Several schemes for the diagnosis and clinical classification of multiple sclerosis (MS) have been advanced [l}. The best known is that published by Schumacher et alC31. The criteria for this scheme were established in order to select patients for participation in therapeutic trials, and pertain only to what might be called definite MS. No provision was made for incorporating supportive laboratory data into the diagnostic criteria.As no reliable specific laboratory test for the diagnosis of MS has been discovered, the diagnosis remains a clinical one, and there is still a need for clinical diagnostic criteria. However, several laboratory and clinical procedures have been developed within the last decade which aid greatly in demonstrating neurological dysfunction attributable to lesions, and even the lesions themselves.One problem with the various published diagnostic classifications is their discrepant terminology: what is considered "probable" in one is called "definite" in another. Another problem is that all the proposed schemes require much subjective judgment, a difficulty which cannot be completely overcome but can be diminished by adding to the clinical evaluation the results of laboratory, neuroimaging, neuropsychological, and neurophysiological procedures. Today there is a need for more exact criteria than existed earlier in order to conduct therapeutic trials in multicenter programs, to compare epidemiological surveys, to evaluate new diagnostic procedures, and to estimate the activity of the disease process in MS. Method and ProcedureOn April 26 and 27, 1982, the following persons participated The participants reviewed in detail historical and clinical symptomatology in MS; immunological observations; cerebrospinal fluid (CSF) tests; neurophysiological procedures including visual, brainstern auditory, trigeminal, and somatosensory evoked potential measurements; the evoked blink reflex; a variety of physiological and psychophysiological procedures; neuropsychological assessment; tissue imaging procedures such as computer assisted tomography (CT scanning) and nuclear magnetic resonance (NMR); and urological studies of bladder, bowel, and sexual dysfunction. This re-~

Background: Fatigue is the most commonly reported symptom in multiple sclerosis (MS). Purpose: This brief narrative review addresses the clinical features, pathophysiology, and management of MS fatigue, as well as the varied approaches to its definition and measurement. Methods: A literature search was conducted through Medline of studies published since 1984, with a focus on findings reported since 2008. Results: Studies of MS fatigue have primarily relied on the definition of fatigue as a subjective sense of tiredness measured through self-report. Additional studies have measured fatigability in MS, as demonstrated by a decline in cognitive or motor performance over time. The pathogenesis of fatigue remains poorly understood but disease characteristics, including structural and physiologic cerebral alterations as well as immune, endocrine, and psychological factors, may all contribute to its expression. Fatigue therapy has included pharmacologic approaches which have had either methodological limitations (e.g., small sample sizes) or inconclusive results and non-pharmacologic interventions, some of which have been effective in reducing fatigue. Conclusions: Fatigue remains a challenging symptom in MS. The most effective measurement approaches will likely be multidimensional and include both subjective and objective indicators, whereas therapy will likely require more than one type of intervention.

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