1203 enhanced after administration of Gd-DTPA in a Tl-weighted image. Case 2 (24, M).-3 weeks before admission he noticed orthostatic problems and had low blood pressure. 12 days before admission he had numbness on the left side of his tongue and inside his mouth; this worsened. 3 days before admission he felt dizzy and his gait became unsteady. On admission there was nystagmus and saccadic pursuit on lateral gaze, facial paraesthesia, and brisk reflexes of the arms; the left leg showed an increased knee jerk and ankle clonus; Babinski reflex was negative on both sides. There was ataxia of arms, legs, and trunk. Vibration and joint position sense were reduced in both legs. Clinical examination was otherwise normal, as were evoked potentials. Tests for antibodies to viruses and to Borrelia burgdorferi were normal. Ultrasound scans of extracranial vessels were normal. CSF contained 13 cells/fI, protein 36 mg/ml, IgG index 0 53 mg/ml, and fourteen oligoclonal bands. At MRI on the day of admission the T2-weighted scan revealed multiple hyperintense lesions (figure), one being enhanced on the Tl- weighted image after administration of gadolinium-DTPA. No set of diagnostic criteria can be a substitute for a sound clinical opinion, after the exclusion of other possible explanations in individual cases of suspected MS. However, in that setting, a combination of enhanced and unenhanced MRI scans may permit the very early diagnosis of MS. Early diagnosis may be of little value at present but could be important when more effective and less toxic treatments are available. Max Planck Society Clinical Research Unit for Multiple Sclerosis, 8700 Wurzburg, West Germany; and Departments of Neurology and Neuroradiology, University of Wurzburg R. HEUN L. KAPPOS S. BITTKAU D. STAEDT E. ROHRBACH B. SCHUKNECHT 1 Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis guidelines for research protocols. Ann Neurol 1983, 13: 227-31. 2. Schumacher GA, Beebe G, Kibler RF, et al. Problems of experimental trials of therapy in multiple sclerosis. Ann NY Acad Sci 1965; 122: 552-68. 3. Young IR, Hall AS, Pallis CA, Legg NJ, Bydder GM, Steiner RE. Nuclear magnetic resonance imaging of the brain in multiple sclerosis. Lancet 1981; ii: 1063-66. 4 Paty DW, Asbury AK, Hemdon RM, et al. Use of magnetic resonance imaging in the diagnosis of multiple sclerosis: policy statement. Neurology 1986; 36: 1575. 5. Ormerod IEC, Miller DH, McDonald WI, et al. The role of NMR imaging in the assessment of multiple sclerosis and isolated neurological lesions. Brain 1987; 110: 1579-616. 6 Weller WO Pathology of multiple sclerosis. In: Matthews WB, ed. McAlpine’s multiple sclerosis. Edinburgh: Churchill Livingstone, 1985: 301-43. 7. Grossmann RI, Gonzalez-Scarano F, Atlas SW, Galetta S, Silberberg DH. Multiple sclerosis gadolinium enhancement in MR imaging. Radiology 1986; 161: 721-25 8 Kappos L, Staedt D, Rohrbach E, Keil W. Time course of gadolinium enhancement in MRI of patients with multiple sclerosis effects of corticosteroid treatment. J Neurol 1988; 235: 10. 9 Miller DH, Rudge P, Johnson G, et al. Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis. Brain 1988; 111: 927-39 EARLY LESION OF MULTIPLE SCLEROSIS SIR,-Crucial to the understanding of the pathogenesis of multiple sclerosis (MS) is a knowledge of the evolution of the lesion. The histology of the MS plaque suggests that vascular changes are important. Contrast enhanced computerised tomographic1.2 and magnetic resonance imaging (MRI)3A scans provided evidence for a breakdown in the blood-brain barrier (BBB), especially in new lesions. We have observed lesions to appear over 48 hours, all of which enhanced on gadolinium-DTPA (Schering) MRI. Because the detail of the evolution of permeability changes is unknown we have done dynamic and serial Gd-DTPA enhanced MRI in 28 patients with MS. Informed consent was obtained. Unenhanced MRIs (SE2000/60 and SE500!40) were done in a Picker 05 T superconducting MR imager followed by bolus injection of Gd-DTPA 0-1-02 mmol/kg. The patient remained in the scanner for precise image registration.s Serial scans (SE500/40) were obtained every 4 min. The longest study was 380 min, including rest breaks. Follow-up scans, in some cases multiple, were done after 1-12 weeks. Multiple periventricular and discrete white-matter lesions were seen in all unenhanced scans. In all patients showing enhancement some areas of lesions enhanced and others did not. 3 min after injection of Gd-DTPA two patterns of enhancement were seen. Most lesions larger than about 5 mm had a nng-like appearance (fig 1). Smaller (and a few larger; lesions enhanced uniformly. 15 min after injection most lesions now appeared to enhance uniformly (fig 2). At 5 h the area of enhancement of single lesions appeared larger. The outer margins were blurred, and the original ring was less intense than the centre. Many of the lesions enhancing uniformly at 3 min in the first scan converted to nng enhancing lesions after 1-3 weeks. The lesions of chronic relapsmg experimental allergic encephalomyelitis, which histologically resemble those of MS, enhance in areas that correspond to areas of breakdown of the BBB with active inflammation and demyelination.1 If, as seems likely, similar mechanisms operate in MS, the different patterns of enhancement can be interpreted as follows. The lesions enhancing uniformly at 3 mlll are probably of recent origin with a striking and fairly uniform breakdown of the BBB. Ring enhancement probably arises from recent inflammation at the periphery of a lesion in which the BBB defect is partly or completely repaired in the inner, older parts. These interpretations are consistent with histological descriptions.’ We have also seen unequivocal enlargement of Fig 1--SE500l40 MRI 3 min post-contrast showing large ring lesio and smaller uniformly enhancing lesions. Non-enhancing lesions are not visible when this sequence is used. Fig 2-Same slice as in fig 1 15 min post-contrast showing uniform enhancement of larger lesions.