Consequences of intraventricular hemorrhage in a rabbit pup model.

BACKGROUND AND PURPOSE: Intraventricular hemorrhage (IVH) is a common complication of prematurity that results in neurological sequelae, including cerebral palsy, posthemorrhagic hydrocephalus, and cognitive deficits. Despite this, there is no standardized animal model exhibiting neurological consequences of IVH in prematurely delivered animals. We asked whether induction of moderate-to-severe IVH in premature rabbit pups would produce long-term sequelae of cerebral palsy, posthemorrhagic hydrocephalus, reduced myelination, and gliosis. METHODS: The premature rabbit pups, delivered by cesarean section, were treated with intraperitoneal glycerol at 2 hours postnatal age to induce IVH. The development of IVH was diagnosed by head ultrasound at 24 hours of age. Neurobehavioral, histological, and ultrastructural evaluation and diffusion tensor imaging studies were performed at 2 weeks of age. RESULTS: Although 25% of pups with IVH (IVH pups) developed motor impairment with hypertonia and 42% developed posthemorrhagic ventriculomegaly, pups without IVH (non-IVH) were unremarkable. Immunolabeling revealed reduced myelination in the white matter of IVH pups compared with saline- and glycerol-treated non-IVH controls. Reduced myelination was confirmed by Western blot analysis. There was evidence of gliosis in IVH pups. Ultrastructural studies in IVH pups showed that myelinated and unmyelinated fibers were relatively preserved except for focal axonal injury. Diffusion tensor imaging showed reduction in fractional anisotropy and white matter volume confirming white matter injury in IVH pups. CONCLUSION: The rabbit pups with IVH displayed posthemorrhagic ventriculomegaly, gliosis, reduced myelination, and motor deficits, like humans. The study highlights an instructive animal model of the neurological consequences of IVH, which can be used to evaluate strategies in the prevention and treatment of posthemorrhagic complications.

Congenital Guillain-Barré syndrome associated with maternal inflammatory bowel disease is responsive to intravenous immunoglobulin.

A 34-week floppy preterm infant born to a mother with acute ulcerative colitis presented with a progressive reduction in spontaneous limb movements, severe generalized hypotonia, areflexia, autonomic dysfunction and respiratory failure. Electromyography revealed pronounced denervation activity and markedly slow nerve conduction velocity (3 m/s) with evidence of conduction block. These findings indicated demyelination with additional axonal features. The infant was diagnosed with congenital Guillain-Barré syndrome, was treated with intravenous immunoglobulin and showed clinical improvement within 48 hours of treatment. The relationship between inflammatory bowel syndrome and inflammatory demyelinating polyneuropathy is discussed.

Hemophagocytic lymphohistiocytosis presenting with thrombocytopenia in the newborn.

Hemophagocytic lymphohistiocytosis (HLH) may present with thrombocytopenia during the newborn period. Three neonates (one term and two preterm) presented during the newborn period with thrombocytopenia. Transient recovery occurred in two newborns. The diagnosis of HLH was made after the recurrence of thrombocytopenia and the clinical symptoms at 5 and 7 weeks. The third infant was a premature baby diagnosed at 8 days of age after manifesting the clinical and laboratory features of HLH. All three neonates were treated with chemotherapy and responded well. After hematologic and clinical remission was achieved, the two newborns received hematopoietic stem cell transplantation from allogeneic donors. The third neonate is currently receiving chemotherapy. Persistent or recurrent thrombocytopenia of undetermined cause during the neonatal period should raise the suspicion of HLH, even though other symptoms or signs are not yet evident.