Schizencephaly and nonlissencephalic cortical dysplasias.

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