Folinic acid-responsive neonatal seizures.

We report three cases of folinic acid-responsive intractable neonatal seizures. All patients were born at term following normal gestation and delivery. In the first infant, seizures began on the 5th day of life and were unresponsive to phenobarbital, pyridoxine, and valproate, but stopped within 24 hours of initiation of folinic acid treatment at the age of 6 months. Her sibling had died at age 6 months with intractable seizures. In the second infant, seizures began in the 2nd hour of life. These were initially controlled with phenobarbital; however, at 3 months of age she developed status epilepticus refractory to anticonvulsants, steroids, and pyridoxine and she required repeated induction of pentobarbital coma. Seizures stopped within 24 hours of starting folinic acid. Seizures and encephalopathy were noted in the third infant on the 2nd day of life. These were controlled with phenobarbital, but at 8 weeks of age seizures recurred and were difficult to control despite the addition of phenytoin. Immediately after folinic acid was initiated the seizures stopped. Breakthrough seizures in all patients have responded to increases in folinic acid; two of the three remain on standard anticonvulsants. All patients have global developmental delay. Cranial magnetic resonance imaging in the second patient shows diffuse atrophy, and in the third patient shows increased signal on T2 images in the white matter of the frontal and parietal lobes. Analysis of cerebrospinal fluid from these patients using high-performance liquid chromatography with electrochemical detection has consistently revealed an as-yet unidentified compound, which can be used as a marker for this condition. We suggest that cerebrospinal fluid be analyzed for the presence of this compound and a trial of folinic acid be considered in neonates with unexplained early onset intractable seizures.

Magnetic resonance spectroscopy of normal and diseased muscles.

Phosphorus magnetic resonance spectroscopy (P MRS) affords and innovative approach to the study of the oxidative enzyme content of normal and diseased muscles. Examples of the evaluation of the enzyme content of normal muscles by an exercise protocol are provided. The protocol affords a hyperbolic work/cost profile, the Vmax of which is calculated by the reciprocal plots giving the enzyme content and the "effective Michaelis constant" with an evaluation of the resting metabolism. This steady state protocol clearly illustrates enzyme adaptation, on the one hand, and tissue atrophy particularly in the case of tissue injury, Duchenne's dystrophy, and genetic deletion of specific enzymes, on the other hand. The method is rapid, safe, and affords a quantitative evaluation of the disease process and possibilities for following appropriate therapies. So far, approx 1000 examinations of normal and diseased human limbs have been carried out in our laboratory in over the past four years.