1009 MR of Neuronal Migration Anomalies A. James Barkovich 1,2 Migration anomalies are congenital malformations caused by insults to migrating Sylvester H. Chuang3 neuroblasts during the third to fifth gestational months. Included in this group are agyria, David Norman2 pachygyria, polymicrogyria, unilateral megalencephaly, schizencephaly, and gray matter heterotopias. Patients who have these conditions present clinically with developmental delay and seizures, and abnormal motor skills are noted in the more severely affected infants. To determine the utility of MR as a method for imaging in these patients, we used MR to evaluate 13 patients who had the full spectrum of migration anomalies. MR was more sensitive than CT in detecting these anomalies because of its better contrast between gray and white matter. We found that MR was particularly more sensitive in detecting schizencephaly, where recognizing the presence of gray matter lining the cleft is critical to distinguishing that disease from porencephaly, and in detecting polymicrogyria, where critical details of cortical architecture are obscured on CT by the overlying bone. Multiplanar capabilities were also found to be essential, since narrow clefts may not be detected when the imaging plane is parallel to the cleft. MR should be the primary imaging method for infants who have seizures or develop­ mental delay. Abnormalities of cell migration are characterized by ectopiC location of neurons in the cerebral cortex. This broad group of anomalies includes agyria, pachygyria, polymicrogyria, schizencephaly, unilateral megalencephaly, and gray matter heter­ otopias. All these entities have been characterized pathologically and in vivo by sonography and CT. MR is an imaging technique uniquely suited to study these This article appears in the November/Decem­ anomalies because of its exceptional differentiation between gray and white matter ber 1987 issue of AJNR and the January 1988 and its high-resolution multi planar display of anatomy. issue of AJR. In a review of 537 MR studies in the pediatric age group, we identified 13 Received March 13, 1987; accepted June 1, 1987. patients with migration anomalies. We review the salient features of these anom­ alies and their MR appearance. The relationship of the pathologic anatomy to The views expressed in this article are those of the authors and do not reflect the official policy or theories of pathogenesis is emphasized . position of the Department of the Army, Department of Defense, or the U.S. Government. Presented in part at the annual meeting of the Subjects and Methods American Society of Neuroradiology, New York, May 1987. Thirteen patients with migration anomalies were scanned, including two with lissencephaly, , Department of Radiology, Letterman Army four with schizencephaly, two with unilateral megalencephaly, two with isolated polymicro­ Medical Center, Presidio of San Francisco, CA gyria, and three with isolated gray matter heterotopias. The four patients with schizencephaly 94129-6700. Address reprint requests to Technical also had foci of polymicrogyria. One of the patients with unilateral megalencephaly had foci Publications Editor HSHH-ZCT. of ectopic gray matter. The patients' ages ranged from 4 months to 21 years, with a mean 2 Department of Radiology, Neuroradiology Sec­ of 6.6 years and a median age of 3.5 years. The mean age is skewed by two patients with tion, University of California School of Medicine, schizencephaly who were 17 and 21 years old. The patients were referred for imaging San FranCiSCO, CA 94143. because of seizures, mental retardation, developmental delay, or enlarging head size (see 3 Department of Radiology, Neuroradiology Sec­ Table 1). tion, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. Ten patients were examined on a 1.5-T GE Signa unit. Three patients were examined on a 0.35-T Diasonics MT/S scanner. Slice thickness was 5 mm with a 2.5-mm interslice gap. AJNR 8:1009-1017, November/December 1987 0195-6108/87/0806-1009 Spin echo (SE) images were obtained with a TR of 2000 msec and TE of 35-40 msec and © American Society of Neuroradiology 70-80 msec in the transverse and coronal planes and a TR of 600 msec and TE of 25 msec 1010 BAR KOVICH ET AL. AJNR :8, November/December 1987 TABLE 1: Summary of Patient Data Presenting Patient Age MR Diagnosis Symptoms· 1 4 mo S Lissencephaly 2 4y S,DD Lissencephaly 3 8y DD Polymicrogyria 4 2y S, DD Polymicrogyria 5 12 mo S, DD Schizencephaly (bilateral vertical clefts: one narrow, one wide); polymicrogyria in and adjacent to clefts 6 7 mo S,DD Schizencephaly (bilateral horizontal clefts: both narrow); polymicrogy­ ria and pachygyria in adjacent brain 7 17 Y S,DD Schizencephaly (unilateral horizontal wide cleft); polymicrogyria in and Cortical plate adjacent to cleft; ectopic gray matter 8 21 Y S Schizencephaly (unilateral vertical Fig. 1.-Schematic drawing shows relationship of the germinal matrix cleft with fused lips) in wall of lateral ventricle to the developing cortical plate. There is a one­ 9 2y S,DD, H Unilateral megalencephaly to-one correspondence between the site of cell proliferation within the germinal zone and its eventual destination within the cortical plate. Cor­ 10 8 Y S, DD Unilateral megalencephaly responding regions are connected by radial glial cells that span entire 11 7 Y S Heterotopic gray matter thickness of hemisphere. Neurons migrate along these radial cells, even­ 12 2 Y S Heterotopic gray matter tually arriving at predestined locations on the enlarged, convoluted cortical 13 3 Y S Heterotopic gray matter surface. (Adapted from [4].) • Abbreviations: S = seizures; DO = developmental delay; H = hemiplegia. in the axial, coronal, or sagittal plane, as indicated. The results of Leading these studies are included in the Discussion section. process Pathologic confirmation was not obtained. Migration anomalies were diagnosed from the characteristic gross morphology of the affected brains, which has been established from pathologic and CT experience. Radial fiber Discussion The phenomenon of neuronal migration has been known since the turn of the century [1]. The neurons that constitute the mammalian brain are generated in proliferative zones situated along the ventricular surface of the developing brain Trailing process [1-4]. At the end of the second gestational month, the neu­ rons migrate from their site of origin along radially aligned glial cells to relatively distant final positions [3, 4] (Figs. 1 and 2). At this point they differentiate further, grow axons and den­ drites, and develop synaptic contacts with other neurons [4]. The final position of the neurons within the cortex varies inversely with the time of cell origin. Those cells generated earlier migrate to the deeper cortical layers relatively Ciuickly Glial cell (3-4 days). The cells generated later end their migration in Germinal the more superficial cortex; this migration takes place over zone several weeks. The major cell migration activity lasts about 2 months, beginning in the eighth fetal week and ending at about week 16 [4, 5]. Smaller waves of cell migration continue up to week 25 . Any insult to the brain during this period results in a migration anomaly. The normal human cerebral cortex is six-layered, the sizes of the layers varying with the location. There is a marginal Fig. 2.-lIIustration of relationship of migrating neurons to fibers of the layer (I), external granular layer (II), external pyramidal layer radial glial cells. Migrating neuron is seen ascending the glial fiber (radial (III) , internal granular layer (IV), internal pyramidal layer (V), fiber) led by multiple pseudopodia. Any damage to radial glial fiber will presumably cause an arrest of cell migration at that point. (Adapted from and fusiform layer (VI) (Fig. 3). The common underlying feature [4].) AJNR :8. November/December 1987 MR OF MIGRATION ANOMALIES 1011 Fig. 3.-Cortical architecture in agyric (labeled lissencephaly) and pachygyric regions of brain as com­ pared with normal cortical architecture. , In agyric cortex there is a large cell­ ~ . "0. , sparse layer (open arrow) that sepa­ .,' 0 rates a disorganized cortex (outer cel­ lular layer) from a thick layer of ectopic · ' ····0 o neurons located medially. Pachygyric ", '. ~ -, :' . " • 0 .. .0 I> o~ . ' ' . 0. • cortex is more organized into normal 0 _ 0 00 ; ' ,0- ; 0 : " I) 0 cortical layers and cell-sparse layer o o . (closed arrow) is thinner and populated by more cells. In general. there is a thinner layer of heterotopic neurons in the pachygyric cortex. (Adapted from [11].) LISSENCEPHALY PACHYGYRIA NOR MAL of the migration anomalies is an abnormal location of neurons within the layer of necrosis [11]. The cortex remains thick both within and outside of the cortex. In general the cortex is because it encompasses the radial columns of migrating cells thickened by a large, disorganized layer of neurons whose that are arrested in mid-migration. The subcortical white migration has been prematurely halted. The subcortical layer matter is thin because the organization phase during which of white matter is thinned because organization of the neu­ axonal and dendritic connections are established is markedly rons, which subsequently stimulates axonal growth, has not diminished (Fig. 4). occurred [1-4]. Dobyns and associates [9, 10, 12] have recently described It was generally believed that migration anomalies were this entity as a series of "syndromes with lissencephaly." They sporadic events that occurred