Development of hypointense lesions on T1-weighted spin-echo magnetic resonance images in multiple sclerosis: relation to inflammatory activity.

OBJECTIVE To evaluate whether degree of inflammatory activity in multiple sclerosis, expressed by frequency of gadolinium enhancement, has prognostic value for development of hypointense lesions on T1-weighted spin-echo magnetic resonance images, a putative marker of tissue destruction. DESIGN Cohort design with long-term follow-up. Thirty-eight patients with multiple sclerosis who in the past had been monitored with monthly gadolinium-enhanced magnetic resonance imaging for a median period of 10 months (range, 6-12 months) were reexamined after a median period of 40.5 months (range, 33-80 months). SETTING Magnetic Resonance Center for Multiple Sclerosis Research, Amsterdam, the Netherlands, referral center. MAIN OUTCOME MEASURES The new enhancing lesion rate (median number of gadolinium-enhancing lesions per monthly scan) during initial monthly follow-up; hypointense T1 and hyperintense T2 lesion load at first and last visit. RESULTS The number of enhancing lesions on entry scan correlated with the new enhancing lesions rate (r = 0.64; P<.001, Spearman rank correlation coefficient). The new enhancing lesion rate correlated with yearly increase in T1 (r = 0.42; P<.01, Spearman rank correlation coefficient) and T2 (r = 0.47; P<.01, Spearman rank correlation coefficient) lesion load. Initial T1 lesion load correlated more strongly with yearly increase in T1 lesion load (r = 0.68; P<.01, Spearman rank correlation coefficient). CONCLUSIONS Degree of inflammatory activity only partially predicted increase in T1 (and T2) lesion load at long-term follow-up. Initial T1 lesion load strongly contributed to subsequent increase in hypointense T1 lesion load, suggesting that there is a subpopulation of patients with multiple sclerosis who are prone to develop destructive lesions.

[1]  F. Barkhof,et al.  Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis , 1996, Annals of neurology.

[2]  D. Paty,et al.  Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis , 1993, Neurology.

[3]  A J Thompson,et al.  Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. , 1996, Brain : a journal of neurology.

[4]  R H Edwards,et al.  Magnetic resonance relaxation time mapping in multiple sclerosis: normal appearing white matter and the "invisible" lesion load. , 1994, Magnetic resonance imaging.

[5]  J A Frank,et al.  Serial contrast‐enhanced magnetic resonance imaging in patients with early relapsing–remitting multiple sclerosis: Implications for treatment trials , 1994, Annals of neurology.

[6]  H. Lassmann,et al.  Histopathology and the blood–cerebrospinal fluid barrier in multiple sclerosis , 1994, Annals of neurology.

[7]  F. Barkhof,et al.  Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR. , 1998, AJNR. American journal of neuroradiology.

[8]  P. Albert,et al.  Blood‐brain barrier disruption on contrast‐enhanced MRI in patients with mild relapsing‐remitting multiple sclerosis , 1995, Neurology.

[9]  A J Thompson,et al.  Clinical and Magnetic Resonance Imaging Predictors of Disability in Primary and Secondary Progressive Multiple Sclerosis , 1996, Multiple sclerosis.

[10]  F. Barkhof,et al.  Treatment of multiple sclerosis with the monoclonal anti-CD4 antibody cM-T412: Results of a randomized, double-blind, placebo-controlled MR-monitored phase II trial , 1997, Neurology.

[11]  R E Lenkinski,et al.  Correlation of spectroscopy and magnetization transfer imaging in the evaluation of demyelinating lesions and normal appearing white matter in multiple sclerosis , 1994, Magnetic resonance in medicine.

[12]  C. Granger,et al.  Intramuscular interferon beta‐1a for disease progression in relapsing multiple sclerosis , 1996, Annals of neurology.

[13]  P. Scheltens,et al.  MR of the spinal cord in multiple sclerosis: relation to clinical subtype and disability. , 1997, AJNR. American journal of neuroradiology.

[14]  F. Barkhof,et al.  Relapsing-remitting multiple sclerosis: sequential enhanced MR imaging vs clinical findings in determining disease activity. , 1992, AJR. American journal of roentgenology.

[15]  F. Barkhof,et al.  Accumulation of hypointense lesions ("black holes") on T1 spin-echo MRI correlates with disease progression in multiple sclerosis , 1996, Neurology.

[16]  R I Grossman,et al.  Quantitative volumetric magnetization transfer analysis in multiple sclerosis: Estimation of macroscopic and microscopic disease burden , 1996, Magnetic resonance in medicine.

[17]  H. Tobi,et al.  Correlating MRI and clinical disease activity in multiple sclerosis , 1995, Neurology.

[18]  A. Thompson,et al.  Major differences in the dynamics of primary and secondary progressive multiple sclerosis , 1991, Annals of neurology.

[19]  F. Barkhof,et al.  Specific power calculations for magnetic resonance imaging (MRI) in monitoring active relapsing-remitting multiple sclerosis (MS): implications for phase II therapeutic trials , 1997, Multiple Sclerosis.

[20]  P. Duquette,et al.  Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. The IFNB Multiple Sclerosis Study Group. , 1993 .

[21]  J. Kurtzke Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[22]  A. Thompson,et al.  Gadolinium enhanced MRI predicts clinical and MRI disease activity in relapsing-remitting multiple sclerosis. , 1997, Journal of neurology, neurosurgery, and psychiatry.

[23]  J. W. Rose,et al.  Copolymer 1 reduces relapse rate and improves disability in relapsing‐remitting multiple sclerosis , 1995, Neurology.

[24]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

[25]  J. Taubenberger,et al.  Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis , 1993, Annals of neurology.

[26]  B E Kendall,et al.  Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. , 1990, Brain : a journal of neurology.

[27]  D. N. Landon,et al.  Duration and selectivity of blood-brain barrier breakdown in chronic relapsing experimental allergic encephalomyelitis studied by gadolinium-DTPA and protein markers. , 1990, Brain : a journal of neurology.

[28]  H. McFarland,et al.  Clinical worsening in multiple sclerosis is associated with increased frequency and area of gadopentetate dimeglumine–enhancing magnetic resonance imaging lesions , 1993, Annals of neurology.

[29]  F. Barkhof,et al.  Correlations between monthly enhanced MRI Lesion rate and changes in T2 Lesion volume in multiple sclerosis , 1998, Annals of neurology.

[30]  Hans Lassmann,et al.  Inflammatory central nervous system demyelination: Correlation of magnetic resonance imaging findings with lesion pathology , 1997, Annals of neurology.

[31]  F. Barkhof,et al.  Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis , 1998, Neurology.