Neurophakomatoses
Matthew Thomas Whitehead1
1George Washington University, Washington, DC, United States

Synopsis

Neurophakomatoses comprise a diverse group of disorders affecting structures derived from ectoderm and/or mesoderm, leading to skin and intracranial abnormalities. MRI plays an important role in diagnosis, prognosis, and surveillance. Frequently, the imaging pattern is diagnostic or highly suggestive; the radiologist may be the first to suggest the diagnosis. In this lecture, I will attempt to strike a balance between depth and breadth, beginning with detailed examples of the 5 most common phakomatoses including neurofibromatosis type 1, Tuberous sclerosis, Sturge-Weber syndrome, Von-Hippel Lindau, and neurofibromatosis type 2, with a rapid review of rarer neurophakomatoses with specific neuroimaging patterns to follow.

Abstract

Neurophakomatoses comprise a diverse group of disorders affecting structures derived from ectoderm and/or mesoderm, leading to skin and intracranial abnormalities. MRI plays an important role in diagnosis, prognosis, and surveillance. Frequently, the imaging pattern is diagnostic or highly suggestive; the radiologist may be the first to suggest the diagnosis. In this lecture, I will attempt to strike a balance between depth and breadth, beginning with detailed examples of the 5 most common phakomatoses including neurofibromatosis type 1, Tuberous sclerosis, Sturge-Weber syndrome, Von-Hippel Lindau, and neurofibromatosis type 2, with a rapid review of rarer neurophakomatoses with specific neuroimaging patterns to follow.

Summary of Main Findings

Neurofibronin deficiency in Neurofibromatosis type 1 causes cellular dysregulation, abnormal bone formation/remodeling, and loss of vascular wall maintenance leading to cardinal features: optic pathway gliomas, neurofibromas, distinctive bone lesions (i.e. sphenoid wing dysplasia), myelin vacuolization, and vascular abnormalities.
Tuberous sclerosis is caused by deficient hamartin (TSC1) or tuberin (TSC2) with secondary mTOR pathway activation. The triad of tubers, radial migration lines, and subependymal nodules is diagnostic. Tuber size, number, signal, and mineralization status are factors influencing seizure potential/neurologic outcome. MR surveillance for subependymal giant cell tumors is recommended q1-3 years up to age 25.
Sturge-Weber syndrome (SWS) results from a sporadic GNAQ mutation. The SWS phenotype is predicated on when the mutation occurs during development. Classical SWS manifests a facial port-wine stain, leptomeningeal angiomatosis, and ocular choroidal angiomas.
Von-Hippel Lindau syndrome is caused by a VHL tumor suppressor gene mutation or deletion. Hemangioblastomas of the brain, spine, and/or retina are the most common imaging findings, followed by pancreatic cysts, renal cysts, renal cell carcinoma, pheochromocytoma, pancreatic neuroendocrine tumors, and serous cystadenoma of pancreas.
Neurofibromatosis type 2 is a misnomer in that this syndrome typically comprises multiple schwannomas, meningiomas, and ependymomas. NF2 gene loss-of-function causes merlin dysfunction, a tumor suppressor. Merlin is found in Schwann cells and meningeal, nerve, and lens fibers.
Rarer phakomatoses with specific skin and neuroimaging manifestations including PHACES syndrome, ataxia telangiectasia, hereditary hemorrhagic telangiectasia, neurocutaneous melanosis, basal cell nevus syndrome, Menkes syndrome, Gomez-Lopez-Hernandez syndrome, and Parry-Romberg syndrome are briefly reviewed.

Takeaway Messages

MRI plays an important role in diagnosis, prognosis, and surveillance of phakomatoses
Young age, mild or atypical clinical phenotypes, and lack of subspecialty evaluation are a few of the reasons that the dermatologic exam may be unreliable
Fetal MR can diagnose NF1, Tuberous sclerosis, neurocutaneous melanosis, and PHACES
Carefully scrutinize the vascular flow-voids in all NF1 MRI exams; MRA threshold is low
Malignant peripheral nerve sheath tumors may be suggested by a large, growing tumor with loss of normal targetoid architecture, reduced diffusion, necrosis, peripheral edema, early enhancement, and hypermetabolism
Noncontrast brain MR is sufficient to monitor for SEGAs in Tuberous sclerosis
Tuber size, number, signal, and mineralization status are factors influencing seizure potential/neurologic outcome in Tuberous sclerosis
Hemangioblastomas of the brain, spine, and/or retina are the most common imaging findings in Von-Hippel Lindau syndrome
NF2 comprises multiple schwannomas, meningiomas, and ependymomas

Neuroimaging features that may suggest a rare phakomatoses include:
PHACES: concurrent vascular and posterior fossa anomalies
Ataxia telangiectasia: cerebellar atrophy with telangiectasias or cavernomas
Neurocutaneous melanosis: melanotic lesions in the brain and/or leptomeninges
Basal cell nevus syndrome: dural calcifications, sellar bridging, and OKCs
Menkes syndrome: vascular elongation/tortuosity
GLH syndrome: rhombencephalosynapsis with trigeminal hypoplasia
Parry-Romberg: hemifacial atrophy, ipsilateral cerebral white matter lesions

Acknowledgements

No acknowledgement found.

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Proc. Intl. Soc. Mag. Reson. Med. 29 (2021)