History and Physical
A 6-week-old boy presented with 1 week of episodic bilateral arm flexion and upward eye rolling. These episodes occurred in clusters (4–5 seizures/cluster, 3 times a day). There was no associated developmental regression. Birth history was notable for the use of vaginal forceps, but he was born full-term with no complications. Family history was unremarkable. During presentation, a full septic workup was performed with no abnormalities. Prolonged video-EEG captured multiple epileptic spasms associated with electrodecremental responses. Associated symptoms consisted of flexion and subtle upward tonic eye deviation ( Fig. 18.1A ). There was also right-dominant hypsarrhythmia and several focal seizures originating in the right temporal region. Clinically, these were either monosymptomatic or were characterized by left arm extension ( Fig. 18.1B ). Occasional intermittent theta activity was observed in the right posterior quadrant.
Electroencephalography (EEG) in a 6-week-old male with infantile epileptic spasms. (A) Hypsarrhythmia during sleep, maximal in the right hemisphere ( arrows ). (B) Nonconvulsive focal seizure with onset in the right central and mid-posterior temporal lobe, electrodes C4- T4 ( arrows ).
Diagnostic Workup
Head CT was normal. Brain MRI showed asymmetric gyration in the right posterior quadrant, with thickening of right middle and inferior temporal cortex, blurring of gray-white matter interface, and decreased white matter volume. These findings were suggestive of focal cortical dysplasia (FCD) involving the right posterior temporal lobe ( Fig. 18.2 ).
Infantile epileptic spasms syndrome. Brain MRI, (A) axial and (B) coronal T2 show aberrant sulcation and gray-white blurring in the right temporal lobe ( arrows ) with asymmetric white matter signal and volume.
Genetic epilepsy panel revealed a missense pathogenic variant in NPRL3 (p.Arg92Gln) in addition to an exon 4 to 8 duplication. Both missense variants were inherited from the asymptomatic father (with a normal brain MRI) and paternal grandfather. The patient’s NPRL3 abnormality was responsible for GATOR1 complex dysfunction, which in turn caused disinhibition of mTORC1. Pathogenic variants in NPRL3 have been associated with focal epilepsies, with the presence of FCD suggesting a second-hit somatic mutation.
Clinical Differential Diagnosis
Infantile epileptic spasms (previously known as West) syndrome (IESS) is a developmental epileptic encephalopathy characterized by epileptic spasms in infancy, a highly chaotic EEG pattern termed hypsarrhythmia , and developmental arrest or regression. Over 200 causative factors have been associated including structural, metabolic, toxic, and genetic etiologies. Structural etiologies account for the majority of cases but can overlap with other conditions.
Imaging Differential Diagnosis
The abnormalities found in neuroimaging in this patient with epileptic spasms and focal seizures were suggestive of FCD. FCDs are histologically classified by the International League Against Epilepsy (ILAE) into type I (cortical lamination disorders: A = abundant microcolumns; B = abnormal layering; C = vertical and horizontal abnormalities); type II (cortical dysplastic neuron disorder: A = dysmorphic neurons; B = dysmorphic neurons and balloon cells). The best surgical response is seen with transmantle or bottom-of-the-sulcus dysplasias (BOSD) classified as type IIB ( Fig. 18.3 ). FCDs associated with other lesions are classified as type III ( Fig. 18.4 ).
