White matter involvement in young non-demented Down's syndrome subjects: a tract-based spatial statistic analysis.

PURPOSE: Cognitive decline in Down syndrome generally shows neurodegenerative aspects similar to what is observed in Alzheimer's disease. Few studies reported information on white matter integrity. The aim of this study was to evaluate white matter alterations in a cohort of young Down subjects, without dementia, by means of DTI technique, compared to a normal control group. METHODS: The study group consisted of 17 right-handed subjects with DS and many control subjects. All individuals participating in this study were examined by MR exam including DTI acquisition (32 non-coplanar directions); image processing and analysis were performed using FMRIB Software Library (FSL version 4.1.9, http://www.fmrib.ox.ac.uk/fsl )) software package. Finally, the diffusion tensor was estimated voxel by voxel and the FA map derived from the tensor. A two-sample t test was performed to assess differences between DS and control subjects. RESULTS: The FA is decreased in DS subjects, compared to control subjects, in the region of the anterior thalamic radiation, the inferior fronto-occipital fasciculum, the inferior longitudinal fasciculum, and the cortico-spinal tract, bilaterally. CONCLUSIONS: The early white matter damage visible in our DS subjects could have great impact in the therapeutic management, in particular in better adapting the timing of therapies to counteract the toxic effect of the deposition of amyloid that leads to oxidative stress.

Cortical Brain Changes in Patients With Locked-In Syndrome Experiencing Hallucinations and Delusions.

Previous evidence suggests that hallucinations and delusions may be detected in patients with the most severe forms of motor disability including locked-in syndrome (LIS). However, such phenomena are rarely described in LIS and their presence may be underestimated as a result of the severe communication impairment experienced by the patients. In this study, we retrospectively reviewed the clinical history and the neuroimaging data of a cohort of patients with LIS in order to recognize the presence of hallucinations and delusions and to correlate it with the pontine damage and the presence of any cortical volumetric changes. Ten patients with LIS were included (5 men and 5 women, mean age 50.1 ± 14.6). According to the presence of indicators of symptoms, these patients were categorized as hallucinators (n = 5) or non-hallucinators (n = 5). MRI images of patients were analyzed using Freesurfer 6.0 software to evaluate volume differences between the two groups. Hallucinators showed a selective cortical volume loss involving the fusiform (p = 0.001) and the parahippocampal (p = 0.0008) gyrus and the orbital part of the inferior frontal gyrus (p = 0.001) in the right hemisphere together with the lingual (p = 0.01) and the fusiform gyrus (p = 0.01) in the left hemisphere. Moreover, a volumetric decrease of bilateral anterior portions of the precuneus was recognized in the hallucinators (right p = 0.01; left p = 0.001) as compared to non-hallucinators. We suggested that the presence of hallucinations and delusions in some LIS patients could be accounted for by the combination of a damage of the corticopontocerebellar pathways with cortical changes following the primary brainstem injury. The above areas are embedded within cortico-cortical and cortico-subcortical loops involved in self-monitoring and have been related to the presence of hallucinations in other diseases. The two main limitations of our study are the small sample of included patients and the lack of a control group of healthy individuals. Further studies would be of help to expand this field of research in order to integrate existing theories about the mechanisms underlying the generation of hallucinations and delusions in neurological patients.

Disembodied Mind: Cortical Changes Following Brainstem Injury in Patients with Locked-in Syndrome.

Locked-in syndrome (LIS) following ventral brainstem damage is the most severe form of motor disability. Patients are completely entrapped in an unresponsive body despite consciousness is preserved. Although the main feature of LIS is this extreme motor impairment, minor non-motor dysfunctions such as motor imagery defects and impaired emotional recognition have been reported suggesting an alteration of embodied cognition, defined as the effects that the body and its performances may have on cognitive domains. We investigated the presence of structural cortical changes in LIS, which may account for the reported cognitive dysfunctions. For this aim, magnetic resonance imaging scans were acquired in 11 patients with LIS (6 males and 5 females; mean age: 52.3±5.2SD years; mean time interval from injury to evaluation: 9±1.2SD months) and 44 healthy control subjects matching patients for age, sex and education. Freesurfer software was used to process data and to estimate cortical volumes in LIS patients as compared to healthy subjects. Results showed a selective cortical volume loss in patients involving the superior frontal gyrus, the pars opercularis and the insular cortex in the left hemisphere, and the superior and medium frontal gyrus, the pars opercularis, the insular cortex, and the superior parietal lobule in the right hemisphere. As these structures are typically associated with the mirror neuron system, which represents the neural substrate for embodied simulation processes, our results provide neuroanatomical support for potential disembodiment in LIS.

Age-Related Cortical Thickness Reduction in Non-Demented Down's Syndrome Subjects.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the characteristic pattern of age-related cortical thinning in patients with Down Syndrome (DS), as assessed by MRI and automatic cortical thickness measurements. METHODS: Ninety-one non-demented subjects with DS (range 11-53 years) were examined using a 1.5 T scanner. MRI-based quantification of cortical thickness was performed using FreeSurfer software package., The Pearson product-moment correlation coefficient between age and mean cortical thickness was evaluated for all subjects participating in the study. RESULTS: A significant negative correlation between cortical thickness and age was found bilaterally in the frontal, temporal, parietal and cingulate gyrus. Specific investigation of cerebral lobes showed a more evident involvement of the frontal one, compared to others. Moreover, the age related reduction of cortical thickness appeared to be more significant and rapid in patients between 20 and 30 years of age. CONCLUSIONS: Our findings showed that Down Syndrome subjects are affected by a diffuse cortical thinning. The involvement of cortical structures can be observed at an earlier age than previous studies have reported.

Age effects on cortical thickness in young Down's syndrome subjects: a cross-sectional gender study.

INTRODUCTION: The aim of this study was to determine differences in the characteristic pattern of age-related cortical thinning in men and women with Down's syndrome (DS) by means of MRI and automatic cortical thickness measurements and a cross-sectional design, in a large cohort of young subjects. METHODS: Eighty-four subjects with DS, 30 females (11-35 years, mean age ± SD = 22.8 ± 5.9) and 54 males (11-35 years, mean age ± SD = 21.5 ± 6.5), were examined using a 1.5-T scanner. MRI-based quantification of cortical thickness was performed using FreeSurfer software package. For all subjects participating in the study, the Pearson product-moment correlation coefficient between age and mean cortical thickness values has been evaluated. RESULTS: A significant negative correlation between cortical thickness and age was found in female DS subjects, predominantly in frontal and parietal lobes, bilaterally. In male DS subjects, a significant negative correlation between cortical thickness and age was found in the right fronto-temporal lobes and cingulate regions. Whole brain mean cortical thickness values were significantly negative correlated with age only in female DS subjects. CONCLUSIONS: Females with Down's syndrome showed a strong correlation between cortical thickness and age, already in early age. We suggest that the cognitive impairment due to hormonal deficit in the postmenopausal period could be emphasized by the early structural decline of gray matter in female DS subjects.

A cervical flexion-extension MRI study in Down syndrome.

OBJECTIVE: To assess what kind of information MR examination in flexed and extended positions provides in Down syndrome subjects with suspected cranio-cervical instability. METHODS: Between 2005 and 2008, 35 subjects with DS were recruited in the study. Ethics committee approval was granted and a signed informed consent was obtained from the parents. All the subjects were affected by hypotonic status and ligament laxity established by clinical evaluation, but were asymptomatic about focal neurological symptoms due to medullar damage caused by cranio-cervical instability. Each patient underwent lateral supine radiographs and MR imaging in the neutral, active flexed and extended positions. For evaluating the atlanto-axial and atlanto-occipital joint stability, multiple measurements were calculated. RESULTS: A significant reduction of anterior subarachnoid space in flexed position was evident in DS subjects compared to healthy controls in neutral and flexed positions. Both, space available for cord and ligamentous thickness showed significant differences between DS subjects and healthy controls. In DS subjects with occipito-cervical instability, the anterior subarachnoidal space reduction was significantly reduced in flexed position. CONCLUSIONS: In DS subjects with asymptomatic cranio-cervical instability, anterior subarachnoidal evaluation and ligamentous status could add new information about the risk of spinal cord damage.

Whole-brain voxel-based morphometry study of children and adolescents with Down syndrome.

In order to investigate alterations in brain morphology and a possible temporal pattern of neuroanatomical abnormalities in the gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) of young patients with Down syndrome (DS), high-resolution magnetic resonance imaging (MRI) voxel-based morphometry (VBM) was performed on 21 children and adolescents with this chromosomal aberration and 27 age-matched participants as controls. In comparison with control subjects, children and adolescents with DS showed not only an overall smaller whole-brain volume, but also volume reductions of the GM in the cerebellum, frontal lobes, frontal region of the limbic lobe, parahippocampal gyri and hippocampi and of the WM in the cerebellum, frontal and parietal lobes, sub-lobar regions and brainstem. By contrast, volume preservation was observed in the GM of the parietal lobes, temporal lobe and sub-lobar regions and in the WM of the temporal lobe and temporal regions of the limbic lobe. A lower volume of CSF was also detected in the frontal lobes. This study is the first to use the high-resolution MRI VBM method to describe a whole-brain pattern of abnormalities in young DS patients falling within such a narrow age range and it provides new information on the neuroanatomically specific regional changes that occur during development in these patients.