SPECIAL ARTICLE New Diagnostic Criteria for Multiple Sclerosis: Guidelines for Research Protocols Charles M. Poser, MD,l Donald W. Paty, MD,’ Labe Scheinberg, MD,3 W. Ian McDonald, FRCP,4 Floyd A. Davis, MD,’ George C. Ebers, MD,‘ Kenneth P. Johnson, MD,’ William A. Sibley, MD,8 Donald H. Silberberg, MD,9 and Wallace W. Tourtellotte, MD” Several schemes for the diagnosis and clinical clas- Method and Procedure sification of multiple sclerosis (MS) have been ad- On April 26 and 27, 1982, the following persons participated vanced [l}. The best known is that published by in a Workshop on the Diagnosis of Multiple Sclerosis, held in Schumacher et alC31. The criteria for this scheme were Washington, DC, for the purpose of establishing new diag- established in order to select patients for participation nostic criteria for MS: Bruce Becker (National Naval Medical in therapeutic trials, and pertain only to what might be Center),Jerry Blaivas (Columbia), Keith Chiappa (Harvard), called definite MS. No provision was made for incor- Floyd Davis (Rush), Burton Drayer (Duke), George Ebers porating supportive laboratory data into the diagnostic (Western Ontario), Andrew Eism (British Columbia), criteria. Robert Herndon (Rochester, NY), Kenneth Johnson (Mary- As no reliable specific laboratory test for the diag- land), Ian McDonald (National Hospital, London), Dale nosis of MS has been discovered, the diagnosis remains McFarlin (NINCDS), Donald Paty, Co-chairman (British a clinical one, and there is still a need for clinical diag- Columbia),Janis Peyser (Vermont), Charles Poser, Chairman nostic criteria. However, several laboratory and clinical (Boston), David Regan (Dalhousie), Daniel Sax (Boston), Labe Scheinberg, Co-chairman (Albert Einstein), Simon procedures have been developed within the last decade Sears (Texas-Houston), William Sibley (Arizona), Donald which aid greatly in demonstrating neurological dys- Silberberg (Pennsylvania), Robert Slater (National MS Soci- function attributable to lesions, and even the lesions ety), Emanuel Stadlan (NINCDS), Wallace Tourtellotte themselves. (Wadsworth VAIUCLA), and Byron Waksman (National MS One problem with the various published diagnostic Society). Dr Robert Daroff (Case-Western Reserve) made classifications is their discrepant terminology: what is many useful suggestions. The disciplines represented in- considered “probable” in one is called “definite” in cluded neurology, neuropsychology, urology, immunology, another. Another problem is that all the proposed neuroradiology, neuroophthalmology, clinical neurophysiol- schemes require much subjective judgment, a difficulty ogy, and neuropathology. which cannot be completely overcome but can be di- The participants reviewed in detail historical and clinical minished by adding to the clinical evaluation the results symptomatology in MS; immunological observations; cere- brospinal fluid (CSF) tests; neurophysiological procedures in- of laboratory, neuroimaging, neuropsychological, and cluding visual, brainstern auditory, trigeminal, and somato- neurophysiological procedures. Today there is a need sensory evoked potential measurements; the evoked blink for more exact criteria than existed earlier in order to reflex; a variety of physiological and psychophysiological conduct therapeutic trials in multicenter programs, to procedures; neuropsychological assessment; tissue imaging compare epidemiological surveys, to evaluate new procedures such as computer assisted tomography (CT scan- diagnostic procedures, and to estimate the activity of ning) and nuclear magnetic resonance (NMR); and urological the disease process in MS. studies of bladder, bowel, and sexual dysfunction. This re- ~ ‘Department of Neurology, Boston University School of Medicine, sity of Maryland School of Medicine, Baltimore, MD, ’Department Boston, MA, ’Division of Neurology, Vancouver General Hospital, of Neurology, university of Arizona School of Medicine, Tucson, University of British Columbia, Vancouver BC, Canada, ’Multiple AZ, 9Department of Neurology, University of Pennsylvania School Sclerosis Center, Albert Einstein College of Medicine, Bronx, NY, of Medicine, Philadelphia, PA “’Wadsworth VA Medical Center, *National Hospital, Queen Square, London, England, 5Departrnent University of California School of Medicine, Los Angeles, CA. of Neurological Sciences, Rush-Presbyterian-St. Luke’s Medical Address reprint requests to D~ poser, D~~~~~~~~of ~~~~~l~~~, Center, Chicago, IL, ‘Division of Neurology, University of Western Boston University Medical Center, 80 E Concord St, Boston, MA Ontario, London, Ont, Canada, ’Department of Neurology, IJniver- 02 18, 227 view resulted in formulation of guidelines for the perfor- 5. Typical of MS: MS is known to involve certain mance of these procedures and for evaluation of the results parts of the CNS much more frequently than others, that will be published with recommendations regarding their and thus certain signs and symptoms are more fre- usefulness in the diagnosis of MS 12). The diagnostic criteria quently noted. Gray matter lesions occur rarely enough presented here represent the views of the majority of the in MS that they should not be considered in establish- workshop participants. ing the diagnosis. Lesions of the peripheral nervous system, except when accounted for by their in- Definitions tramedullary course (e.g., oculomotor, trigeminal, or 1. Attack (bout, episode, exacerbation): The occurrence of facial nerves), may not be counted. Complaints such as a symptom or symptoms of neurological dysfunction, headaches, convulsive seizures, depression, or alter- with or without abjective confirmation, lasting more ations of the state of consciousness are too nonspecific than 24 hours constitutes an attack. This may be com- to be considered in the diagnostic construct. pletely subjective and anamnestic, eg., the patient re- 6. Remission: A definite improvement of signs, symp- ports having had double vision for three days but did toms, or both that has been present for at least 24 not consult a physician; or numbness and tingling of a hours is called a remission for the purpose of these leg caused a visit to a physician who was unable to guidelines. A remission must last at least one month to demonstrate objective changes; or the patient was hos- be considered significant. pitalized because of severe ataxia and was found to 7. Separate lesions: Separate signs or symptoms cannot have signs of cerebellar dysfunction, bilateral Babinski be explainable on the basis of a single lesion; simulta- signs, and left facial weakness. Individual symptoms, neously occurring internuclear ophthalmoplegia, facial however, may last for considerably less time than that: weakness, and signs of involvement of the corticospinal e.g., a Lhermitte sign (which is really a symptom) or tracts could have been caused by a single lesion (e.g., vertigo may last for only seconds; these manifestations brainstem infarction) and thus would not be acceptable. cannot be considered attacks in this context. Optic neuritis involving both eyes occurring simulta- 2. Historical infomtion: The description of symp- neously, or the second eye becoming involved within toms by the patient. The example just cited (under the 15 days of the first (provided that compression of the definition of attack) of the episode of diplopia would be chiasm by tumor or aneurysm has been ruled out), is historical, and so would the leg numbness, although considered to represent a single lesion. Only lesions medical corroboration would strengthen the latter. Ide- that involve distinctly different parts of the CNS are ally, medical records which confirm anamnestic infor- called separate lesions. mation should be obtained. 8. Laboratoy support: The term is applied here only 3. Clinical evidence ofa lesion: Signs of neurological to the examination of CSF for oligoclonal bands and dysfunction demonstrable by neurological examina- increased production of immunoglobulin G (1gG). All tion. Such neurological signs are acceptable even if no other laboratory procedures, such as evoked responses longer present, provided that they were elicited and or tissue imaging techniques, are considered to be ex- recorded in the past by a competent examiner. tensions of the clinical examination. 4. PararlinicaP evidnce of a lesion: The demonstration by means of various tests and procedures of the exis- General Considerations tence of a lesion of the central nervous system (CNS) The acceptable age of onset for research purposes is which has not produced signs of neurological dysfunc- between 10 and 59 years inclusive. The manifestations tion but which may or may not have caused symptoms in of the disease offered in evidence must be shown to be the past. Such tests and procedures include the hot characteristic of MS and not attributable to another bath test, evoked response studies, tissue imaging pro- condition. Such a decision must be made by a physician cedures, and reliable, expert urological assessment, who is experienced in clinical neurology. It is strongly provided that these tests and procedures follow the recommended that the diagnosis of MS be established guidelines and are interpreted according to the newly only by a competent neurologist. Although extended established criteria to be published [Z}. These diag- and expensive investigations are not encouraged, other nostic procedures represent various options, all of illnesses capable of producing signs and symptoms of which may not be available and some