Articolo del 9 marzo 2013 preso da www.ccsviitalia.org.
di Matteo Scibilia
Per molto tempo si è ritenuto che i problemi cognitivi, tipici di molti pazienti con la SM fossero collegati alla Materia Bianca (WM). Questa visione è stata recentemente messa in discussione da diversi ricercatori, che hanno indirizzato le loro ricerche al ruolo della Materia Grigia (GM). Uno per tutti, Zivadinov (vedi QUI), che si esprime così:
"Come stabilito in numerosi studi, il danno GM costituisce un migliore indicatore di disabilità fisica e deterioramento cognitivo rispetto ai danni WM. Monitorare l'evoluzione del danno GM sta diventando un indicatore importante nel predire il futuro corso della malattia e la risposta alla terapia in pazienti con SM."
Una recente Review rimette la palla al centro. (vedi QUI)
Lo studio, finanziato dalla Dutch MS Research Foundation - e con rapporti con diverse aziende farmaceuriche (1) - , utilizzando una tecnica di RM avanzata - diffusion tensor imaging (DTI) (2) - ha trovato danni alla sostanza bianca in alcune regioni del cervello, molte deile quali erano già note per la loro importanza per le funzioni cognitive.
Nello studio precedentemente citato, dice Zivadinov :
TUTTE le attuali terapie farmacologiche si propongono di intervenire sull'infiammazione della sostanza bianca: ma si ha solo un qualche riscontro di come esse impattino sulle lesioni della sostanza bianca e l'infiammazione, mentre non sappiamo se e come agiscono sull' infiammazione o degenerazione della materia grigia. Molti specialisti di SM suppongono che la riduzione dell'infiammazione della materia bianca si debba necessariamente tradurre in una minore degenerazione della materia grigia, ma questa è una supposizione basata su una ipotesi - NON DIMOSTRATA - che l'infiammazione cominci dalla WM, per poi provocare danni alla GM.
Si potrebbe pensare che riportare l'attenzione verso la Materia Bianca comporti conseguentemente avallare le attuali terapie farmacologiche. Questo tirare la coperta una volta dalla parte della Sostanza Bianca ed un'altra da quella della Materia Grigia, al di là del dibattito scientifico e dell'interesse del paziente, ha certamente anche l'Industria Farmaceutica come spettatore attivo, e ceertamente non didinteressato.
Study authors reported relationships with Pfizer, Novartis, Merck Serono, Biogen Idec, Synthon, Danone, Bayer Schering, UCB, Roche, Actelion, GlaxoSmithKline, Teva, Janssen, and Lundbeck
A differenza della risonanza magnetica standard, l' imaging del tensore di diffusione consente misurazioni quantitative dell'integrità microstrutturale dei tratti di sostanza bianca, sia nelle zone 'normali' che in quelle con lesioni della sclerosi multipla
Significant differences were seen in sophisticated MRI brain scans between multiple sclerosis (MS) patients with cognitive impairments and those without, apparently unrelated to classic MS lesions, researchers said.
Among impaired patients only, diffusion tensor imaging (DTI) revealed damage to white matter in multiple brain regions, many of which were already known to be important for cognitive function, according to Hanneke Hulst, MSc, of VU University Medical Center in Amsterdam, and colleagues.
Unlike standard MRI scans, diffusion tensor imaging "allows for quantitative measurements of the microstructural integrity of white matter tracts both in the normal-appearing white matter and in areas with MS lesions," they explained in the March 12 issue of Neurology. "DTI might be a powerful tool when monitoring cognitive impairment in MS."
Up to 65% of all MS patients develop cognitive impairment, Hulst and colleagues noted. Although previous studies have linked this complication to standard MRI measures such as T1 and T2 lesion volume and overall brain atrophy, these associations do not account for all the variation between patients.
In particular, conventional MRI does not pick up small-scale alterations in white matter, which also could contribute to cognitive problems in MS patients.
To explore the question further, Hulst and colleagues performed conventional MRI and diffusion tensor imaging scans in 55 MS patients and 20 healthy controls. Patients and controls were mostly middle-age (means in the three groups ranged from 46 to 50) and, in line with the distribution of MS in the general population, were mostly female. Disease duration in the patients was about 12 years.
All participants underwent neuropsychological testing in such domains as verbal memory and learning, spatial memory, working memory, semantic memory, and processing speed. Patients with total scores at least two standard deviations below the mean for healthy controls were classed as cognitively impaired.
Hulst and colleagues classified 35 of the patients as cognitively normal and 20 as impaired.
Significant differences were seen in the impaired patients versus both the unimpaired patients and the healthy controls in standard MRI measures, including normalized volumes of gray matter and the brain overall.
Also, mean T1 and T2 lesion volumes were substantially larger in impaired versus unimpaired patients, although the differences just missed statistical significance at the P=0.05 level.
There was no difference between the two patient groups in normalized white matter volume on conventional MRI. But the diffusion tensor imaging scans revealed important structural differences.
In particular, fractional anisotropy was significantly lower -- a sign of reduced functionality -- in the corpus callosum, superior and inferior longitudinal fasciculus, corticospinal tracts, forceps major, cingulum, and fornices, according to Hulst and colleagues. Abnormalities in these areas were present in both patient groups but were worse in the impaired patients.
Some white-matter regions showed damage only in the impaired patients, the researchers found. These included cortical areas, the thalamus, uncinate fasciculus, brainstem, and cerebellum.
"These findings were independent of [conventional] lesion location and regional gray matter volume," Hulst and colleagues wrote, adding that "a next step will be to investigate the sensitivity and specificity of DTI to detect changes over time and the exact relation with cognitive deterioration."
The researchers observed that diffusion tensor imaging is now a readily available tool, "although standardized acquisition protocols are necessary."
Limitations to the analysis included older age in the cognitively impaired patients relative to controls, but Hulst and colleagues sought to control for the difference in their statistical analyses.
di Matteo Scibilia
Per molto tempo si è ritenuto che i problemi cognitivi, tipici di molti pazienti con la SM fossero collegati alla Materia Bianca (WM). Questa visione è stata recentemente messa in discussione da diversi ricercatori, che hanno indirizzato le loro ricerche al ruolo della Materia Grigia (GM). Uno per tutti, Zivadinov (vedi QUI), che si esprime così:
"Come stabilito in numerosi studi, il danno GM costituisce un migliore indicatore di disabilità fisica e deterioramento cognitivo rispetto ai danni WM. Monitorare l'evoluzione del danno GM sta diventando un indicatore importante nel predire il futuro corso della malattia e la risposta alla terapia in pazienti con SM."
Una recente Review rimette la palla al centro. (vedi QUI)
Lo studio, finanziato dalla Dutch MS Research Foundation - e con rapporti con diverse aziende farmaceuriche (1) - , utilizzando una tecnica di RM avanzata - diffusion tensor imaging (DTI) (2) - ha trovato danni alla sostanza bianca in alcune regioni del cervello, molte deile quali erano già note per la loro importanza per le funzioni cognitive.
Nello studio precedentemente citato, dice Zivadinov :
TUTTE le attuali terapie farmacologiche si propongono di intervenire sull'infiammazione della sostanza bianca: ma si ha solo un qualche riscontro di come esse impattino sulle lesioni della sostanza bianca e l'infiammazione, mentre non sappiamo se e come agiscono sull' infiammazione o degenerazione della materia grigia. Molti specialisti di SM suppongono che la riduzione dell'infiammazione della materia bianca si debba necessariamente tradurre in una minore degenerazione della materia grigia, ma questa è una supposizione basata su una ipotesi - NON DIMOSTRATA - che l'infiammazione cominci dalla WM, per poi provocare danni alla GM.
Si potrebbe pensare che riportare l'attenzione verso la Materia Bianca comporti conseguentemente avallare le attuali terapie farmacologiche. Questo tirare la coperta una volta dalla parte della Sostanza Bianca ed un'altra da quella della Materia Grigia, al di là del dibattito scientifico e dell'interesse del paziente, ha certamente anche l'Industria Farmaceutica come spettatore attivo, e ceertamente non didinteressato.
Study authors reported relationships with Pfizer, Novartis, Merck Serono, Biogen Idec, Synthon, Danone, Bayer Schering, UCB, Roche, Actelion, GlaxoSmithKline, Teva, Janssen, and Lundbeck
A differenza della risonanza magnetica standard, l' imaging del tensore di diffusione consente misurazioni quantitative dell'integrità microstrutturale dei tratti di sostanza bianca, sia nelle zone 'normali' che in quelle con lesioni della sclerosi multipla
Significant differences were seen in sophisticated MRI brain scans between multiple sclerosis (MS) patients with cognitive impairments and those without, apparently unrelated to classic MS lesions, researchers said.
Among impaired patients only, diffusion tensor imaging (DTI) revealed damage to white matter in multiple brain regions, many of which were already known to be important for cognitive function, according to Hanneke Hulst, MSc, of VU University Medical Center in Amsterdam, and colleagues.
Unlike standard MRI scans, diffusion tensor imaging "allows for quantitative measurements of the microstructural integrity of white matter tracts both in the normal-appearing white matter and in areas with MS lesions," they explained in the March 12 issue of Neurology. "DTI might be a powerful tool when monitoring cognitive impairment in MS."
Up to 65% of all MS patients develop cognitive impairment, Hulst and colleagues noted. Although previous studies have linked this complication to standard MRI measures such as T1 and T2 lesion volume and overall brain atrophy, these associations do not account for all the variation between patients.
In particular, conventional MRI does not pick up small-scale alterations in white matter, which also could contribute to cognitive problems in MS patients.
To explore the question further, Hulst and colleagues performed conventional MRI and diffusion tensor imaging scans in 55 MS patients and 20 healthy controls. Patients and controls were mostly middle-age (means in the three groups ranged from 46 to 50) and, in line with the distribution of MS in the general population, were mostly female. Disease duration in the patients was about 12 years.
All participants underwent neuropsychological testing in such domains as verbal memory and learning, spatial memory, working memory, semantic memory, and processing speed. Patients with total scores at least two standard deviations below the mean for healthy controls were classed as cognitively impaired.
Hulst and colleagues classified 35 of the patients as cognitively normal and 20 as impaired.
Significant differences were seen in the impaired patients versus both the unimpaired patients and the healthy controls in standard MRI measures, including normalized volumes of gray matter and the brain overall.
Also, mean T1 and T2 lesion volumes were substantially larger in impaired versus unimpaired patients, although the differences just missed statistical significance at the P=0.05 level.
There was no difference between the two patient groups in normalized white matter volume on conventional MRI. But the diffusion tensor imaging scans revealed important structural differences.
In particular, fractional anisotropy was significantly lower -- a sign of reduced functionality -- in the corpus callosum, superior and inferior longitudinal fasciculus, corticospinal tracts, forceps major, cingulum, and fornices, according to Hulst and colleagues. Abnormalities in these areas were present in both patient groups but were worse in the impaired patients.
Some white-matter regions showed damage only in the impaired patients, the researchers found. These included cortical areas, the thalamus, uncinate fasciculus, brainstem, and cerebellum.
"These findings were independent of [conventional] lesion location and regional gray matter volume," Hulst and colleagues wrote, adding that "a next step will be to investigate the sensitivity and specificity of DTI to detect changes over time and the exact relation with cognitive deterioration."
The researchers observed that diffusion tensor imaging is now a readily available tool, "although standardized acquisition protocols are necessary."
Limitations to the analysis included older age in the cognitively impaired patients relative to controls, but Hulst and colleagues sought to control for the difference in their statistical analyses.
Source: www.medpagetoday.com
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