Coronary artery disease in patients with cerebrovascular disease: a prospective study

Coronary artery disease is the cause of death in most patients who have transient ischemic attacks or stroke. Evaluation for this condition is not routinely performed in such patients, and no prospective studies have been reported. We prospectively examined 50 consecutive patients with transient ischemic attacks or mild stroke to determine the prevalence and importance of coronary artery disease. All patients were examined by a cardiologist and underwent both exercise thallium-201 scintigraphy and exercise radionuclide ventriculography. Sixteen patients were suspected to have coronary artery disease on the basis of clinical evaluation. In 15 of these the was confirmed by the nuclear scans. The remaining 34 patients had no clinical evidence of heart disease, yet 14 had abnormal cardiac scans. Twenty of 22 patients with abnormal scans who underwent cardiac catheterization had significant coronary artery disease or a cardiomyopathy. The discovery of heart disease altered clinical management in 13 patients. Overall, 29 of 50 patients had significant coronary artery disease, compared with a 7% prevalence of the condition in other patients of similar age at the same institution.     

Clinical diagnosis of Parkinson's disease. Proposal of diagnostic subgroups classified at different levels of confidence

The objective of this paper is to evaluate the accuracy of conventional diagnostic criteria for Parkinson's disease and give an overview of alternative causes to parkinsonian syndromes. We also propose a new approach to the clinical diagnosis of Parkinson's disease, which may improve the diagnostic accuracy. The available information on autopsy findings in patients clinically diagnosed as Parkinson's disease shows that 20 to 30% of these patients do not have the typical neuropathological features with Lewy bodies and cell loss in the substantia nigra. The use of selected additional clinical criteria improves the diagnostic accuracy, however, at the cost of rejecting a rather large group of patients with idiopathic disease verified by autopsy. Based on this fact and a review of the literature on parkinsonian syndromes that may be confused with idiopathic Parkinson's disease, we propose criteria for diagnostic subgroups of the disease classified at different levels of confidence. The suggested diagnostic subgroups are clinical definite, probable and possible Parkinson's disease with a decreasing level of specificity and an increasing level of sensitivity in the different patient categories. The clinical features given special importance in this classification includes presence of resting tremor, asymmetrical disease, response to dopamine agonism and presence of atypical clinical features like dementia and clinical autonomic failure at onset and pyramidal or cerebellar signs at examination. In addition, a history indicating possible etiology for another parkinsonian syndrome will exclude the diagnosis.     

New hypointense lesions on MRI in relapsing-remitting multiple sclerosis patients

BACKGROUND: Preliminary observational studies with multiple sclerosis (MS) patients have reported strong correlations between an increase in hypointense lesion load (black holes) on T1-weighted spin echo images, and an increase in disability. OBJECTIVE: We assessed the relationship of hypointense lesions to the clinical course of disease among 50 relapsing-remitting MS patients in the controlled setting of a randomized clinical trial. METHODS: Fifty patients with relapsing-remitting disease were enrolled in a randomized double-blind two-arm (cladribine vs. placebo) clinical trial of 1-year duration. All patients had monthly clinical evaluations and MRIs over the course of the trial. Multivariate techniques were used to identify predictors of clinical severity from information on exacerbations, MRIs, baseline clinical parameters, and demographics. RESULTS: At baseline, clinical severity is weakly related to counts of black holes, with rank correlations between counts and clinical scores (EDSS and SNRS) of absolute magnitude 0.3. Rates of appearance of new black holes over the course of the trial are higher for patients with more severe disease at baseline (EDSS > or = 4) than for the less severe patients. Changes in clinical severity over the course of the trial are best predicted by baseline neurologic scores and numbers of exacerbations, with black holes adding no further improvement in prediction. CONCLUSIONS: Numbers of exacerbations seem more critical to short-term clinical outcomes in relapsing-remitting MS, as reflected by patients' clinical scores, rather than black holes. Various imaging methods and MRI indices capture complementary information relating to MS disease processes. The determination of which processes are affected by different drugs should lead to more effective treatment of MS patients.     

Differential diagnosis of Parkinson's disease, multiple system atrophy, and Steele-Richardson-Olszewski syndrome: discriminant analysis of striatal 18F-dopa PET data.

Clinicopathological series indicate that the clinical diagnosis of Parkinson's disease is correct in only 80% of cases. Multiple system atrophy (MSA) and Steele-Richardson-Olszewski syndrome (SRO) comprise most of the misdiagnoses. By means of 18F-dopa PET the pattern of nigrostriatal dopaminergic dysfunction in 28 patients with clinically probable Parkinson's disease, 25 with MSA, and 10 patients with SRO, was assessed and compared with the pattern in 27 normal subjects. Discriminant function analysis was used to assess the ability of 18F-dopa PET to categorize individual parkinsonian patients on the basis of their caudate and putamen tracer uptake. Discriminant function analysis assigned all control subjects a normal category. One Parkinsonian patient out of 63 was classified as "normal" on the basis of PET findings, although this patient had significantly reduced putamen 18F-dopa uptake. Discriminant function analysis was less effective at distinguishing different categories of akinetic-rigid syndrome on the basis of their striatal 18F-dopa uptake, as judged against clinical criteria. Patients clinically labelled as having typical or atypical Parkinsonian syndromes were assigned the same category on PET criteria 64% and 69% of the time, respectively. When all three categories of Parkinson's disease, MSA, and SRO were considered together, clinical and 18F-dopa PET findings correlated in 64% of patients assigned a diagnosis of Parkinson's disease and 70% of those given a diagnosis of SRO; MSA was less readily discriminated, patients with MSA being assigned to MSA, Parkinson's disease, and SRO groups with equal frequency. The correlation between clinical and discriminant function analysis assignment improved when separate comparisons were made between Parkinson's disease and MSA, or Parkinson's disease and SRO groups. In these analyses, clinical and PET categorisation of MSA and Parkinson's disease agreed in 60% of cases, and of SRO and Parkinson's disease in 90% of cases. In summary, (18)F-dopa PET successfully discriminates normal subjects from parkinsonian patients, and patients with Parkinson's disease from patients with SRO, but is less reliable in distinguishing Parkinson's disease from MSA. The concomitant assessment of striatal neuronal function with additional PET tracers may be necessary to reliably differentiate typical and atypical parkinsonian syndromes.     

How valid is the clinical diagnosis of Parkinson's disease in the community?

BACKGROUND: Many patients diagnosed with Parkinson's disease are later found to have an erroneous diagnosis, often only when they come to necropsy; conversely, many patients with Parkinson's disease in the community remain undiagnosed. OBJECTIVE: To assess the validity of a clinical diagnosis of parkinsonism in the general population according to strict published criteria. METHODS: As part of a population based study on the prevalence of Parkinson's disease in London, all patients were identified with a diagnosis of parkinsonism, tremor with onset over age 50 years, or who had ever received antiparkinsonian drugs. All patients who agreed to participate were diagnosed according to strict clinical diagnostic criteria, after a detailed neurological interview and examination and discussion of the findings with examination of their video recordings. Follow up information was obtained over a period of at least one year, and atypical cases were reviewed at the end of the study. RESULTS: A diagnosis of probable Parkinson's disease was confirmed in 83% of patients with this diagnosis, including three (2%) in whom atypical features were found that were insufficient to discard a diagnosis of Parkinson's disease. Two additional patients (2%) were found to have possible Parkinson's disease. However, in 15% of patients the diagnosis was unequivocally rejected. Conversely, 13 patients who had previously not been diagnosed with Parkinson's disease (19%) were found to have this disorder. CONCLUSIONS: At least 15% of patients with a diagnosis of Parkinson's disease in the population do not fulfil strict clinical criteria for the disease, and approximately 20% of patients with Parkinson's disease who have already come to medical attention have not been diagnosed as such.     

Controversies in Alzheimer's disease drug development

Understanding of the pathophysiological basis of Alzheimer's disease (AD) is increasing rapidly and a variety of potential treatment modalities have emerged based on these improved mechanistic insights. The optimal way of proceeding with disease-modifying drug development remains to be clarified and controversies have emerged regarding the definition of Alzheimer's disease, the participation of mild cognitive impairment patients in clinical trials, the definition of disease modification, the potential impediments to satisfaction from patients receiving disease-modifying therapy, the importance of add-on therapy with symptomatic agents, the optimal clinical trial design to demonstrate disease modification, the best means of minimizing time spent in Phase II of drug development, the potential role of adaptive designs in clinical trials, the use of enrichment designs in clinical trials, the role of biomarkers in clinical trials, the treatment of advanced patients with disease-modifying agents, and distinctions between disease modification and disease prevention. The questions surrounding these issues must be resolved as disease-modifying therapies for AD are advanced. These controversies are framed and potential directions towards resolution described.     

Clinical, radiological and cerebrospinal fluid presentation of neurocysticercosis: a prospective study

The wide clinical spectrum of neurocysticercosis has led to many attempts at clinical, radiological, CSF and other classifications. Based on an objective review of the relevant literature and on a prospective study of 42 patients with active neurocysticercosis, a new classification is proposed, based on clinical, tomographic, magnetic resonance and CSF evidence of viability of cysts. The first step is to define whether the disease is active or not. Inactive disease may be parenchymal calcifications or hydrocephalus. Active disease may be intraparenchymal, extraparenchymal or mixed. Statistical analysis of 42 cases with active disease shows intraparenchymal disease to occur in younger patients, perhaps more frequently in females, and to have a better prognosis than extraparenchymal of mixed disease. The latter appears to have the worst prognosis. Therapeutic implications are that only active disease warrants etiological therapy. There remain doubts about the best therapy for some infrequent subtypes of extraparenchymal and mixed disease.     

Vaccinations and steroids in MS: effects on disease progression and mood

OBJECTIVE: To investigate the effects of vaccinations and steroids on disease progression and mood in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Twenty-three patients with clinically definite MS were questioned with respect to vaccination history and the cumulative dose of steroids given during their life-time. EDSS scores and MRI scans of the brain were obtained and used to quantify clinical and MRI disease progression. Mood was assessed by using a self-estimated adjective mood scale. RESULTS: The number of vaccinations showed no effect on disease progression or mood. High cumulative steroid doses were associated with rapid MRI disease progression and the number of supratentorial MRI lesions. The absence of band-like MRI lesions was correlated with rapid clinical and MRI disease progression. Self-estimated mood tended to be worse in patients with chronic-progressive MS compared to those with relapsing-remitting MS. CONCLUSION: Neither clinical nor MRI-documented disease progression nor mood are influenced by the total number of vaccinations whereas high cumulative steroid doses and the absence of band-like MRI lesions indicate rapidly progressive MS. Self-estimated mood tends to be worse in patients with chronic-progressive MS compared to patients with relapsing-remitting MS.     

Controversies in Alzheimer's disease drug development

Understanding of the pathophysiological basis of Alzheimer's disease (AD) is increasing rapidly and a variety of potential treatment modalities have emerged based on these improved mechanistic insights. The optimal way of proceeding with disease-modifying drug development remains to be clarified and controversies have emerged regarding the definition of Alzheimer's disease, the participation of mild cognitive impairment patients in clinical trials, the definition of disease modification, the potential impediments to satisfaction from patients receiving disease-modifying therapy, the importance of add-on therapy with symptomatic agents, the optimal clinical trial design to demonstrate disease modification, the best means of minimizing time spent in Phase II of drug development, the potential role of adaptive designs in clinical trials, the use of enrichment designs in clinical trials, the role of biomarkers in clinical trials, the treatment of advanced patients with disease-modifying agents, and distinctions between disease modification and disease prevention. The questions surrounding these issues must be resolved as disease-modifying therapies for AD are advanced. These controversies are framed and potential directions towards resolution described.     

Validation of a clinical antisaccadic eye movement test in the assessment of dementia

The ability to generate antisaccades (eye movements deliberately made in the direction opposite to that of a visual stimulus) may be used to assess central nervous system function in a variety of neurologic and psychiatric disorders. However, the usefulness of this paradigm in clinical practice is limited by the need for an oculographic laboratory. We describe a clinical version of such an antisaccadic task and present normative data from 332 subjects. We also examined clinical antisaccades and cognitive performance in 30 patients with Alzheimer's disease, five patients with Huntington's disease, and 12 patients with pseudodementia. In Alzheimer's disease, error rates in the clinical antisaccadic test correlated well with those from a laboratory-based antisaccadic task measured on the same day by infrared oculography, confirming that the clinical antisaccadic test is a valid analog of the more sophisticated laboratory paradigms. Clinical antisaccadic error rates correlated strongly with the severity of dementia in Alzheimer's disease, and correlations with cognitive performance suggested that the clinical antisaccadic test may have some specificity for frontal lobe dysfunction. Patients with pseudodementia had normal clinical antisaccadic error rates, and the test may therefore be of use in differentiating dementia from pseudodementia. This clinical antisaccadic test provides a simple, reliable, and inexpensive quantitative clinical tool that is of value in the assessment of disturbances of higher cortical function.     

Steroid-responsive encephalopathy subsequently associated with Alzheimer's disease pathology: a case series

Background: Steroid-responsive encephalopathies can be considered vasculitic or non-vasculitic. Clinicopathological studies of non-vasculitic steroid-responsive encephalopathy are unusual, but can explain the range of diagnoses consistent with a steroid-responsive presentation in life. Objective: To extend the range of clinical features and pathological findings consistent with steroid-responsive encephalopathy. Design, methods, and patients: A clinicopathological case series of four patients (two women, ages 54-71 years) with steroid-responsive encephalopathy followed at this institution until the time of death. Results: Clinical features were suggestive of Creutzfeld-Jakob disease (CJD), dementia with Lewy bodies (DLB), and parkinsonism, but pathological examination revealed only Alzheimer's disease-related findings without evidence of Lewy bodies or prion disease in all cases. All patients demonstrated marked, sustained improvement following steroid treatment, based on clinical, magnetic resonance imaging, and/or electroencephalogram studies. Alzheimer's disease was not diagnosed in life due to the atypical clinical features, lack of hippocampal atrophy on brain imaging, and a dramatic symptomatic response to steroids. Conclusions: Steroid-responsive encephalopathy is the clinical presentation of some patients with Alzheimer's disease-related pathology at autopsy, and can be consistent with the clinical diagnoses of parkinsonism, DLB, or CJD disease in life.     

Alzheimer's disease: choline acetyltransferase activity in brain tissue from clinical and pathological subgroups

Choline acetyltransferase activity was measured postmortem in five brain regions to determine if such activity provided biochemical support for clinical and pathological subgrouping of Alzheimer's disease. Seven patients with Alzheimer's disease were divided into groups based on age at onset, severity of neuropathological changes, history of myoclonus, family history of dementia, cerebellar amyloid plaques, and congophilic angiopathy. Thirty-two age-matched normal control subjects and 17 neurological control patients with Huntington's disease were also studied. Patients with early-onset and late-onset Alzheimer's disease did not differ in the clinical duration of their disease. Choline acetyltransferase activity was significantly lower in patients with early-onset Alzheimer's disease than in age-matched control subjects in frontal cortex, temporal cortex, hippocampus, and cerebellum. In contrast, choline acetyltransferase activity in patients with late-onset Alzheimer's disease was significantly lower than in age-matched control subjects only in hippocampus. There was a tendency for choline acetyltransferase activity to be lower in cortex from patients with early-onset Alzheimer's disease compared with cortex from the late-onset group, and this difference was significant in temporal cortex. Choline acetyltransferase activity was also measured in the substantia innominata from 9 patients with Alzheimer's disease and 5 age-matched control subjects. Subjects with early-onset Alzheimer's disease had significantly lower choline acetyltransferase activity in substantia innominata than did control subjects. Patients with Alzheimer's disease and a history of myoclonus had significantly lower choline acetyltransferase activity than did affected patients without myoclonus. Multivariate regression analysis showed myoclonus to be the single best predictor of low brain choline acetyltransferase activity. These results provide further evidence for clinical, pathological, and biochemical heterogeneity in Alzheimer's disease.     

Autonomic nervous system testing may not distinguish multiple system atrophy from Parkinson's disease

BACKGROUND: Formal laboratory testing of autonomic function is reported to distinguish between patients with Parkinson's disease and those with multiple system atrophy (MSA), but such studies segregate patients according to clinical criteria that select those with autonomic dysfunction for the MSA category. OBJECTIVE: To characterise the profiles of autonomic disturbances in patients in whom the diagnosis of Parkinson's disease or MSA used criteria other than autonomic dysfunction. METHODS: 47 patients with parkinsonism and autonomic symptoms who had undergone autonomic laboratory testing were identified and their case records reviewed for non-autonomic features. They were classified clinically into three diagnostic groups: Parkinson's disease (19), MSA (14), and uncertain (14). The performance of the patients with Parkinson's disease was compared with that of the MSA patients on five autonomic tests: RR variation on deep breathing, heart rate changes with the Valsalva manoeuvre, tilt table testing, the sudomotor axon reflex test, and thermoregulatory sweat testing. RESULTS: None of the tests distinguished one group from the other with any statistical significance, alone or in combination. Parkinson's disease and MSA patients showed similar patterns of autonomic dysfunction on formal testing of cardiac sympathetic and parasympathetic, vasomotor, and central and peripheral sudomotor functions. CONCLUSIONS: This study supports the clinical observation that Parkinson's disease is often indistinguishable from MSA when it involves the autonomic nervous system. The clinical combination of parkinsonism and dysautonomia is as likely to be caused by Parkinson's disease as by MSA. Current clinical criteria for Parkinson's disease and MSA that direct patients with dysautonomia into the MSA group may be inappropriate.     

Rate of clinical progression in Parkinson's disease. A prospective study.

Few prospective data on the clinical progression of Parkinson's disease (PD) in patient groups outside treatment trials in selected patients are available, and controversy exists on the rate of clinical disease progression with advancing disease. In this study, we investigated the rate of clinical progression of PD in a clinic-based sample of 145 patients over 1 year and in a community-based sample of 124 patients over 4 years. Depending on the sample and clinical scale used, mean deterioration of motor and disability scores ranged from 2.4 to 7.4% of the maximum possible score per year, and standard deviations indicated that there was considerable variability of progression rates between individuals. The progression of motor scores decreased with follow-up over 4 years and significantly decreased in more advanced disease stages. Deterioration of disability scores did not differ between disease stages; this may reflect the increasing rate of disease complications, which contribute to increasing disability in addition to motor impairment alone, in more advanced disease. Thus, motor fluctuations, hallucinations, depression, memory problems, and bladder symptoms were all reported more often at follow-up in the community-based sample (all P < 0.01), and dyskinesias, motor fluctuations, falls, and hallucinations were more common and cognitive and depression scores worse in higher disease stages in the clinic-based sample (all P < 0.001). We conclude that progression of motor scores in PD decreases with advancing disease in PD. However, disability continues to deteriorate with advancing disease and with the development of disease complications that are likely to be related to additional extrastriatal pathology.     

Neurologic disorders associated with inflammatory bowel disease

Background and purpose: The study is aimed to report neurologic manifestations in a population of patients with inflammatory bowel disease in order to address its clinical characteristics. Methods: We conducted a retrospective study based on a computer‐guided search, of patients with Crohn′s disease or ulcerative colitis diagnosed at three hospitals in Spain spanning from 2000 through 2008. Patients were classified into different clinical groups based on the type of neurologic involvement. Only patients without iatrogenic complications, vitamin deficiencies, or known cerebrovascular risk factors were included. Results: We identified and reviewed the records of eighty‐four inflammatory bowel disease patients with neurologic symptoms: thirteen patients with ulcerative colitis and twelve patients with Crohn′s disease associated with neurologic complications were identified. Their ages ranged from 17 to 74 years. There was a slight predominance of women. Only four of them have another extra‐intestinal manifestation. Most of the patients developed neurologic manifestations coincidental or after digestive symptoms appeared. Demyelinating disease was the most frequent manifestation observed (8 patients). Cerebrovascular, peripheral nerve, and epilepsy disorders were diagnosed in 6, 5, and 3 patients, respectively. One patient with myoclonus, one with amyotrophic lateral sclerosis, and one with sensorineural hearing loss were found. Conclusions: Although an incidence could not be obtained, this population of patients with inflammatory bowel disease have a low frequency of severe neurologic disorders. Neurologic diseases, such as cerebrovascular disease, demyelinating disease, and peripheral neuropathy, could be associated with Crohn′s disease and ulcerative colitis.     

Monitoring relapsing remitting MS patients.

The availability of safe and partially effective disease modifying therapies necessitates changes in how neurologists monitor patients with relapsing remitting multiple sclerosis (RRMS). Neurologists need to make the diagnosis of MS as soon as possible to be able to initiate therapy early in the course of disease. In deciding whom to treat, neurologists should consider information on disease activity and burden acquired from the neurologic history and examination and magnetic resonance imaging (MRI). Patients not on a disease modifying therapy should undergo yearly clinical assessments and periodic cerebral MRI to monitor for changes in disease activity. Patients on disease modifying therapy should undergo regular clinical assessments to monitor for side-effects and disease activity. Cerebral MRI scanning may also be useful in assessing patients on therapy, particularly when considering changes in therapy.     

AChR抗体阳性重症肌无力合并舌肌萎缩2例报道并文献分析

目的 探讨重症肌无力(MG)患者合并舌肌萎缩的发病特点及机制。方法 分析武汉同济医院神经内科住院部2例乙酰胆碱受体(AChR)抗体阳性MG患者合并舌肌萎缩的临床资料,检索MG合并舌肌萎缩的文献报道,总结此类疾病的特点、萎缩机制、治疗方法及预后。结果 在临床上MG合并舌肌萎缩并不多见,大多数患者伴有血清肌肉特异性酪氨酸肌酶(MuSK)抗体阳性,伴AChR抗体阳性者较为罕见,肌肉萎缩的发病机制具体不详; 该类患者除发病时间较长外,通常提示更严重的病情、更差的治疗反应、更不良的预后。结论 MG舌肌萎缩临床少见,严重影响着患者的言语、咀嚼和吞咽等功能,除病程较长外,其肌肉萎缩机制暂不清楚,有待临床进一步探索,以改善此类患者预后和生活质量。     

The role of depression severity in the cognitive functioning of elderly subjects with central nervous system disease

OBJECTIVE: To examine the hypothesis that there is a causal relation between depression and cognitive dysfunction in patients with central nervous system (CNS) disease. DESIGN: Retrospective analysis of a clinical database. SETTING: Tertiary geriatric day hospital. PATIENTS: Sixty-five patients with depression and CNS disease, and 201 patients with depression but without CNS disease. OUTCOME MEASURES: Scores on the Hamilton Depression Rating Scale (Ham-D) and the Mattis Dementia Rating Scale (MDRS). RESULTS: A logistic regression analysis using MDRS status as the dependent variable, and a number of clinical variables as the predictor variables, showed that, in patients with CNS disease, only the Ham-D score predicted MDRS status (R = -0.19, p = 0.02). Ham-D score even more strongly predicted scores on a frontal system subtest of the MDRS (R = -0.262, p = 0.005). Ham-D score did not predict MDRS status in patients without CNS disease. Mean Mini Mental State Examination scores for the group with CNS disease were 25.1 at admission and 26.1 at discharge (p < 0.001). CONCLUSIONS: These findings suggest that depression contributes to frontal cognitive dysfunction in patients with CNS disease.     

Influence of homozygosity for methionine at codon 129 of the human prion gene on the onset of neurological and hepatic symptoms in Wilson disease

BACKGROUND: The clinical heterogeneity of Wilson disease expression cannot be fully explained by the various mutations of the Wilson disease gene. The prion-related protein (PrP) has been shown to bind copper in vitro and might therefore influence Wilson disease. OBJECTIVE: To examine the effect of the PrP polymorphism at codon 129, resulting in either methionine or valine (M129V), on the clinical phenotype of patients with Wilson disease. DESIGN AND SETTING: Retrospective cross-sectional study at a university hospital. PARTICIPANTS: A total of 134 patients were grouped according to their PrP M129V genotypes and initial clinical symptoms (hepatic vs neurological). RESULTS: The onset of symptoms was significantly delayed in patients homozygous for the 129M allele as compared with patients with at least 1 V allele (mean +/- SD age, 20.90 +/- 11.9 years vs 15.5 +/- 7.6 years; P = .003). No significant correlation was found when analyzing the impact of the PrP M129V genotype on the clinical symptoms at initial manifestation (hepatic vs neurological; P = .44). CONCLUSION: This study shows for the first time, to our knowledge, that the human PrP polymorphism M129V influences the onset of symptoms in patients with the copper storage disorder Wilson disease.     

Serial cranial and spinal cord magnetic resonance imaging in multiple sclerosis.

Twenty-nine mildly disabled patients with multiple sclerosis underwent serial clinical and magnetic resonance imaging (MRI) evaluations (pre- and postgadolinium cranial and spinal cord MRI) on at least 3 occasions at 13-week intervals and during periods of suspected relapse. Using clinical judgment of the presence of recent active disease as the gold standard, combined MRI studies confirmed the clinical impression of active disease in 93% of follow-up visits (sensitivity) and the absence of active MS in 63% of follow-up visits (specificity). None of the cranial and spinal MRI-detected abnormalities disappeared. Gadolinium administration particularly increased the yield of spinal MRI. Cranial MRI alone detected 80% of the MRI-active visits. Clinical and MRI concordance was significantly better for the presence of recent disease activity than for the anatomical localization of the presumed site of activity. MRI evidence of apparent ongoing disease activity was seen more frequently in patients believed to have active multiple sclerosis in the preceding year (13 of 21) than in patients who had been in clinical remission for at least the 2 preceding years (2 of 8). Although clinical evidence of new disease activity was much less common in patients with active, chronic-progressive disease (1 of 8) than in patients with active, relapsing disease (9 of 13), the proportion of patients with either infrequent relapses, frequent relapses, or slow chronic-progressive disease in the preceding year in whom MRI activity developed and the pattern of this new MRI activity was similar between these types of active patients.(ABSTRACT TRUNCATED AT 250 WORDS)