Comparison of electroencephalographic dipoles of interictal spikes from prolonged scalp video-electroencephalography and magnetoencephalographic dipoles from short-term recording in children with extratemporal lobe epilepsy.

We retrospectively compared electroencephalographic (EEG) dipoles of interictal spikes from prolonged video-EEG monitoring with magnetoencephalographic dipoles from short-term recording in four children with extratemporal lobe epilepsy. We analyzed both sets of dipoles using individual interictal spikes and single moving dipole modeling and evaluated the profiles of spike appearance, dipole position, and orientation in EEG and magnetoencephalography. We obtained more than 100 magnetoencephalographic spikes in two patients who manifested frequent interictal EEG spikes throughout both day and night but fewer than 40 magnetoencephalographic spikes in two patients who had interictal EEG spikes mainly during sleep. The dipole positions of EEG and magnetoencephalography were in close proximity and included in the surgical resection area. Most of the dipoles between EEG and magnetoencephalography were oriented perpendicularly. A combination of EEG dipole analysis from prolonged video-EEG monitoring and magnetoencephalographic dipole analysis provides complementary information for presurgical evaluation in children with intractable extratemporal lobe epilepsy.

Predictive value of lesions for relapses in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Recent studies have suggested that enhancing lesions on contrast-enhanced T1-weighted MR images are predictive of impending exacerbations in cases of relapsing-remitting multiple sclerosis. We examined whether enhancing lesions, new enhancing lesions, and new hypointense lesions ("black holes") could accurately predict exacerbations in a cohort of 50 patients with relapsing-remitting multiple sclerosis within a time frame of up to 6 months. METHODS: Data were obtained from 50 patients with relapsing-remitting disease. All patients underwent monthly MR imaging and clinical examinations for a period of 12 months. Putative predictors of clinical relapse were defined from enhancing lesions, new enhancing lesions, and new black hole outcomes, and their operating characteristics were studied. RESULTS: Overall, the positive predictive values (PV+) of enhancing lesions, new enhancing lesions, or new black holes for an exacerbation did not exceed 0.25 and the negative predictive values (PV-) were all near 0.9. The best predictor for new enhancing lesions was the occurrence of new enhancing lesions in each of the previous 3 months (PV+: 0.79 [95% confidence interval, 0.651-0.900]; PV-: 0.83 [95% confidence interval, 0.751-0.887]). Similarly, new black holes were predicted best by the occurrence of new black holes in each of the previous 2 months (PV+: 0.54 [95% confidence interval: 0.372-0.697]; PV-: 0.85 [95% confidence interval, 0.790-0.896]). CONCLUSION: None of the MR markers could predict an impending relapse with any reasonable degree of precision. Rather, the absence of MR markers is associated with a more favorable clinical course (ie, fewer relapses).

MEG predicts epileptic zone in lesional extrahippocampal epilepsy: 12 pediatric surgery cases.

PURPOSE: To discover whether the spatial distribution of spike sources determined by magnetoencephalography (MEG) provides reliable information for planning surgery and predicting outcomes in pediatric patients with lesional extrahippocampal epilepsy. METHODS: We retrospectively studied 12 children with extrahippocampal epilepsy secondary to cortical dysplasia (CD), tumor, or porencephalic cyst. We compared interictal MEG spike source locations and somatosensory evoked fields derived from equivalent-current dipole modeling with intraoperative or extraoperative electrocorticography (ECoG). RESULTS: MEG spike sources were found in proximity to the lesion in all patients and extended from lesions in five patients with CD. Marginal spike sources were noted in three patients with tumors, one patient with a cyst, and one with CD, and extramarginal sources in three patients with tumors. Three patients with tumors underwent lesionectomy only; two had further cortical excisions. One patient with CD underwent lesionectomy only, three had lesionectomy and cortical excisions, and two had lesionectomy and multiple subpial transection. Asymmetric MEG spike sources correlated with ECoG findings in all patients. Residual epileptiform discharges on postexcisional ECoG corresponded to spike sources in three patients with tumors and one patient with a cyst. Eleven patients have been seizure free for 1-6 years (mean, 4 years). One patient had residual seizures after incomplete excision of right temporal CD. CONCLUSIONS: MEG delineated asymmetric epileptogenicity surrounding lesions and the eloquent cortex. Complete tumor resection produced favorable outcomes despite residual postexcisional ECoG spikes and extramarginal MEG spike sources. CD characterized by clusters of MEG spike sources within and extending from lesions seen on magnetic resonance imaging (MRI) should be removed to prevent seizures.

New hypointense lesions on MRI in relapsing-remitting multiple sclerosis patients.

BACKGROUND: Preliminary observational studies with multiple sclerosis (MS) patients have reported strong correlations between an increase in hypointense lesion load (black holes) on T1-weighted spin echo images, and an increase in disability. OBJECTIVE: We assessed the relationship of hypointense lesions to the clinical course of disease among 50 relapsing-remitting MS patients in the controlled setting of a randomized clinical trial. METHODS: Fifty patients with relapsing-remitting disease were enrolled in a randomized double-blind two-arm (cladribine vs. placebo) clinical trial of 1-year duration. All patients had monthly clinical evaluations and MRIs over the course of the trial. Multivariate techniques were used to identify predictors of clinical severity from information on exacerbations, MRIs, baseline clinical parameters, and demographics. RESULTS: At baseline, clinical severity is weakly related to counts of black holes, with rank correlations between counts and clinical scores (EDSS and SNRS) of absolute magnitude 0.3. Rates of appearance of new black holes over the course of the trial are higher for patients with more severe disease at baseline (EDSS > or = 4) than for the less severe patients. Changes in clinical severity over the course of the trial are best predicted by baseline neurologic scores and numbers of exacerbations, with black holes adding no further improvement in prediction. CONCLUSIONS: Numbers of exacerbations seem more critical to short-term clinical outcomes in relapsing-remitting MS, as reflected by patients' clinical scores, rather than black holes. Various imaging methods and MRI indices capture complementary information relating to MS disease processes. The determination of which processes are affected by different drugs should lead to more effective treatment of MS patients.

Magnetoencephalography in children with Landau-Kleffner syndrome and acquired epileptic aphasia.

BACKGROUND AND PURPOSE: Landau-Kleffner syndrome (LKS) is epileptiform aphasia acquired during childhood and occurring in children with previously normal language development. The epileptiform activity in these children is thought to result in a functional ablation of eloquent speech areas. The purpose of this study was to investigate the usefulness of magnetoencephalography (MEG) for localizing the source of epileptiform activity in these patients. METHODS: Nineteen patients with acquired aphasia and a suspected diagnosis of LKS were referred for MEG evaluation. Patients ranged in age from 4 to 14 years. Fourteen MEG studies were performed on a 74-channel system, four on a 148-channel whole-head system, and one on a 37-channel system. RESULTS: Thirteen of the 19 patients had perisylvian MEG spikes. In 10 of the patients, the spikes were bilateral, and in three they were unilateral. Four other patients had non-sylvian spikes, and two patients had no spikes recorded. The results of MR imaging were normal or noncontributory for all 19 patients. CONCLUSIONS: MEG can play a useful role in evaluating children with LKS and acquired epileptiform aphasia, both in diagnosis and in aiding presurgical localization of epileptiform activity when surgery is being considered.

Hypointense and hyperintense lesions on magnetic resonance imaging in secondary-progressive MS patients.

Cranial magnetic resonance imaging (MRI) is widely used to monitor disease activity in clinical trials in multiple sclerosis (MS). The purpose of this study is to examine lesion burden as determined from hypointense regions on postcontrast T1-weighted scans (or black holes), and lesion burden on conventional T2-weighted scans, from a cohort of secondary progressive MS patients who participated in a placebo-controlled, randomized, double-blind cross-over trial assessing the therapeutic efficacy of cladribine. T2 lesion volumes and black hole volumes are approximately normal distributed when log-transformed, and are highly correlated (adjusted R2 = 0.63). Changes in clinical scores could be predicted with a reasonable degree of precision from baseline scores and changes in T2 lesion volumes (adjusted R2 values 0.52-0.7). Stratification schemes for clinical trials should include the acute proportion of the disease (enhancing T1 lesions), degree of permanent damage (black holes), and T2 lesion volume.

Determinants of P3 amplitude and response to alcohol in Native American Mission Indians.

Native Americans have some of the highest rates of alcohol abuse and dependence, yet potential biological risk factors associated with the problem drinking seen in some tribes remain relatively unknown. The amplitude of the P3 component of the event-related potential (ERP) is perhaps the most studied electrophysiological "marker" of potential vulnerability to alcohol dependence, yet it has not been investigated in Native Americans. Forty-seven, non-alcohol-dependent Native American Mission Indian men between the ages of 18 and 25 years participated in the study. ERPs were collected at 60 minutes following both alcohol (0.56 g/kg) and placebo intake. No relationship was found between P3 amplitude and degree of Native-American heritage (NAH), or family history (FH) of alcohol dependence. The results of this study did, however, replicate previous findings that the P3 component of the ERP is sensitive to the effects of alcohol. A reduction in the P3a component across the scalp was found in these Native American men following alcohol when compared with placebo ingestion. P3 response to alcohol, although not influenced by a subject's NAH or FH, was influenced by the presence of a polymorphism in the alcohol metabolizing enzyme alcohol dehydrogenase (ADH). Men with an ADH2 x 3 allele had significantly higher amplitude P3 components at placebo and also demonstrated more alcohol-induced reductions in P3 amplitude than men with ADH2 x 1 alleles only. In addition, individuals with low P3 amplitude in the placebo condition had less of a reduction or an actual increase in P3a and P3b amplitudes following alcohol intake. Given that a less intense response to alcohol has been associated with greater risk for the development of alcohol-related problems, these data suggest the presence of certain biological variables within this Native American population that may confer both risk and protection for the future development of alcohol dependence.

Magnetic source imaging of abnormal low-frequency magnetic activity in presurgical evaluations of epilepsy.

PURPOSE: Regional cortical dysfunction associated with epileptogenic activity was predicted from interictal localized abnormal low frequency neuromagnetic activity (ALFMA) using Magnetic Source Imaging (MSI). ALFMA can be detected in patients who show no interictal spikes. METHODS: A large array biomagnetometer was used in a blinded, rapid screening protocol. The MSI procedure required no alteration in epileptic medications. MSI results were compared with the presumed epileptogenic region as determined by a consensus of standard techniques, which included MR and electroclinical monitoring. RESULTS: One or more sites of localized abnormality were detected by MSI ALFMA in 29 of the 33 epileptic patients. ALFMA mapped with MSI showed a 48.5% specificity with respect to the presumed epileptogenic region. MSI ALFMA was in agreement with the final consensus as often as was ictal noninvasive video EEG monitoring, and was exceeded in specificity overall only by invasive ictal video EEG monitoring, which was required for conventional localization in 21 of the 33 patients tested with MSI. CONCLUSIONS: ALFMA measurements with MSI may augment the array of noninvasive methods used for reaching a consensus for epilepsy surgery.

A decrease in the size of the basal ganglia in children with fetal alcohol syndrome.

Magnetic resonance imaging was conducted on six children and adolescents with fetal alcohol syndrome and seven matched normal controls. Detailed volumetric analyses demonstrated significant reductions in the cerebral vault, basal ganglia, and diencephalon in the children with fetal alcohol syndrome, compared with control children. In addition, the volume of the cerebellar vault was smaller than controls in 4 of the 6 children with fetal alcohol syndrome, although the group difference did not reach significance. When the basal ganglia were divided into the caudate and lenticular nuclei, both of these regions were significantly reduced in the children with fetal alcohol syndrome. Finally, when the overall reduction in brain size was controlled, the proportional volume of the basal ganglia and, more specifically, the caudate nucleus was reduced in the children with fetal alcohol syndrome. These results may relate to behavioral findings in both humans and animals exposed to alcohol prenatally.

Abnormal development of the cerebellar vermis in children prenatally exposed to alcohol: size reduction in lobules I-V.

Abnormalities of the cerebellar vermis have been well documented in animal models of fetal alcohol syndrome. At this point, it is not known if the same brain region is affected in humans prenatally exposed to alcohol. In this study, the area of the cerebellar vermis was measured from brain magnetic resonance images of 9 children and young adults with prenatal alcohol exposure and 24 control subjects in the same age range. Six of the exposed children met standard criteria for fetal alcohol syndrome. The remaining three subjects had significant histories of prenatal exposure to alcohol, but did not have enough of the classic facial features for the diagnosis. For each subject with a suitable midsagittal section, three vermal areas were circumscribed: anterior vermis (vermal lobules I-V), posterior vermis (vermal lobules VI and VII), and the remaining vermal area (including lobules VIII-X). Statistical analyses revealed that the anterior region of the vermis was significantly smaller in subjects with prenatal alcohol exposure, whereas the posterior region and the remaining vermal area did not differ between groups. Previous findings from an animal model of neonatal alcohol exposure have documented Purkinje cell loss in vermal lobules I-V and IX-X, with notable sparing in lobules VI-VII. Thus, the results of both studies indicate similar patterns of abnormal brain development in the anterior vermal region, with apparent sparing in the posterior vermal region. Our findings, for the first time, suggest that regionally specific Purkinje cell death may also occur in humans prenatally exposed to alcohol.

Cerebral aneurysm thrombosis, shrinkage, then disappearance after subarachnoid hemorrhage.

The case is presented of a 37-year-old man with spontaneous thrombosis of a 10-mm left posterior communicating artery aneurysm, following presumed subarachnoid hemorrhage with negative angiography. Sequential magnetic resonance angiography and magnetic resonance source imaging (at 2 weeks, 3 months, 2 years, and 2 years, 5 months) showed progressive shrinkage and disappearance of the aneurysm.

Potential contribution of bilateral magnetic source imaging to the evaluation of epilepsy surgery candidates.

The current procedures that are used to evaluate candidates for epilepsy surgery are time-consuming, costly, and often invasive. Magnetic source imaging (MSI), the combination of magnetoencephalography and anatomic imaging modalities, has shown promise as an efficient noninvasive means of localizing and characterizing seizure sources for possible resection. However, MSI has been limited by the inability to conduct simultaneous bilateral monitoring. In this study, a newly developed dual-magnetometer system was employed to record bilaterally the interictal activity in 30 candidates for epilepsy surgery. A standard monitoring protocol that included concurrent electroencephalographic recording and required a 2- to 3-hour examination period for each patient was developed. As a first step in a series of studies, the resultant MSI indications were compared with the information available from standard magnetic resonance imaging and concurrent electroencephalographic results. In 83% of the cases, this MSI protocol provided new information about the location of interictal epileptic activity that could be directive for subsequent patient care. Based on these results, it seems that MSI may become a cost-effective early step in epilepsy surgery evaluation. To continue the development on this basis, a study intended to validate the accuracy of MSI indicated by comparison with invasive electroencephalography has been initiated.

Abnormalities of the corpus callosum in children prenatally exposed to alcohol.

For 20 years, it has been known that fetal alcohol syndrome (FAS) is associated with abnormal brain development. Early autopsy studies point to the corpus callosum as one area affected by heavy alcohol exposure. Little is known, however, about the integrity of the brain in alcohol-exposed children who survive the perinatal period. This study was designed to assess the corpus callosum in living children exposed to high doses of alcohol prenatally. Thirteen children with histories of significant prenatal alcohol exposure and 12 normal control children were evaluated using magnetic resonance imaging. Using the midsagittal section, images were measured for the area of the corpus callosum using a computer-assisted measurement technique. In addition to the overall area, five equiangular regions were determined for each corpus callosum. Of the 13 alcohol-exposed children assessed, two had agenesis of the corpus callosum. The remaining alcohol-exposed children had significantly smaller overall callosal areas, as well as smaller regional areas of four of the five callosal regions, when compared with the normal control children. Importantly, when corrected for brain size, three of the five callosal regions were still smaller in the alcohol-exposed children, although overall area of the corpus callosum was no longer significantly different. These results suggest that prenatal exposure to high levels of alcohol is associated with abnormalities of the corpus callosum. They verify callosal agenesis in children with FAS, which previously had only been noted in autopsy reports.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult medulloblastoma: review of 13 cases with emphasis on MRI.

Medulloblastomas are generally associated with childhood, but 14-30% occur in adults, accounting for 1% of adult central nervous system tumors. While approximately one third of adult medulloblastomas present as vermian tumors similar to those seen in childhood, the majority differ substantially from the childhood variety. In this series of 13 patients, 5 had lateral, seemingly extra-axial masses in the cerebellopontine angle or at the tentorium, simulating meningiomas or acoustic neuromas, but angiographic hypovascularity in 2 of the latter suggested a diagnosis other than meningioma. Of 4 paramedian tumors, 3 diffusely infiltrated the cerebellar white matter, showed little or no gadolinium enhancement and were not associated with hydrocephalus. Hydrocephalus was present in less than half of our patients; in childhood the reported incidence is 85-100%. A possible association with pregnancy was noted.

Intracranial neurosurgery guided by functional imaging.

Neurosurgery on eloquent cortex entails important risks of functional deficits complicating aggressive lesion resection. In this study, advanced biomagnetic functional imaging of somatosensory and motor cortex combined with surface rendered magnetic resonance imaging displays including vascular anatomy were used in conjunction with a new nonintrusive intraoperative guided instrumentation system to resect a tumor in eloquent cortex. Intraoperative verification of the accuracy of pre-operative motor localization demonstrated highly accurate results comparing direct stimulation and noninvasive presurgical mapping. The applicability of surface rendered combined functional and anatomic maps of cortex is directly evident on comparison of preoperative computer images and intraoperative pictures. This combination of new technologies has a significant potential for reduced risk and improved outcome in neurosurgery of eloquent cortex.

Noninvasive presurgical neuromagnetic mapping of somatosensory cortex.

Rapid presurgical neuromagnetic localization of the somatosensory cortex was performed successfully on five patients with a large-array biomagnetometer by a protocol called magnetic source imaging (MSI). Determination of the location of the central sulcus is important in assessing operative risk and determining the optimal operative approach to structural lesions in the vicinity of the motor strip. The use of magnetic resonance imaging anatomical methods and intraoperative visual identification can be imprecise, whereas invasive localization prolongs operative time, adds cost, and entails added risk. Until the recent development of large-array biomagnetometer systems, neuromagnetic localization of the central sulcus had been demonstrated in research but was so time consuming and laborious as to preclude routine clinical use. In this study, the validity of MSI localizations was confirmed intraoperatively by direct cortical recording of somatosensory evoked potentials and/or direct motor stimulation. Complete agreement was found between MSI and intraoperative mapping in locating the central sulcus. Objective confirmations considered together with the speed and reliability of the procedure and with the presurgical availability of the results suggests the potential utility of MSI for routine surgical planning.

Locating the central sulcus: comparison of MR anatomic and magnetoencephalographic functional methods.

PURPOSE: To compare MR anatomic and magnetoencephalographic (MEG) functional methods in locating the central sulcus. METHODS: Eleven healthy subjects and five patients with focal cerebral lesions were studied. The central sulcus was located anatomically with MR by two independent observers using axial vertex and sagittal (midline and lateral) images. Locations via the MEG functional method were based on detecting the somatosensory-evoked magnetic fields elicited by painless tactile stimuli. RESULTS: The axial method yielded the most consistent interrater results, with complete agreement in 76% of sections in both control subjects and patients. The intermethod discordance of the sagittal midline and lateral methods was 32% in control subjects and 33% in patients. The concordance of MR and MEG methods ranged from 55% to 84% in control subjects and 65% to 67% in patients. CONCLUSION: MR anatomic techniques can usually identify the central sulcus, but in the presence of anatomic distortion, the MEG functional method adds significant information.

Neuromagnetic mapping of brain function.

Magnetic source imaging, a technique that combines magnetoencephalography (MEG) and magnetic resonance (MR) imaging, was used to localize the somatosensory and auditory cortex in seven healthy subjects. Functional neuromagnetic data were obtained with a 37-channel biomagnetometer. Structural MR imaging data were obtained with a 1.5-T superconducting imager. Coordinates used in defining MEG and MR imaging space were reconciled to produce magnetic source images that displayed the putative locations of somatosensory and auditory activity in relation to brain anatomy. Sources of somatosensory activity were typically localized to the postcentral gyrus; sources of auditory activity were localized to the superior temporal plane. Extension of these results to patients with tumors (or other disorders) that distort normal brain anatomy has the potential to make noninvasive magnetic source imaging examinations clinically useful in guiding neurosurgical interventional procedures.

Embolic stroke as a sequela of cardiopulmonary bypass.

Tha pathophysiology of brain injury in patients undergoing cardiopulmonary bypass remains unclear despite several decades of inquiry. The advent of noninvasive high-resolution brain and cerebrovascular imaging by magnetic resonance, computed tomography, and pulsed Doppler ultrasonography now permits in vivo assessment of pathophysiological mechanisms. Neuroradiographic and carotid duplex studies were performed in patients who developed neurological deficits following cardiopulmonary bypass. Among 30 symptomatic patients undergoing magnetic resonance or computed tomography brain scans, 18 (60%) had findings of acute ischemic injury. Embolic infarction was evident in 14 (78%) of these 18 patients. Watershed injury was the predominant finding in a single patient, while findings consistent with global anoxia were present in another patient. Carotid atheroemboli were excluded as a possible source of embolism in 11 patients whose carotid duplex studies were unremarkable preoperatively as well as in 3 further patients whose neuroradiographic findings did not correspond with their moderate carotid disease. It is concluded that infarction due to noncarotid embolism is the primary pathophysiology of neurological deterioration following cardiopulmonary bypass.