LAUSR

To the Editor: Type II Chiari malformation (CMII), also known as “Arnold-Chiari malformation,” is a rare hindbrain anomality characterized by a small posterior fossa with downward descent of cerebellum, brainstem, and fourth ventricle (1). Although it has been described for more than a century, the etiology and neuropathology are still largely unknown (2). Despite advanced surgical treatment, it continues to be the leading cause of pediatric death in children with neural tube defects (1). Here, we present an autopsy study in a female patient with CMII and a structurally abnormal X chromosome who survived 17 months after multiple surgeries and interventions. To our knowledge, this is the first report in the CMII population with this specific genetic alteration. A 17-month-old girl with a complicated medical history, including CMII with hydrocephalus (status post ventriculoperitoneal [VP] shunt placement; Fig. 1A), myelomeningocele (status post initial repair and revision), vocal cord paralysis requiring tracheostomy, and chromosomal abnormalities, was brought to the emergency department for unresponsiveness and dyspnea. She was in her normal state of health until she had a sudden decrease in oxygen saturation and was struggling to breathe. A left frontal external ventricular drain was emergently placed. Head CT showed a mild increase in ventricular size and increased cerebellar tonsillar herniation. VP shunt had slow flow proximally, concerning for shunt failure. Her condition continually worsened and there was minimal improvement in intracerebellar pressure despite adequate drainage. She was transitioned to comfort measures only and passed away. At autopsy, she was a well-developed African-American girl without dysmorphic facial features. The myelomeningocele repair scar at the lumbar sacral region was wellhealed without signs of infection. The external ventricular drain was inserted at the frontal scalp with an underlying soft tissue hematoma. The distal VP shunt tip in the peritoneal cavity was in place and without gross obstruction. The striking neuropathologic findings included the presence of a fenestrated Luckenschadel skull with multiple deep and shallow pits or lacunae (Fig. 1B, C) (3). The internal table was remodeled, as the indentations likely reflected the underlying brain gyri pattern. External examination of the brain showed normal covering transparent leptomeninges with no macroscopic evidence of meningitis (Fig. 1D). The brain was irregularly shaped with an abnormal gyrification pattern. Small compacted gyri were separated by shallow sulci, indicating the presence of stenogyria, which has been reported rarely in CMII patients (1). Upon sectioning, partial agenesis of the posterior corpus callosum as well as partial absence of the cingulate gyrus were identified (Fig. 1E). The ventricles were enlarged without intraventricular hemorrhage. The cerebellar tonsils, vermis, and brainstem were herniated downward through the foramen magnum, compressing the fourth ventricle. The cerebellar folia were unremarkable but there was cerebellar hypoplasia (Fig. 1F). The cerebral cortical ribbon was identified but important anatomic structures such as basal ganglia showed architectural malorganization. Misdirected aberrant bundles of white matter were present and focally appeared parallel to the lateral ventricles (Probst bundle; Fig. 1G), associated with agenesis of corpus callosum. Histologically, both the peritoneal and the ventricular shunt ends were patent without obstruction and meningitis was not identified. The cerebrum showed preserved laminar and columnar architecture of the cortex but mildly decreased neuronal cell density with dispersion of pyramidal neurons (Fig. 2A, B). Glial fibrillary acidic protein immunostain