Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years.

T1 black holes (BHs) on MRIs may represent either areas of oedema or axonal loss in patients with multiple sclerosis. BHs begin as contrast enhancing lesions (CELs) and evolve differently from patient to patient, and within the same patient over time. We analysed BHs formation over a 4-year period. Forty-eight monthly MRIs of nine non-treated multiple sclerosis patients were evaluated for numbers of CELs and BHs. A BH was defined as a hypointense lesion on a T1 pre-contrast image that coincided with a region of high signal intensity on the T2-weighted images. A BH was considered as acute (ABH) when it occurred coincidently with the presence of enhancement and as persisting (PBH) when present after the cessation of enhancement. The present study aimed to analyse: (i) the incidence of CELs and new PBHs, and the accumulation of PBHs; (ii) the relationship between the quantity of the CELs in a given month and the likelihood of accumulating PBHs in the subsequent month; and (iii) the relationship between the duration of CELs and PBHs. Pitman's correlation test evaluated the effect of time on either the increase of CELs and new PBHs or the accumulation of PBHs, while a multiple logistic regression analysis evaluated the relationship between progression of time and CELs, and the increase of PBHs in a multivariate model. The relationship between the enhancing lesions duration and the PBHs duration, or the time to revert back to an isointense lesion was analysed using Kaplan-Meier survival models. PBHs accumulated (P < 0.001) in all patients, but the formation of new PBHs increased in four patients (P < or = 0.007) in conjunction with an increase in either the quantity of CELs (P < 0.001, for two patients) or the proportion of CELs turning into PBHs (P < or = 0.02, for two patients). Logistic regression analysis showed that neither progression of time nor the number of CELs in a given month were able to predict the probability of increasing the number of PBHs in the subsequent month in any patient. Out of 397 ABHs, 55.7% evolved to a PBH. The duration of PBHs correlated with the duration of enhancement. PBHs preceded by CELs observable on a single MRI persisted for a shorter time (P < 0.002) than those preceded by CELs visible on > or =2 monthly MRIs. The formation of a new PBH was found to be related to CELs activity; however, duration of PBHs is most likely a consequence of the duration of the enhancement.

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

[2]  F. Barkhof,et al.  Axonal loss in multiple sclerosis lesions: Magnetic resonance imaging insights into substrates of disability , 1999, Annals of neurology.

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

[4]  F. Lublin,et al.  Linomide in relapsing and secondary progressive MS , 2000, Neurology.

[5]  J. Parisi,et al.  Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination , 2000, Annals of neurology.

[6]  M. Gobbini,et al.  Enhancing magnetic resonance imaging lesions and cerebral atrophy in patients with relapsing multiple sclerosis. , 2001, Archives of neurology.

[7]  Roland Martin,et al.  Using gadolinium‐enhanced magnetic resonance imaging lesions to monitor disease activity in multiple sclerosis , 1992, Annals of neurology.

[8]  F. Jolesz,et al.  MRI contrast uptake in new lesions in relapsing-remitting MS followed at weekly intervals , 2003, Neurology.

[9]  F. Barkhof,et al.  The effect of IFNβ-1b on the evolution of enhancing lesions in secondary progressive MS , 2001, Neurology.

[10]  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.

[11]  M. Filippi,et al.  Magnetization transfer ratios of multiple sclerosis lesions with variable durations of enhancement , 1998, Journal of the Neurological Sciences.

[12]  J H Simon,et al.  A longitudinal study of T1 hypointense lesions in relapsing MS , 2000, Neurology.

[13]  D. Paty,et al.  Magnetic resonance techniques to monitor the long term evolution of multiple sclerosis pathology and to monitor definitive clinical trials. , 1998, Journal of neurology, neurosurgery, and psychiatry.

[14]  R. Rudick,et al.  Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS , 2001, Neurology.

[15]  N. Patronas,et al.  Serial gadolinium‐enhanced magnetic resonance imaging scans in patients with early, relapsing‐remitting multiple sclerosis: Implications for clinical trials and natural history , 1991, Annals of neurology.

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

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

[18]  J. Frahm,et al.  Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy. , 1999, AJNR. American journal of neuroradiology.

[19]  F Barkhof,et al.  Neuronal damage in T1‐hypointense multiple sclerosis lesions demonstrated in vivo using proton magnetic resonance spectroscopy , 1999, Annals of neurology.

[20]  O. Ciccarelli,et al.  Magnetic resonance outcome of new enhancing lesions in patients with relapsing‐remitting multiple sclerosis , 1999, European Journal of Neurology.

[21]  H. McFarland,et al.  Ring-enhancement in multiple sclerosis: marker of disease severity , 2001, Multiple sclerosis.

[22]  C. Pozzilli,et al.  Serial study of gadolinium‐DTPA MRI enhancement in multiple sclerosis , 1990, Neurology.

[23]  P. Good,et al.  Permutation Tests: A Practical Guide to Resampling Methods for Testing Hypotheses , 1995 .

[24]  A. Thompson,et al.  T(1) hypointense lesions in secondary progressive multiple sclerosis: effect of interferon beta-1b treatment. , 2001, Brain : a journal of neurology.

[25]  P M Matthews,et al.  Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. , 1998, Brain : a journal 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]  F. Barkhof,et al.  Gadolinium enhancement increases the sensitivity of MRI in detecting disease activity in multiple sclerosis. , 1993, Brain : a journal of neurology.

[28]  J. Wolinsky,et al.  Linomide in relapsing and secondary progressive MS , 2000, Neurology.

[29]  A J Thompson,et al.  T1 lesion load and cerebral atrophy as a marker for clinical progression in patients with multiple sclerosis. A prospective 18 months follow‐up study , 2001, European journal of neurology.

[30]  N. Richert.  Glatiramer acetate reduces the proportion of new MS lesions evolving into "black holes". , 2002, Neurology.

[31]  D. Goodin,et al.  Randomized, comparative study of interferon β-1a treatment regimens in MS , 2002, Neurology.

[32]  David H. Miller.  MRI monitoring of MS in clinical trials , 2002, Clinical Neurology and Neurosurgery.

[33]  R. Rudick,et al.  Axonal transection in the lesions of multiple sclerosis. , 1998, The New England journal of medicine.

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

[35]  C. Lucchinetti,et al.  A longitudinal MRI study of histopathologically defined hypointense multiple sclerosis lesions , 2001, Annals of neurology.

[36]  À. Rovira,et al.  Evolution of multiple sclerosis lesions on serial contrast-enhanced T1-weighted and magnetization-transfer MR images. , 1999, AJNR. American journal of neuroradiology.