Pathology of Chiari Malformations in Children

Pathophysiology

Chiari I malformation

• Cerebellar tonsils too low: Cerebellar tonsillar descent into the foramen magnum.
• Syringomyelia commonly associated: Syringomyelia may coexist in 60–70% of patients, resulting in progressive scoliosis in 30% of these patients (23, 28).
• Occasional skull anomalies: There is occasional association with skull base abnormalities such as platybasia, ventral compression, and basilar invagination.

Chiari II malformation

• Tonsils and brainstem too low: Herniation of the vermis, medulla, and fourth ventricle into the spinal canal is present.
• Myelomeningocele: Chiari II malformation occurs in >90% of patients with myelomeningocele and is exclusive to this population.

Chiari III malformation

• Suboccipital encephalocele: Herniation occurs of all brainstem structures into the foramen magnum as well as through a defect in the posterior fossa wall (posterior fossa encephalocele). A suboccipital mass is noted on physical examination.

Chiari IV malformation

• Cerebellar hypoplasia or aplasia: Chiari IV malformation typically refers to an extreme hypoplasia or frank aplasia of the cerebellum. There can also be hypoplasia of the pons and a small posterior fossa. The term is not widely used.
• Probably of multifactorial etiology: Chiari IV malformation may be related to a collection of developmental brain anomalies and teratogenic insults from materials such as drugs.

Molecular/Genetic Pathology

• Not clear but suggestive evidence: Even though a genetic basis has been suggested, presently the type of inheritance or particular genes associated with cases support a genetic basis for a subset of patients with Chiari I malformations. Recent studies suggest linkage to chromosomes 9 and 15 (47).
• Possible mesodermal disorder in Chiari I: Chiari I malformations may be related to a mesodermal disorder that results in abnormal posterior fossa formation and size. The Pax-1 gene has been particularly associated with improper segmentation and differentiation, making it a reasonable candidate gene. However, no studies to date have proven a clear genetic association (48).