Lissencephaly

Somatosensory maps were determined in three patients with hemimegalencephaly using magnetic resonance imaging (MRI) and magnetoencephalography (MEG). MRIs were characterized by thickened gray matter with clearly aberrant lamination patterns. Somatosensory Evoked Fields (SEFs), as measured by MEG, were absent from the affected hemisphere in the two patients with severe cortical lamination defects. The third patient presented with relatively preserved cortical lamination in the frontal lobe and clear cortical SEFs in this region, indicating somatotopical reorganization. These findings suggest that the presence and location of MEG-derived somatosensory maps reflect the severity of the cortical lamination defects in hemimegalencephaly. [Neurol Res 2002; 24: 459-462]

Keywords: Hemimegalencephaly, somatosensory evoked magnetic fields; cortical lamination; primary sensory cortex; epilepsy surgery

INTRODUCTION

Hemimegalencephaly is a dysplastic disorder characterized macroscopically by unilateral hypertrophy of the brain and an abnormal gyral pattern. Diagnosis is based on neuroimaging (typically magnetic resonance imaging (MRI)), clinical and radiographic evidence. The electrophysiological profile of individuals with hemimegalencephaly is also of interest, due to the frequent comorbidity of intractable epilepsy1,2. To date, the majority of hemimegalencephaly research has focused on radiographic and electrophysiological features of its structure and epileptogenicity1-6.

By comparison, little research has been done on the organization of primary somatosensory cortex in hemimegaIencephaly7,8. To date, only five somatosensory evoked potential (SEP) case studies have been reported, each failing to show activity over the malformed hemisphere. However, two constraints need to be taken into account when evaluating such research. First, scalp SEPs do not accurately reflect the brain electrical activity, because their electrical fields are wide distributed over the scalp by volume conduction Second, hemimegalencephaly is characterized by irregular head shape and/or whole-brain shift, potentially causing scalp electrode displacement1. An alternative to SEPs involves the recording of somatosensory evoked magnetic fields (SEFs) through magnetoencephalography (MEG).

MEG is a noninvasive method for recording and localizing brain activity while overcoming the constraints of traditional SEPs in two ways. First, SEFs can be localized with significantly higher resolution than SEPs". Second, when paired with MRI, MEG data can account for irregular head shape and/or whole brain shift. Indeed, the accuracy of MEG is comparable to invasive electrophysiological measures11,12. In this study, MEG was used to examine SEFs to map somatosensory organization and determine the correlation between neurophysiological responses and cortical anomalies in three children with hemimegalencephaly.

MATERIALS AND METHODS

Patients

Three infants with hemimegalencephaly who underwent routine pre-surgical MEG evaluation were examined, ranging in age from 8 to 26 months (mean age 18.3 months). Neurological examination showed unilateral, spastic hemiparesis or hemianopsia related to the malformed hemisphere (Table 1).

SEF recording

Somatosensory evoked magnetic field (SEF) recordings were performed with a 148 channel whole-head magnetometer (Magnes WH2500, 4D Neuroimaging, San Diego, CA, USA) in a magnetically shielded room. The distal phalanx of the index finger was stimulated mechanically via a pneumatic stimulator (with a 1 msec rise time) located outside the magnetically shielded room. A total of 800 stimuli were used to construct average responses.

The responses were bandpass filtered at 1-100 Hz, and digitized at a sampling rate of 560 Hz. The intracranial location of the source of the recorded magnetic field distribution at the peak of the earliest discernible response was modeled as an equivalent current dipole (ECD). In order to visualize the results with respect to brain anatomy, the ECD locations were projected on Ti- or T2-weighted MR images with a 1.4mm slice thickness (Signa, GE, Milwaukee, WI, USA). Prior to MRI, lipid markers were placed at three fiducial points on the patient's head (the nasion and left/ right external meati). The position of the same fiducial points were recorded at the beginning of the MEG recording session, relative to the magnetometer sensor, thus establishing a common spatial reference for 3-D overlay of MEG onto MRI data. The principles underlying MEG generation, recording, and source localization are reviewed elsewhere

RESULTS

In all three patients, MRIs were characterized by dysplastic and enlarged left hemisphere with thickened gray matter and reduced cortical sulcation. The delineation between white matter and cerebral cortex was unclear in some areas, indicating cortical laminar defects. No definite anatomical abnormalities were seen in the right hemisphere (Figure 1).

These findings were most prominent in Cases 1 and 2 where SEF recordings disclosed total absence of any response on the dysplastic side (Figure 2). In Case 3, the MRI revealed a less severe cortical lamination defect while the SEF showed a clear early component peaking at approximately 25 msec. This component corresponds to the N22m SEP peak". The estimated dipole source location at the peak of this response was more anterior, medial and deeper than expected, indicating unique somatotopic organization (Figure 3). In all three cases, scalp SEP recordings failed to show brain responses after electrical median nerve stimulation contralateral to the malformed hemisphere.

DISCUSSION

In humans, evoked potential responses require the presence of an anatomically intact cerebral hemisphere 7. Hemimegalencephaly, therefore, presents a particular challenge to the use of SEPs. Using SEPs, Di Capua et al.7 demonstrated the total absence of early (N20) and late components over the malformed hemispheres in four patients (see also Shields et al.8). Histologically, hemi megalencephaly manifests as thickened gray matter with an absence of normal lamination, white matter gliosis, and giant neurons that are scattered throughout the cortex and in ectopic white matter locations15,16. Therefore, Di Capua et al.7 concluded that SEP abnormalities identified in hemimegalencephaly correspond to the underlying anatomical anomalies, especially unilateral laminar defect. The degree of primary somatosensory reorganization appears dependent upon the extent of cortical pathology. Unilateral, limited hemisphere pathology may result in somatosensor reorganization within the contralateral hemisphere17-20. More extensive embryonic lesions are often associated with reorganization of sensory projections into the intact, unilateral hemisphere

In this study, Cases 1 and 2 were marked by severe unilateral hemisphere damage. These patients did not show any magnetic response in the affected hemisphere when stimuli were applied to the contralateral hand. The MRI of the third patient revealed less severe cortical lamination defects than the other two patients. SEF responses in the affected hemisphere of this patient were present, but showed unusual source localization (frontal lobe).

Let us now discuss the potential neurological causes of this SEF profile. Hemimegalencephaly is the result of hemisphere over-development and delayed frontal lobe maturation during infancy2 . This delay in frontal lobe development may have spared, or preserved, the region's cortical lamination even as other brain regions were damaged, at least in Case 3. Subsequently, the intact frontal cortex took on somatosensory functions, resulting in a unique SEF profile. Given that this patient did not show significant focal sensory deficits, nor were such deficits reported in infancy, this reorganization was probably complete at birth or during early infancy.

Irregular head shape and whole-brain shift encountered in hemimegalencephaly can result in scalp electrode displacement with respect to underlying cortical generators. Applying conventional SEP recording methods to this disease may not accurately reflect brain activity10. MEG, on the other hand, can detect whole-brain electromagnetic activity with higher sensitivity than EEG. When paired with MRI, patterns of activation can be precisely localized beyond what is possible using SEPs. This discrepancy was supported by the present data. Additionally, the degree of underlying anatomical anomalies correlate with SEF results. Given these abnormalities, MEG may help us understand somatosensory reorganization in hemimegalencephaly, and predict possible functional deficits (or lack of them) after epilepsy surgery.

ACKNOWLEDGEMENT

We wish to thank Mr. Eric Y. Caballero, 4-D Neuroimaging, for his technical assistance. This study was supported in part by NIH Grant NS37941 -01 to Dr A.C. Papanicolaou.

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Hideaki Ishibashi*, Panagiotis G. Simos*, James E. Whelesstl^,^^, Wenbo Zhang*, James E. Baumgartner sec, Eduardo M. Castillo* and Andrew C. Papanicolaou*

*Department of Neurosurgery, Vivian L. Smith Center for Neurologic Research ^Department of Neurology, ^^Department of Pediatrics, Department of Pediatric surgery (Neurosurgery) Texas Comprehensive Epilepsy Program, The University of Texas Health Science Center at Houston, TX, USA

Correspondence and reprint requests to: Hideaki Ishibashi, MD, PhD, Vivian L. Smith Center for Neurologic Research, Division of Clinical Neurosciences, Department of Neurosurgery, The University of Texas Health Science Center at Houston, Jesse Jones Library Building, 1133 MD Anderson Blvd., Suite 304, Houston, TX 77030, USA.

[Hideaki. Ishibashi@uth.tmc.edu] Accepted for publication March 2002.

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