Sara M. Koenig, MD Wilson B. Altmeyer, MD Carlos Bazan III, MD Maria P. Valencia, MD

No financial disclosures

Our purpose is to review the collective radiographic findings of common individual phakomatoses, focusing on: Neurofibromatosis I and II Tuberous Sclerosis Sturge-Weber Ataxia Telangiectasia The phakomatoses are multi-system disorders involving the neurocutaneous tissues and other tissues throughout the body. These disorders frequently demonstrate a large number of radiographic findings that all radiologists should know, especially in neuroradiologic imaging. Understanding the spectrum of the radiographic findings for these diseases is important and may be diagnostic, affect prognosis, or affect treatment.

A retrospective review of neuroradiology cases at the University of Texas Health Science Center at San Antonio was performed to identify patients with a diagnosis of phakomatosis. Characteristic neurocutaneous findings and systemic manifestations of the specific diseases were identified on imaging and organized into a review of neuroradiologic and other findings in the phakomatosis diseases. As well, we reviewed literature for imaging of these diseases.

Multisystem neurocutaneous disorder Autosomal dominant chromosome 17 mutation Most common phakomatosis The differential includes: NF spectrum, Demyelination, Gliomatosis Cerebri Diagnostic Criteria: (must have >2 of the following) ->6 cafe au lait spots evident during 1 year -2 or > neurofibromas or 1 plexiform -Optic nerve glioma -Distinctive osseous lesion -Sphenoid wing dysplasia -2 or > iris hamartomas (Lisch nodules) -Axillary or inguinal freckling -1st relative with NF 1 with above criteria Neuroimaging Findings -Focal areas of signal intensity in deep grey / white matter (myelin vacuolization) -Optic Nerve Glioma (manifest with enlarged optic foramen) -Progressive sphenoid wing dysplasia -Lambdoid suture defects -Dural calcification at vertex -Moya Moya Phenomenon: rare -Buphthalmos

Sagittal T1WI shows enlarged isointense optic chiasm (arrow). Coronal T1WI with Gd shows no abnormal enhancement of enlarged optic chiasm (arrow). Coronal T2WI shows multiple bilateral rounded paraspinal hyperintense lesions (arrows), consistent with neurofibromas.

Coronal T1 + Gd and axial T2 weighted images demonstrating optic pathway gliomas. Axial T2 FLAIR images showing hyperintense supra and infratentorial lesions throughout the deep gray/white matter, consistent with myelin vacuolization.

Axial T2 WI (top) and coronal FLAIR (bottom) images demonstrate scattered hyperintense lesions throughout the deep gray/white matter, most pronounced in the bilateral globus pallidi, thalami, splenium of the corpus callosum and cerebellum.

Axial and coronal T2 FS images demonstrate thickening of the bilateral optic nerves, right greater than left, consistent with optic pathway gliomas.

Multisequence MRI demonstrates an infiltrative heterogeneous solid enhancing right temporal scalp mass, extending into the right orbit and right cavernous sinus. Please note the typical “target sign” (arrow), presumable secondary to dense central area of collagenous stroma. T1WI T2WI T1 + Gd

T2 FS sagittal and axial images of the lumbar spine demonstrate multiple hyperintense well circumscribed lobulated lesions consistent with neurofibromas along the bilateral nerve roots.

Multisystem neurocutaneous disorder secondary to an autosomal dominant chromosome 22 abnormality. Diagnosis peaks in the 20s, usually presenting with hearing loss from vestibular schwannomas. Neuroimaging Findings -Schwannomas of cranial nerves and spinal nerve roots -Meningiomas -Ependymomas -Most commonly intramedullary spinal cord lesions

Axial T2WI shows bilateral intracanalicular lesions extending from the porus acusticus (arrows). Axial T1WI + Gd shows solid enhancement of the lesions (arrows), consistent with Schwannomas. Sagittal T1WI + Gd shows dural based solid enhancing lesions along the tentorium and anterior falx (arrows), consistent with meningiomas.

Sagittal T1WI FS post contrast (left), Sagittal T2WI (center) & Sagittal T2 STIR (right) images show well circumscribed, solid enhancing, hyperintense T2/STIR expansile intramedullary lesions, consistent with ependymomas.

-Axial T1WI and T2WI FS images (top) show an iso to hyperintense intramedullary superior cervical cord lesion consistent with ependymoma (white arrow). -Axial and Coronal T2WI (bottom) show a circumscribed hyperintense lesion in the left parapharyngeal space displacing the left carotid space vessels antero-laterally, consistent with a left vagal nerve Schwannoma (yellow arrow). T2WI T1WI T2WI

Sagittal T1W pre and post contrast images (left) showing isointense solid enhancing spinal nerve root masses. Sagittal and axial T2WI (right) showing hyperintense signal in those masses, consistent with Schwannomas.

Autosomal dominant multisystem neurocutaneous disorder caused by mutations of the TSC1 (9q) and TSC 2 (16p) genes. Can be diagnosed with major and minor criteria. Clinical symptoms: Seizures, facial nevus, mental deficiency Although there are many features, most common are: Multiple partially calcified subependymal nodules Subcortical tubers Radial migration of white matter lines Subepependymal giant cell astrocytoma (SEGA) White matter cyst-like lesions

Definite TS = 2 major OR 1 major + 2 minor criteria Probable TS = 1 major + 1 minor criteria Possible TS = 1 major OR 2 minor criteria Major Criteria Ungual or Periungual fibroma Facial angiofibroma > 3 hypomelanotic macules Shagreen patch Multiple retinal nodular hamartomas Cortical tubers Subependymal nodule Subependymal Giant Cell Astrocytoma (SEGA) Cardiac Rhabdomyoma Lymphangiomyosarcoma Renal angiomyolipoma Minor Criteria Multiple dental/enamel pits Gingival fibromas Non-renal hamartoma Retinal achromic patch Multiple renal cysts Bone cysts White matter migration lines Multiple confetti-like hypopigmented skin lesions

Axial CT image (left) demonstrating a calcified subependymal nodule (arrow) at the atrium of the right lateral ventricle. Axial and coronal T2W images (center & right) demonstrate multiple hypointense subependymal nodules.

-Axial and Coronal FLAIR images (top) show multiple hyperintense subcortical foci within the frontoparietal lobes consistent with tubers. -Axial T2WI and T1 IR images (bottom) demonstrate multiple subependymal nodules (arrows) and abnormal subcortical and periatrial white matter signal consistent with tubers (yellow arrows).

Coronal and axial T2WI demonstrate diffuse atrophy and decreased signal intensity throughout the left temporal lobe consistent with a calcified hamartomatous left temporal lobe.

T1WI T1+Gd FLAIR -Multisequence brain MRI demonstrates an enhancing subpendymal mass within the right foramen of Monro (arrow), with surrounding abnormal hyperintense FLAIR signal, consistent with SEGA.

Also known as encephalotrigeminal angiomatosis. Clinically patient’s demonstrate: Port wine stain and over growth of soft tissue Seizures Mental deficiency Imaging findings include: Pial angiomatosis and leptomeningeal enhancement Parenchymal volume loss and atrophy Ipsilateral choroid plexus enlargement Gyriform cortical calcifications

Axial T1W images post contrast demonstrate abnormal leptomeningeal enhancement throughout the right hemisphere and abnormal right facial/periorbital soft tissue enhancement (arrow) consistent with likely port wine stain and pial angiomatosis.

Axial and coronal T1W post contrast images (left & center) and Axial T2WI (right) demonstrate ipsilateral choroid plexus enlargement (arrows) and right hemispheric atrophy.

Multisystem neurocutaneous disorder characterized by: CNS and Retinal hemangioblastomas Hemangioblastoma and one: Renal, pancreatic, hepatic, epididymal cyst Pheochromocytoma Renal cancer Conditions associated with VHL include Angiomatosis Hemangioblastomas Pheochromocytoma Renal cell carcinoma Pancreatic cysts Endolymphatic sac tumor Bilateral papillary cystadenomas of the epididymis or broad ligament of the uterus.

Axial T1(left), Axial T2 (center) & Axial T1W with Gd images show circumscribed cystic lesion in the right cerebellum with a peripheral solid enhancing nodule (arrow). This lesion was resected and proven to be hemangioblastoma.

Axial head CT images in bone (left) & brain (right) windows, show extensive bone erosion and the "moth-eaten" petrous bone secondary endolymphatic sac tumor (ELST). Tissue sampling confirmed the diagnosis.

Axial T1 pre and post contrast (top), Axial FLAIR, T2WI & DWI (bottom) images demonstrate heterogeneous signal and enhancement in the noncystic components of the left cerebellopontine angle mass, without restricted diffusion, proven to be ELST.

Rare multi system autosomal recessive neurocutaneous disorder. Includes both ocular telangiectasia cerebellar ataxia Symptoms: Cerebellar ataxia - progressive and present in all cases Oculo-mucocutaneous telangiectasias Greater susceptibility to types of infection (partial combined immunodeficiency) and neoplasms Differential Diagnosis : Diffuse cerebellar atrophy Normal aging EtOH Drugs (e.g phenytoin) Multisystem Atrophy Friedriech Ataxia Paraneoplastic Degeneration Olivopontocerebellar Atrophy Neuroimaging Findings There is cerebellar volume loss, compensatory enlargement of the 4 th ventricle. Hemorrhages may be evident due to telangiectatic vessel rupture.

Axial GRE images (top) show innumerable punctate foci of susceptibility artifact in the bilateral cerebral hemispheres, consistent with petechial hemorrhages. Axial T2W images (bottom) show scattered hyperintense T2 weighted lesions (arrows) in the frontoparietal subcortical white matter.

Coronal FLAIR images (top), demonstrate multiple abnormal long TR subcortical white matter lesions. Sagittal T1WI (bottom left) shows significant cerebellar atrophy and Axial DWI (bottom right), demonstrates lack of restricted diffusion in the white matter lesions.

Basal Cell Nevus Syndrome lesions of mandible and maxilla resembling odontogenic keratocysts extensive calcification of falx cerebri frontal and parietal bossing medulloblastoma PHACES Syndrome posterior fossa malformations, often unilateral cerebellar hypoplasia cortical dysplasia vascular abnormalities eye abnormalities Neurocutaneous Melanosis giant or multiple benign and/or malignant lesions of the central nervous system leptomeningeal melanosis and melanoma

The phakomatoses are a collection of neurocutaneous disorders which frequently involve multiple organ systems and tissues. In radiology, it is important to understand the spectrum of findings in these diseases as it may pertain to the patient's diagnosis, prognosis, symptoms, and/or treatment.

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