Articolo preso da www.ccsviitalia.org
di Matteo Scibilia
Abbiamo precedentemente citato diversi articoli e studi relativi alla importanza che riveste il monitoraggio dello stato della materia grigia, ai fini della valutazione della progressione della SM. (Vedi anche QUI)
Su Multiple Sclerosis Journal di Luglio è stato pubblicato questo Articolo italo-canadese (Arnold e De Stefano) dal titolo abbastanza indicativo "Prevenire l'atrofia cerebrale dovrebbe essere il gold standard della efficacia della terapia nella sclerosi multipla (dopo il primo anno di trattamento)"
Gli autori ricordano che per secoli l'atrofia cerebrale è stata utilizzata per calcolare la perdita di tessuto cerebrale, e che pertanto lo si può considerare un valido ed incontrovertibile marcatore del livello di neuro-degenerazione.
Si chiedono, quindi, perché l'uso dell' atrofia cerebrale come misura per verificare la validità dei trattamenti nella SM sia argomento di dibattito. Ci sono alcune questione tecniche alla base di questo, e così concludono.
In conclusione, l'intera atrofia cerebrale a lungo termine è una misura di sintesi interessante di perdita di tessuto nella SM che ha la maggiore accettazione da parte di esperti della SM e le maggior possibilità di accettazione da parte delle autorità di regolamentazione.
Rimane sempre inevasa la domanda come mai i neurologi insistono per esaminare essenzialmente l'andamento della Materia Bianca!
Preventing brain atrophy should be the gold standard of effective therapy in multiple sclerosis (after the first year of treatment): Commentary
DL Arnold1
N De Stefano2
1Montreal Neurological Institute, McGill University, Canada
2Department of Medicine Surgery and Neuroscience, University of Siena, Italy
DL Arnold, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC, H3A 2B4, Canada. Email: doug@mrs.mni.mcgill.ca
Cerebral atrophy has been used for centuries by pathologists as a marker of the loss of cerebral tissue due to injury or degeneration, and the tissue damage and loss associated with atrophy has been well documented. Thus, atrophy as a marker of neurodegeneration has incontrovertible face validity, at least over the long term. So, why is the use of whole brain atrophy as an outcome measure in multiple sclerosis (MS) the subject of debate?
Magnetic resonance imaging (MRI)-based computational methods provide sensitive and reproducible measures of brain volumes that are capable of detecting changes on the order of 0.2%: changes that are much smaller than those described at the time of postmortem examination. The interpretation of such small changes, particularly over the short term, involves subtleties that are not relevant over the long term. For example, small physiological fluctuations, due to shifts in water,1 can produce brain volume fluctuations of this order. Furthermore, the accelerated atrophy seen after initiation of some anti-inflammatory therapies, often referred to as pseudoatrophy, also complicates the interpretation of changes in brain volume. Although the pathophysiological mechanisms responsible for pseudoatrophy are still unclear, pseudoatrophy appears to be related to the nature of the anti-inflammatory therapy and the amount of inflammation present at the start of therapy.
Despite these limitations, as argued by Rudick and Fisher, a substantial body of evidence supports the use of whole brain atrophy, at least after the first year following initiation of anti-inflammatory therapy, as a marker of the end-stage of tissue injury of whatever sort and, as such, as a candidate for the best MRI marker of effective therapy in MS.
Filippi and Rocca also value atrophy as an outcome measure but, because it is an end-stage process, argue for outcome measures that provide a more pathologically specific indication of the processes that contribute to tissue loss, including gray matter (GM) atrophy, magnetization transfer imaging (MTI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS). Each of these measures has advantages and disadvantages.
Since GM is less inflamed than white matter (WM) in MS, it should be less susceptible to pseudoatrophy. However, the correct segmentation of GM on MRI is challenging2 and less precise than the segmentation of whole brain. Changes in magnetization transfer have relative specificity for changes in myelin density, which is of particular interest in MS. However, the changes that occur in whole brain magnetization transfer are extremely small3 and, as in the case of whole brain atrophy, the interpretation of such small changes may involve subtleties related not only to remyelination but also to other physiological changes that affect myelin density, such as changes in brain water or the relative partial volume of other cell types. DTI seems to be less pathologically specific for axons or myelin than one would like. MRS is pathologically specific and can report on improvements in axonal integrity related to therapy.4 However, MRS is not generally available and may not be sensitive to change in later stages of MS.
In conclusion, whole brain atrophy over the long term is an attractive summary measure of tissue loss in MS that has the greatest acceptance by MS experts and the greatest chance of acceptance by regulators. GM atrophy and non-conventional MRI outcomes help to understand the pathological basis of changes in brain volume and, as such, provide important complementary information. The answer to which is the best gold standard has to be interpreted, like MRI, in terms of shades of gray.
di Matteo Scibilia
Abbiamo precedentemente citato diversi articoli e studi relativi alla importanza che riveste il monitoraggio dello stato della materia grigia, ai fini della valutazione della progressione della SM. (Vedi anche QUI)
Su Multiple Sclerosis Journal di Luglio è stato pubblicato questo Articolo italo-canadese (Arnold e De Stefano) dal titolo abbastanza indicativo "Prevenire l'atrofia cerebrale dovrebbe essere il gold standard della efficacia della terapia nella sclerosi multipla (dopo il primo anno di trattamento)"
Gli autori ricordano che per secoli l'atrofia cerebrale è stata utilizzata per calcolare la perdita di tessuto cerebrale, e che pertanto lo si può considerare un valido ed incontrovertibile marcatore del livello di neuro-degenerazione.
Si chiedono, quindi, perché l'uso dell' atrofia cerebrale come misura per verificare la validità dei trattamenti nella SM sia argomento di dibattito. Ci sono alcune questione tecniche alla base di questo, e così concludono.
In conclusione, l'intera atrofia cerebrale a lungo termine è una misura di sintesi interessante di perdita di tessuto nella SM che ha la maggiore accettazione da parte di esperti della SM e le maggior possibilità di accettazione da parte delle autorità di regolamentazione.
Rimane sempre inevasa la domanda come mai i neurologi insistono per esaminare essenzialmente l'andamento della Materia Bianca!
Preventing brain atrophy should be the gold standard of effective therapy in multiple sclerosis (after the first year of treatment): Commentary
DL Arnold1
N De Stefano2
1Montreal Neurological Institute, McGill University, Canada
2Department of Medicine Surgery and Neuroscience, University of Siena, Italy
DL Arnold, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC, H3A 2B4, Canada. Email: doug@mrs.mni.mcgill.ca
Cerebral atrophy has been used for centuries by pathologists as a marker of the loss of cerebral tissue due to injury or degeneration, and the tissue damage and loss associated with atrophy has been well documented. Thus, atrophy as a marker of neurodegeneration has incontrovertible face validity, at least over the long term. So, why is the use of whole brain atrophy as an outcome measure in multiple sclerosis (MS) the subject of debate?
Magnetic resonance imaging (MRI)-based computational methods provide sensitive and reproducible measures of brain volumes that are capable of detecting changes on the order of 0.2%: changes that are much smaller than those described at the time of postmortem examination. The interpretation of such small changes, particularly over the short term, involves subtleties that are not relevant over the long term. For example, small physiological fluctuations, due to shifts in water,1 can produce brain volume fluctuations of this order. Furthermore, the accelerated atrophy seen after initiation of some anti-inflammatory therapies, often referred to as pseudoatrophy, also complicates the interpretation of changes in brain volume. Although the pathophysiological mechanisms responsible for pseudoatrophy are still unclear, pseudoatrophy appears to be related to the nature of the anti-inflammatory therapy and the amount of inflammation present at the start of therapy.
Despite these limitations, as argued by Rudick and Fisher, a substantial body of evidence supports the use of whole brain atrophy, at least after the first year following initiation of anti-inflammatory therapy, as a marker of the end-stage of tissue injury of whatever sort and, as such, as a candidate for the best MRI marker of effective therapy in MS.
Filippi and Rocca also value atrophy as an outcome measure but, because it is an end-stage process, argue for outcome measures that provide a more pathologically specific indication of the processes that contribute to tissue loss, including gray matter (GM) atrophy, magnetization transfer imaging (MTI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS). Each of these measures has advantages and disadvantages.
Since GM is less inflamed than white matter (WM) in MS, it should be less susceptible to pseudoatrophy. However, the correct segmentation of GM on MRI is challenging2 and less precise than the segmentation of whole brain. Changes in magnetization transfer have relative specificity for changes in myelin density, which is of particular interest in MS. However, the changes that occur in whole brain magnetization transfer are extremely small3 and, as in the case of whole brain atrophy, the interpretation of such small changes may involve subtleties related not only to remyelination but also to other physiological changes that affect myelin density, such as changes in brain water or the relative partial volume of other cell types. DTI seems to be less pathologically specific for axons or myelin than one would like. MRS is pathologically specific and can report on improvements in axonal integrity related to therapy.4 However, MRS is not generally available and may not be sensitive to change in later stages of MS.
In conclusion, whole brain atrophy over the long term is an attractive summary measure of tissue loss in MS that has the greatest acceptance by MS experts and the greatest chance of acceptance by regulators. GM atrophy and non-conventional MRI outcomes help to understand the pathological basis of changes in brain volume and, as such, provide important complementary information. The answer to which is the best gold standard has to be interpreted, like MRI, in terms of shades of gray.
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