Patrizia Pantano

fMRI evidence of brain reorganization during attention and memory tasks in multiple sclerosis

Functional magnetic resonance imaging (fMRI) data on motor function have shown adaptive functional changes related to brain injury in multiple sclerosis (MS). We investigated whether patients with MS have altered fMRI activation patterns during attention and memory tasks, and whether functional changes in the brain correlate with the extent of overall tissue damage on conventional MRI. Twenty-two right-handed patients with relapsing-remitting MS (RRMS) and no or only mild deficits at neuropsychological testing and 22 matched healthy subjects were scanned during the Paced Auditory Serial Addition Test (PASAT) and a recall task. fMRI data were analyzed using Statistical Parametric Mapping (SPM99). The relation between fMRI changes during both tasks and T2 lesion load was investigated. During both tasks, patients exhibited significantly greater brain activation than controls and recruited additional brain areas. Task-related functional changes were more significant in patients whose performance matched that of controls than in patients with a lower performance. During the PASAT, brain functional changes involved the right supplementary motor area and cingulate, the bilateral prefrontal, temporal and parietal areas, whereas during the recall task they involved the prefrontal and temporal cortex and basal ganglia bilaterally, and the left thalamus. In patients, activation in specific brain areas during performance of both tasks positively correlated with T2 brain lesions. Patients with RRMS exhibit altered patterns of activation during tasks exploring sustained attention, information processing and memory. During these tasks, fMRI activity is greater in patients with better cognitive function than in those with lower cognitive function. Functional changes in specific brain areas increase with increasing tissue damage suggesting that they may also represent adaptive mechanisms that reflect underlying neural disorganization or disinhibition, possibly associated with MS.

Neural Basis of Maternal Communication and Emotional Expression Processing during Infant Preverbal Stage

During the first year of life, exchanges and communication between a mother and her infant are exclusively preverbal and are based on the mothers ability to understand her infants needs and feelings (i.e., empathy) and on imitation of the infants facial expressions; this promotes a social dialog that influences the development of the infant self. Sixteen mothers underwent functional magnetic resonance imaging while observing and imitating faces of their own child and those of someone elses child. We found that the mirror neuron system, the insula and amygdala were more active during emotional expressions, that this circuit is engaged to a greater extent when interacting with ones own child, and that it is correlated with maternal reflective function (a measure of empathy). We also found, by comparing single emotions with each other, that joy expressions evoked a response mainly in right limbic and paralimbic areas; by contrast, ambiguous expressions elicited a response in left high order cognitive and motor areas, which might reflect cognitive effort.

Predictive value of brain perfusion single-photon emission computed tomography in acute ischemic stroke.

We investigated 32 patients with completed ischemic stroke less than or equal to 6 hours after the onset of symptoms by means of computed tomography, cerebral angiography, and technetium-99m-labeled hexamethylpropyleneamine oxime single-photon emission computed tomography to study cerebral blood flow. Follow-up computed tomography and cerebral blood flow studies were performed 1 week and 1 month after admission. Poor outcome at 1 month was evident in 18 (78%) of the 23 patients with severe neurologic deficit on admission and in 11 (92%) of the 12 patients with severe hypoperfusion in the affected hemisphere on admission. All 10 patients with severe impairment of both neurologic status and cerebral blood flow had a poor outcome at 1 month. We detected severe hypoperfusion in patients with large lesions on computed tomograms or cerebral artery occlusions on angiograms. Cerebral blood flow had increased at the 1-week follow-up despite different clinical outcomes. Our data provide evidence that early evaluation of cerebral blood flow with single-photon emission computed tomography is useful to detect subgroups of patients with different clinical outcomes during the acute phase of ischemic stroke.

SPECT, MRI and cognitive functions in multiple sclerosis.

Seventeen patients with relapsing remitting multiple sclerosis (MS) and mild physical disability had neuropsychological testing, magnetic resonance imaging (MRI) and single photon emission computerised tomography (SPECT) using technetium 99m (99mTc) hexamethyl-propyleneamine oxime (HMPAO). Performance in verbal fluency, naming and memory testing appeared to be impaired in MS patients compared with 17 age-sex and education matched normal controls. Weighted periventricular and confluent lesion scores and the width of the third ventricle, proved to be the most sensitive MRI measures in differentiating more cognitively impaired patients from those who were relatively unimpaired. Ratios of regional to whole brain activity, measured by SPECT, showed significant reduction in the frontal lobes and in the left temporal lobe of MS patients. A relationship was found between left temporal abnormality in 99mTc-HMPAO uptake and deficit in verbal fluency and verbal memory. Finally, asymmetrical lobar activity indicated a predominant left rather than right temporo-parietal involvement.

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.

Delayed Increase in Infarct Volume After Cerebral Ischemia: Correlations with Thrombolytic Treatment and Clinical Outcome

BACKGROUND AND PURPOSE Growing experimental evidence indicates that the development of cerebral ischemic damage is slower than previously believed. The aims of this work were (1) to study the evolution of CT hypoattenuation between 24 to 36 hours and 7 days in ischemic stroke patients; (2) to evaluate whether thrombolytic treatment given within 6 hours of stroke affects delayed infarction evolution; and (3) to investigate possible correlations between lesion volume changes over time and clinical outcome. METHODS Of 620 patients included in the European Cooperative Acute Stroke Study 1 (ECASS1), we selected 450 patients whose control CT scans at day 1 (CT1) and day 7 (CT7) were available. They had been randomly divided into 2 groups: 206 patients had been treated with rtPA and 244 with placebo. CT1 and CT7 were classified according to the location of the infarct. The volume of CT hypoattenuation was measured using the formula AxBxC/2 for irregular volumes. The 95% confidence interval of inter- and intrarater variability was used to determine whether significant changes in lesion volume had occurred between CT1 and CT7. Clinical severity was evaluated by means of the Scandinavian Stroke Scale (SSS) at entry (SSS0) and at day 30 (SSS30). RESULTS Mean lesion volumes were significantly (P<0.0001) higher at day 7 than at day 1 in all the subgroups of patients and particularly in patients with a subcortical lesion. Of the 450 patients studied, 287 (64%) did not show any significant change in lesion volume between CT1 and CT7, 143 (32%) showed a significant increase and the remaining 20 (4%) a significant decrease. No significant correlation was observed between treatment and lesion evolution between CT1 and CT7. Both clinical scores (SSS0 and SSS30) and degree of neurological recovery were significantly (P<0.05) lower in the subgroup of patients with a significant lesion volume increase than in the other 2 groups. CONCLUSIONS In approximately two thirds of patients, infarct size is established 24 to 36 hours after stroke onset, whereas in the remaining one third, changes in lesion volume may occur later than the first 24 to 36 hours. Many factors may be responsible for delayed infarct enlargement and for a lower degree of clinical recovery, both of which may occur despite early recombinant tissue plasminogen activator treatment.

Effect of corpus callosum damage on ipsilateral motor activation in patients with multiple sclerosis: A functional and anatomical study

Functional MRI (fMRI) studies have shown increased activation of ipsilateral motor areas during hand movement in patients with multiple sclerosis (MS). We hypothesized that these changes could be due to disruption of transcallosal inhibitory pathways. We studied 18 patients with relapsing‐remitting MS. Conventional T1‐ and T2‐weighted images were acquired and lesion load (LL) measured. Diffusion tensor imaging (DTI) was performed to estimate fractional anisotropy (FA) and mean diffusivity (MD) in the body of the corpus callosum (CC). fMRI was obtained during a right‐hand motor task. Patients were studied to evaluate transcallosal inhibition (TCI, latency and duration) and central conduction time (CCT). Eighteen normal subjects were studied with the same techniques. Patients showed increased MD (P < 0.0005) and reduced FA (P < 0.0005) in the body of the CC. Mean latency and duration of TCI were altered in 12 patients and absent in the others. Between‐group analysis showed greater activation in patients in bilateral premotor, primary motor (M1), and middle cingulate cortices and in the ipsilateral supplementary motor area, insula, and thalamus. A multivariate analysis between activation patterns, structural MRI, and neurophysiological findings demonstrated positive correlations between T1‐LL, MD in the body of CC, and activation of the ipsilateral motor cortex (iM1) in patients. Duration of TCI was negatively correlated with activation in the iM1. Our data suggest that functional changes in iM1 in patients with MS during a motor task partially represents a consequence of loss of transcallosal inhibitory fibers. Hum Brain Mapp, 2006.

Functional Brain Reorganization in Multiple Sclerosis: Evidence from fMRI Studies

In patients with multiple sclerosis (MS), the severity of clinical signs is not closely related to indices of structural brain damage provided by conventional magnetic resonance MR. Accordingly, patients with MS may show symptom recovery while progressively accumulating tissue damage.

Correlation between MRI findings and long-term outcome in patients with severe brain trauma

Abstract Our aim was to relate MRI findings in patients with severe traumatic brain injury (TBI) to clinical severity and long-term outcome. We studied 37 patients with severe TBI, who were submitted to clinical assessment for disability and cognition and to MRI 60–90 days after trauma. Clinical assessment was also performed 3, 6 and 12 months later. The number and volume of lesions in various cerebral structures were calculated semiautomatically from FLAIR and fast field-echo images. Possible correlations between total and regional lesion volume and clinical deficits were then investigated. The frontal and temporal lobes were most frequently involved. Total lesion volume on FLAIR images correlated significantly with clinical outcome, whereas that on FFE images did not. Regional analysis showed that FLAIR lesion volume in the corpus callosum correlated significantly with scores on disability and cognition scales at the first clinical assessment. FLAIR lesion volume in the frontal lobes correlated significantly with clinical scores 1 year later.

A cerebral blood flow study on tonic pain activation in man

&NA; This study examined brain areas involved in tonic pain perception. Cerebral blood flow was assessed by dynamic Xenon‐133 inhalation single‐photon emission tomography (SPET) in 7 healthy right‐handed male volunteers undergoing the cold pressor test (CPT). In single experimental sessions, each subject was scanned twice, once in the resting state and once while immersing the left hand in freezing water (0°C ± 1). Immersion of the hand induced severe pain (visual analogue scale: 6.9 ± 1.9) in all subjects. After correction for pCO2, cerebral blood flow was analyzed by placing a template of square regions of interest (ROIs) over 5 selected tomographic slices. Relative to the resting‐state values, during the CPT, flow determinations revealed a 7–8% regional blood flow increase in the contralateral frontal lobe and bilateral temporal regions and a 15% flow increase in a ROI located over the primary sensorimotor cortex in the tomogram at 80 mm above the orbito‐meatal line (corresponding to the cortical somatotopic representation of the hand) contralateral to the stimulated side. The tonic pain induced by the CPT thus appears to activate the contralateral frontal and bilateral temporal regions and more prominently, the primary sensorimotor cortex. This pattern of activation suggests that tonic painful stimuli activate the cortex partly via complex circuits and partly via direct somatosensory pathways.