An 8 year old boy with genetically confirmed neurofibromatosis type 1 presents with first generalized seizure.
Laura C. Speltz, MD
An 8 year old boy is transferred from a community hospital to a tertiary care center after experiencing a first time generalized seizure. He has an extensive past medical history including a genetically confirmed diagnosis of neurofibromatosis type 1, autism spectrum disorder, strabismus repair, and an optic glioma on magnetic resonance imaging (MRI) of the brain.
The child was born at term via vaginal delivery without complications. His early gross motor milestones were delayed and he started walking at 18 months of age. He was diagnosed with hypotonia and enrolled in physical therapy. Subsequently, he was referred to a neurocutaneous clinic due to the presence of café au lait spots and inguinal freckling. A diagnosis of neurofibromatosis type 1 was confirmed with genetic testing. Initial brain MRI was within normal limits. At 3 years of age he was seen for a neuropsychological evaluation and diagnosed with an autism spectrum disorder.
At 5 years of age, he developed new episodes of headaches and emesis. His mother reported that he would develop a red rash on his chest and turn very pale. He would complain of brief headaches lasting less than 5 minutes and report an odd taste in his mouth. He would proceed to retch and vomit for several minutes; occasionally the symptoms could wax and wane over the course of several hours. With some of these events he would have urinary incontinence. His mother also reported secondary urinary incontinence and enuresis unrelated to the episodes of recurrent emesis. He was referred for a gastrointestinal evaluation and had a normal upper endoscopy. He was seen by urology for his incontinence but no cause was found.
He continued to have episodes of emesis and headache on a nearly monthly basis. He was seen by a neurologist and repeat head imaging was obtained. He had developed a right optic nerve glioma as well as a non-enhancing FLAIR hyperintensity in his left cerebral peduncle consistent with a neurofibromatosis-associated bright object. He had a normal routine EEG. He was diagnosed with cyclic vomiting syndrome and was started on cyproheptadine for migraine prophylaxis. He was prescribed sumatriptan as needed without significant improvement.
The events in question escalated in frequency and severity over the course of several years. He was seen repeatedly in the local emergency room and admitted for dehydration. During one such hospitalization, he was prescribed lorazepam 1 mg every 8 hours as needed for agitation. This treatment appeared to improve his gastrointestinal symptoms by shortening the duration of the episodes of retching and emesis. His mother began to treat him with this benzodiazepine therapy at home as needed for the recurrence of his symptoms.
First Clinical Seizure
During a subsequent hospitalization, the patient was retching and had experienced repeated bouts of emesis for approximately 1 hour when he abruptly developed clinical seizure activity associated with head deviation to the left, stiffening of his extremities, lip smacking, and urinary incontinence. This clinical seizure activity lasted 10 minutes before resolving with administration of lorazepam intravenously. He was sleepy and confused thereafter. His electrolytes and glucose were within normal limits.
The patient was loaded with intravenous levetiracetam and transferred to a tertiary care center for further evaluation. His routine EEG was, again, normal. An MRI revealed mild subcortical and cortical edema in the bilateral frontal and parietal lobes which was attributed to his prolonged seizure activity. He was discharged home on levetiracetam prophylaxis. After discharge he had no additional episodes of vomiting and/or headache for 2 years. His secondary urinary incontinence also resolved.
In the fall of 2019, he developed recurrent episodes of daytime and night time urinary incontinence. He reported no memories of the events. His levetiracetam dose was increased and these episodes resolved. Subsequently, he had an episode at school concerning for breakthrough seizure activity. After gym, his school Registered Nurse called his mother because he was very pale and curled up in a fetal position. He was incoherent and speaking gibberish, but wasn't able to respond to his mother. When he tried to respond, his speech was very slow. He was retching, but had not yet vomited. He developed his typical vascular rash over his chest as well. His mother came to the school and administered 7.5 mg of buccal diazepam. Thereafter, he threw up but did not return to his baseline. The constellation of symptoms above persisted, so his mother took him to the Emergency Room where he was given a loading dose of levetiracetam with symptom resolution. He was admitted for a video EEG that was normal for 48 hours. His levetiracetam dose was increased and his symptoms again have resolved for the past month.
Epilepsy in neurofibromatosis is relatively common. A recent analysis found that 26 of 184 patients with neurofibromatosis were also diagnosed with epilepsy; of this group 17 (65%) had localization related epilepsy.1 Migraines and migraine variants are also common in the pediatric population and can be challenging to differentiate from epilepsy due to the similarities in symptomatology and the frequent comorbidity of the 2 conditions.2Taking a detailed history and monitoring for response to initial therapies can help narrow the differential diagnosis. A normal EEG does not exclude the possibility of an underlying seizure disorder. Clinicians should have an increased degree of suspicion for seizures in children with risk factors for epilepsy including neurocutaneous syndromes and autism spectrum disorders.
1. Pecoraro A, Arehart E, Gallentine W, et al. Epilepsy in neurofibromatosis type 1. Epilepsy Behav. 2017;73:137-141. doi: 10.1016/j.yebeh.2017.05.011.
2. Oakley CB, Kossoff EH. Migraine and epilepsy in the pediatric population. Curr Pain Headache Rep. 2014;18(3):402. doi: 10.1007/s11916-013-0402-3.