patients were mildly dysnomic, the RR patients were not generally impaired on visual confrontation naming and they did not exhibit perseverative responding on verbal fluency measures. The pattern of neuropsychological deficits exhibited by RR patients closely approximates the profile observed in other subcortical dementias and does not contain the features of cortical dementia evident in some CP patients. The impairment of RR patients on cognitive tests were less severe than those observed in CP patients in our previous studies. Differences in the age of patients in the CP and RR groups did not account for group differences in the severity of cognitive impairments, but differences in disease duration or severity of disability, as well as disease course, could explain why CP patients exhibit more serious cognitive disturbances than RR patients.

Adult↗
PubMed1989

Frontal lobe dysfunction and memory impairment in patients with chronic progressive multiple sclerosis.

Deficits in semantic encoding have been described in patients with frontal lobe disease who also show memory impairments. As a group, patients with multiple sclerosis (MS) exhibit memory impairment, fail to make effective use of semantic encoding to aid memory, and perform poorly on verbal fluency and concept formation tests which are sensitive to frontal lobe damage. In the present study the semantic encoding capacity of MS patients was measured using a modification of Wicken's release from proactive interference (PI) paradigm. Individual patients varied considerably in the severity of their impairments on verbal fluency, verbal recognition memory and on Wisconsin Card Sorting Task, but even patients who evidenced both memory impairment and signs of frontal lobe dysfunction showed normal release from PI after a categorical shift. Memory disturbances in MS are unlikely to result from an incapacity for semantic encoding, which seems preserved in MS, but may arise instead from deficits in processing information rapidly.

Adult↗
PubMed1988

Anterograde and retrograde amnesia in patients with chronic progressive multiple sclerosis.

The performance of 38 patients with chronic progressive multiple sclerosis was compared with that of 26 age- and education-matched controls on a battery of tests of information-processing speed, verbal fluency, naming, egocentric perception, and anterograde and remote memory. Although there were marked differences in the extent and severity of cognitive disturbance among individual patients, as a group they were impaired compared with controls on all measures. Deficits were most striking on the Symbol-Digit Modalities Test and the verbal fluency measures, tests that require rapid information processing. More than 75% of the patients scored below the tenth percentile for controls on the Symbol-Digit Modalities Test, while 61% scored below the tenth percentile on verbal fluency. Memory disturbances were also common. More than 45% of the patients scored below the tenth percentile. The proportion of impaired patients was quite similar for anterograde and remote memory tests and for recall and recognition procedures. The pattern of memory disturbance and slowed information processing resembled deficits generally observed in subcortical dementias, such as Huntington's disease, but in addition, the patients with multiple sclerosis showed naming difficulties that are usually associated with cortical dementias, such as Alzheimer's disease.

Adult↗
PubMed1988

Upper extremity function in multiple sclerosis: improving assessment sensitivity with box-and-block and nine-hole peg tests.

The need for standardized operational definitions, as well as a more sensitive, easily applied, and reproducible upper extremity functional assessment for following patients in multiple sclerosis clinical trials is evident. Experience with the use of two upper extremity functional assessment instruments--the nine-hole peg test (9HPT) and the box-and-block test (BBT)--is described. The patients, who were followed for six months, experienced subjective change in functional status but failed to show significant change on the pyramidal, cerebellar, or visual functional scores of the Kurtzke Expanded Disability Status Scale (EDSS). The prevalence of upper extremity dysfunction in multiple sclerosis, as measured by the 9HPT and the BBT, is higher than previously appreciated. The 9HPT and BBT are more sensitive in detecting upper extremity functional status change than the EDSS and should prove helpful in following patients in clinical trials.

Adult↗
PubMed1987

Cyclophosphamide in chronic progressive multiple sclerosis. Maintenance vs nonmaintenance therapy.

Twenty-seven patients with chronic progressive multiple sclerosis were treated with high-dose intravenous cyclophosphamide induction on either an impatient or outpatient basis. Following induction, patients were randomized to alternate-month outpatient "maintenance" or "no maintenance" therapy. These groups, as well as 24 nonrandomized control patients, were compared with each other after 12, 18, and 24 months of follow-up. All groups were similar in age, sex, duration of disease, and degree of disability before treatment. Fifty-nine percent of all cyclophosphamide-treated patients were stable at 12 months compared with 17% of all patients in the nonrandomized control group at 12 months. A statistically significant difference persisted at 18 and 24 months. A trend favoring maintenance therapy when compared with no maintenance therapy was evident at 12, 18, and 24 months, but was not statistically significant. Inpatient vs outpatient induction therapy failed to influence treatment outcome. Toxic side effects of nausea and vomiting presented a serious obstacle to maintenance therapy as administered in this protocol.

Administration, Oral↗