Effects of Interferon Beta-1b on Black Holes in Multiple Sclerosis Over a 6-Year Period With Monthly Evaluations

New natural history of interferon‐β–treated relapsing multiple sclerosis

“…The results of this study suggest that IFNβ delays the inevitable and irreversible clinical worsening that is the hallmark of the late phase of this disease. These data are in accordance with recent magnetic resonance imaging (MRI) longitudinal studies showing a significant effect of IFNβ on slowing brain atrophy progression and the formation of chronic, hypointense black holes,39, 40 which are important markers of tissue destruction and are correlated with disability status41 in RRMS. Proposed mechanisms by which IFNβ might slow clinical disability and atrophy rate include increasing nerve growth factors,42 limiting immune‐mediated destructive inflammation,43 or limiting toxic mechanisms such as pathological iron deposition 44.…”

New natural history of interferon‐β–treated relapsing multiple sclerosis

“…The results of this study suggest that IFNβ delays the inevitable and irreversible clinical worsening that is the hallmark of the late phase of this disease. These data are in accordance with recent magnetic resonance imaging (MRI) longitudinal studies showing a significant effect of IFNβ on slowing brain atrophy progression and the formation of chronic, hypointense black holes,39, 40 which are important markers of tissue destruction and are correlated with disability status41 in RRMS. Proposed mechanisms by which IFNβ might slow clinical disability and atrophy rate include increasing nerve growth factors,42 limiting immune‐mediated destructive inflammation,43 or limiting toxic mechanisms such as pathological iron deposition 44.…”

Multiple Sclerosis Lesions and Irreversible Brain Tissue Damage

“…To our knowledge, the present study is the first to demonstrate that, at ultrahigh-field strength, every T2 hyperintense lesion detected on T2-weighted FLASH sequences directly corresponds to a T1 hypointense lesion on a MPRAGE sequence. Our finding challenges previous studies [11][12][13]32 as well as our own data obtained at 1.5-T MRI, in which only 80% of T2, TIRM, or DIR hyperintense lesions were visible on MPRAGE images. In the past, the prevalence and natural evolution of black holes were assessed in longitudinal studies using spin-echo sequences.…”

“…It has also been demonstrated that remyelination processes may reverse plaque hypointensity. 12,13 Such ex vivo data are corroborated by in vivo magnetic resonance spectroscopy findings of decreased N-acetylaspartate levels in black holes as a further surrogate marker of axonal injury and loss. [14][15][16] Black holes are reported to correlate better with clinical disability compared with T2 lesion load 17 and are therefore suggested as outcome parameters in clinical studies.…”

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

“…Trials of interferon beta-1b in SPMS showed a reduction in T1 hole formation, although this may have been due to an overall decrease in new lesion activity [63]. In RRMS, interferon beta-1b decreased the accumulation of T1 black holes but did not decrease their persistence [64]. A similar benefit was reported with interferon beta-1a SQ [65].…”

New natural history of interferon‐β–treated relapsing multiple sclerosis

“…The results of this study suggest that IFNβ delays the inevitable and irreversible clinical worsening that is the hallmark of the late phase of this disease. These data are in accordance with recent magnetic resonance imaging (MRI) longitudinal studies showing a significant effect of IFNβ on slowing brain atrophy progression and the formation of chronic, hypointense black holes,39, 40 which are important markers of tissue destruction and are correlated with disability status41 in RRMS. Proposed mechanisms by which IFNβ might slow clinical disability and atrophy rate include increasing nerve growth factors,42 limiting immune‐mediated destructive inflammation,43 or limiting toxic mechanisms such as pathological iron deposition 44.…”

Multiple Sclerosis Lesions and Irreversible Brain Tissue Damage

“…To our knowledge, the present study is the first to demonstrate that, at ultrahigh-field strength, every T2 hyperintense lesion detected on T2-weighted FLASH sequences directly corresponds to a T1 hypointense lesion on a MPRAGE sequence. Our finding challenges previous studies [11][12][13]32 as well as our own data obtained at 1.5-T MRI, in which only 80% of T2, TIRM, or DIR hyperintense lesions were visible on MPRAGE images. In the past, the prevalence and natural evolution of black holes were assessed in longitudinal studies using spin-echo sequences.…”

“…It has also been demonstrated that remyelination processes may reverse plaque hypointensity. 12,13 Such ex vivo data are corroborated by in vivo magnetic resonance spectroscopy findings of decreased N-acetylaspartate levels in black holes as a further surrogate marker of axonal injury and loss. [14][15][16] Black holes are reported to correlate better with clinical disability compared with T2 lesion load 17 and are therefore suggested as outcome parameters in clinical studies.…”

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

“…Trials of interferon beta-1b in SPMS showed a reduction in T1 hole formation, although this may have been due to an overall decrease in new lesion activity [63]. In RRMS, interferon beta-1b decreased the accumulation of T1 black holes but did not decrease their persistence [64]. A similar benefit was reported with interferon beta-1a SQ [65].…”

New natural history of interferon‐β–treated relapsing multiple sclerosis

“…The results of this study suggest that IFNβ delays the inevitable and irreversible clinical worsening that is the hallmark of the late phase of this disease. These data are in accordance with recent magnetic resonance imaging (MRI) longitudinal studies showing a significant effect of IFNβ on slowing brain atrophy progression and the formation of chronic, hypointense black holes,39, 40 which are important markers of tissue destruction and are correlated with disability status41 in RRMS. Proposed mechanisms by which IFNβ might slow clinical disability and atrophy rate include increasing nerve growth factors,42 limiting immune‐mediated destructive inflammation,43 or limiting toxic mechanisms such as pathological iron deposition 44.…”

Multiple Sclerosis Lesions and Irreversible Brain Tissue Damage

“…To our knowledge, the present study is the first to demonstrate that, at ultrahigh-field strength, every T2 hyperintense lesion detected on T2-weighted FLASH sequences directly corresponds to a T1 hypointense lesion on a MPRAGE sequence. Our finding challenges previous studies [11][12][13]32 as well as our own data obtained at 1.5-T MRI, in which only 80% of T2, TIRM, or DIR hyperintense lesions were visible on MPRAGE images. In the past, the prevalence and natural evolution of black holes were assessed in longitudinal studies using spin-echo sequences.…”

“…It has also been demonstrated that remyelination processes may reverse plaque hypointensity. 12,13 Such ex vivo data are corroborated by in vivo magnetic resonance spectroscopy findings of decreased N-acetylaspartate levels in black holes as a further surrogate marker of axonal injury and loss. [14][15][16] Black holes are reported to correlate better with clinical disability compared with T2 lesion load 17 and are therefore suggested as outcome parameters in clinical studies.…”

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

“…Trials of interferon beta-1b in SPMS showed a reduction in T1 hole formation, although this may have been due to an overall decrease in new lesion activity [63]. In RRMS, interferon beta-1b decreased the accumulation of T1 black holes but did not decrease their persistence [64]. A similar benefit was reported with interferon beta-1a SQ [65].…”