Novel pathological abnormalities of deep brain structures including dysplastic neurons in anterior striatum associated with focal cortical dysplasia in epilepsy.

OBJECT: Some patients are not seizure free even after epileptogenic cortical resection. The authors recently described a case of frontal lobe epilepsy cured after the resection of periventricular white matter and striatum, in which dysplastic neurons were revealed. The authors attempted to confirm similar cases. METHODS: They reviewed the records of 8 children with frontal lobe epilepsy who had daily (7) or monthly (1) seizures and underwent resections including deep brain structures. RESULTS: Five patients underwent multiple resections. Neuroimaging of the deep structures showed the transmantle sign in 3 patients, ictal hyperperfusion in 6, reduced iomazenil uptake in 2, and spike dipole clustering in 6. All patients became seizure free postoperatively. Focal cortical dysplasia of various types was diagnosed in all patients. Dysmorphic neurons were found in the cortex and subcortical white matter of 5 patients. The striatum was verified in 3 patients in whom dysmorphic neurons were scattered. In the periventricular white matter, prominent astrocytosis was evident in all cases. CONCLUSIONS: Pathological abnormalities such as dysmorphic neurons and astrocytosis in deep brain structures would play a key role in epileptogenesis.

Anterior striatum with dysmorphic neurons associated with the epileptogenesis of focal cortical dysplasia.

The epileptogenesis of the striatum is unknown. We describe the case of a 12-year-old girl with intractable epilepsy who was treated by surgical interventions. Magnetic resonance imaging (MRI) showed ambiguous corticomedullary boundary in the left frontal lobe, and magnetoencephalography (MEG) revealed spike dipoles in the vicinity of the left ventral striatum. The epileptic seizures disappeared after partial resection of the frontal lobe, but recurred within 2 months and remained intractable. Neuropathological examination confirmed the presence of focal cortical dysplasia in the resected brain tissue. Ictal single photon emission computed tomography at this period displayed hyperperfusion of the left anterior striatum. At the second surgery, intraoperative electrocorticography exhibited spike discharges from the anterior striatum. After the removal of this structure and adjacent brain tissues, the patient remains seizure-free for 33 months, without any neurological deficits. Histopathological examination of the resected tissue revealed a large number of dysmorphic neurons distributed widely in the cerebral cortex, subcortical white matter, striatum, and insular cortex. These findings suggest that microscopic dysplasia of basal ganglia can accompany certain cases of focal cortical malformations, and may play a critical role in the epileptogenesis through their interaction with cortical structures.

Tlx controls proliferation and patterning of lateral telencephalic progenitor domains.

We showed previously that the orphan nuclear receptor Tlx is required for the correct establishment of the pallio-subpallial boundary. Loss of Tlx results in a dorsal expansion of ventral markers (e.g., the homeodomain protein GSH2) into the ventralmost pallial region, i.e., the ventral pallium. We also observed a disproportionate reduction in the size of the Tlx mutant lateral ganglionic eminence (LGE) from embryonic day 14.5 onward. Here we show that this reduction is caused, at least in large part, by a proliferation defect. Interestingly, in Tlx mutants, the LGE derivatives are differentially affected. Although the development of the Tlx mutant striatum is compromised, an apparently normal number of olfactory bulb interneurons are observed. Consistent with this observation, we found that Tlx is required for the normal establishment of the ventral LGE that gives rise to striatal projection neurons. This domain is reduced by the dorsal and ventral expansion of molecular markers normally confined to progenitor domains flanking the ventral LGE. Finally, we investigated possible genetic interactions between Gsh2 and Tlx in lateral telencephalic development. Our results show that, although Gsh2 and Tlx have additive effects on striatal development, they differentially regulate the establishment of ventral pallial identity.

Patterning of the lateral ganglionic eminence by the Gsh1 and Gsh2 homeobox genes regulates striatal and olfactory bulb histogenesis and the growth of axons through the basal ganglia.

The function of the Gsh1 and Gsh2 homeobox transcription factors during development of the mouse telencephalon was studied using loss of function mutations. No telencephalic phenotype was observed in Gsh1 mutants, whereas Gsh2 and Gsh1/2 mutants showed progressively more severe defects in development of neurons derived from the lateral ganglionic eminence (LGE). These defects arise from abnormal dorsoventral specification of LGE progenitor cells. Mice lacking both Gsh1 and Gsh2 have severe hypoplasia of the striatum, olfactory tubercle, and interneurons that migrate from the dorsal LGE to the olfactory bulb. In addition, Gsh function is linked to the development of telencephalic dopaminergic neurons. These observations show that Gsh1 and Gsh2 have early roles in defining the identity of LGE progenitor cells. As a result of the basal ganglia defects in the Gsh1/2 mutants, there are pallial heterotopia near the cortical/subcortical limit and defects in the pathfinding of corticofugal and thalamocortical fibers. These findings highlight the developmental interdependence of adjacent telencephalic structures.

Holoprosencephaly: an analysis of callosal formation and its relation to development of the interhemispheric fissure.

PURPOSE: To correlate the degree of hemispheric fusion in holoprosencephaly with degree of callosal formation, with degree of thalamic and basal ganglia fusion, and with presence or absence of dorsal cyst. METHODS: MR, CT, and ultrasonography from 19 patients with holoprosencephaly was retrospectively reviewed. The imaging studies were graded according to extent of the hemispheric fusion, thalamic fusion, corpus striatum fusion, callosal formation, and the presence or absence of a dorsal cyst. These factors were statistically correlated with each other using Kendall rank correlation coefficient. RESULTS: There were significant correlations between hemispheric fusion and failure of corpus callosum formation, presence of dorsal cyst and failure of corpus callosum formation, and hemispheric fusion and presence of dorsal cyst. Additional correlations were noted between thalamic fusion and corpus striatum fusion. CONCLUSIONS: Our results suggest that the presence of an interhemispheric fissure is necessary for callosal formation, and the presence of a dorsal cyst may interfere with callosal formation in holoprosencephaly.

[Agenesis of the corpus callosum associated with interhemispheric cyst. A case report].

A 7-year-old boy was admitted because of convulsive seizures. He was diagnosed as agenesis of corpus callosum associated with interhemispheric cyst by CT scan and angiography. Metrizamide CT cisternography and cystography disclosed no communication between interhemispheric cyst and the third ventricle. By means of metrizamide CT cisternography and cystography, the authors considered this interhemispheric cyst gradually increased by some kinds of ball-valve mechanism. Cysto-peritoneal shunt was carried out. Postoperative course was uneventful and follow-up CT revealed disappearance of interhemispheric cyst and typical findings of the acallosal brain. Improvement of clinical symptoms and EEG findings occurred after operation. Agenesis of the corpus callosum associated with interhemispheric cyst is rare. The authors can find only one case of this brain anomaly in the literature in which there is no communication between interhemispheric cyst and the third ventricle. Metrizamide CT cisternography and cystography was very useful in diagnosis and selection of treatment.