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Summary
Phenylketonuria (PKU) is characterized by phenylalanine accumulation due to phenylalanine hydroxylase deficiency. Up to 50% of PKU patients experience seizures. We evaluated an adult PKU patient who suffered from absences and primarily generalized tonicclonic seizures, associated with generalized spikeand-wave discharges (GSWs) on EEG. An analysis of blood oxygenation level-dependent (BOLD) signal changes during interictal epileptiform discharges showed early activation of the left perirolandic cortex followed by a BOLD signal decrease within cortical regions belonging to the default mode network and left frontoparietal cortex. Moreover, deactivation of the head of the right caudate nucleus and the left thalamus was observed. The fMRI pattern observed in our patient during GSWs is similar but not identical to that observed in idiopathic generalized epilepsy, suggesting different neurophysiological mechanisms. This is the first description of BOLD-fMRI patterns in a PKU patient with epilepsy. Similar studies in more patients might help to uncover the pathophysiology of seizures in this disease.
KEY WORDS: absences, BOLD, EEG-fMRI, generalized spike-andwaves, phenylketonuria.
Introduction
Phenylketonuria (PKU) is a metabolic disorder, characterized by accumulation of phenylalanine (Phe) due to phenylalanine hydroxylase (PAFI) deficiency. If untreated, it leads to an abnormal phenotype including growth failure, intellectual impairment and seizures. PKU patients may experience different types of seizures, including generalized ones.
We report the blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) features recorded during interictal epileptiform discharges (lEDs) in an adult patient affected by PKU, who had experienced absence seizures and primarily generalized tonic-clonic seizures in adolescence and early adulthood, associated with features of idiopathic generalized epilepsy (IGE) on EEG.
Case report
History and clinical features
A 45-year-old Caucasian male was admitted as an outpatient to our epilepsy center at the age of 40. His childhood history showed, from the age of two years, delayed acquisition of walking and language milestones and mild learning difficulties. At the age of 16 years, he experienced a first seizure characterized by eyelid myoclonias and brief psychomotor arrest. In the following months he experienced similar seizures, sometimes triggered by watching television. A year later a generalized tonicclonic seizure occurred. Carbamazepine induced an increase in seizure frequency, and was thus substituted with ethosuximide and primidone, which gave reasonable seizure control. At the age of 18 years, the patient was diagnosed...