Drug resistant ADLTE and recurrent partial status epilepticus with dysphasic features in a family with a novel LGI1mutation: electroclinical, genetic, and EEG/fMRI findings.

PURPOSE: We characterized a family with autosomal dominant lateral temporal epilepsy (ADLTE) whose proband presented uncommon electroclinical findings such as drug-resistant seizures and recurrent episodes of status epilepticus with dysphasic features. METHODS: The electroclinical characteristics and LGI1 genotype were defined in the family. In the proband, the ictal pattern was documented during video-EEG monitoring and epileptic activity was mapped by EEG/fMRI. RESULTS: The affected members who were studied had drug-resistant seizures. In the proband, seizures with predominant dysphasic features often occurred as partial status epilepticus. The video-EEG-documented ictal activity and fMRI activation clearly indicated the elective involvement of the left posterior lateral temporal cortex. Sequencing of LGI1 exons revealed a heterozygous c.367G>A mutation in exon 4, resulting in a Glu123Lys substitution in the protein sequence. CONCLUSIONS: The uncommon clinical pattern (high seizure frequency, drug-resistance) highlights the variability of the ADLTE phenotype and extends our knowledge of the clinical spectrum associated with LGI1 mutations.

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.

Metabolic alteration transients during paroxysmal activity in an epileptic patient with fixation-off sensitivity: a case study.

The purpose of this study was to investigate short-time metabolic variations related to continuous epileptic activity elicited by fixation-off sensitivity (FOS). Time-resolved magnetic resonance spectroscopy was performed on a patient on whom previous clinical findings clearly indicated presence of FOS. The epileptic focus was localized with a simultaneous electroencephalographic and functional magnetic resonance imaging study. The results showed a linear increase of the sum of glutamate and glutamine with time of paroxysmal activity in epileptic focus and much greater concentration of choline-containing compounds in focus than in the contralateral side.

Visualization of evolving status epilepticus with diffusion and perfusion MR imaging.

Since Kojewnikoff's first description of epilepsia partialis continua, isolated case reports and small case series have elucidated the disease. However, few imaging studies have been performed. We report a case in which serial diffusion and perfusion MR imaging allowed monitoring of the changes in hemodynamic and cell membrane permeability until the resolution of clinical and electrical epileptic activity.

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.

29 Year-old man with new onset seizures.

Imaging of a 29-year-old man with seizures showed a frontal lobe mass with curvilinear narrow calcifications, cystic components and multiple flow-voids. An AVM was considered. A DSA confirmed the hypervascular nature of the lesion. It was resected and microscopic examination showed an anaplastic oligodendroglioma remarkable for a diffuse and hypertrophic vasculature with areas of frank vascular proliferation. The marked vascularity seen on the MRI, the gyriform calcifications and the cystic degeneration are all features which can be encountered in an AVM. This case illustrates that highly vascular malignant gliomas can simulate vascular lesions by radiology and may require an angiogram for diagnosis.

MRI findings in lymphomatosis cerebri: description of a case and revision of the literature.

Lymphomatosis cerebri (LC) is a rare form of primary central nervous system lymphoma; we report a case of LC mainly involving the brainstem and cerebellum. This diagnosis should be considered in patients presenting with diffuse white matter disease, and a subacute clinical history of cognitive deficits, ataxic gait, and personality changes. We present our findings along with a review of the neuroradiological literature.

Neuroplastic changes in the brain: a case of two successive adaptive changes within the motor cortex.

We describe a case of neuroplasticity associated with both arteriovenous malformation (AVM) and stroke, which occurred in two successive events in the same patient. Functional magnetic resonance imaging (fMRI) during right-hand movement in a young man with a left rolandic AVM detected activation of a region corresponding to the left premotor cortex. The AVM was embolized. A few hours after the last embolization session, the patient sustained an ischemic complication in the left subcortical white matter. A second fMRI detected a lower degree of left premotor cortex activation and strong activation of the contralesional right primary motor cortex and bilateral supplementary motor areas. One month later, in association with clinical recovery, the fMRI activation returned to that observed in the first fMRI, ie, selective activation of the ipsilesional left premotor cortex. This is, to our knowledge, the first description of two distinct functional cortical changes determined by an AVM and a stroke within the motor network.

Functional MRI changes in the central motor system in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a multisystemic disease involving multiple organ systems including central nervous system (CNS) and muscles. Few studies have focused on the central motor system in DM1, pointing to a subclinical abnormality in the CNS. The aim of our study was to investigate patterns of cerebral activation in DM1 during a motor task using functional MRI (fMRI). Fifteen DM1 patients, aged 20 to 59 years, and 15 controls of comparable age were scanned during a self-paced sequential finger-to-thumb opposition task of their dominant right hand. Functional MRI images were analyzed using SPM99. Patients underwent clinical and genetic assessment; all subjects underwent a conventional MR study. Myotonic dystrophy type 1 patients showed greater activation than controls in bilateral sensorimotor areas and inferior parietal lobules, basal ganglia and thalami, in the ipsilateral premotor area, insula and supplementary motor area (corrected P<.05). Analysis of the interaction between disease and age showed that correlation with age was significantly greater in patients than in controls in bilateral sensorimotor areas and in contralateral parietal areas. Other clinical and MR characteristics did not correlate with fMRI. Functional changes in DM1 may represent compensatory mechanisms such as reorganization and redistribution of functional networks to compensate for ultrastructural and neurochemical changes occurring as part of the accelerated aging process.

Neurophysiological and functional MRI evidence of reorganization of cortical motor areas in cerebral arteriovenous malformation.

Functional magnetic resonance imaging (fMRI) research has shown that brain arteriovenous malformations (AVMs) lead to reorganization of cortical motor areas. Since it is known that blood oxygenation level-dependent signal in fMRI may be influenced by the hemodynamic perturbation associated with the presence of the AVM, in the present study, a combined exploration with fMRI and transcranial magnetic stimulation was performed in a patient with a right rolandic AVM in order to explore the relationship between neuronal and hemodynamic activity. The combined protocol of investigation adopted in this study was able to provide significant information regarding neuronal activity of the different cortical areas that partake to post-lesional reorganization.

Semiquantitative human cerebral perfusion assessment with ultrasound in brain space-occupying lesions: preliminary data.

OBJECTIVE: Transcranial Duplex ultrasound imaging with ultrasound contrast agents is an emerging technique for evaluating brain perfusion. The aim of this study was to evaluate cerebral perfusion with ultrasound in brain space-occupying lesions to identify different perfusion patterns. METHODS: Twenty patients with brain space-occupying lesions underwent ultrasound assessment of brain perfusion with a contrast pulse sequencing nonharmonic ultrasound technique and an ultrasound contrast agent bolus. Data were analyzed with software for semiquantitative analysis. RESULTS: Contrast pulse sequencing imaging with the semiquantitative analysis software allowed identification of qualitative and semiquantitative brain perfusion. Brain hemorrhages showed lower or absent perfusion compared with normal tissue. Meningiomas and glioblastomas without large necrotic areas showed higher perfusion compared with normal tissue. Glioblastomas with large necrotic areas showed overall reduced perfusion compared with normal tissue but higher than that of brain hemorrhages. In glioblastomas with large necrotic areas, it was possible to distinguish between solid and necrotic tissue. CONCLUSIONS: This bedside ultrasound technique, if validated by larger-scale studies, may add helpful information in noninvasive staging of brain tumors. Further potential applications may be in follow-up imaging to evaluate postoperative tumor recurrence or the presence of radionecrosis.

Pituitary macroadenomas: preoperative evaluation of consistency with diffusion-weighted MR imaging--initial experience.

PURPOSE: To prospectively evaluate use of diffusion-weighted (DW) magnetic resonance (MR) images and apparent diffusion coefficient (ADC) maps for determination of the consistency of macroadenomas. MATERIALS AND METHODS: The study protocol was approved by the institutional ethics committee, and informed consent was obtained from all patients. Twenty-two patients with pituitary macroadenoma (10 men, 12 women; mean age, 54 years +/- 17.09 [standard deviation]; range, 21-75 years) were examined. All patients underwent MR examination, which included T1-weighted spin-echo and T2-weighted turbo spin-echo DW imaging with ADC mapping and contrast material-enhanced T1-weighted spin-echo imaging. Regions of interest (ROIs) were drawn in the macroadenomas and in normal white matter on DW images, ADC maps, and conventional MR images. Consistency of macroadenomas was evaluated at surgery and was classified as soft, intermediate, or hard. Histologic examination was performed on surgical specimens of macroadenomas. Mean ADC values, signal intensity (SI) ratios of tumor to white matter within ROIs on conventional and DW MR images, and degree of enhancement were compared with tumor consistency and with percentage of collagen content at histologic examination by using analysis of variance for linear trend. RESULTS: The mean value of ADC in the soft group was (0.663 +/- 0.109) x 10(-3) mm(2)/sec; in the intermediate group, (0.842 +/- 0.081) x 10(-3) mm(2)/sec; and in the hard group, (1.363 +/- 0.259) x 10(-3) mm(2)/sec. Statistical analysis revealed a significant correlation between tumor consistency and ADC values, DW image SI ratios, T2-weighted image SI ratios, and percentage of collagen content (P < .001, analysis of variance). No other statistically significant correlations were found. CONCLUSION: Findings in this study suggest that DW MR images with ADC maps can provide information about the consistency of macroadenomas.

EEG/fMRI study of ictal and interictal epileptic activity: methodological issues and future perspectives in clinical practice.

PURPOSE: Electroencephalography/functional magnetic resonance imaging (EEG/fMRI) has been proposed recently as a tool to study electrophysiological activity and, consequently, detect brain regions activated during epileptiform EEG abnormalities. The purpose of the study was to review our two-year experience with studying ictal and interictal activities in patients with epilepsy. METHODS: Using EEG/fMRI, we studied hemodynamic changes associated with ictal and interictal EEG abnormalities in 43 patients with partial (31 cases) or generalized (12 cases) epilepsy. Using two different paradigms (block design and event-related design), we studied several forms of EEG activity consisting of (i) interictal abnormalities constantly elicitable by specific stimulation (8 cases); (ii) focal and generalized interictal activity, such as focal spikes or typical and atypical generalized spike-and-wave discharges (18 cases); and (iii) focal and generalized ictal electro-clinical activity, such as tonic seizures or pseudo-absences in frontal lobe epilepsy, typical absences in idiopathic generalized epilepsy, complex partial seizures in temporal lobe epilepsy, and perisylvian seizures in special syndromes (17 patients). RESULTS: EEG/fMRI revealed clear hemodynamic changes related to EEG abnormalities in 21 patients. In 18 of these patients, the changes were highly concordant with electro-clinical findings. In the remaining 22 patients, fMRI analysis data failed to show activation or deactivation clusters, probably owing either to lack or inadequate amount of temporal distribution of abnormal EEG activity, or to intrinsic methodological problems. CONCLUSIONS: By defining the electro-clinical and hemodynamic correlates of EEG activity, fMRI may shed light on the neurophysiological mechanisms underlying epileptic phenomena. However, as several methodological issues have yet to be addressed, further studies are warranted to assess the reliability and usefulness of EEG/fMRI in clinical practice.

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.

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.

Cortical motor reorganization after a single clinical attack of multiple sclerosis.

In order to evaluate whether cortical motor reorganization occurs in the earliest phase of multiple sclerosis, we studied patients after a first clinical attack of hemiparesis. From a consecutive series of 70 patients enrolled in a study of patients with clinically isolated syndrome and serial MRI findings indicative of multiple sclerosis, we retrospectively selected 10 patients with hemiparesis as the onset symptom and no further clinical episode [mean age 32 +/- 9 years, disease duration 24 +/- 14 months, median Expanded Disability Status Score (EDSS) 1.25]. Ten age-matched, healthy subjects served as controls. Each subject was submitted to two functional MRI trials (one per hand) using a 1.5 T magnet during a sequential finger-to-thumb opposition task. Image analysis was performed using SPM99 software. Movements of both the 'affected' and the 'unaffected' hand activated significantly larger areas in patients than in controls in both the contralateral and ipsilateral cortical motor areas. Patients activated a greater number of foci than controls during both the right-hand and the left-hand movement. Most of these foci were located in cortical areas which were less or not at all activated in controls, such as the lateral premotor cortex [Brodmann area (BA) 6], the insula and the inferior parietal lobule (BA 40). Between-group analysis of patients versus controls showed significant (P < 0.001) foci in these areas, principally located in the ipsilateral hemisphere during right-hand movement and in both the cerebral hemispheres during left-hand movement. Time since clinical onset showed a significant positive correlation with the extent of activation in the ipsilateral motor areas (P = 0.006) during the right-hand movement and with the extent of activation in both the ipsilateral (P = 0.02) and contralateral (P = 0.006) motor areas during the left-hand movement. The T(1) lesion load along the motor pathway showed a significant positive correlation (P = 0.007) with the extent of activation in the contralateral motor areas during right-hand movement. Our study shows functional adaptive changes that involve both the symptomatic and asymptomatic hemisphere during a simple motor task in patients who had suffered a single clinical attack of hemiparesis. The extent of these changes increased with the time elapsed since disease onset and the severity of brain damage.