Characterization of a population of neural progenitor cells in the infant hippocampus.

AIMS: Abnormalities of the hippocampus are associated with a range of diseases in children, including epilepsy and sudden death. A population of rod cells in part of the hippocampus, the polymorphic layer of the dentate gyrus, has long been recognized in infants. Previous work suggested that these cells were microglia and that their presence was associated with chronic illness and sudden infant death syndrome. Prompted by the observations that a sensitive immunohistochemical marker of microglia used in diagnostic practice does not typically stain these cells and that the hippocampus is a site of postnatal neurogenesis, we hypothesized that this transient population of cells were not microglia but neural progenitors. METHODS: Using archived post mortem tissue, we applied a broad panel of antibodies to establish the immunophenotype of these cells in 40 infants dying suddenly of causes that were either explained or remained unexplained, following post mortem investigation. RESULTS: The rod cells were consistently negative for the microglial markers CD45, CD68 and HLA-DR. The cells were positive, in varying proportions, for the neural progenitor marker, doublecortin, the neural stem cell marker, nestin and the neural marker, TUJ1. CONCLUSIONS: These data support our hypothesis that the rod cells of the polymorphic layer of the dentate gyrus in the infant hippocampus are not microglia but a population of neural progenitors. These findings advance our understanding of postnatal neurogenesis in the human hippocampus in health and disease and are of diagnostic importance, allowing reactive microglia to be distinguished from the normal population of neural progenitors.

How commonly do children with complex cerebral arteriopathy have renovascular disease?

AIM: To describe the frequency of renovascular abnormalities and hypertension in an opportunistic cohort of children with complex cerebrovascular disease from a single tertiary/quaternary referral centre. METHOD: This was a retrospective case note and imaging review of children who had had cerebral and renal angiography, with a diagnosis of moyamoya or other occlusive cerebrovascular disease (OCVD). Hypertension was defined as at least three systolic blood pressure readings of the 95th centile or above. RESULTS: Of 34 children (12 males, 22 females; median age 5y 11mo, range 2mo-15y 3mo; 20 with moyamoya, 14 with OCVD), primary presentation was neurological in 29 (arterial ischaemic stroke, transient ischaemic attack, or headache) and with hypertension in five. Renovascular abnormalities were identified in 17, of whom 10 had main renal artery stenosis. Renovascular involvement was not predictable according to arteriopathy diagnosis. Blood pressure was rarely plotted on centile charts. Using the 50th height centile for blood pressure, and based on a median of five systolic blood pressure readings per patient, 20 out of 34 met the definition for hypertension (15/29 patients with primary neurological presentation). INTERPRETATION: Renovascular abnormalities were common in this group of children with complex cerebrovascular disease. Blood pressure was frequently abnormal but rarely measured and infrequently plotted on centile charts. Neurologists should be alert to potential systemic vascular involvement and its sequelae in children with complex cerebrovascular disease.