Prenatal diagnosed cyst of the quadrigeminal cistern in Aicardi syndrome.

Aicardi syndrome is an X-linked dominant disorder characterized by the pathognonomic association of three clinical signs: agenesis of the corpus callosum, infantile spasms, and chorioretinal lacunae. This is a severe syndrome with an estimated survival rate of 76% at 6 years and 40% at 14 years and a maximum developmental level like a 12-month-old baby in 91% of cases. We illustrate a case of Aicardi syndrome with bilateral, small chorioretinal lacunae, infantile spasms with a typical hypsarrhythmia, defects of thoracic vertebra and bilateral absence of the 12th rib associated with an arachnoid cyst of the quadrigeminal cistern, and presence of the corpus callosum with a favorable outcome.

Covert orienting to exogenous and endogenous cues in children with spina bifida.

Children with spina bifida meningomyelocele and hydrocephalus (SBM) have congenital dysmorphology of the midbrain and thinning of the posterior cortex, brain regions associated with the control of covert orienting. We studied cued covert orienting in 92 children with SBM, and 40 age-matched typically developing controls. Cues were of three types: exogenous (luminance change in a peripheral box either valid or invalid for upcoming target location), endogenous arrow (a central arrow either valid or invalid for upcoming target location), or endogenous word (a central word either valid or invalid for upcoming target location). Compared to controls, children with SBM showed slowed covert orienting to both exogenous and endogenous cues and a higher cost of attentional disengagement (e.g., a greater cue-validity effect) for exogenous although not for endogenous cues. Covert orienting deficits were associated with midbrain dysmorphology in the form of beaking of the tectum, and with right posterior brain volume loss.

Disruption of PAX6 function in mice homozygous for the Pax6Sey-1Neu mutation produces abnormalities in the early development and regionalization of the diencephalon.

Pax6 expression in the diencephalon of the mouse embryo is restricted both antero-posteriorly and dorso-ventrally, with changes in level occurring at prosomere boundaries. Small eye (Pax6Sey-1Neu) mice homozygous for Pax6 mutations have multiple defects in early forebrain development. In the diencephalon of Pax6Sey-1Neu/Pax6Sey-1Neu mice there is an apparent enlargement of the zona limitans (the boundary region between prosomeres p2 and p3), and a blurring of the p1-p2 boundary. PAX6 function is also required for the normal development of the posterior commissure at the midbrain-p1 boundary. In the posterior diencephalon PAX6 appears to regulate its own transcription, and that of Wnt7b. In p2 and p3, ventral markers are expressed more dorsally than normal, and this is accompanied in p3 by a reduction in the size of the zona incerta. Thus, PAX6 is essential for the normal development and regionalization of the diencephalon.

Dorsal brain stem lipomas: case report.

Intracranial lipomas are uncommon and rarely symptomatic lesions accounting for 0.06 to 0.46% of intracranial lesions. The management of symptomatic dorsal brain stem lipomas was once limited to cerebrospinal fluid diversion, but with recent advances in microsurgery, they now may be directly treated. We report three patients with dorsal brain stem lipomas, two of which involved the quadrigeminal cistern and one of which was in the cisterna magna region. Antenatal documentation by ultrasound examination in one patient represents the first reported in utero diagnosis of quadrigeminal cistern lipoma. Computed tomographic and magnetic resonance imaging scans were diagnostic. The surgical experience in two symptomatic patients is discussed. Microsurgical decompression was performed in each without neurological deficit, and clinical symptoms postoperatively subsided. No patient required a permanent cerebrospinal fluid shunt. The management of symptomatic dorsal brain stem lipomas is discussed, and an algorithm is proposed.

Tecto-cerebellar dysraphia with occipital encephalocele.

We report four cases with the rare syndrome of tecto-cerebellar dysraphia with occipital encephalocele. The clinical features seen in these patients included episodic tachypnea and irregular breathing, opsoclonus, ataxia, marked hypotonia of the limbs, coloboma, and polydactyly. All four patients had midline occipital encephalocele. The cranial computed tomography scan showed partial to total agenesis of the vermis with a large communication between cisterna magna and the fourth ventricle. The computed tomography scan also showed partial deficiency of the midbrain tectum. We discuss the clinical and radiological findings and review the literature.

Tectocerebellar dysraphism with vermian encephalocele.

Tectocerebellar dysraphism is a very rare malformation associated with encephalocele and tectal deformity. This article presents tectocerebellar dysraphism with a solely vermian content of encephalocele and tectal beaking defined by magnetic resonance imaging (MRI) in a 5-month-old girl who was successfully treated surgically and demonstrated excellent prognosis at the 4-year follow-up.

Lmx1b is essential for Fgf8 and Wnt1 expression in the isthmic organizer during tectum and cerebellum development in mice.

Secreted factors FGF8 and WNT1 are essential either for the inductive activity of the isthmus organizer or for the regionalization of the midbrain-hindbrain boundary (MHB). However, transcriptional regulation of these secreted factors during development remains to be elucidated. Here we show that the LIM homeobox gene Lmx1b is expressed in the anterior embryo as early as E7.5 and its expression becomes progressively restricted to the isthmus at E9.0. Analysis of gene expression in the MHB of the mutant embryos showed that many genes were lost by E9.5. In the MHB of Lmx1b-/- embryos, the expression of Fgf8, which normally occurs at the 4-somite stage, was completely absent, whereas Wnt1 was downregulated before the 4-somite stage. Moreover, transcription factors En1 and Pax2 were also downregulated prior to the 4-somite stage, whereas Gbx2 downregulation occurred at the 4-somite stage. By contrast, Otx2 and Pax6 expression was not affected in Lmx1b-/- embryos. The requirement of specific Lmx1b expression in the MHB was further confirmed by Wnt1-Cre-mediated region-specific conditional knockout of Lmx1b. As a result of these molecular defects, the development of the tectum and cerebellum was severely impaired in Lmx1b-/- mice. Taken together, our results indicate that Lmx1b plays an essential role in the development of the tectum and cerebellum by regulating expression of Fgf8, Wnt1 and several isthmus-related transcription factors in the MHB, and is a crucial component of a cross-regulatory network required for the induction activity of the isthmic organizer in the MHB.

Cephalocele detection in utero: sonographic and clinical features.

Sonographic and clinical features of 26 fetal cephaloceles were reviewed retrospectively. The most frequent reason for referral was elevated maternal serum alpha-fetoprotein levels. The smallest lesion identified was 0.4 x 0.5 cm (frontal, at 20 weeks); the largest was 9.0 x 10.0 cm (frontal, at 27 weeks). Twenty-four of 26 cephaloceles were detected on prenatal ultrasound examination; in 13 of these, more than 50% of the intracranial contents were exteriorized. Fifteen of 24 cephaloceles detected prenatally had a sulcal pattern (identified between 16 and 36 weeks' gestation); five were solid without a sulcal pattern (identified between 13 and 21 weeks' gestation), three were cystic, and one underwent a change in appearance from solid at 21 weeks to cystic at 26 weeks. Other cranial features were evaluated and included visible skull defect, seen in 23/24 (96%), ventriculomegaly, in 6/26 (23%); microcephaly, in 12/24 (50%); beaked tectal plate, in 6/16 (38%); and flattened basiocciput, in 9/24 (38%). Of the 26 cases, 14 had normal amniotic fluid volume, five had oligohydramnios and seven had polyhydramnios. Fetuses with oligohydramnios had the highest incidence of concurrent fetal abnormalities; four of five fetuses (80%) with oligohydramnios had additional structural abnormalities. In the overall population, a very high incidence of other abnormalities was found; 17/26 (65%) cases showed additional abnormalities, some of which were not detected by ultrasound. Five fetuses had Meckel-Gruber syndrome and three had amniotic band syndrome. Only one of the 18 karyotypes obtained was abnormal (trisomy 18). Survival was very poor; only two of the eight who survived until birth are currently living.