Phakomatoses - Radiology Resident Guide

1. Neurofibromatosis Type 1 (NF-1)

CNS Imaging Findings

• Present in 60-80% of NF-1 children; up to 95% with coexistent OPG
• T2/FLAIR hyperintense foci, no mass effect, no enhancement
• Typical sites: pons, cerebellar white matter, internal capsules, basal ganglia (may be slightly T1 hyperintense here), thalami, hippocampi
• Age-dependent: rare <4 years, peak 4-10 years, virtually absent after age 20
• Key distinction from glioma: no growth, no enhancement; enhancement or increasing mass effect should raise concern for tumour transformation

Fig. 76.27 - NF-1. (A) T2 axial: hyperintense UBOs in lentiform nuclei. (B) Coronal: UBOs in brainstem and midbrain. (C) T2 axial: bilateral optic nerve gliomas extending into the chiasm (arrows). - Grainger & Allison's

• Most common brain abnormality in NF-1 (up to 15%); usually WHO grade I pilocytic astrocytoma
• NF-1 OPGs more often affect optic nerves (vs. chiasm/postchiasmatic in sporadic cases); better prognosis
• Fusiform optic nerve expansion; widening of optic foramen on CT
• MRI preferred: fat-suppressed T1+Gd and STIR sequences; 3 mm slices
• Once chiasm/hypothalamus involved: risk of precocious puberty and visual loss

• Major diagnostic criterion; multinodular, involve multiple nerve fascicles
• Classic site: orbit along ophthalmic V1, associated with sphenoid wing dysplasia
• CT: hypodense, minimal enhancement
• MRI: T1 low SI, T2 heterogeneous hyperintense; variable Gd enhancement; "target sign" (central T2 hypointensity) in neurofibromas
• Extension into pterygomaxillary fissure, orbital apex, cavernous sinus
• Malignant transformation to fibrosarcoma: 2-12%

• Produces the "bare/empty orbit" sign on plain radiograph
• Temporal lobe herniation through the orbit
• Pulsatile exophthalmos (CSF pulsations transmitted through defect)

2. Neurofibromatosis Type 2 (NF-2)

• Bilateral vestibular schwannomas (pathognomonic) - shown on MRI/CT or histology
• OR first-degree relative with NF-2 + unilateral 8th nerve tumour
• OR first-degree relative with NF-2 + any two of: neurofibroma, meningioma, schwannoma, glioma, or juvenile posterior subcapsular lens opacity

• Bilateral vestibular (acoustic) schwannomas - enhancing masses at the internal auditory canals (IAC); adults present with hearing loss; children more often with seizures or facial palsy
• Multiple meningiomas (often en plaque)
• Cranial nerve schwannomas (CN V, VII common)
• Ependymomas (especially spinal; cervical cord)
• Spinal schwannomas on cauda equina roots - dumbbell morphology, foraminal widening
• MRI protocol: Contrast-enhanced T1 with thin cuts through posterior fossa; FIESTA/CISS sequences for IAC; full spine survey

3. Tuberous Sclerosis Complex (TSC)

• TSC1 - chromosome 9q34.3 - hamartin
• TSC2 - chromosome 16p13.3 - tuberin (adjacent to PKD1; more severe phenotype, more SEN nodules, renal angiomyolipomas)
• Both products form a functional unit regulating the mTOR pathway

CNS Imaging Findings

• Hamartomatous cortical dysplasias; hallmark lesion; cause epilepsy
• CT: often calcified (higher density); may be occult early
• MRI: T2/FLAIR hyperintense; involves cortex + subcortical white matter; signal may invert (become T1 bright) as child matures

• Project into ventricles along the caudate eminences ("candle drippings" appearance)
• Calcify with age → T2 hypointense on MRI (hyperdense on CT)
• Stable, non-enhancing; typically benign

• Most important complication: arise from SENs at/near the foramen of Monro
• Enhancing mass; causes obstructive hydrocephalus
• WHO grade I tumour; surgical or mTOR inhibitor (everolimus) treatment
• MRI: T1/T2 heterogeneous, avid Gd enhancement; size >1 cm and growth are key criteria

Fig. 76.29 - Tuberous Sclerosis. (A) T2 axial: multiple cortical/subcortical tubers; bilateral lesions at foramina of Monro consistent with giant cell astrocytomas (arrows). (B) T2 axial: subependymal nodules projecting into ventricles; markedly hypointense calcified nodule (arrowhead). - Grainger & Allison's

• T2 hyperintense lines extending from ventricle to cortex
• Reflect abnormal neuronal migration; not visible on CT

Systemic Imaging Findings

4. Von Hippel-Lindau (VHL) Disease

• Type 1 (no phaeochromocytoma): haemangioblastomas + renal/pancreatic lesions
• Type 2 (with phaeochromocytoma): subdivided by presence of RCC

Imaging Findings

• Benign, slow-growing vascular tumours
• Sites: cerebellum (~50%, hemispheres >> vermis), spinal cord (intramedullary), medulla (area postrema)
• Classic MRI appearance: cyst with enhancing mural nodule (nodule is avid, cyst wall does not enhance)
• Solid variants occur (more common in brainstem)
• Spinal haemangioblastomas → syringomyelia (common)
• Screening: contrast-enhanced MRI brain + spine (pre + post T1 with thin posterior fossa cuts)

Fig. 99.17 - VHL: Multiple bilateral enhancing cerebellar haemangioblastomas. - Bradley & Daroff's

5. Sturge-Weber Syndrome

1. Port-wine naevus (facial capillary haemangioma - forehead/upper eyelid distribution; V1 territory)
2. Ipsilateral leptomeningeal angioma (parieto-occipital predominance)
3. Glaucoma (ipsilateral; two age peaks: infancy and late childhood)

Imaging Findings

• "Tramline calcifications" - gyriform cortical calcifications (visible by ~2 years)
• Leptomeningeal angioma may not be visible without contrast in early life
• Ipsilateral hemispheric atrophy in established disease

• Diffuse pial enhancement over affected hemisphere (variable thickness) - most sensitive finding
• Underlying cortical atrophy; T2 hypointensity within gyri (calcification)
• Ipsilateral choroid plexus enlargement - characteristic, due to collateral venous drainage
• Dilated transparenchymal medullary veins (T2 hypointense flow voids) communicating superficial-deep venous systems
• Bilateral involvement in ≥15% of patients (including some with unilateral nevus)
• "Burnt-out" cases: pial angioma may no longer enhance; shrunken calcified hemisphere remains
• Polymicrogyria may coexist

Fig. 76.30 - Sturge-Weber in a child with port-wine stain. (A) Coronal T1 post-contrast: enhancing pial angioma over atrophic right hemisphere; enlarged right choroid plexus; gyral calcification as T1 hypointense foci. (B) T2 axial: prominent superficial and ependymal veins (arrows). (C) Axial post-contrast T1: bilateral choroidal angiomas (arrows) plus pial angioma. - Grainger & Allison's

Quick-Reference Comparison Table

Additional / Less Common Phakomatoses

• Giant congenital melanocytic naevi (skin) + intracranial melanosis
• MRI: T1 shortening (melanin) in anterior/mesial temporal lobe, cerebellum, pons
• CT: areas of increased density (less conspicuous)
• Hydrocephalus from leptomeningeal involvement; rare malignant transformation

• Racemose (arteriovenous) malformations in retina
• Ipsilateral intracranial AVM (mid-brain/optic pathway); no treatment required unless symptomatic

• Posterior fossa malformations (Dandy-Walker), facial Haemangiomas, Arterial anomalies, Cardiac/eye anomalies, Sternal cleft

• Multiple basal cell carcinomas, odontogenic keratocysts
• Calcification of falx cerebri (pathognomonic on CT/skull XR)
• Medulloblastoma (desmoplastic type); bifrontal cortical dysplasia

Key Radiology Pearls

1. NF-1 UBOs: T2 bright, no enhancement, no mass effect → watch for change; if they enhance = suspect glioma
2. NF-1 "bare orbit": Sphenoid wing dysplasia on plain film/CT
3. TSC SEGAs: Grow at the foramen of Monro → obstructive hydrocephalus; any SEN >1 cm + enhancing = SEGA
4. TSC AML: Fat attenuation on CT (<-10 HU); spontaneous retroperitoneal haemorrhage ("Wunderlich syndrome") if >4 cm
5. VHL haemangioblastoma: Cyst + mural nodule in cerebellum of young adult → first think VHL (especially if multiple or spinal)
6. Sturge-Weber: Early MRI may be normal - pial enhancement is the earliest MRI sign, calcifications come later; enlarged ipsilateral choroid plexus is characteristic
7. NF-2: Any bilateral IAC masses = NF-2 until proven otherwise