Researchers from Duke University Medical Center, Durham, NC report the EEG and seizure manifestations in 2 patients with folate receptor autoimmune antibody-mediated primary cerebral folate deficiency. Case 1, a boy presented at age 6 months with flexion spasms of the trunk and extension of the arms occurring multiple times each day. The seizures were diagnosed as infantile spasms and the EEG showed hypsarrhythmia. Treatment with various anticonvulsant drugs and ACTH 80 U/m2 provided only minor seizure control. Decreased CSF 5-MTHF and elevated serum folate receptor antibodies discovered at age 3.25 years were consistent with an autoimmune etiology of cerebral folate deficiency. Treatment with folinic acid started at 1 mg/kg/day resulted in marked clinical and EEG improvement. MRI revealed diffuse brain volume loss. Case 2, a girl aged 4 years had a history of developmental delay and tonic seizures that increased in frequency after age 5 years. She had progressive regression with language deficits, hand wringing, and gait difficulty. Tests for Rett syndrome and related disorders were negative. With increasing age her seizures were multiple and refractory. The EEG showed subclinical electrical status epilepticus during sleep, covering >85% of the slow wave sleep background. Cerebral folate deficiency was identified at age 16 years, and seizure frequency and intensity improved with folinic acid initiated at a dosage of 0.5 mg/kg/day. The EEG showed less frequent multifocal spikes, and electrical status epilepticus during sleep resolved. 
COMMENT. Patients with developmental regression, refractory seizures or spasms, and EEG showing hypsarrhythmia or electrical status epilepticus during sleep should be tested for cerebral folate deficiency and considered for treatment with folinic acid. The authors list seizure onset during the first 2 years, tonic, myoclonic-astatic, absence, or generalized tonic-clonic seizures, and an EEG showing generalized spike-slow waves and multifocal spikes as important in the index of suspicion of this disorder.