C LEADING ARTICLE j THE DIAGNOSIS OF MULTIPLE SCLEROSIS C B Tan SINGAPORE MED J 1992; Vol 33: 561-562 Demyelinating diseases in adults, in which the pathology is tomatic dissemination in space or detect evidence of inflam- in the white matter predominantly of the central nervous sys- mation in the central nervous system are useful aids in the tem, are caused by a variety of viral infections and anoxic - diagnosis of MS. The risk of developing MS following an toxic conditions"). However, the most common primary isolated acute syndrome of brainstem or spinal cord is much demyelinating disease is multiple sclerosis (MS) which is char- higher in patients with disseminated lesions on MRI and in acterised by multifocal inflammatory demyelination in the cen- those with positive oligoclonal band1"). Similarly, the risk of nervous tral system and recognised by its relapsing and remit- developing MS in isolated optic neuritis may be higher in ting character. As there are no pathognomonic laboratory tests, patients who have abnormal white matter lesions on MRIOt). the diagnosis has always been a clinical one. Diagnostic crite- The existing diagnostic criteria for MS were revised at a Work- ria have continued to evolve since its delineation as a disease shop on the Diagnosis of Multiple Sclerosis in 1982 whereby entity by Charcot more than a century ago. The disease typi- paraclinical findings were incorporated for the purpose of ex- young cally occurs in women of northern European Caucasian tending the limits of the diagnostic criteria thus making a larger descent in temperate countries1). The prevalence of the disease reservoir of patients for investigative purposes101. A new cat- is low in Asian countries and the optic -spinal form, often with egory of laboratory -supported definite multiple sclerosis severe visual impairment, is by far the most common pattern (LSDMS) was proposed for use in research protocols although of presentation among Orientals131. it is now widely used in clinical practice. The diagnosis of MS has always depended upon the clini- The diagnosis of LSDMS is dependent on the presence of cal recognition of white matter lesions disseminated in both oligoclonal bands or an increased IgG synthesis rate in the time and space for which another cause cannot be established. CSF. When such immunological abnormalities are present, The Schumacher Panel criteria, published in 1965, for the di- LSDMS can be diagnosed with a history of 2 episodes of agnosis of clinically definite multiple sclerosis (CDMS) had neurological disturbance and clinical evidence of one lesion served as the standard diagnostic guide for many years and has and paraclinial evidence for a second lesion. When the CSF an accuracy of 90-95%"). Several other proposed classifica- changes are present, LSDMS may also be diagnosed in pa- tions followed, building upon the Schumacher criteria to in- tients with steadily progressive deficit from onset, provided the clude categories of probable and possible MS when the the illness has been present for at least 6 months and sequen- diagnostic criteria fall short of those for definite MS131. tial discrete involvement of the CNS white matter can be dem- Over the past decade, newer diagnostic tools to detect im- onstrated clinically or paraclinically. The category of probable munological evidence of central nervous system inflammation MS for patients in whom all criteria are not fulfilled was also or evidence of clinically asymptomatic lesions have been de- expanded to include CSF and other investigative results. The veloped. The oligonal IgG band in the cerebrospinal fluid (CSF) diagnosis of LSDMS could certainly be made earlier and more of patients with MS correlates with the presence of plasma readily than the diagnosis of CDMS. In a short follow-up study, cells in MS plaques and is present in 90% of patients with 10% of patients who qualified for LSDMS went on to develop CDMS161. Multimodality evoked potentials and central motor clinically definite MS in less than one year"). However, only conduction using a magnetic stimulator are now widely used long-term follow-up studies will show how well the category in evaluating patients with suspected demyelinating diseases. of LSDMS predicts the development of CDMS. -shift visual Pattern evoked potential (VEP) is abnormal in up The use of these laboratory aids however must be put into to 85% of clinically classified definite MS. For brainstem au- the proper perspective. None of the laboratory abnormalities ditory evoked response (BAER) and somatosensory evoked are specific for MS. Oligoclonal bands can be found in other potentials (SSEP) the yield is about 67% and 77% respectively inflammatory conditions like subacute sclerosing in CDMS"). In Oriental patients, the abnormality rate for BAER panencephalitis chronic meningitis, neurosyphilis, vasculitis, is much lower while abnormal VEPs tend to involve loss of sarcoidosis and T-Iymphotropic virus type I related amplitude rather than prolonged latency reflecting the differ- myelopathy"'1. An abnormal visual evoked response may be ing disease pattern alluded to earlier"-". Magnetic resonance due to a compressive lesion on the optic nerve. Similarly, imaging (MRI) is extremely sensitive in detecting white mat- abnormal BAER and SSEP may be due to compressive lesions ter lesions in the cerebral hemisphere, brainstem and the spinal or degenerative and vascular diseases. In serial MRI studies in cord. It is superior to CT scan in demonstrating MS lesions MS patients, it has been shown that asymptomatic new lesions and has been reported to be abnormal in 87-93 % of patients may appear and disappear. Among the paraclinical tests, MRI with CDMS"Òt. These paraclinical findings which show asymp- has the most frequent overall abnormality rate and in one study it could identify all the patients that could be diagnosed as Neurological Unit having LSDMSt101. However, MRI is also extremely sensitive Tan Tock Seng Hospital in demonstrating white matter lesions from a variety of dis- Moulmein Road eases including migraine, encephalitis, vasculitis, head trauma Singapore 1130 and often even in the normal aged. The specificity of these MRI lesions dubbed "UBO" (unidentified bright object) is still C B Tan- MBBS, MMed (Int Med) not established, partly because of lack of adequate. clinico - Consultant pathological correlative studies"). Hence, a conservative tip - 561 proach must be taken in interpreting MRI to avoid making 5. Km eke JF. Multiple sclerosis: what's in a name? Neurology 1988; 38:30911 Kaufmann ICU, Gilbert 11, Nose' tonhy ill. Armstrong ILA, Ebers GC- false positive diagnoses of multiple sclerosis. 6. Farrell MA. Oligoclon:l bands in multiple sclerosis: clinical -pathologic correlation Neurology 1985; There is as yet no effective treatment for the disease and in 33: 212-8 diagnosis of multiple sclerosis. Neurologic the words of Foster Kennedy, the diagnosis of MS is also a ]. Chmppa KlI Use of evoked potentials for Climes 1988;6(4)'861-80. prognosis of utter disaster to any human to whom it is givenp6t 8. Shubasakt F1. Kurmwa l'. Pattern reversal signal evoked potentials in Japanese delimits It is therefore essential that the physician should sort out the will) multiple sclerosis.l Neurol Neurosurg Psychiatry 1982; 45:1139-43. clinical and paraclinieal findings to exclude other potentially 9. Tan CI', Leong S. Evoked response study among Malaysian multiple sclerosis patients l 1992; 33: treatable conditions before ascribing them to multiple sclero- Singapore Mal _ 10. May OW, Oger DP, Kash-idol)" I.F. ei al. MRI in the diagnosis of MS: a prospective sis. Most clinicians would also agree that the diagnosis of MS study with comparison of clinical evaluation. evoked potentials, oligoclonal banding and must be based on clinical evidence of dissemination and not CT. Neurology 1988; 38: 180-5 laboratory tests. I1. Miller D11 Onnerod IEC, Rudge P et al Me early risk of multiple sclerosis following solely on the basis of isolated acute syndromes of the brainstem and spinal cord. Ann Neurol 1989:26: 635-9. 12. Sharief MK, Thompson Er- The predictive value of introibecal immnnoglobulis synthesis REFERENCES amd magnetic resonance imaging In acute isolated syndromes for subsequent develop- ment of multiple sclerosis Amt Neurol 1991; 29: 142-51. I landbook Clinical Neurology, volume a]. Am- 1 Koetsier IC Denryebnating Diseases. of after sterdam: Elsevier Science Publishers 1985 13 Miller DI I. Omerwl IEC. McDonald WI ei a1. The early risk of multiple sclerosis optic neuritis. J Neurol Neurosmg Psychiatry 1988:51: 1569-71 2- Kranz IS, Kurland L.T- General overview of Me epidemiology of multiple sclerosis with emphasis on the geographic pattern and long-term trend. In' Kuroiwa Y, Kurland LT. cils. 14. Parr CM. Pair DW, Schemlwrg Let al. New diagnostic criteria for multiple sclerosis' Multiple Sclerosis East and West. Japan: Kyushu University Press, 1982.3-29. guidelines for research protocols. Ann Neurol 1983, 13. 227-31. in multiple sclerosis. In: Poser 3. Kuroiwa Y, 5hubasaki I1, Tabtra T, Iloyams Y. Clinical picture of multiple sclerosis in IS. 'ronricl lone WW, Walsh Ml- Cerebrospinal fluid profile New York: Asia. In: Kuroiwa Y, Kurland LT. eds. Multiple Sclerosis Past sad Nest. Japan. Kyushu CAI. Vàry DW. Seheinberg L ei al. eds. The Diagnosis of Multiple Sclerosis. University Press. 1982: 31-42. Th¢me Stratton Inc 198.1:165-]8. Proc Assoc Res New Ment Dis 1950; 4 Schumacher GA, Beebe G, Kibler RF et al. Problems of experimental trials of therapy m 16. Kennedy I' On the diagnosis of multiple sclerosis. multiple sclerosis: repon of the panel on 'he evaluation of experimental vials of ihcrapy 28:524-31. in multiple sclerosis Ann NY :mad Sci 1965; 122. 552-68 Are we looking to enter the Guinness Book of Records? Not exactly. That's how many executives enjoyed conferences at the Pan Pacific Hotel last year. And used one of our spectacular lifts to reach 'WIC CAN PiT 50,000 d311SIINESSAIEN IN THIS LIFE their guest room after a day of productive meetings.