Abstracts

RATIONALE: Krabbe disease is a progressive neurological disorder. We descibe two infants who presented with severely abnormal electroencephalograms (EEG), and clinically demonstrated rapid neurological decline and death.
METHODS: The infants, a boy and girl, presented in the neonatal period with seizure activity. Each had multiple EEGs and biochemical analysis of serum, urine, and skin fibroblasts, Each also had histochemical and structural analysis of skin and muscle biopsy material. Both patients underwent CT and MRI scans of the brain. Final diagnosis of Krabbe disease was based on [beta]-galactocerebrosidase activity in cultured skin fibroblasts.
RESULTS: The girl presented with seizure activity at birth, described as eye deviation with tonic stiffening of the limbs. She had multiple seizures per day uncontrolled by medication. The inital EEG, at one month of life, showed multifocal independent spikes (MSID) as well as EEG seizures. At 2 months of life, a second EEG showed the same MSID, but with a more regular background. The boy presented with rhythmic arm jerking during the first weeks of life, followed by tonic stiffening in his limbs, and staring with behavioral arrest at 3 months of age. EEGs performed at 3 and 4 months of life and showed generalized slowing with infrequent MSID and subsequently with more frequent MSID, both without EEG seizures. A repeat EEG at 7 months of life showed hypsarrhythmia with no clinical manifestations of epileptic spasms. A final EEG performed at 8 months of age showed generalized slowing of the background and regional right occipital and temporal spikes.
Both patients developed irritatability and multiple GI problems of vomiting and feeding difficulties within the first month of life. The boy[ssquote]s CT scan (at 3 months) showed bilateral basal ganglion califications. The girl[ssquote]s performed at about the same time was normal. Subsequent brain MRI (5 months) of the boy, showed T2 hyperintensities within the thalami and posterior limbs of internal capsule and along cortical spinal tracts. The girl[ssquote]s MRI (4 months) only showed mild global atrophy. The boy[ssquote]s skin biopsy showed mitochondria containing crystalloid. Both had muscle fiber-type disproportion. The girl had 5-10% [beta]-galactocerebrosidase acitivity while the boy had 0% detected enzyme activity. The girl died at 6 months while the boy died at 8 months.
CONCLUSIONS: Unlike other published reports, our patients showed generalized background slowing and MISD with initial EEG recordings, presumably during the early stages of the disease. The evolving frequency of spikes and amplitude between 100-200 [micron]volts suggests the MSID syndrome. The boy evolved into a frank hypsarrhythmia pattern in the later stages of the disease and then with ACTH treatment into a more focal EEG discharge pattern with background slowing. The girl only had EEGs performed during the early stages. The severely abnormal EEG having frequent epileptiform discharges may be related to the low to zero detected enzyme activity, the rapid neurological decline, and early death.