Iron Deposition on SWI-Filtered Phase in the Subcortical Deep Gray Matter of Patients with Clinically Isolated Syndrome May Precede Structure-Specific Atrophy

Hagemeier, Jesper; Weinstock‐Guttman, Bianca; Bergsland, Niels; Heininen-Brown, Mari; Carl, Ellen; Kennedy, Cheryl; Magnano, Christopher; Hojnacki, David; Dwyer, Michael G.; Zivadinov, Robert

doi:10.3174/ajnr.a3030

Cited by 56 publications

(63 citation statements)

References 53 publications

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“…Hagemeier et al (2012) 41 42 CIS and 65 controls Patients with CIS showed significantly increased content and volume of iron, as determined by abnormal SWI-phase measurement in the various SDGM structures, especially in the pulvinar nucleus of thalamus, suggesting that iron deposition may precede structure-specific atrophy.…”

Section: Mesaros Et Al (2011)mentioning

confidence: 99%

The thalamus and multiple sclerosis

Minagar¹,

Barnett²,

Benedict³

et al. 2013

Neurology

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310

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The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS, and that iron deposition and atrophy of deep gray nuclei are closely related to the magnitude of inflammation. Extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS. In this review, we characterize the neuropathologic, neuroimaging, and clinical features of thalamic involvement in MS. Further, we underscore the contention that neuropathologic and neuroimaging correlative investigations of thalamic derangements in MS may elucidate not heretofore considered pathobiological underpinnings germane to understanding the ontogeny, magnitude, and progression of the disease process. Neurology â 2013;80:210-219 GLOSSARY CIS 5 clinically isolated inflammatory demyelinating syndrome; DIR 5 double inversion recovery; DTI 5 diffusion tensor imaging; EDSS 5 Expanded Disability Status Scale; GM 5 gray matter; LGN 5 lateral geniculate nucleus; MS 5 multiple sclerosis; NAGM 5 normal-appearing gray matter; NAWM 5 normal-appearing white matter; SWI 5 susceptibility-weighted imaging; WM 5 white matter.Multiple sclerosis (MS) is a progressive inflammatory and degenerative disease of the human CNS that leads to demyelination and neuronal/axonal loss. Both the etiology and cure for MS remain elusive, and for many years scientific research into the pathogenesis of MS has heavily focused on a disease principally affecting CNS white matter (WM).Notwithstanding the traditional focus upon WM as the predominant target of the disease mechanisms in MS, recent findings, which indicate significant gray matter (GM) involvement, are an important and substantial refinement in our understanding of the pathobiological underpinnings of the disease process in MS, of particular relevance to cognitive decline as well as overall disease worsening.1,2 Neuropathologic data implicate significant cortical demyelination and neuro-axonal and synaptic loss in both the early and late phases of the disease process.2-5 Both cortical 3 and subcortical demyelination are observed during the course of MS, targeting a landscape of GM-rich struct...

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Section: Mesaros Et Al (2011)mentioning

confidence: 99%

The thalamus and multiple sclerosis

Minagar¹,

Barnett²,

Benedict³

et al. 2013

Neurology

Self Cite

310

222

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“…5 Even in clinically isolated syndrome, this representation of increased iron accumulation was found in the putamen and pulvinar. 6 In a pediatric MS cohort, analysis of LPV reflected increased iron accumulation in both the thalamus and pulvinar while the volume of the LPV was increased in the pulvinar. 7 LPV volume was also increased in clinically isolated syndrome in the caudate nucleus, putamen, and pulvinar, 6 and magnetic susceptibility (also indicative of iron level) was increased in the caudate nucleus, putamen, globus pallidus, and pulvinar.…”

mentioning

confidence: 99%

“…6 In a pediatric MS cohort, analysis of LPV reflected increased iron accumulation in both the thalamus and pulvinar while the volume of the LPV was increased in the pulvinar. 7 LPV volume was also increased in clinically isolated syndrome in the caudate nucleus, putamen, and pulvinar, 6 and magnetic susceptibility (also indicative of iron level) was increased in the caudate nucleus, putamen, globus pallidus, and pulvinar. 8 Contemporary research shows that brain atrophy is predictive of cognitive disability in MS, more so than lesion burden.…”

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confidence: 99%

Iron and Volume in the Deep Gray Matter: Association with Cognitive Impairment in Multiple Sclerosis

Modica

Zivadinov²,

Dwyer

et al. 2014

American Journal of Neuroradiology

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BACKGROUND AND PURPOSE:There is a well-established correlation between deep gray matter atrophy and cognitive dysfunction in MS. However, the cause of these signs of neurodegeneration is poorly understood. Iron accumulation in the deep gray matter is higher in patients with MS compared with age-and sex-matched healthy controls, and could contribute to disease progression. Our objective was to evaluate the relationship between iron and cognition in several deep gray matter structures while accounting for the influence of volume loss.

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“…Owing to the lack of increased deposition in CIS, and the fact that iron deposition was significantly elevated in relapsingremitting MS compared with CIS, the authors suggested that iron accumulation is an epiphenomenon of the disease process, although they did not exclude the possibility that once iron accumulates, it could still promote oxidative damage [3]. In other studies, 1.5 T MRI revealed that the left head of the caudate had a significantly reduced T2 hypointensity, which is indicative of iron, in CIS patients compared with healthy controls [4], and a 3 T system using susceptibility-weighted imaging revealed greater signal attenuation, indicative of iron, in the putamen and pulvinar nucleus [5]. Taken together, these studies paint an ambiguous picture about iron in CIS; that is, is iron significantly elevated in CIS patients relative to age-matched controls, and if so, in which structures?…”

Section: Discussionmentioning

confidence: 99%

“…It is unknown whether the accumulated iron has a role in the pathogenesis of MS; however, establishing when iron first accumulates in the course of disease could provide information that has bearing on this question. MRI studies on clinically isolated syndrome (CIS), which is the initial presentation of symptoms associated with a high probability of developing into definite MS, have yielded conflicting results relative to the accumulation of iron [3][4][5]. Al-Radaideh et al have utilized a MRI technique with enhanced sensitivity over other procedures to study the deposition of iron in CIS [6].…”

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confidence: 99%