Familial aggregation of white matter lesions in myotonic dystrophy type 1

Costanzo, Alfonso Di; Santoro, Lucio; Cristofaro, M. De; Manganelli, Fiore; Salle, Francesco Di; Tedeschi, Gioacchino

doi:10.1016/j.nmd.2008.01.008

Cited by 16 publications

(19 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, there are a multitude of neuroimaging studies that have examined the relation of brain affection and CTG repeat lengths. However, results are highly controversial, and most studies failed to find any correlations (Kassubek et al ., 2003; Antonini et al ., 2004; Di Costanzo et al ., 2008). This might be due to the marked somatic mosaicism of CTG repeat lengths.…”

Section: Discussionmentioning

confidence: 99%

“…While some studies showed correlations of brain morphological changes with neuropsychological and clinical parameters including CTG repeat sizes in myotonic dystrophy type 1 (Ota et al ., 2006; Kuo et al ., 2008; Romeo et al ., 2010; Weber et a l., 2010; Wozniak et al ., 2011), others failed to do so (Kassubek et al ., 2003; Antonini et al ., 2004; Fukuda et al ., 2005; Di Costanzo et al ., 2008). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease

Minnerop

Weber

Schoene-Bake

et al. 2011

Brain

196

291

View full text Add to dashboard Cite

Myotonic dystrophy types 1 and 2 are progressive multisystemic disorders with potential brain involvement. We compared 22 myotonic dystrophy type 1 and 22 myotonic dystrophy type 2 clinically and neuropsychologically well-characterized patients and a corresponding healthy control group using structural brain magnetic resonance imaging at 3 T (T1/T2/diffusion-weighted). Voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics were applied for voxel-wise analysis of cerebral grey and white matter affection (Pcorrected < 0.05). We further examined the association of structural brain changes with clinical and neuropsychological data. White matter lesions rated visually were more prevalent and severe in myotonic dystrophy type 1 compared with controls, with frontal white matter most prominently affected in both disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel-based morphometry analyses demonstrated extensive white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted to myotonic dystrophy type 1. Accordingly, we found more prominent white matter affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by diffusion tensor imaging. Association fibres throughout the whole brain, limbic system fibre tracts, the callosal body and projection fibres (e.g. internal/external capsules) were affected in myotonic dystrophy types 1 and 2. Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We found mild executive and attentional deficits in our patients when neuropsychological tests were corrected for manual motor dysfunctioning. Regression analyses revealed associations of white matter affection with several clinical parameters in both disease entities, but not with neuropsychological performance. We showed that depressed mood and fatigue were more prominent in patients with myotonic dystrophy type 1 with less white matter affection (early disease stages), contrary to patients with myotonic dystrophy type 2. Thus, depression in myotonic dystrophies might be a reactive adjustment disorder rather than a direct consequence of structural brain damage. Associations of white matter affection with age/disease duration as well as patterns of cerebral water diffusion parameters pointed towards an ongoing process of myelin destruction and/or axonal loss in our cross-sectional study design. Our data suggest that both myotonic dystrophy types 1 and 2 are serious white matter diseases with prominent callosal body and limbic system affection. White matter changes dominated the extent of grey matter changes, which might argue against Wallerian degeneration as the major cause of white matter affection in myotonic dystrophies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease

Minnerop

Weber

Schoene-Bake

et al. 2011

Brain

196

291

View full text Add to dashboard Cite

show abstract

“…Visual assessment and lesion probability maps showed that WMHs were mainly located in the anterior temporal, frontal, parieto-occipital and periventricular WM regions. Several MRI studies have shown that DM1 patients have WMHs, which are generally more prominent in the frontal, parietal and temporal regions and increase with the progression of the disease [7], [10]–[13], [15], [41]–[43]. However, they used qualitative scales to evaluate the spatial distribution of WMHs.…”

Section: Discussionmentioning

confidence: 99%

Cognitive Impairment in Myotonic Dystrophy Type 1 Is Associated with White Matter Damage

et al. 2014

View full text Add to dashboard Cite

ObjectiveTo investigate grey (GM) and white matter (WM) abnormalities and their effects on cognitive and behavioral deficits in a large, phenotypically and genotypically well-characterized cohort of classic adult (aDM1, age at onset ≥20 years) or juvenile (jDM1, age at onset <20 years) patients with myotonic dystrophy type 1 (DM1).MethodsA case-control study including 51 DM1 patients (17 jDM1 and 34 aDM1) and 34 controls was conducted at an academic medical center. Clinical, cognitive and structural MRI evaluations were obtained. Quantitative assessments of regional GM volumes, WM hyperintensities (WMHs), and microstructural WM tract damage were performed. The association between structural brain damage and clinical and cognitive findings was assessed.ResultsDM1 patients showed a high prevalence of WMHs, severe regional GM atrophy including the key nodes of the sensorimotor and main cognitive brain networks, and WM microstructural damage of the interhemispheric, corticospinal, limbic and associative pathways. WM tract damage extends well beyond the focal WMHs. While aDM1 patients had severe patterns of GM atrophy and WM tract damage, in jDM1 patients WM abnormalities exceeded GM involvement. In DM1, WMHs and microstructural damage, but not GM atrophy, correlated with cognitive deficits.ConclusionsWM damage, through a disconnection between GM structures, is likely to be the major contributor to cognitive impairment in DM1. Our MRI findings in aDM1 and jDM1 patients support the hypothesis of a degenerative (premature aging) origin of the GM abnormalities and of developmental changes as the principal substrates of microstructural WM alterations in DM1.

show abstract

“…CTG repeat-length, as measured in blood, is an imperfect index of disease severity because of the variable expression across tissue types. A number of studies have found significant correlations between CTG-repeats and macro-level measures like IQ (13, 44, 45) or the extent of white matter disease (19), but some have not found an association (23, 46, 47). In the current study, we observed a relationship with MDiff in two tracts, the corticospinal tract and cingulum.…”

Section: Discussionmentioning

confidence: 99%

Tractography reveals diffuse white matter abnormalities in Myotonic Dystrophy Type 1

Wozniak

Mueller

Lim

et al. 2014

Journal of the Neurological Sciences

View full text Add to dashboard Cite

Cerebral involvement in Myotonic Dystrophy Type 1 (DM1) is well-established but not well characterized. This study applied new Diffusion Tensor Imaging (DTI) tractography to characterize white matter disturbance in adults with DM1. Forty-five participants with DM1 and 44 control participants had MRIs on a Siemens 3T TIM Trio scanner. Data were processed with TRActs Constrained by UnderLying Anatomy (TRACULA) and 7 tracts were evaluated. Bilateral disturbances in white matter integrity were seen in all tracts in participants with DM1 compared to controls. There were no right-left hemisphere differences. The resulting DTI metrics were correlated with cognitive functioning, particularly working memory and processing speed. Motor speed was not significantly correlated with white matter microstructural integrity and, thus, was not the core explanation for the working memory and processing speed findings. White matter integrity was correlated with important clinical variables including the muscular impairment rating scale (MIRS). CTG repeat length was moderately associated with white matter status in corticospinal tract and cingulum. Sleepiness (Epworth Sleepiness Scale) was moderately associated with white matter status in the superior longitudinal fasciculus and cingulum. Overall, the results add to an emerging literature showing widespread white matter disturbances in both early-onset and adult-onset DM1. Results suggest that further investigation of white matter pathology is warranted in DM1 and that non-invasive measures such as DTI have potentially important clinical value in characterizing the status of individuals with DM1.

show abstract

Familial aggregation of white matter lesions in myotonic dystrophy type 1

Cited by 16 publications

References 37 publications

The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease

The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease

Cognitive Impairment in Myotonic Dystrophy Type 1 Is Associated with White Matter Damage

Tractography reveals diffuse white matter abnormalities in Myotonic Dystrophy Type 1

Contact Info

Product

Resources

About