Infratentorial hypointense lesion volume on T1-weighted magnetic resonance imaging correlates with disability in patients with chronic cerebellar ataxia due to multiple sclerosis

Hickman, Simon J.; Brierley, C. M. H.; Silver, N. C.; Moseley, I. F.; Scolding, Neil; Compston, D. A. S.; Miller, David H.

doi:10.1016/s0022-510x(01)00519-6

Cited by 25 publications

(27 citation statements)

References 17 publications

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“…Recurrent falls were reported by patients who had a greater length of COP path in the CE condition, that correspond to an elevated energy expenditure to maintain balance, and a prominent lesion burden on the MCP and brainstem. These data are consistent with evidence reporting that clinically eloquent sites, such as the brainstem and cerebellum, may have a major impact on clinical disability in MS [25][26][27][28][29][30], even in the early stage of the disease [31]. In our study, we also found significant correlations between the velocity on the ML axis and length of the COP path (both measured with open eyes) and the brainstem T2-LV.…”

Section: Discussionsupporting

confidence: 92%

The relationship between infratentorial lesions, balance deficit and accidental falls in multiple sclerosis

Prosperini

Kouleridou

Petsas

et al. 2011

Journal of the Neurological Sciences

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Section: Discussionsupporting

confidence: 92%

The relationship between infratentorial lesions, balance deficit and accidental falls in multiple sclerosis

Prosperini

Kouleridou

Petsas

et al. 2011

Journal of the Neurological Sciences

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“…Our findings raise the possibility that perturbations in the expression of mGluR1 and its downstream effectors as well as abnormal increases in NFH in Purkinje neurons might be a cause of cerebellar dysfunction in the PMCA2-null mouse. It is worth noting that cerebellar pathology occurs in several neurological diseases including ataxia and multiple sclerosis (Black et al, 2000;Muller et al, 2000;Hickman et al, 2001;Downey et al, 2002;Saab et al, 2004;Li et al, 2004;Pantano et al, 2005). Therefore, our findings might have relevance to these conditions, a possibility that requires further investigations.…”

Section: Discussionmentioning

confidence: 69%

Molecular alterations in the cerebellum of the plasma membrane calcium ATPase 2 (PMCA2)-null mouse indicate abnormalities in Purkinje neurons

Kurnellas

Lee

et al. 2007

Molecular and Cellular Neuroscience

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PMCA2, a major calcium pump, is expressed at particularly high levels in Purkinje neurons. Accordingly, PMCA2-null mice exhibit ataxia suggesting cerebellar pathology. It is not yet known how changes in PMCA2 expression or activity affect molecular pathways in Purkinje neurons. We now report that the levels of metabotropic glutamate receptor 1 (mGluR1), which plays essential roles in motor coordination, synaptic plasticity, and associative learning, are reduced in the cerebellum of PMCA2-null mice as compared to wild type littermates. The levels of inositol 1,4,5-triphosphate receptor type 1 (IP3R1), an effector downstream to mGluR1, which mediates intracellular calcium signaling, and the expression of Homer 1b/c and Homer 3, scaffold proteins that couple mGluR1 to IP3R1, are also reduced in somata and dendrites of some Purkinje cell subpopulations. In contrast, no alterations occur in the levels of mGluR1 and its downstream effectors in the hippocampus, indicating that the effects are region specific. The reduction in cerebellar mGluR1, IP3R1 and Homer 3 levels are neither due to a generic decrease in Purkinje proteins nor extensive dendritic loss as immunoreactivity to total and non-phosphorylated neurofilament H (NFH) is increased in Purkinje dendrites and microtubule associated protein 2 (MAP2) staining reveals a dense dendritic network in the molecular layer of the PMCA2-null mouse cerebellum. PMCA2 coimmunoprecipitates with mGluR1, Homer 3 and IP3R1, suggesting that the calcium pump is a constituent of the mGluR1 signaling complex. Our results suggest that the decrease in the expression of mGluR1 and its downstream effectors and perturbations in the mGluR1 signaling complex in the absence of PMCA2 may cumulatively result in aberrant metabotropic glutamate receptor signaling in Purkinje neurons leading to cerebellar deficits in the PMCA2-null mouse.

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“…Recently, an ultrahigh field MRI studies suggested that MS white matter lesions were most frequently located in the periventricular white matter and centered by a small vein, but NMOSD lesions were predominantly located in the subcortical/deep white matter without central venule [35], [36]. Furthermore, in MS, fewer than 40% of newly formed lesions evolve into persistent or chronic black holes that show hypointensity on T1-WI compared with the surrounding tissue [37], [38], but cystic lesions rarely presented in the brain. Otherwise, 47% of chronic lesions in NMOSD presented focal T1-hypointense lesions and, in particular, 18% revealed cystic changes in specific areas, involving mainly the corticospinal tract, corpus callosum, and parieto-occipital white matter.…”

Section: Discussionmentioning

confidence: 99%

A Longitudinal Brain Magnetic Resonance Imaging Study of Neuromyelitis Optica Spectrum Disorder

et al. 2014

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Brain involvement is commonly seen in patients with neuromyelitis optica spectrum disorder (NMOSD). However, little is known about the chronic changes of acute brain lesions on MRI over time. Here, our objective was to evaluate how acute brain MRI lesions in NMOSD changed on follow-up MRI. We reviewed the MRIs of 63 patients with NMOSD who had acute brain lesions and follow-up MRI over an interval of at least 3 months. Of the 211 acute brain lesions, 24% of lesions disappeared completely on T2-weighed images (WI) and a decrease in size ≥50% on T2-WI was observed in 58% of lesions on follow-up MRI. However, 47% of lesions revealed focal T1-hypointensity and, in particular, 18% showed focal cystic changes. Cystic changes were observed most commonly in corticospinal tract and corpus callosal lesions whereas the vast majority of lesions in the cerebellum, basal ganglia and temporal white matter resolved completely. MRI remission on T2-WI occurred in 82% of lesions, while approximately half of the lesions presented foci of T1-hypointensity, which may be considered a severe tissue injury over time. The extent of brain injury following an acute brain lesion in NMOSD may depend on the location of the lesion.

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Infratentorial hypointense lesion volume on T1-weighted magnetic resonance imaging correlates with disability in patients with chronic cerebellar ataxia due to multiple sclerosis

Cited by 25 publications

References 17 publications

The relationship between infratentorial lesions, balance deficit and accidental falls in multiple sclerosis

The relationship between infratentorial lesions, balance deficit and accidental falls in multiple sclerosis

Molecular alterations in the cerebellum of the plasma membrane calcium ATPase 2 (PMCA2)-null mouse indicate abnormalities in Purkinje neurons

A Longitudinal Brain Magnetic Resonance Imaging Study of Neuromyelitis Optica Spectrum Disorder

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