Severe gyration and migration disorder in fetofetal transfusion syndrome: two case reports and a review of the literature on the neurological outcome of children with lesions on neuroimaging.

INTRODUCTION: Fetofetal transfusion syndrome is a dreaded cause of morbidity and mortality in monochorionic pregnancies. CASE REPORTS: We present two pairs of twins one of which we have followed for more than 6 years. The donors suffer from cerebral palsy, orofacial, and motor problems, and both are significantly smaller than their recipient twins. Interestingly, cranial MRI revealed medial frontal lobe polymicrogyria, ventriculomegaly, and decreased thickness in both parietal lobes in both donors. We suggest this as a possible feature of fetofetal transfusion syndrome. REVIEW: A minireview of the literature on neuroimaging and neurodevelopmental outcome in fetofetal transfusion syndrome is presented. CONCLUSION: While the close resemblance of the imaging features of both cases is likely incidental further study of a connection between migration and gyration disorders and fetofetal transfusion syndrome is warranted.

Three-dimensional regulation of radial glial functions by Lis1-Nde1 and dystrophin glycoprotein complexes.

Radial glial cells (RGCs) are distinctive neural stem cells with an extraordinary slender bipolar morphology and dual functions as precursors and migration scaffolds for cortical neurons. Here we show a novel mechanism by which the Lis1-Nde1 complex maintains RGC functions through stabilizing the dystrophin/dystroglycan glycoprotein complex (DGC). A direct interaction between Nde1 and utrophin/dystrophin allows for the assembly of a multi-protein complex that links the cytoskeleton to the extracellular matrix of RGCs to stabilize their lateral membrane, cell-cell adhesion, and radial morphology. Lis1-Nde1 mutations destabilized the DGC and resulted in deformed, disjointed RGCs and disrupted basal lamina. Besides impaired RGC self-renewal and neuronal migration arrests, Lis1-Nde1 deficiencies also led to neuronal over-migration. Additional to phenotypic resemblances of Lis1-Nde1 with DGC, strong synergistic interactions were found between Nde1 and dystroglycan in RGCs. As functional insufficiencies of LIS1, NDE1, and dystroglycan all cause lissencephaly syndromes, our data demonstrated that a three-dimensional regulation of RGC's cytoarchitecture by the Lis1-Nde1-DGC complex determines the number and spatial organization of cortical neurons as well as the size and shape of the cerebral cortex.

Micropolygyria in an infant born to a patient with severe anorexia nervosa: a case report.

We report the case of an anorexia nervosa (AN) patient with extremely low body weight who became pregnant following ovulation induction and subsequently delivered an infant with micropolygyria. To the best of our knowledge, no previous report has described live birth for a patient with such low body weight. The patient underwent hMG-hCG therapy for ovulation induction. Despite becoming pregnant, weight loss continued with extreme anemia occurring during the pregnancy. However, blood transfusion therapy was used for successful treatment. Despite the therapeutic and protective measures instituted, the child was born with micropolygyria. Pregnancy in an AN patient with extremely low body weight needs therapeutic intervention during early pregnancy with aggressive precautionary measures, particularly against anemia. On the basis of our experience, we consider that ovulation induction therapy should not be administered without sufficient caution for an AN patient with low body weight.

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III.

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria-lissencephaly.

Post-section recruitment of epileptiform discharges in electrocorticography during callosotomy in 48 patients with Lennox-Gastaut syndrome.

We aimed to clarify the relationships between post-sectional recruitment of epileptiform discharges (PRED) seen in electrocorticograms (ECoG) during callosotomy in patients with Lennox-Gastaut syndrome (LGS) and postoperative seizure outcome. We retrospectively analyzed ECoG obtained during subtotal callosotomy (6 cm) in 48 patients with LGS (32 males, 16 females; age range, 1-20 years; mean age, 7.6 years) from July 1993 to November 1996 and compared recorded findings with postoperative seizure outcome. At analysis, all patients had been followed postoperatively for more than 10 years. Of 48 patients, 15 (31.3%) had PRED in their post-section ECoG. Of these patients, 11 (73%) achieved significant (at least 50%) overall seizure reduction postoperatively. The phenomenon of PRED in callosotomy did not predict a better postoperative seizure outcome (p>0.05). We concluded that post-sectional ECoG recruitment of electrical discharges during callosotomy did not predict postoperative prognosis. However, this finding should be supported and elucidated by further studies. The heterogenous ECoG findings during callosotomy in our series might suggest a complicated role of the corpus callosum in the epileptogenesis of Lennox-Gastaut syndrome.

Neuronal migration mechanisms in development and disease.

Neuronal migration is a fundamental process that determines the final allocation of neurons in the nervous system, establishing the basis for the subsequent wiring of neural circuitry. From cell polarization to target identification, neuronal migration integrates multiple cellular and molecular events that enable neuronal precursors to move across the brain to reach their final destination. In this review we summarize novel findings on the key processes that govern the cell biology of migrating neurons, describing recent advances in their molecular regulation in different migratory pathways of the brain, spinal cord, and peripheral nervous system. We will also review how this basic knowledge is contributing to a better understanding of the etiology and pathophysiology of multiple neurological syndromes in which neuronal migration is disrupted.

Diffusion tensor imaging of heterotopia: changes of fractional anisotropy during radial migration of neurons.

PURPOSE: Diffusion tensor imaging provides better understanding of pathophysiology of congenital anomalies, involving central nervous system. This study was aimed to specify the pathogenetic mechanism of heterotopia, proved by diffusion tensor imaging, and establish new findings of heterotopia on fractional anisotropy maps. MATERIALS AND METHODS: Diffusion-weighted imaging data from 11 patients (M : F = 7 : 4, aged from 1 to 22 years, mean = 12.3 years) who visited the epilepsy clinic and received a routine seizure protocol MRI exam were retrospectively analyzed. Fractional anisotropy (FA) maps were generated from diffusion tensor imaging of 11 patients with heterotopia. Regions of interests (ROI) were placed in cerebral cortex, heterotopic gray matter and deep gray matter, including putamen. ANOVA analysis was performed for comparison of different gray matter tissues. RESULTS: Heterotopic gray matter showed signal intensities similar to normal gray matter on T1 and T2 weighted MRI. The measured FA of heterotopic gray matter was higher than that of cortical gray matter (0.236 +/- 0.011 vs. 0.169 +/- 0.015, p < 0.01, one way ANOVA), and slightly lower than that of deep gray matter (0.236 +/- 0.011 vs. 0.259 +/- 0.016, p < 0.01). CONCLUSION: Increased FA of heterotopic gray matter suggests arrested neuron during radial migration and provides better understanding of neurodevelopment.