The
progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (
PEHO) syndrome is a pediatric disorder of unknown origin, characterized by a combination of postnatally progressive
encephalopathy,
hypsarrhythmia, and
optic atrophy. The pathological findings are early progressive
atrophy of the cerebellum, brainstem, and optic nerves.
Nitric acid (NO) has recently been implicated in the mechanisms of seizure activity and neurodegeneration, which are both very active in the
PEHO syndrome. However, recent studies have provided evidence that
insulin-like growth factor 1 (IGF-1) may prevent the NO-mediated neuronal damage and is essential for the survival of the cerebellar granule cells. These cells will degenerate in the
PEHO syndrome. In this study, we set out to test the hypothesis that NO production is activated in the
PEHO syndrome and that NO production may be correlated with the reduced production of
IGF-1 in the brain. Cerebrospinal fluid
IGF-1 was determined with an RIA kit and NO metabolites by the Griess calorimetric method. In patients with the
PEHO syndrome, as compared with controls, the levels of
IGF-1 were reduced and the levels of
nitrite/
nitrate were markedly elevated. Defective production of
IGF-1 probably reflects the underlying neurodegeneration and the increase in NO production probably reflects the seizure activity and/or neurodegeneration. These are the first biochemical abnormalities found in the
PEHO syndrome and their study may lead to a better understanding of this devasting disease.