The clinical spectrum of nodular heterotopias in children: report of 31 patients.

PURPOSE: The phenotypic and etiologic spectrum in adults with nodular heterotopias (NHs) has been well characterized. However, there are no large pediatric case series. We, therefore, wanted to review the clinical features of NHs in our population. METHODS: Hospital records of 31 patients with pathology or imaging-confirmed NHs were reviewed. Two-sided Fisher's exact t-test was used to assess associations between distribution of NHs and specific clinical features. KEY FINDINGS: NHs were distributed as follows: 8 (26%) unilateral focal subependymal, 3 (10%) unilateral diffuse subependymal, 5 (16%) bilateral focal subependymal, 12 (39%) bilateral diffuse subependymal, and 3 (10%) isolated subcortical. The phenotypic spectrum in our population differs from that described in adults. Significant morbidity and mortality are associated with presentation in childhood. Twenty-two of 31 patients (71%) died in the neonatal period or in childhood. Additional cerebral malformations were found in 80% and systemic malformations in 74%. The majority of patients had developmental delay, intellectual deficit, and intractable epilepsy. Patients with unilateral focal NHs were more likely to have ventriculomegaly (p = 0.027), and those with bilateral diffuse NHs more likely to have cerebellar abnormalities (p = 0.007). Isolated subcortical NHs were associated with multiple malformations (p = 0.049) and cardiac abnormalities (p = 0.027). Underlying etiology was heterogeneous and determined in only six cases (19%): del chr 1p36, del chr 15q11, pyruvate dehydrogenase deficiency, sialic acidosis type 1, Aicardi syndrome, and FLNA mutation. SIGNIFICANCE: NHs are present in childhood as part of multiple cerebral and systemic malformations; developmental delay and refractory seizures are the rule rather than the exception. Milder forms go unrecognized until seizure onset in adulthood.

Dendroarchitecture of relay cells in thalamic barreloids: a substrate for cross-whisker modulation.

A double-labeling protocol was used to determine how the dendroarchitecture of relay cells relates to the three-dimensional structure of barreloids in the ventral posterior medial nucleus of the rat thalamus. Single barreloids were retrogradely labeled by injecting Fluoro-Gold in identified barrel columns, and single relay cells activated by the same whisker, or by an adjacent whisker located on the same arc, were juxtacellularly labeled with biotinylated dextran. Results show that the dendritic field of relay cells is asymmetric, variously oriented with respect to the geometry of the barreloids, and that all cells extend dendrites in surrounding barreloids. Extrabarreloid dendrites are of small size (<1.5 microm) and represent up to 54% (range, 11-54%) of the total dendritic length. In contrast, the thick proximal dendrites remain confined to the home barreloid of the cell, being directed toward its center or along its margin. There is a trend for cells located dorsally in barreloids to form more elaborate trees with a larger proportion of extrabarreloid dendrites. Electron microscopic examination of labeled cells shows that extrabarreloid dendrites are exclusively contacted by synaptic terminals of cortical and reticular thalamic origin, whereas intrabarreloid dendrites also receive contacts from lemniscal terminals. Because corticothalamic and reticular thalamic cells establish point-to-point connections with homotopic barreloids, it is proposed that the spatial arrangement of dendrites determines the combination of whisker deflection that best modulates cell firing. Because relay cell responses are direction sensitive, maximal modulation would occur if dendritic field orientation relates to the direction selectivity of responses.

Substrate for cross-talk inhibition between thalamic barreloids.

A double-labeling protocol was used to determine whether thalamocortical and reticular thalamic cells with overlapping receptive fields form open or closed loop connections in the vibrissal system of the rat. Results show that individual reticular cells exclusively project to the barreloid representing the principal whisker of their receptive field. Furthermore, solid retrograde labeling of relay cells reveals that a large number extend dendrites outside their home barreloid. This feature, together with previous demonstrations that reticular thalamic axons principally contact the dendrites of relay cells, provide a morphological substrate for cross-talk inhibition between thalamic barreloids.