Gray matter atrophy in multiple sclerosis: A longitudinal study

Fisher, Elizabeth; Lee, Jar-Chi; Nakamura, Kunio; Rudick, Richard A.

doi:10.1002/ana.21436

Cited by 621 publications

(588 citation statements)

References 39 publications

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“…32 Over the past few years, several studies have used MRI derived methods to assess brain volume changes, revealing that atrophy can be present even in the early stages of MS, and that it advances over the disease course (Figure 2). 33,34 Generally speaking, brain volume changes can be an important measure of tissue damage in patients with MS. 32 Indeed, baseline atrophy and high rates of subsequent volume loss are associated with cognitive impairment, fatigue and disability progression over the long term. 32,[35][36][37][38][39][40][41] In a complex disease such as MS, brain volume loss results from the sum of and interactions between various destructive pathological processes, 42 including irrever sible demyelination, and axonal and/or neuronal loss.…”

Section: Focal Lesionsmentioning

confidence: 99%

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

2015

Nat Rev Neurol

402

147

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Section: Focal Lesionsmentioning

confidence: 99%

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

2015

Nat Rev Neurol

402

147

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“…Our findings suggest, therefore, that future studies should concentrate more on understanding the pathogenetic mechanisms leading to selective SDGM rather than to cortical GM damage in patients with early RRMS. Central atrophy development in early RRMS (10% larger NLVV than that in patients with CIS) emphasizes the need for better understanding of pathogenetic mechanisms leading to selective central and SDGM atrophy.The disparate findings of GM atrophy in patients with CIS between different studies [7][8][9]11,14,16,21 point to the heterogeneity of the disease in patients with CIS and the inclusion criteria for the studies in which they are enrolled. A recent study revealed significant global GM volumetric differences in contrast to our own between patients with CIS and RRMS 16 ; however, patients with CIS did not have to fulfill the oligoclonal bands criterion.…”

mentioning

confidence: 99%

Subcortical and Cortical Gray Matter Atrophy in a Large Sample of Patients with Clinically Isolated Syndrome and Early Relapsing-Remitting Multiple Sclerosis

Bergsland

Horáková²,

Dwyer

et al. 2012

AJNR Am J Neuroradiol

139

134

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BACKGROUND AND PURPOSE:Recent studies have shown that selective regional, but not global, GM atrophy occurs from clinical onset to conversion to clinically definite MS. Our aim was to investigate the difference in the extent of SDGM and cortical atrophy in a large sample of patients with CIS and early RRMS and to explore the relationship between SDGM and cortical atrophy and other MR imaging and clinical outcomes. MATERIALS AND METHODS:Two hundred twelve patients with CIS recruited at the first clinical event (mean age, 29.3 years; median EDSS, 1.5; median disease duration, 3 months) and 177 patients with early RRMS (mean age, 30.7 years; median EDSS, 2.0; median disease duration, 47 months) were imaged on a 1.5T scanner by using a high-resolution 3D T1 spoiled gradient-recalled sequence. Volumetric data for SDGM structures were obtained by using FSL FIRST, while whole-brain, GM, white matter, cortical, and lateral ventricle volumes were estimated by using SIENAX software. Comparisons between the groups were adjusted for age and sex. RESULTS:Patients with early RRMS showed significantly lower SDGM but not cortical volumes compared with patients with CIS. The most apparent SDGM differences were evident in the caudate and thalamus (P Ͻ .0001), total SDGM (P ϭ .0001), and globus pallidus (P ϭ .01). Patients with CIS with a median T2 lesion volume Ͼ4.49 mL showed lower total SDGM, caudate, thalamus (P Ͻ .001), globus pallidus (P ϭ .007), hippocampus (P ϭ .004), and putamen (P ϭ .01) volumes and higher lateral ventricle volume (P ϭ .001) than those with a median T2 lesion volume Ͻ4.49 mL. Decreased thalamic volume showed the most consistent relationship with MR imaging outcomes (P Ͻ .0001) in patients with CIS.CONCLUSIONS: Significant SDGM, but not cortical, atrophy develops during the first 4 years of the RRMS. GM atrophy is relevant for disease progression from the earliest clinical stages.ABBREVIATIONS: ASA ϭ Avonex-Steroid-Azathioprine; CIS ϭ clinically isolated syndrome; EDSS ϭ Expanded Disease Status Scale; FSL ϭ FMRIB Software Library; GM ϭ gray matter; NBV ϭ normalized brain volume; NCV ϭ normalized cortical volume; NGMV ϭ normalized gray matter volume; NLVV ϭ normalized lateral ventricle volume; NWMV ϭ normalized white matter volume; RRMS ϭ relapsing remitting MS; SDGM ϭ subcortical deep gray matter; SET ϭ Study of Early Interferon ␤ 1a Treatment in High Risk Subjects after CIS M R imaging is a vital tool enabling clinicians to diagnose, monitor, and predict the progression of MS. Conventional MR imaging has proved to be very sensitive for detecting focal changes in the WM, yet it is relatively insensitive to involvement of the GM in MS. GM pathology in MS is quite different from that in WM, with only mild blood-brain barrier disruption and little-to-no inflammation due to minimal Tcell infiltration.1 Hence, the difference between lesion and normal GM relaxation times on MR imaging is less than that seen between lesion and normal white matter. 2In the past decade, continuous effort has been made to develop n...

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“…Brain atrophy during RRMS is highly relevant, however, as it has been shown to predict future ambulatory 13 and cognitive 9 disability. Accelerated gray matter atrophy occurs in patients at all stages of MS as well 14 and correlates better with disability than other MRI measures. 11 The picture emerges of a disease that is pathologically active from onset, in which CNS tissue may be damaged or destroyed without obvious clinical manifestations during early disease stages.…”

Section: Irreversible Axon and Myelin Injury Occurs Early In The Courmentioning

confidence: 93%

Controversy: To Treat or Not to Treat in Clinically Isolated Syndrome

Herndon¹

2009

International Journal of MS Care

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99The decision whether to treat or not to treat patients presenting with a clinically isolated syndrome suggestive of multiple sclerosis (MS) can be a difficult one. If the results of magnetic resonance imaging (MRI) are normal, most clinicians would not treat, as the risk of development of MS is low. If the MRI is abnormal, however, the decision is considerably more difficult. At present, we do not have any good markers that would allow us to determine which individuals will go on to develop MS and which individuals will remain stable.An advantage of early treatment is a 15% to 20% further reduction in attack frequency over and above the approximately 30% decrease that occurs with later treatment. This has been a consistent finding with early treatment with the interferons and glatiramer acetate. Nevertheless, with early treatment we are subjecting many patients to a regimen that will not help them in order to improve the outcome in those who will develop clinically definite MS. This "medicalizes" those patients, who will suffer the same side effects as those who need the medication.On the other hand, the placebo patients from the phase 3 trials who were treated with their second attack subsequently have more attacks than those treated early, and probably more disability. The long-term subcutaneous interferon beta-1b (Betaseron) results showed a much higher 17-year mortality rate in those receiving placebo than in those treated with either low-dose or high-dose Betaseron in the phase 3 trial.

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Gray matter atrophy in multiple sclerosis: A longitudinal study

Cited by 621 publications

References 39 publications

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

MAGNIMS consensus guidelines on the use of MRI in multiple sclerosis—establishing disease prognosis and monitoring patients

Subcortical and Cortical Gray Matter Atrophy in a Large Sample of Patients with Clinically Isolated Syndrome and Early Relapsing-Remitting Multiple Sclerosis

Controversy: To Treat or Not to Treat in Clinically Isolated Syndrome

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