Commentary ------

Schizencephaly and Nonlissencephalic Cortical Dysplasias

Peter G. Barth 1 result in such a condition. Therefore, some dis­ ruptive event that involves loss of developing The refinements of neuroimaging have brought tissue in the process must be implied. The cov­ to the fo reground a wealth of conditions that ering of the "lips" of the lesion with aberrant were previously the restricted domain of clinical neocortex is witness to the very early stage of neuropathology. This fascinating (and often be­ development involved, probably lying between 8 wildering) harvest, includes primary malforma­ and 16 weeks of gestational age. During this tions and intrauterine disruptions of the brain. To period, most of the neurons that will populate the the first category belong chromosomal abnor­ future neocortex are generated at the lateral ven­ malities and genetic or cryptogenic malforma­ tricular wall and, moving over a network of radial tions. The latter category is caused by pathologic glial fibers that span the trajectory, migrate to the events that interfere with the normal shaping cortical plate, the future neocortex. The aberrant process of the central , and in­ neocortical layer in schizencephaly is most likely cludes hypoxic/ischemic accidents in utero, in­ the result of a neuronal migration failure, caused fectious diseases, and inherited neurometabolic by destruction of the radial glial system. disorders. Diagnosis may depend heavily on neu­ The analysis of the authors is helped by their roimaging, which is the case in lissencephalies ability to bring together a large number of patients type I or II, or schizencephaly. In other cases, with this rare disorder. Correlating clinical and diagnosis depends as much on magnetic reso­ MR findings in patients with schizencephaly, they nance (MR) imaging as on data derived from other show that certain clinical manifestations, such as procedures, demanding added professional skill degree of motor deficit, laterality, and speech to integrate the output of the various procedures. development correlate well with the outcome of Examples are malformation syndromes such as the MR scaling. Although this may not seem Aicardi syndrome or Joubert syndrome. Some­ surprising, the series contains some highly inter­ times prenatal pathology, as revealed by MR, esting observations, such as the favorable intel­ may be distinctive enough for labeling it to a lectual outcome for cases with small-sized unilat­ morphologic category, but not specific enough to eral schizencephaly. Equally important is their narrow etiologic consideration to a single condi­ observation of contralateral cortical dysplasias in tion, and other diagnostic tools may not help us unilateral schizencephalies in three patients. The further. The latter situation exists in many cases authors compare these contralateral focal cortical of cortical dysplasia. dysplasias to the ipsilateral schizencephaly. Based In this issue of the Journal two contributions in part upon these findings, they have developed from Barkovich and Kjos (1 , 2) highlight the field. a tentative, though plausible and useful, scheme One concerns schizencephaly and the other, what posing schizencephaly as the end of a continuum is called "nonlissencephalic cortical dysplasia." ranging from focal cortical dysplasia without What do we know about schizencephaly? For mantle defects to full scale mantle defects, lined a start, two conditions have been defined as by aberrant cortex. The finding of such contra­ schizencephaly by Yakovlev and Wadsworth, lateral focal dysplasias in unilateral schizence­ called, respectively, schizencephaly with closed phaly should have influence on the individual lips and schizencephaly with open lips (3 , 4). Both prognosis, although this has not been borne out conditions essentially represent mantle defects of in the study because of interference from other full thickness. Schizencephaly differs from the factors. The observation also unveils a more usual malformations, in that no arrest of normal fundamental aspect bearing on the etiology, be­ brain development can be conceived that would cause bilateral lesions are more likely to result

1 Professor in Pediatric , Academisch Ziekenhuis bij de Universiteit van Amsterdam Amsterdam, The Netherlands. Index terms: Migration anomalies; Magnetic resonance, in infants and children; Commentaries

AJNR 13:104- 106, Jan/ Feb 1992 0195-6108/ 92/ 1301 -0104 © American Society of Neuroradiology 104 AJNR: 13, January/ February 1992 105 from systemic insults than unilateral lesions. The crogyria (a lesion distinct from sclerotic micro­ literature on schizencephaly until now does not gyria) may be obvious on MR imaging under ideal link the condition to inherited or chromosomal conditions. However, more often, focal cortical disorders. This is contrary to typical malforma­ abnormalities may be picked up by MR without tions, eg , where Mendelian inherit­ sufficient clue as to the histopathology of the ance or chromosomal abnormality is the rule, or lesion involved. Therefore, the descriptive term callosal dysgenesis and , "cortical dysplasia" for MR purposes as applied where such factors may play a role. Schizence­ by the authors is well chosen. Interestingly, in phaly compares best, it seems, with entire thick­ some cases subcortical gliosis is indicated by ness porencephalies, a destructive event of later prolonged TE lesions. Since gliosis rarely accom­ pregnancy. Differences can be explained by the panies lesions occurring earlier than a gestational state of development at the time that the lesion age of 26 weeks, this may provide us with a clue is acquired. In the case of entire thickness poren­ to the temporal origin of the lesion, the more so cephalies, only the outer part of the pore is since late acquisition of cortical dysplasia may layered with cortex, continuous with the adjacent extend to this time. While useful conclusions can normal cortex, but the trajectory that links the be drawn from the study of this group of patients, outer pore with the often is scar tissue. we are left nonetheless with a relatively large, Although scarring in entire-thickness porence­ probably heterogenous group that defies our at­ phaly may cause the neocortex to "roll in" slightly tempts at etiologic classification (9). Some cases at the edges, this should not be mistaken for a 1 of cortical dysplasia may be difficult to find on migration disorder. Moreover, in , MR. This should be kept in mind in the case of glial scarring is often present in the parenchyma milder developmental deficits that would not as below the superficial lesion. The propensity to a rule be brought in for neurologic investigation, glial scarring is acquired during the later phases such as dyslexia (10). What is left to consider of pregnancy (5), therefore, the presence or the when routine investigations beside MR fail to absence of gliosis as evidenced by prolonged TE provide us with an answer in the case of cortical lesions may provide the clinician with another dysplasia? Of course, events in early pregnancy, clue to the temporal origin of the lesion, besides infections, and chromosomal disorders should be the presence or absence of aberrant cortex cov­ considered. Inherited conditions are not easily ering the lesion. No scarring is found in schizen­ ruled out in the absence of further clues. Recent cephaly. Schizencephaly is extremely rare, no . experience has shown that metabolic disorders reliable estimates of its incidence yet being avail­ may cause prenatal disruptions of a severe kind, able. This has hampered systematic studies of its in addition to ongoing postnatal degeneration. link with pathologic events in early pregnancy. Examples are generalized peroxisomal disorders, Allusion has been made to blood loss in early pregnancy (6), to adoption (7) , and, quite re­ isolated disorders of peroxisomal beta-oxidation cently, to prenatal exposure to cocaine and other · (not being x-linked adrenoleukodystrophy), glu­ street drugs (8). All this points to the interest of taric aciduria type II, mitochondrial respiratory correlative studies on schizencephaly: As the chain disorders. They all may cause cortical dys­ number of serial studies on this rare disorder plasias, and each of these causes may be missed increases, we may gain important clues not only on "routine" metabolic screening. Therefore, the on the individuals' prognosis, but also on chances MR finding of cortical dysplasia, especially gen­ of recurrence for the parents involved, and on eralized cortical dysplasia, should encourage us possible preventive measures. to check for gaps in our diagnostic system. In In the second article (2) the authors describe this respect, the delineation of a large group of their correlative investigation of 36 patients with patients with "nonlissencephalic cortical dyspla­ cortical dysplasias, distinct from lissencephaly, sias" represents a useful addition to an MR system and after exclusion of patients with known ge­ for the classification of prenatal disorders, as well netic syndromes. Comparison is made between as a big challenge to future research. the degree of involvement on MR to the degree and kind of neurologic handicap. The authors give a general definition of neocortical malfor­ References mation not due to lissencephaly or schizence­ 1. Barkovich AJ, Kjos BO. Schizencephaly: correlation of clinical find­ phaly as "cortical dysplasia." Developmental mi- ings with MR characteristics, AJNR 1992; 13:85-94 106 AJNR: 13, January/ February 1992

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