Cognitive Decline and White Matter Integrity Degradation in Myotonic Dystrophy Type I.

BACKGROUND AND PURPOSE: Myotonic Dystrophy Type I (DM1) is a neurodegenerative, genetic, and multisystemic disorder with a large variety of symptoms due to a CTG trinucleotide expansion located on Dystrophia Myotonica Protein Kinase (DMPK) gene. Previous reports have shown cognitive deterioration in these patients. Given that white matter (WM) degradation has also been reported in DM1 patients, here we explored if alterations in the cognitive profile of DM1 patients could be related to the deterioration of WM. METHODS: A total of 22 classic DM1 patients with age range (18-56 years) and 22 matched healthy control subjects were neuropsychological evaluated by the Cambridge Neuropsychological Test Automated (CANTAB). Patients were evaluated with the Muscular Impairment Rating Scale (MIRS). We then evaluated the cerebral WM integrity using the Fractional Anisotropy (FA) index obtained from the Diffusion Tensor Imaging (DTI) data acquired with a 3T MR scanner. RESULTS: DM1 patients showed generalized reduction of WM integrity across the brain. Similarly, patients' neuropsychological evaluation showed significant deficits in memory and problem-solving tasks. Correlation analyses showed a significant correlation between FA deterioration at frontal, temporomedial, and parietal lobes and delayed matched to sample deficits. CONCLUSIONS: Our results suggest that despite the pervasive WM integrity loss in DM1 disorder, specific memory impairments can be associated to discreet areas of WM deterioration in these patients.

Longitudinal Analysis of the Relation Between Clinical Impairment and Gray Matter Degeneration in Spinocerebellar Ataxia Type 7 Patients.

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease characterized by progressive ataxia and retinal degeneration. Previous cross-sectional studies show a significant decrease in the gray matter of the cerebral cortex, cerebellum, and brainstem. However, there are no longitudinal studies in SCA7 analyzing whole-brain degeneration and its relation to clinical decline. To perform a 2-year longitudinal characterization of the whole-brain degeneration and clinical decline in SCA7, twenty patients underwent MRI and clinical evaluations at baseline. Fourteen completed the 2-year follow-up study. A healthy-matched control group was also included. Imaging analyses included volumetric and cortical thickness evaluation. We measured the cognitive deterioration in SCA7 patients using MoCA test and the motor deterioration using the SARA score. We found statistically significant differences in the follow-up compared to baseline. Imaging analyses showed that SCA7 patients had severe cerebellar and pontine degeneration compared with the control group. Longitudinal follow-up imaging analyses of SCA7 patients showed the largest atrophy in the medial temporal lobe without signs of a progression of cerebellar and pontine atrophy. Effect size analyses showed that MRI longitudinal analysis has the largest effect size followed by the SARA scale and MoCA test. Here, we report that it is possible to detect significant brain atrophy and motor and cognitive clinical decline in a 2-year follow-up study of SCA7 patients. Our results support the hypothesis that longitudinal analysis of structural MRI and MOCA tests are plausible clinical markers to study the natural history of the disease and to design treatment trials in ecologically valid contexts.

Extensive cerebellar and thalamic degeneration in spinocerebellar ataxia type 10.

INTRODUCTION: Spinocerebellar ataxia type 10 (SCA10) is a hereditary neurodegenerative disorder caused by repeat expansions in the ATXN10 gene. Patients present with cerebellar ataxia frequently accompanied by seizures. Even though loss of cerebellar Purkinje neurons has been described, its brain degeneration pattern is unknown. Our aim was to characterize the gray and white matter degeneration patterns in SCA10 patients and the association with clinical features. METHODS: We enrolled 18 patients with molecular diagnosis of SCA10 and 18 healthy individuals matched for age and sex. All participants underwent brain MRI including high-resolution anatomical and diffusion images. Whole-brain Tract-Based Spatial Statistics (TBSS) and Voxel-Based Morphometry (VBM) were performed to identify white and grey matter degeneration respectively. A second analysis in the cerebellum identified the unbiased pattern of degeneration. Motor impairment was assessed using the SARA Scale. RESULTS: TBSS analysis in the patient group revealed white matter atrophy exclusively in the cerebellum. VBM analysis showed extensive grey matter degeneration in the cerebellum, brainstem, thalamus, and putamen. Significant associations between cerebellar degeneration and SARA scores were found. Additionally, degeneration in thalamic GM and WM in the cerebellar lobule VI were significantly associated with the presence of seizures. CONCLUSION: The results show that besides cerebellum and brainstem, brain degeneration in SCA10 includes predominantly the putamen and thalamus; involvement of the latter is strongly associated with seizures. Analysis of the unbiased degeneration pattern in the cerebellum suggests lobules VIIIb, IX, and X as the primary cerebellar targets of the disease, which expands to the anterior lobe in later stages.

Motor and cognitive impairments in spinocerebellar ataxia type 7 and its correlations with cortical volumes.

Spinocerebellar Ataxia Type 7 (SCA7) is a neurodegenerative disorder caused by cytosine-adenine-guanine (CAG) repeat expansion. It is clinically characterized by ataxia and visual loss. To date, little is known about SCA7 cognitive impairments and its relationship with grey matter volume (GMV) changes. The aim of this study was to explore SCA7 patients' performance in specific components of auditory-verbal neuropsychological tests and to correlate their scores with genetic mutation, severity of ataxia and GMV. We assessed verbal memory and verbal fluency proficiencies in 31 genetically confirmed SCA7 patients, and compared their results with 32 healthy matched volunteers; we also correlated CAG repeats and severity of motor symptoms with performance in the auditory-verbal tests. SCA7 patients exhibited deficiencies in several components of these cognitive tasks, which were independent of motor impairments and showed no relation to CAG repeats. Based on Resonance Images performed in 27 patients we found association between ataxia severity and GMV in "sensoriomotor" cerebellum, as well as correlations of impaired verbal memory and semantic fluency scores with GMV in association cortices, including the right parahippocampal gyrus. To our knowledge, this is the first report of deficits in the organization of semantic information and in the evocation of verbal material, as well as greater susceptibility to proactive interference in SCA7 patients. These findings bring novel information about specific cognitive abilities in SCA7 patients, particularly verbal memory and fluency, and their relation with GMV variations in circumscribed brain regions, including association cortices known to have functional relationships with the cerebellum.