James Barkovich
I chose the topic of disorders of microtubule function because I was seeing a lot of patients with brain malformations due to mutations of tubulin genes (such as TUBA1A, TUBB2B, TUBG1, etc.) and microtubule-associated protein (MAP) genes (such as DCX, LIS1, and DYNCH1H1) and saw that they had characteristic features that could be detected by imaging. The abnormalities are always easier to recognize if you understand what causes them and why they look the way they do, so I thought a paper would be useful to my colleagues in neuroradiology.
There are several features of brains with mutations of MAP genes that are characteristic; the most obvious are pachygyria, a condition in which the cerebral cortex is broad and flat, with thick gyri separated by shallow sulci, and “band heterotopia,” a band of undermigrated neurons lying deep to the pachygyric cortex.
Mutations of the tubulin genes themselves most commonly cause nearly complete agyria, with a small brain and diminished white matter. White matter anomalies may include abnormalities of the corpus callosum (often thin or short), an absence of the anterior limb of the internal capsule, and in some patients, an absence of olfactory nerves; the cerebellum is very commonly small or smooth and the quadrigeminal plate may be enlarged. Once a physician recognizes the imaging features of these disorders, they are rather easy to diagnose.
I hope my colleagues have found this paper useful in their practices. I continue to be interested in microtubules and the many functions they perform both in development and physiology. There are many very important processes in development (e.g., cell division, neuron migration, axon navigation) and in homeostasis (e.g., maintaining tight epithelial tight junctions, formation of cilia and flagella). However, disorder of these functions results in more complex phenotypes that are somewhat difficult to diagnose by imaging.