Assessment of Whole-Brain White Matter by DTI in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

Oğuz, Kader K.; Haliloğlu, Göknur; Temuçin, Çağrı Mesut; Göçmen, Rahşan; Has, Arzu Ceylan; Doerschner, Katja; Dolgun, Anıl; Alikaşifoğlu, Mehmet

doi:10.3174/ajnr.a3488

Cited by 16 publications

(11 citation statements)

References 37 publications

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“…To the best of our knowledge, Turkish patients with ARSACS have been previously reported. [ 6 7 8 ] Detected mutations in previously reported Turkish patients were different from that of our patient. We identified the same mutation that was reported in a study by Synofzik et al .…”

Section: Discussioncontrasting

confidence: 85%

Autosomal-recessive spastic ataxia of Charlevoix-Saguenay: A Turkish child

2018

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Autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by mutations of the SACS gene, characterized by late-infantile-onset spastic ataxia and other neurological features. ARSACS has a high prevalence in northeastern Quebec, Canada. Recently, several ARSACS cases have been reported from outside Canada. We report typical clinical and neuroimaging features in a Turkish child, which confirmed genetic diagnosis of ARSACS.

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Section: Discussioncontrasting

confidence: 85%

Autosomal-recessive spastic ataxia of Charlevoix-Saguenay: A Turkish child

2018

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“…This limitation is increasingly important to emphasize as specific pathologic white matter changes are now commonly implied in human studies based solely upon directional diffusion metrics in the absence of ground truth pathologic validation. [34][35][36][37][38][39][40] Although EB demyelination has been extensively utilized to study mechanisms of endogenous and graft-mediated remyelination, 23,[41][42][43] to our knowledge this is the first study to examine MRI features of EB-induced injury. EB demyelination does not precisely replicate Color image is available online at www.liebertpub.com/neu any known clinical disease; however, it is ideally suited for evaluating diffusion MRI correlates of myelin pathology in vivo in the absence of significant secondary axonal injury or primary inflammatory response.…”

mentioning

confidence: 99%

Diffusion-Weighted Magnetic Resonance Imaging Characterization of White Matter Injury Produced by Axon-Sparing Demyelination and Severe Contusion Spinal Cord Injury in Rats

TalbottJason

Nout-LomasYvette

WendlandMichael

et al. 2016

Journal of Neurotrauma

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Alterations in magnetic resonance imaging (MRI)-derived measurements of water diffusion parallel (D∥) and perpendicular (D⊥) to white matter tracts have been specifically attributed to pathology of axons and myelin, respectively. We test the hypothesis that directional diffusion measurements can distinguish between axon-sparing chemical demyelination and severe contusion spinal cord white matter injury. Adult rats received either unilateral ethidium bromide (EB) microinjections (chemical demyelination) into the lateral funiculus of the spinal cord at C5 or were subjected to unilateral severe contusion spinal cord injury (SCI). Diffusion MRI metrics in the lateral funiculus were analyzed at early and late time-points following injury and correlated with histology. Early EB-demyelination resulted in a significant elevation in D⊥ and significant reduction in D∥ at the injury epicenter, with histological evidence of uniform axon preservation. Alterations in D⊥ and D∥ at the epicenter of early EB-demyelination were not significantly different from those observed with severe contusion at the epicenter, where histology demonstrated severe combined axonal and myelin injury. Diffusion abnormalities away from the injury epicenter were seen with contusion injury, but not with EB-demyelination. Chronic EB lesions underwent endogenous remyelination with normalization of diffusion metrics, whereas chronic contusion resulted in persistently altered diffusivities. In the early setting, directional diffusion measurements at the injury epicenter associated with chemical demyelination are indistinguishable from those seen with severe contusive SCI, despite dramatic pathologic differences between injury models. Caution is advised in interpretation of diffusion metrics with respect to specific white matter structural alterations. Diffusion analysis should not be limited to the epicenter of focal spinal lesions as alterations marginal to the epicenter are useful for assessing the nature of focal white matter injury.

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“…The first mutations were observed in 2004: this study reported two missense (W1196R and N3799D) mutations and two indels (L3193-fsX3199 and T2683-fsX2708)[ 55 , 56 ]. Later, additional mutations were also discovered: Oguz et al analyzed nine unrelated families and revealed eight novel mutations in the SACS gene (5019A>G/F4011S, 14370G>T/S894X, 12841T>A/K1404X, 5031 G>A/ S4007F, 12660A>G/ I1464T, 8346–8347insT, 5677G>A/ R3801, 5566delC), and one variant (6945A>G/V3369A) [ 57 ]. Kurt et al reported a homozygous G2772A mutation in a Turkish female patient with ataxia and spondyloepiphyseal dysplasia, but it was heterozygous in unaffected family members.…”

Section: Sacs Genetics and Mutationsmentioning

confidence: 99%

Genetics of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Role of Sacsin in Neurodegeneration

Bagaria

Bagyinszky

2022

IJMS

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Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that was originally discovered in the population from the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region in Quebec. Although the disease progression of ARSACS may start in early childhood, cases with later onset have also been observed. Spasticity and ataxia could be common phenotypes, and retinal optic nerve hypermyelination is detected in the majority of patients. Other symptoms, such as pes cavus, ataxia and limb deformities, are also frequently observed in affected individuals. More than 200 mutations have been discovered in the SACS gene around the world. Besides French Canadians, SACS genetics have been extensively studied in Tunisia or Japan. Recently, emerging studies discovered SACS mutations in several other countries. SACS mutations could be associated with pathogenicity either in the homozygous or compound heterozygous stages. Sacsin has been confirmed to be involved in chaperon activities, controlling the microtubule balance or cell migration. Additionally, sacsin may also play a crucial role in regulating the mitochondrial functions. Through these mechanisms, it may share common mechanisms with other neurodegenerative diseases. Further studies are needed to define the exact functions of sacsin. This review introduces the genetic mutations discovered in the SACS gene and discusses its pathomechanisms and its possible involvement in other neurodegenerative diseases.

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Assessment of Whole-Brain White Matter by DTI in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

Abstract: BACKGROUND AND PURPOSE:Extension and characteristics of WM involvement other than the brain stem remain inadequately investigated in ARSACS. The aim of this study was to investigate whole-brain WM alterations in patients with ARSACS.

Cited by 16 publications

References 37 publications

Autosomal-recessive spastic ataxia of Charlevoix-Saguenay: A Turkish child

Autosomal-recessive spastic ataxia of Charlevoix-Saguenay: A Turkish child

Diffusion-Weighted Magnetic Resonance Imaging Characterization of White Matter Injury Produced by Axon-Sparing Demyelination and Severe Contusion Spinal Cord Injury in Rats

Genetics of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Role of Sacsin in Neurodegeneration

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