Abnormal Resting-State Functional Connectivity in Progressive Supranuclear Palsy and Corticobasal Syndrome.

BACKGROUND: Pathological and MRI-based evidence suggests that multiple brain structures are likely to be involved in functional disconnection between brain areas. Few studies have investigated resting-state functional connectivity (rsFC) in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). In this study, we investigated within- and between-network rsFC abnormalities in these two conditions. METHODS: Twenty patients with PSP, 11 patients with CBS, and 16 healthy subjects (HS) underwent a resting-state fMRI study. Resting-state networks (RSNs) were extracted to evaluate within- and between-network rsFC using the Melodic and FSLNets software packages. RESULTS: Increased within-network rsFC was observed in both PSP and CBS patients, with a larger number of RSNs being involved in CBS. Within-network cerebellar rsFC positively correlated with mini-mental state examination scores in patients with PSP. Compared to healthy volunteers, PSP and CBS patients exhibit reduced functional connectivity between the lateral visual and auditory RSNs, with PSP patients additionally showing lower functional connectivity between the cerebellar and insular RSNs. Moreover, rsFC between the salience and executive-control RSNs was increased in patients with CBS compared to HS. CONCLUSION: This study provides evidence of functional brain reorganization in both PSP and CBS. Increased within-network rsFC could represent a higher degree of synchronization in damaged brain areas, while between-network rsFC abnormalities may mainly reflect degeneration of long-range white matter fibers.

Functional disconnection of thalamic and cerebellar dentate nucleus networks in progressive supranuclear palsy and corticobasal syndrome.

AIM: To assess functional rearrangement following neurodegeneration in the thalamus and dentate nucleus in patients with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). METHODS: We recruited 19 patients with PSP, 11 with CBS and 14 healthy subjects. All the subjects underwent resting-state (rs) fMRI using a 3T system. Whole brain functional connectivity of the thalamus and dentate nucleus were calculated by means of a seed-based approach with FEAT script in FSL toolbox. Thalamic volume was calculated by means of FIRST, and the dentate area by means of Jim software. RESULTS: Both thalamic volume and dentate area were significantly smaller in PSP and CBS patients than in healthy subjects. No significant difference emerged in thalamic volume between PSP and CBS patients, whereas dentate area was significantly smaller in PSP than in CBS. Thalamic functional connectivity was significantly reduced in both patient groups in various cortical, subcortical and cerebellar areas. By contrast, changes in dentate nucleus functional connectivity differed in PSP and CBS: it decreased in subcortical and prefrontal cortical areas in PSP, but increased asymmetrically in the frontal cortex in CBS. CONCLUSIONS: Evaluating the dentate nucleus size and its functional connectivity may help to differentiate patients with PSP from those with CBS.

MRI gray and white matter measures in progressive supranuclear palsy and corticobasal syndrome.

We evaluated MRI measures of gray and white matter damages in 19 patients with progressive supranuclear palsy (PSP), 11 with corticobasal syndrome (CBS), and 14 healthy subjects (HS) to differentiate patients with PSP from those with CBS. We calculated surface-based maps of the cortical volume, cortical thickness, surface area, and voxel level maps of sub-cortical volume, and diffusion tensor imaging parameters using automated scripts implemented in FreeSurfer and FSL toolboxes. No significant differences in cortical volume loss were observed between PSP and CBS. When cortical volume was divided into cortical thickness and surface area, cortical thickness in peri-rolandic brain regions was significantly smaller in CBS than in PSP patients, whereas surface area was significantly smaller in PSP than HS. We also found widespread volume loss in sub-cortical structures in patients with PSP and CBS in comparison to HS. Both patient groups displayed diffusion tensor imaging abnormalities: compared to HS, widespread fractional anisotropy and radial diffusivity changes were observed in PSP, whereas axial and radial diffusivity changes were prominent in CBS. Mini-mental state examination positively correlated with diffusion changes in patients with PSP. In conclusion, cortical thickness, surface area, and diffusion tensor imaging parameters may be sensitive enough to help differentiate patients with PSP from those with CBS.

Gray and white matter structural changes in corticobasal syndrome.

We investigated gray matter and white matter (WM) changes in corticobasal syndrome (CBS). T1-weighted and diffusion tensor images (3T-magnet) were obtained in 11 patients and 11 healthy subjects (HS). Magnetic resonance imaging data were analyzed using FreeSurfer and Tracts Constrained by Underlying Anatomy to evaluate cortical thickness (CTh), surface area, and subcortical volumes as well as diffusion tensor image parameters along the major WM tracts. Compared with HS, the whole patient group showed decreased CTh in the prefrontal cortex, precentral gyrus, supplementary motor area, insula, and temporal pole bilaterally. When we divided patients into 2 subgroups (left: L-CBS, right: R-CBS) on the basis of the clinically more affected upper limb, the most prominent decrease in CTh occurred in the hemisphere contralateral to the more affected side. The whole patient group also had volume loss in the putamen, hippocampus, and accumbens bilaterally, in the corpus callosum and right amygdala. Finally, we found diffusion changes in several WM tracts with axial diffusivity being altered more than radial diffusivity. The upper limb motor severity negatively correlated with the contralateral CTh in the precentral and/or postcentral gyri and contralateral volumes of putamen and accumbens. The CTh asymmetry in postcentral and/or paracentral gyri also negatively correlated with disease duration. Cortical thinning, volume loss, and fiber tract degeneration in specific brain regions are important pathophysiological abnormalities in CBS.

Neuroimaging correlates of blinking abnormalities in patients with progressive supranuclear palsy.

OBJECTIVE: We aimed to identify the possible relationship between blinking abnormalities and neuroimaging changes in patients with progressive supranuclear palsy. METHODS: We studied 18 patients with progressive supranuclear palsy and 13 healthy subjects. Voluntary and spontaneous blinking were recorded using kinematic techniques. Changes in brain structures were detected by T1-weighted magnetic resonance imaging and voxel-based morphometry. We then sought possible correlations between blinking and neuroimaging abnormalities in patients. RESULTS: Kinematic analysis indicated several abnormalities during voluntary blinking and a markedly reduced spontaneous blink rate in patients compared with healthy subjects. Neuroimaging showed gray matter loss in cortical and subcortical structures and lower white matter volume in the brainstem. Gray matter loss in subcortical structures correlated with the prolonged pause duration between the closing and opening phases, during voluntary blinking. CONCLUSIONS: This study provides a more specific insight into the pathophysiological mechanisms underlying blinking abnormalities in progressive supranuclear palsy.

Cerebral Peduncle Angle: An Objective Criterion for Assessing Progressive Supranuclear Palsy Richardson Syndrome.

OBJECTIVE: Several criteria for time-consuming volumetric measurements of progressive supranuclear palsy Richardson syndrome subtype (PSP-RS) have been proposed. These often require image reconstruction in different planes for proper assessment. The purpose of this study was to evaluate the cerebral peduncle angle as a simple and reproducible measure of midbrain atrophy in patients with PSP-RS. MATERIALS AND METHODS: The records of 15 patients with PSP-RS were retrospectively identified. The records of 31 age-matched healthy control subjects, 15 patients with multiple-system atrophy, and 22 patients with Parkinson disease were included for comparison. Two neuroradiologists individually assessed these studies for midbrain atrophy by evaluating the cerebral peduncle angle, that is, the angle between the two cerebral peduncles. RESULTS: The cerebral peduncle angle measurements were 62.1° (SD, 6.8°) in PSP-RS patients, 51.2° (SD, 10.1°) in healthy control subjects, 55.7° (SD, 11.6°) in patients with multiple-system atrophy, and 53.7° (SD, 8.5°) in patients with Parkinson disease. A statistically significant difference was found in the cerebral peduncle angle measurements (observer 1, p = 0.015; observer 2, p = 0.004) between the PSP-RS patients and the other subgroups. Bland-Altman analysis showed a bias of 0.6° (95% limits of agreement, 6.9°, -5.8°), and intraobserver variability analysis showed a bias of 0.5° (4.1°, -3°). CONCLUSION: The cerebral peduncle angle is a simple, easy-to-calculate, and reproducible measure of midbrain atrophy. It is a useful criterion for differentiating patients with PSP-RS from healthy persons and from patients with multiple-system atrophy or Parkinson disease.

Functional and Structural Brain Plasticity Enhanced by Motor and Cognitive Rehabilitation in Multiple Sclerosis.

Rehabilitation is recognized to be important in ameliorating motor and cognitive functions, reducing disease burden, and improving quality of life in patients with multiple sclerosis (MS). In this systematic review, we summarize the existing evidences that motor and cognitive rehabilitation may enhance functional and structural brain plasticity in patients with MS, as assessed by means of the most advanced neuroimaging techniques, including diffusion tensor imaging and task-related and resting-state functional magnetic resonance imaging (MRI). In most cases, the rehabilitation program was based on computer-assisted/video game exercises performed in either an outpatient or home setting. Despite their heterogeneity, all the included studies describe changes in white matter microarchitecture, in task-related activation, and/or in functional connectivity following both task-oriented and selective training. When explored, relevant correlation between improved function and MRI-detected brain changes was often found, supporting the hypothesis that training-induced brain plasticity is specifically linked to the trained domain. Small sample sizes, lack of randomization and/or an active control group, as well as missed relationship between MRI-detected changes and clinical performance, are the major drawbacks of the selected studies. Knowledge gaps in this field of research are also discussed to provide a framework for future investigations.

Neuroimaging evidence of gray and white matter damage and clinical correlates in progressive supranuclear palsy.

To evaluate gray matter (GM) and white matter (WM) abnormalities and their clinical correlates in patients with progressive supranuclear palsy (PSP). Sixteen PSP patients and sixteen age-matched healthy subjects underwent a clinical evaluation and multimodal magnetic resonance imaging, including three-dimensional T1-weighted imaging and diffusion tensor imaging (DTI). Volumetric and DTI analyses were computed using SPM and FSL tools. PSP patients showed GM volume decrease, involving the frontal cortex, putamen, pallidum, thalamus and accumbens nucleus, cerebellum, and brainstem. Additionally, they had widespread changes in WM bundles, mainly affecting cerebellar peduncles, thalamic radiations, corticospinal tracts, corpus callosum, and longitudinal fasciculi. GM volumes did not correlate with WM abnormalities. DTI indices of WM damage, but not GM volumes, correlated with clinical scores of disease severity and cognitive impairment. The neurodegenerative changes that occur in PSP involve both GM and WM structures and develop concurrently though independently. WM damage in PSP correlates with clinical scores of disease severity and cognitive impairment, thus providing further insight into the pathophysiology of the disease.

Association between anemia and multiple sclerosis.

BACKGROUND/AIMS: The relationship between multiple sclerosis (MS) and anemia has not been clarified sufficiently. In this retrospective, cross-sectional, case-control study we evaluated in MS patients: (1) prevalence of anemia relative to sex- and age-matched controls; (2) relationships between patients' demographic, clinical and drug-related characteristics and anemia; (3) effect of anemia on the risk of developing MS. METHODS: 187 consecutive MS patients (51 males, mean age (±SD) 44.5 ± 10.7 years) and 200 controls (56 males, mean age 45.5 ± 12 years) were included in the study. Anemia was defined as hemoglobin <12 g/dl for females and <13 g/dl for males. RESULTS: There was a significant difference in the prevalence of anemia between MS patients and controls (35 (18.7%) and 19 (9.5%), respectively, p = 0.009). We did not find any association between patients' characteristics and anemia. The occurrence of anemia increased more than twice the risk of developing MS (odds ratio: 2.19, 95% confidence interval 1.19-4.0). CONCLUSION: Our study showed a consistent association between anemia and MS.

Impaired Functional Connectivity Unmasked by Simple Repetitive Motor Task in Early Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Resting brain activity can be modulated by motor tasks to adapt to function. In multiple sclerosis (MS) patients, altered resting-state functional connectivity (RS-FC) has been reported and associated with impaired function and disability; little is known on how RS-FC is modulated by a simple repetitive motor task. OBJECTIVE: To assess changes in RS-FC in early relapsing-remitting MS (RRMS) patients associated with repetitive thumb flexions (RTFs). METHODS: A total of 20 right-handed patients with early RRMS and 14 healthy controls underwent a resting functional magnetic resonance imaging (fMRI) scan, before and after 25 minutes of alternate 30-s blocks of right RTF and rest. Dual-regression analysis of resting fMRI data followed the independent component analysis. Individual spatial maps of coherence between brain areas for 2 networks of interest, sensorimotor and cerebellar, were compared at the group level and correlated with measures of both clinical impairment and brain damage. RESULTS: Significant RTF-induced differences in RS-FC were observed between groups in the cerebellar network because of increased RS-FC in patients but not in controls. In the sensorimotor network, the RS-FC after RTF increased in both groups, with no significant between-group differences. The sensorimotor and the cerebellar RS-FC were intercorrelated only in patients and only after the RTF. The sensorimotor RS-FC increase in patients correlated with structural MRI alterations. CONCLUSIONS: Our study unmasked RS-FC changes of motor-related networks occurring after a simple repetitive motor task in early RRMS patients only. Evaluation of altered RSN dynamics might prove useful for anticipating neuroplasticity and for MRI-informed neurorehabilitation.

A longitudinal fMRI study on motor activity in patients with multiple sclerosis.

Using functional MRI (fMRI), patients with multiple sclerosis showed a greater extent of motor activation than controls. Although functional changes are often interpreted as adaptive and as a contributing factor in limiting the clinical deficit, no longitudinal studies have yet been performed for multiple sclerosis. Sixteen patients with multiple sclerosis, two patients with possible multiple sclerosis and nine age-matched controls underwent two fMRI studies with a time interval of 15-26 months. The motor task consisted of a self-paced sequential finger opposition movement with the right hand. Patients with multiple sclerosis exhibited greater bilateral activation than controls in both fMRI studies. At follow-up, patients showed a reduction in functional activity in the ipsilateral sensorimotor cortex and in the contralateral cerebellum. No significant differences between the two fMRI studies were observed in controls. Activation changes in ipsilateral motor areas correlated inversely with age, extent and progression of T1 lesion load, and occurrence of a new relapse. This study may help the understanding of the evolution of brain plastic changes in multiple sclerosis indicating that, in younger patients with a less structural brain damage and benign clinical course, the brain reorganizes its functional activity towards a more lateralized pattern of brain activation. The tendency towards a normalization of brain functional activity is hampered in older patients and in those developing relapses or new irreversible brain damage.

The relationship between inflammation and atrophy in clinically isolated syndromes suggestive of multiple sclerosis: a monthly MRI study after triple-dose gadolinium-DTPA.

OBJECTIVE: To examine the relationship between inflammation and brain atrophy in patients with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). METHODS: Monthly triple-dose gadolinium (Gd/DTPA)-enhanced MRI scans over 6 months were obtained in 62 consecutive CIS patients with an abnormal baseline MRI scan. Subsequently MRI was performed at months 12 and 18. Patients who developed a clinically definite MS (i. e., a second clinical episode) ended the study at the time of the relapse. For each scan, the number and volume of newly active lesions (Gd-enhancement/new or newly enlarging T2 lesion that did not enhance), and the number and volume of T2 hyperintense lesions (T2-LL) and T1-black holes (T1-LL) were calculated. The percentage of brain volume changes (PBVC) was assessed using a fully automated technique (SIENA; Structural Image Evaluation using Normalization of Atrophy). RESULTS: Twenty-four (39%) developed clinically definite MS by month 18. Thirty-eight (61%) were relapsefree and completed the MRI follow-up. Relapse-free patients showed a progressive median increase between baseline and month 18 in T1-LL (25%, p<0.001), but not in T2-LL (8.5%, p=ns). PBVC decreased by 1.1% (p<0.001) in a time-dependent pattern (Kendall coefficient of concordance=0.85). Exploratory subgroup analyses showed a trend towards progressive decreases in brain volume in active patients (i. e., those with at least one newly active lesion during monthly MRI scanning; Spearman's R=-0.61; p<0.001), but not among inactive patients (Spearman's R=-0.10; p=0.53). Significant differences in median brain volume changes between the active and inactive patient groups were found at months 12 and 18; the difference detected at month 6 was not significant. The cumulative number and volume of new Gd-enhancing lesions developed during the 6 months of frequent MRI scanning were highly correlated with PBVC over the 18-month period (Spearman R values were 0.73 and 0.85, respectively). The strongest predictor of PBVC at 18 months was the cumulative volume of newly active lesions during frequent MRI scanning [ss=-0. 83, standard error (SE)=0.07, p<0.001]. CONCLUSIONS: This study shows that visible inflammation as detected by monthly, triple-dose Gd-enhanced MRI is an important factor in the pathogenesis of brain tissue loss in CIS patients. However, inflammation and brain atrophy do not proceed in parallel: atrophy appeared only after a delay of months following acute inflammation. Frequent MRI scanning allows for the detection of CIS patients who will develop brain atrophy in the short-term.

Henoch-Schönlein syndrome and cerebellar hemorrhage: report of an adolescent case and literature review.

BACKGROUND: Henoch-Schönlein syndrome (HSS) is a systemic necrotizing vasculitis predominantly affecting children. Symptoms are usually self-limited and only rarely do they involve the central nervous system. Only five published reports describe cases of radiologically proven intracranial hemorrhages complicating HSS. CASE DESCRIPTION: In this 17-year-old boy, a cerebellar hemorrhage developed after aspecific symptoms of upper respiratory tract infection. His past medical history and emerging evidence of systemic bleeding yielded a diagnosis of recurrent HSS. This was the fourth time the disease had recurred since the age of 4. The patient underwent surgical treatment and returned to his normal activities. CONCLUSIONS: Intracerebral hemorrhages during HSS share a favorable prognosis and a posterior lobar localization, typically involving the parieto-occipital region. The case described here is unusual because the patient did not have the typical purpuric rash and unlike published cases, the intracranial hemorrhage marked the onset of HSS rather than complicating a typical HSS presentation.

Intraspinous postlaminectomy pseudomeningocele.

Pseudomeningoceles are uncommon complications of lumbar surgery. They are encapsulated cerebrospinal fluid collections developing extradurally as a consequence of incidental dural tears. They are typically located in the paraspinal compartment and occasionally reach the subcutaneous space. We describe the case of a patient in whom a postlaminectomy pseudomeningocele developed over a 10-year period within the L5 spinous process and remained completely encircled within its bony boundaries. The surgical implications of this finding are discussed.

Contribution of corticospinal tract damage to cortical motor reorganization after a single clinical attack of multiple sclerosis.

The objectives of this study were to assess whether cortical motor reorganization in the early phase of multiple sclerosis (MS) is correlated with the clinical presentation and with specific damage to the corticospinal tract. Twenty patients with clinically isolated syndrome (CIS) and serial MR findings indicative of MS were selected. In 10 patients the CIS was hemiparesis (group H), and in 10 patients the CIS was optic neuritis (group ON). There were no significant differences in age, disease duration, total T2 lesion load (LL), and total T1 LL between group H and group ON. Ten age-matched healthy subjects served as controls (group C). All subjects were submitted to fMRI during a sequential finger-to-thumb opposition task of the right hand. Group H showed a significantly higher EDSS score and T1 LL calculated along the corticospinal tract than group ON. Three-group comparison by ANOVA showed significantly higher activation in group H than in the other two groups (P < 0.001). Significant foci were located in the sensory-motor cortex (BA 1-4), the parietal cortex (BA 40), the insula of the ipsilateral hemisphere, and the contralateral motor cortex (BA 4/6). Group ON showed, although at a lower level of significance (P < 0.01), higher activation of the contralateral motor-related areas than group C. Multiple regression analysis showed that T2 and T1 LL along the corticospinal tract and time since clinical onset positively correlated with activation in motor areas in both cerebral hemispheres (P < 0.005). Total T2 LL positively correlated with activation in motor areas in the contralateral hemisphere (P < 0.005). Total T1 LL and EDSS did not show any significant correlation. More severe specific damage to the motor pathway in patients with previous hemiparesis may explain the significantly higher involvement of ipsilateral motor areas observed in group H than in group ON. Furthermore, the significant correlation between the time since clinical onset and activation in motor areas suggests that cortical reorganization develops gradually in concomitance with the subclinical accumulation of tissue damage.

A longitudinal study of MR diffusion changes in normal appearing white matter of patients with early multiple sclerosis.

BACKGROUND AND PURPOSE: The stage at which normal appearing white matter (NAWM) abnormalities first appear in multiple sclerosis (MS) is not clear. The aim of our study was to monitor water diffusion changes over time in NAWM of patients with early MS. METHODS: Out of a consecutive series of patients enrolled in a MR study on clinically isolated syndrome (CIS), we selected 19 subjects who had completed a one year follow-up. The MR scans obtained at baseline and at 12 months were reviewed according to the new criteria on the diagnosis of MS. Lesion load on T2 and T1 weighted images and the trace of the apparent diffusion coefficient in NAWM were measured both at baseline and at 12 months in patients and in 12 healthy controls. RESULTS: In three patients the diagnosis of MS was done at baseline based on MR. Thirteen patients developed MS during the study and in three patients the diagnosis remained "possible MS." TADC in NAWM in patients was significantly higher than in controls at the 12 months' follow-up but not at baseline (controls mean tADC +/- sd = 0.745 +/- 0.02 mm(2)/sec x 10(-3); patients mean tADC(12) +/- sd = 0.767 +/- 0.02 mm(2)/sec x 10(-3); p < 0.02). TADC and T2 lesion load at 12 months were significantly correlated (p < 0.01). Patients exhibiting tADC(12) above a confidence interval had a significantly greater EDSS score at the same time period (EDSS(12) +/- sd = 1.9 +/- 0.5 and = 1.1 +/- 0.4 respectively; p < 0.01). CONCLUSIONS: This study suggests that diffusion MR cannot detect alterations in NAWM of patients with a CIS suggestive of MS. After one year, when most patients develop MS, diffusion MR abnormalities in NAWM become apparent. These abnormalities are correlated with T2 lesion load and may contribute to neurological impairment.