Midbrain-hindbrain involvement in lissencephalies.
OBJECTIVE
To determine the involvement of the midbrain and hindbrain (MHB) in the groups of classic (cLIS), variant (vLIS), and cobblestone complex (CBSC) lissencephalies and to determine whether a correlation exists between the cerebral malformation and the MHB abnormalities.


METHODS
MRI scans of 111 patients (aged 1 day to 32 years; mean 5 years 4 months) were retrospectively reviewed. After reviewing the brain involvement on MRI, the cases were reclassified according to known mutation (LIS1, DCX, ARX, VLDLR, RELN, MEB, WWS) or mutation phenotype (LIS1-P, DCX-P, RELN-P, ARX-P, VLDLR-P) determined on the basis of characteristic MRI features. Abnormalities in the MHB were then recorded. For each structure, a score was assigned, ranging from 0 (normal) to 3 (severely abnormal). The differences between defined groups and the correlation between the extent of brain agyria/pachygyria and MHB involvement were assessed using Kruskal-Wallis and chi(2) McNemar tests.


RESULTS
There was a significant difference in MHB appearance among the three major groups of cLIS, vLIS, and CBSC. The overall score showed a severity gradient of MHB involvement: cLIS (0 or 1), vLIS (7), and CBSC (11 or 12). The extent of cerebral lissencephaly was significantly correlated with the severity of MHB abnormalities (p = 0.0029).


CONCLUSIONS
Our study focused on posterior fossa anomalies, which are an integral part of cobblestone complex lissencephalies but previously have not been well categorized for other lissencephalies. According to our results and the review of the literature, we propose a new classification of human lissencephalies.
Jissendi-Tchofo
Patrice
P
Department of Radiology, University of California, San Francisco, CA, USA. jissendi@gmail.com
Kara
Simay
S
Barkovich
A James
AJ
D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000002:abnormalities*; D002648:Child; D002675:Child, Preschool; D054222:Cobblestone Lissencephaly / Q000145:classification / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D054082:Lissencephaly / Q000145:classification / Q000235:genetics / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008636:Mesencephalon / Q000002:abnormalities*; D010641:Phenotype; D000091042:Reelin Protein; D012189:Retrospective Studies; D012249:Rhombencephalon / Q000002:abnormalities*; D055815:Young Adult