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Washington University Experience | MYELIN (NON-IMMUNE MEDIATED) | Alexander Disease | 1A0 Case 1 History (Neurosurgical)
Case 1 History ---- The patient is a 13 month-old premature female infant, born at an estimated gestational age of 27-4/7 weeks to a 34-year-old G4P4 mother. The pregnancy was complicated by multiple admissions for vaginal and subchorionic bleeding and pre-term labor. She was delivered vaginally following spontaneous rupture of membranes with subsequent Apgars of 2, 6 and 8. She was in immediate respiratory distress and required intubation at the time of delivery. Cardiopulmonary resuscitative efforts were initiated and successful along with surfactant. The patient's postnatal history is significant for chronic lung disease, apnea and bradycardia of prematurity, and anemia of prematurity. She also had cortical visual impairment with response to light but poor tracking and frequent upgaze. A head ultrasound one week later showed no subependymal, intraparenchymal or intraventricular hemorrhage or periventricular leukomalacia. At this time no mass lesions were noted. A follow-up head ultrasound showed moderate bilateral and third ventriculomegaly. She developed an accelerated head growth profile with a bulging fontanelle. MRI showed aqueductal stenosis and obstructive hydrocephalus. A ventriculoperitoneal shunt was placed at 7 weeks of life. MRI from 2 months of age showed underdevelopment of the gyral/sulcal pattern, loss of corticospinal tracks and diffuse abnormal periventricular signal with diffusion restriction suggestive for hypoxic injury. At 5-months of life, the patient developed new onset seizures and repeat MRI showed enhancement in the inferior hypothalamus, just superior to the pituitary stalk and within the bilateral fornices adjacent to the foramen of Monro. Cytogenetics showed an interstitial deletion on the short arm of chromosome 17 (17p13.3) and a maternally inherited interstitial duplication on the long arm of chromosome 22 (22q11.21). At 7 months of age MRI showed multiple lesions in the hypothalamus, medial temporal lobes, tectum, and midbrain which appeared expansile with focal enhancement thought to represent diffuse or multiple gliomas. Right anterior temporal lobe brain biopsy was performed at 8 months of age. Biopsy (illustrated in the next series of images) showed an astrocytic proliferation and astrocytopathy with the electron microscopic appearance of inclusions most resembling Rosenthal material, prompting GFAP gene sequencing that identified a single heterozygous variant of Arg239His in exon 4, consistent with Alexander disease.
