Folinic Acid-Responsive Neonatal Seizures
Incidence
Three cases of folinic acid responsive intractable neonatal seizures has been reported in 1999. Unknown ethiology.
Clinical Characteristics
All patients are born at term following normal gestational delivery. Seizures started in the first five days of life, sometimes associated with encephalopathy. The clinical characteristics are intractable neonatel seizures, encephalopathy, global developmental delay. Treatment sometimes was delayed sometimes after the age of six months. Treatment with folinic acid stopped the seizures. Breakthrough seizures in all patients have responded to increase in folinic acid. All patients have global developmental delay on follow up. Cranial magnetic resonance imaging in one patient shows diffuse atrophy and in another shows increased signal on T2 imaging 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 reveal as yet unidentified compounds which can be used as a marker for this condition. The folinic dose used initially was between 2.5 mg. BID to 5 mg. twice a day. The dose was increased in the patients to 10 to 20 mg. twice a day according to each patient's need to control the seizures. The concentration of the compound in the spinal fluid diminish over time in all patients as they were treated with folinic acid. This compound can be a marker for a new metabolic disorder characterized by intractable seizure in the newborn period from moderate to severe developmental delay. Metabolic basis of this disorder remain unclear. It is probably an intermediate in a pathway that require folate as a co-factor. The compound could be detected easily in cerebrospinal fluid. The metabolic block seems to be located within the central nervous system. The response to folinic acid was marked in all three infants and breakthrough seizures continue to respond to increased doses of folinic acid. Two of the three patients still require anticonvulsant as well. Though folinic acid has aided in the seizure control of these patients, all have shown significant developmental delay. The etiology for the delay is still unclear but it could be due to damage prior to folinic acid treatment. Infants with unexplained seizures should have their cerebrospinal fluid analyzed for the presence of the unknown compound and a trial of folinic acid be considered in neonate infants with unexplained medical refractory seizures. The metabolic basis of this disorder/syndrome remains unclear. The concentration of 5-methyl-THF in CSF was normal in all patients and there were no hematologic complications or other signs of folate deficiency, making it unlikely that the disorder is a primary defect in folate metabolism.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
Analysis of cerebrospinal fluid from these patients using high performance liquid chromatography with electrochemical detection has consistently reveal as yet unidentified compounds which can be used as a marker for this condition.