Appendix e-2: Case descriptions
Patient 22
This 3-year-old boy was bornfrom healthy unrelated parents after an uneventful pregnancy. Birth weight was 4210 g (90th centile), length 53.5 cm (75-90th centile), and head circumference 36 cm (75th centile). Early development was reported to be normal. At the age of 5 months, the boy started having epileptic spasms for which he was treated with nitrazepam, with partial benefit. At 6 months of life, he came to our observation, due to recurrent clusters of symmetricflexorspasms. At examination,no facial dysmorphisms were observable. Neurological examination revealed attenuated responsiveness to verbal andvisual stimuli and discontinuous eye contact. Interictal electroencephalogram showed a hypsarrhtyhmic pattern and focal spikes and slow-waves over the temporal regions of both hemispheres. Diffuse, high amplitude slow wave and spike activity were also recorded. Sleep electroencephalogram showed no physiological patterns. Ictal electroencephalogram revealed diffuse high-voltage slow wave, followed by diffuse low amplitude attenuation with superimposed bilateral fast activity over the frontal-temporal regions. Laboratory analyses showed normal blood count and blood chemistry values, including levels of lactate and ammonia. Plasma amino acid and urine organic acid analyses were normal. Renal and hepatic ultrasonography, echocardiography and electrocardiography revealed no abnormalities. Brain MRI did not show gross abnormalities. Spasms were treated with intramuscular ACTH at the maximum dose of 50 units per day and ceased after 1 week. At the age of 12 months, electroencephalograms showed disappearance of hypsarrhtyhmia but persistence of bitemporal asynchronous paroxysmal activity. Sleep EEGs revealed brief subtle seizures characterized by eyes opening, arrest of suction and increased respiratory and cardiac frequency, associated to a rhythmic fast activity over the occipital-temporal regions. ACTH was tapered after 15 days and discontinued over three weeks. Seizures were first treated with valproate without effect, and subsequently with topiramate with good response. Follow-up EEGs (at age of 16, 20 and 24 months) showed focal slow and paroxysmal activity over the occipital-temporal regions of both hemispheres. A recent evaluation revealed absence of language; Bayley Scales revealed moderate mental retardation.
Patient 36
This 14-year-old boy was the only child of healthy unrelated parents, with unremarkable family history. He was born at term afterspontaneous vaginal delivery. At the age 7 months he started experiencing daily episodes characterized by up rolling eyes with sudden and brief flexion of upper limbs. His electroencephalograms showed a typical hypsarrhtyhmic pattern, allowing the diagnosis of West syndrome. Treatment with ACTH was started with partial benefit. Therefore, vigabatrin was introduced, resulting in the complete resolution of the epileptic manifestations and improvement of the EEG. However, the patient’s development was delayed: he started to walk at 24 months and to talk at 13 months. The patient came to our attention at the age of 3 years to withdrawn antiepileptic therapy. At physical examination no facial dysmorphisms were observed. Neurological examination revealed clumsiness and broad-based gait. He did not show any autistic features, including poor social interactions, repetitive behaviors, or stereotypies. However, he was mildly hyperactive and attended the school with support. At the last follow-up (12 years) no further seizure was reported. His electroencephalogram and MRI were unremarkable.