William W. Orrison

Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders

Background. One-third of children diagnosed with autism spectrum disorders (ASDs) are reported to have had normal early development followed by an autistic regression between the ages of 2 and 3 years. This clinical profile partly parallels that seen in Landau-Kleffner syndrome (LKS), an acquired language disorder (aphasia) believed to be caused by epileptiform activity. Given the additional observation that one-third of autistic children experience one or more seizures by adolescence, epileptiform activity may play a causal role in some cases of autism. Objective. To compare and contrast patterns of epileptiform activity in children with autistic regressions versus classic LKS to determine if there is neurobiological overlap between these conditions. It was hypothesized that many children with regressive ASDs would show epileptiform activity in a multifocal pattern that includes the same brain regions implicated in LKS. Design. Magnetoencephalography (MEG), a noninvasive method for identifying zones of abnormal brain electrophysiology, was used to evaluate patterns of epileptiform activity during stage III sleep in 6 children with classic LKS and 50 children with regressive ASDs with onset between 20 and 36 months of age (16 with autism and 34 with pervasive developmental disorder–not otherwise specified). Whereas 5 of the 6 children with LKS had been previously diagnosed with complex-partial seizures, a clinical seizure disorder had been diagnosed for only 15 of the 50 ASD children. However, all the children in this study had been reported to occasionally demonstrate unusual behaviors (eg, rapid blinking, holding of the hands to the ears, unprovoked crying episodes, and/or brief staring spells) which, if exhibited by a normal child, might be interpreted as indicative of a subclinical epileptiform condition. MEG data were compared with simultaneously recorded electroencephalography (EEG) data, and with data from previous 1-hour and/or 24-hour clinical EEG, when available. Multiple-dipole, spatiotemporal modeling was used to identify sites of origin and propagation for epileptiform transients. Results. The MEG of all children with LKS showed primary or secondary epileptiform involvement of the left intra/perisylvian region, with all but 1 child showing additional involvement of the right sylvian region. In all cases of LKS, independent epileptiform activity beyond the sylvian region was absent, although propagation of activity to frontal or parietal regions was seen occasionally. MEG identified epileptiform activity in 41 of the 50 (82%) children with ASDs. In contrast, simultaneous EEG revealed epileptiform activity in only 68%. When epileptiform activity was present in the ASDs, the same intra/perisylvian regions seen to be epileptiform in LKS were active in 85% of the cases. Whereas primary activity outside of the sylvian regions was not seen for any of the children with LKS, 75% of the ASD children with epileptiform activity demonstrated additional nonsylvian zones of independent epileptiform activity. Despite the multifocal nature of the epileptiform activity in the ASDs, neurosurgical intervention aimed at control has lead to a reduction of autistic features and improvement in language skills in 12 of 18 cases. Conclusions. This study demonstrates that there is a subset of children with ASDs who demonstrate clinically relevant epileptiform activity during slow-wave sleep, and that this activity may be present even in the absence of a clinical seizure disorder. MEG showed significantly greater sensitivity to this epileptiform activity than simultaneous EEG, 1-hour clinical EEG, and 24-hour clinical EEG. The multifocal epileptiform pattern identified by MEG in the ASDs typically includes the same perisylvian brain regions identified as abnormal in LKS. When epileptiform activity is present in the ASDs, therapeutic strategies (antiepileptic drugs, steroids, and even neurosurgery) aimed at its control can lead to a significant improvement in language and autistic features. autism, pervasive developmental disorder–not otherwise specified, epilepsy, magnetoencephalography, Landau-Kleffner syndrome.

Objective documentation of traumatic brain injury subsequent to mild head trauma: multimodal brain imaging with MEG, SPECT, and MRI.

ObjectiveTo determine to what extent magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and magnetoencephalography (MEG) can provide objective evidence of brain injury in adult patients with persistent (>1 year) postconcussive symptoms following mild blunt head trauma. DesignA retrospective and blind review of imaging data with respect to the presence of specific somatic, psychiatric, and cognitive complaints. Setting/ParticipantsThirty complete data sets (with MRI, SPECT, MEG, and neuropsychological testing results) were collected between 1994 and 2000 from the MEG programs at the Albuquerque VAMC and the University of Utah. Main Outcome MeasuresMRI data were evaluated for focal and diffuse structural abnormalities, SPECT data for regions of hypoperfusion, and resting MEG data for abnormal dipolar slow wave activity (DSWA) and epileptiform transients. ResultsStructural MRI was abnormal for 4 patients. SPECT showed regions of hypoperfusion in 12 patients, while MEG showed abnormal activity in 19 patients. None of the imaging methods produced findings statistically associated with postconcussive psychiatric symptoms. A significant association was found between basal ganglia hypoperfusion and postconcussive headaches. For patients with cognitive complaints, abnormalities were more likely to be detected by MEG (86%) than either SPECT (40%) or MRI (18%) (P < .01). MEG also revealed significant (P < .01) associations between temporal lobe DSWA and memory problems, parietal DSWA and attention problems, and frontal DSWA and problems in executive function. ConclusionsFunctional brain imaging data collected in a resting state can provide objective evidence of brain injury in mild blunt head trauma patients with persistent postconcussive somatic and/or cognitive symptoms. MEG proved to be particularly informative for patients with cognitive symptoms.

CHAPTER 9 – Magnetoencephalography and Magnetic Source Imaging

Publisher Summary This chapter discusses megnetocephalography and magnetic source imaging. Neuromagnetic recordings offer several advantages over alternative noninvasive imaging modalities. Magnetoencephalography (MEG), as with electroencephalography (EEG), provides for real-time, direct assessment of brain electrophysiology. MEG, therefore, provides an important complement to structural imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) and to hemodynamic and metabolic techniques such as functional MRI (fMRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). MEG affords certain advantages over EEG. The most salient of these is that neuromagnetic signals penetrate the skull and scalp without significant distortion. The spatial resolution of MEG is higher than that for EEG, and mathematical analyses of the spatial pattern of the neuromagnetic field can offer accurate spatial localization of the neurons responsible for generating neuromagnetic signals. Of the available noninvasive neuroimaging techniques, MEG provides the best balance of temporal and spatial sensitivity to brain physiology.

Magnetic source imaging: a review of the Magnes system of biomagnetic technologies incorporated.

Magnetic source imaging (MSI) is a new, noninvasive technique for defining the relationship between brain function and structure on a patient-to-patient basis. It achieves this by combining detailed neurophysiological data derived from magnetoencephalography with high-quality neuroanatomical data derived via magnetic resonance imaging. By the use of mathematical models, the spatial locations of those neurons that generate neuromagnetic signals of interest are estimated and subsequently marked on spatially aligned magnetic resonance images. There are three prominent types of clinical MSI examinations. These are: 1) functional mapping examinations in which sensory and motor functions are localized; 2) examinations of interictal epileptiform activity; and 3) examinations of abnormal low-frequency magnetic activity, which has been found to be present in a wide range of pathophysiological conditions. Functional mapping provides useful information regarding the relationship between the cortical representation of eloquent function and the location of pathological lesions that may be surgically resectable. This application is of particular utility in cases of intracortical masses that distort and obscure the local neuroanatomy. By defining the primary sites of interictal epileptiform activity, MSI examinations are useful in the surgical planning for the implantation of depth electrodes and the planning of partial lobectomies. Abnormal low-frequency magnetic activity appears to be a neurophysiological correlate of ischemic penumbra associated with stroke, neoplasms, and vascular malformations. Abnormal low-frequency magnetic activity has also been found to be present in several other conditions, including head trauma and psychiatric dysfunction, although the exact pathophysiological mechanisms are presently unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic resonance imaging in minor head injury

STUDY OBJECTIVES To investigate the role of cranial magnetic resonance (MR) imaging in evaluating patients discharged from the emergency department after minor head injury. DESIGN A prospective blinded cohort study. SETTING University hospital ED. TYPE OF PARTICIPANTS Fifty-eight patients with minor head injury who were discharged from the ED with written head injury instructions. Patients admitted to the hospital were excluded. INTERVENTIONS Ultra-low-field cranial MR scans were performed on patients within 24 hours of discharge. Scans were read blindly by two radiologists. MEASUREMENTS AND MAIN RESULTS Fishers exact test was used to compare symptoms in patients with abnormal and normal MR scans. There was no significant difference in symptoms between patients with abnormal and those with normal scans (P greater than .10). The proportion of abnormal MR scans was analyzed using the binomial distribution. Six of the 58 patients (10.3%) had traumatic intracranial abnormalities (proportion, 0.103; SD, 0.04; 95% CI, 0.04-0.21). Three had cortical contusions, and three had small subdural hematomas. Two of the six patients with abnormal MR scans, both with small subdural hematomas, had normal computed tomography scans. CONCLUSION Ten percent of patients discharged from the ED after minor head injury had abnormal ultra-low-field cranial MR scans. Additional research is needed to establish the clinical importance of this unexpected observation.

Traumatic Brain Injury: A Review and High-Field MRI Findings in 100 Unarmed Combatants Using a Literature-Based Checklist Approach

This study reviewed the literature for the extent of neuroimaging findings in boxers, indicative of traumatic brain injury (TBI) as identified in magnetic resonance imaging (MRI). The study then utilized a systematic checklist approach to assess 100 unselected consecutive 1.5- and 3.0-Tesla MRI examinations of professional unarmed combatants to determine the extent of identifiable TBI findings. The percentage of positive findings and the localization of lesions were quantified using the checklist that included the MRI findings previously reported in the medical literature. Seventy-six percent of the unarmed combatants had at least one finding that may be associated with TBI: 59% hippocampal atrophy, 43% cavum septum pellucidum, 32% dilated perivascular spaces, 29% diffuse axonal injury, 24% cerebral atrophy, 19% increased lateral ventricular size, 14% pituitary gland atrophy, 5% arachnoid cysts, and 2% had contusions. Statistical relationships were found between number of bouts and lateral ventricular size (tau-b = 0.149, p = 0.0489), with years of fighting correlating with the presence of dilated perivascular spaces (tau-b = 0.167, p = 0.0388) and diffuse axonal injury (tau-b = 0.287, p = 0.0013) findings. The improved resolution and increased signal-to-noise ratio on 1.5- and 3.0-Tesla high-field MRI systems defines the range of pathological variations that may occur in professional unarmed combatants. Additionally, the use of a systematic checklist approach insures evaluation for all possible TBI-related abnormalities. This knowledge can be used to anticipate the regions of potential brain pathology for radiologists and emergency medicine physicians, and provides important information for evaluating unarmed combatants relative to their safety and long-term neurocognitive outcome.

Utilization of multichannel magnetoencephalography in the guidance of ablative seizure surgery

Abstract Magnetoencephalography (MEG) was used to evaluate 50 seizure surgery candidates. Interictal spikes were recorded in 42 cases. Of 20 cases with other data suggesting a convexity (lateral neocortical) focus, MEG spikes were recorded from 19. In 17, MEG and electrographic data were localized to the same region. Invasive studies were or could have been avoided in 11 cases based on MEG and other noninvasive data. MEG spike data were present in 14 of 18 cases with anteromesial temporal foci, being localized to the same lobe as electrographic data in 11. MEG was not of value in surgical planning of cases with orbitofrontal foci, or depth nonlocalized seizures. Twenty-seven patients with MEG epileptiform data have had postoperative follow-up. Fourteen of 19 with electrographic and MEG data localized to the same region are seizure-free. Four of eight with spatial discordance of MEG and electrographic data are seizure-free. Preliminary conclusions are as follows: When MEG and electrographic data are localized to the same region, seizure-free surgical outcome is more likely. In convexity cases with MEG and noninvasive electrographic data localized to the same region, preoperative invasive studies may be unnecessary.

An MRI Study of Lumbar Puncture Headaches

We studied 11 patients undergoing a routine lumbar puncture to determine if there were cerebrospinal fluid leaks at the puncture site and whether the maximum volume of leakage correlates with a lumbar puncture headache. Patients completed a headache questionnaire before and after the lumbar puncture. Limited magnetic resonance imaging of the lumbar spine was obtained 8 to 36 hours after the lumbar puncture and two patients also had later imaging. In a blinded fashion, the largest diameter of cerebrospinal fluid leakage into the paraspinous area was determined from T2 weighted magnetic resonance images and the maximum possible fluid volume was calculated. Six patients had a small cerebrospinal fluid leakage (< 10 mL), two had a medium leakage (10 to 110 mL), and three had a large leakage (> 110 mL). The volume of cerebrospinal fluid leakage did not corre late with occurrence of a lumbar puncture headache. The study demonstrates that cerebrospinal fluid usually leaks into the paraspinous area after a lumbar puncture, but the volume of escaped fluid does not correlate with a lumbar puncture headache.

Magnetic resonance imaging for stenosis and subluxation in Klippel-Feil syndrome

Magnetic resonance imaging and radiographs in neutral flexion and extension were used to evaluate 20 pediatric Klippel—Feil patients for subluxation and stenosis. Radiographs showed subluxation of 5 mm or greater in 5 (25%) of the 20 patients for an incidence of 25%. Magnetic resonance imaging documented stenosis of 9 mm or less below C1 in 5 (25%) of the 20 patients. Cord abnormalities were discovered in three (12%) of the patients: one hydromyelia with Arnold-Chiari I malformation and diplomyelia in two. The incidence of stenosis and subluxation was higher than the literature would suggest in this pediatric population. Magnetic resonance imaging is a useful tool and should be used to evaluate Klippel—Feil patients for cord abnormalities and cord compression.

Comparison of primary motor cortex localization using functional magnetic resonance imaging and magnetoencephalography

The primary goal of the study was to compare estimates of motor cortex localization from functional magnetic resonance imaging (FMRI) and magnetoencephalography (MEG). Thirteen normal volunteers were studied using both methods. FMRI was performed on a clinical 1.5 T system using gradient‐echo acquisitions and basic t‐test processing. MEG primary motor field was characterized by a single dipole model. Comparisons between the location of the best‐fitting MEG dipole and the FMRI activation results were made using both fixed regions‐of‐interest weighted averaging and clustering analysis to reduce the observed FMRI activations to a single representative location.