A related form lasts days and may require treatment with intravenous glucose before it stabilizes. A few infants, some of diabetic mothers but most usually below about 2500 gm birth weight, continue to be hypoglycemic for days or weeks and are generally treated with intravenous glucose or glucagon if the situation is severe, and monitored in a neonatal intensive care unit. A proportion of these infants will have hypoglycemia that persists for only weeks or months and clears without explanation. This condition is due to congenital hyperinsulinism. The latter may be manifest as near normal insulin levels when the glucose drops below approximately 50 mg/dL. They can be treated with oral diazoxide, a drug formerly used intravenously for the control of severe acute hypertension but in oral form blocks insulin release, or with octreotide. The appropriate threshold for treatment of hypoglycemia has been a matter of debate.
When the condition is persistent or unresponsive to diazoxide, there is either a genetic defect in one of a number of channels responsible for releasing insulin or detecting low serum glucose levels, or tot a proliferation of beta-islet cells is often the cause, more in accord with the original term (now outdated) nesidioblastosis, signifying this excess of pancreatic cells. For the latter, almost total pancreatectomy has been performed but there is subsequent diabetes mellitus.
Many textbooks paint a bleak picture of developmental outcomes for persistent neonatal hypoglycemia based on studies from half a century ago but there have been few critical examinations of outcomes and, as mentioned, the threshold value that represents a risk has not been established. The cohort reported by McKinlay and colleagues reported on a cohort who were mostly under 2500 gm in birth weight, in whom glucose could be maintained above 47 mg/dL. They had no developmental delay at 2 years of age. Furthermore, continuous interstitial tissue monitoring of glucose revealed that many transient episodes of hypoglycemia were undetected by intermittent monitoring and the number or severity of these episodes also did not predict for developmental delay, at least at 2 years of age. Paradoxically, those with rapid correction of glucose and large amounts of time with higher glucose had more developmental delay than those in the low or normal range; this requires confirmation. Some observations have suggested that visuospatial difficulties are a form of deficit attributable to hypoglycemia and that appropriately placed occipital lesions are visible on MRI.
The spastic cerebral diplegias discussed above shade almost imperceptibly into the congenital extrapyramidal syndromes. These children are found in every cerebral palsy clinic, and, ultimately, they reach adult neurology clinics. Corticospinal tract signs may be absent and the student, familiar only with the syndrome of pure spastic diplegia, is always puzzled as to their classification. Some cases of extrapyramidal type are undoubtedly attributable to severe perinatal hypoxia and others to diseases such as erythroblastosis fetalis with kernicterus. To state the probable pathologic basis and future course of these illnesses, it is useful to separate the extrapyramidal syndromes of prenatal-natal origin (which usually become manifest during the first year of life) from the acquired or hereditary postnatal syndromes, such as familial athetosis, Wilson disease, dystonia musculorum deformans, and the hereditary cerebellar ataxias, which become manifest later.