Neurofibromatosis Type 2: Comprehensive Imaging Guide and Clinical Overview
Overview
Neurofibromatosis type 2 is an autosomal dominant tumor predisposition syndrome characterized by multiple neoplasms of the central and peripheral nervous system, most notably bilateral vestibular schwannomas.
The term neurofibromatosis type 2 differentiates this entity from type 1 based on its predominant involvement of cranial and spinal nerves and meninges rather than cutaneous neurofibromas.
The syndrome is caused by pathogenic variants in the NF2 gene on chromosome 22q12 encoding the tumor suppressor protein merlin, leading to loss of growth control in Schwann cells, meningeal cells, and ependymal cells.
Clinical presentation typically occurs in late adolescence or early adulthood with progressive sensorineural hearing loss, tinnitus, and balance disturbances due to bilateral vestibular schwannomas.
Additional clinical findings include cranial neuropathies, myelopathy from spinal tumors, peripheral neuropathy, and ocular abnormalities such as juvenile posterior subcapsular cataracts and retinal hamartomas.
The inheritance pattern is autosomal dominant with high penetrance, though a substantial proportion of cases arise from de novo mutations, including mosaic forms with asymmetric or segmental tumor burden.
Definite diagnostic criteria include bilateral cranial nerve VIII schwannomas on MRI or a first-degree relative with neurofibromatosis type 2 plus characteristic intracranial or intraspinal tumors or juvenile lens opacity.
Key Imaging Features
Neurofibromatosis type 2 is primarily diagnosed and monitored by imaging, with hallmark findings involving the cerebellopontine angle, internal auditory canals, and spinal axis.
Key radiological findings include the following, each described as a complete sentence for clarity:
• Bilateral enhancing masses centered on the internal auditory canals with extension into the cerebellopontine angles on contrast-enhanced MRI are characteristic vestibular schwannomas and represent the imaging signature of neurofibromatosis type 2.
• Vestibular schwannomas in this syndrome typically widen the internal auditory canal and form an “ice cream cone” configuration, with the canal component as the cone and the cerebellopontine angle portion as the ice cream.
• On T1-weighted MRI, vestibular schwannomas are usually iso‑ to hypointense to brain parenchyma and demonstrate strong, often homogeneous post-contrast enhancement, with larger lesions showing cystic or heterogeneous components.
• On T2-weighted MRI and FLAIR, vestibular schwannomas are hyperintense relative to adjacent brainstem, often accompanied by mass effect on the brainstem and fourth ventricle in large tumors.
• Multiple intracranial meningiomas are prevalent, typically seen as strongly enhancing extra-axial, dural-based masses along the falx, convexities, sphenoid wing, tentorium, and skull base with possible dural tails.
• Spinal imaging frequently demonstrates multiple intradural extramedullary tumors, predominantly schwannomas and meningiomas, often located at multiple levels in the cervical and thoracic spine and sometimes forming “string-of-beads” patterns.
• Spinal schwannomas often arise from dorsal nerve roots, show dumbbell morphology with widening of neural foramina, and enhance intensely on contrast-enhanced T1-weighted MRI.
• Spinal meningiomas in neurofibromatosis type 2 are usually intradural extramedullary, dorsal or lateral to the cord, strongly enhancing, and can cause smooth indentation and displacement of the spinal cord.
• Intramedullary ependymomas, particularly in the cervical cord, are common, presenting as expansile cord lesions with T2 hyperintensity, variable enhancement, associated cysts, and sometimes hemorrhagic or calcific foci.
• Additional cranial nerve schwannomas involving the trigeminal, facial, oculomotor, abducens, and lower cranial nerves may be visualized along cisternal segments, within skull base foramina, or in the cavernous sinus region.
• Peripheral nerve and plexus schwannomas may appear as fusiform, well-defined masses along major nerve trunks and brachial or lumbosacral plexus on MR neurography, with target or fascicular appearance on high-resolution sequences.
• Intracranial calcifications, though less common, may be identified on CT within meningiomas or as non-tumoral parenchymal or dural calcifications and can be a useful clue when vestibular schwannomas are small or occult on routine imaging.
• Ocular and orbital involvement may be subtle but can include optic nerve sheath meningiomas and retinal hamartomas, detectable on high-resolution orbital MRI with fat suppression and contrast.
• Whole-neuroaxis tumor burden often evolves over time, with progressive enlargement of existing lesions and emergence of new schwannomas, meningiomas, and ependymomas, making serial imaging crucial for longitudinal assessment.
Pathophysiology
The imaging manifestations of neurofibromatosis type 2 reflect biallelic inactivation of the NF2 tumor suppressor gene in Schwann cells, arachnoid cap cells, and ependymal cells, leading to uncontrolled cellular proliferation.
Loss of merlin disrupts cytoskeletal organization and multiple signal transduction pathways, including those governing contact inhibition, resulting in the formation of schwannomas along cranial and spinal nerves, especially the vestibular division of cranial nerve VIII.
At the internal auditory canal and cerebellopontine angle, proliferating Schwann cells encase and expand the vestibular nerve, producing the characteristic enhancing masses that widen the bony canal and displace the brainstem, which explains the “ice cream cone” appearance on MRI.
Meningiomas arise from neoplastic arachnoid cap cells along dural reflections, explaining their dural-based, extra-axial location and broad-based attachment; their rich vascularity accounts for intense homogeneous enhancement on post-contrast imaging.
Multiple spinal meningiomas and schwannomas produce multilevel extramedullary compression, leading to cord flattening and displacement; the slow, indolent growth explains the often marked mass effect contrasted with relatively preserved cord signal early in disease.
Ependymomas form from transformed ependymal cells lining the central canal, particularly in the cervical spinal cord, producing intramedullary expansion, T2 hyperintensity, cyst formation, and occasional hemorrhage with susceptibility artifacts on gradient-echo or SWI sequences.
The frequent coexistence of schwannomas, meningiomas, and ependymomas within the same patient reflects the shared underlying NF2 pathway deregulation rather than separate etiologies, providing a pathophysiologic basis for the classic triad on imaging.
Mosaic forms of neurofibromatosis type 2 show restricted distribution of mutated cells, leading to asymmetric or segmental tumor burden, which may manifest radiologically as unilateral or regionally clustered tumors rather than diffuse bilateral involvement.
Chronic compression by vestibular schwannomas results in secondary degeneration of cochlear and vestibular structures, correlating with progressive hearing loss and vestibular dysfunction, but imaging often shows only subtle signal changes in the labyrinthine fluids despite marked clinical symptoms.
Tumor vascularity and breakdown of the blood–brain and blood–nerve barriers underpin the avid gadolinium enhancement of schwannomas and meningiomas; cystic degeneration and necrosis in larger lesions explain heterogeneous enhancement patterns and internal fluid–fluid levels on advanced imaging.
Differential Diagnosis
The main imaging differentials for the findings in neurofibromatosis type 2 include sporadic vestibular schwannoma, neurofibromatosis type 1, schwannomatosis, multiple meningiomatosis, and other causes of intramedullary spinal tumors.
Sporadic unilateral vestibular schwannoma typically presents as a single lesion without additional intracranial or spinal tumors; the presence of bilateral vestibular schwannomas plus multiple spinal and intracranial lesions strongly favors neurofibromatosis type 2 over sporadic disease.
Neurofibromatosis type 1 demonstrates multiple cutaneous neurofibromas, plexiform neurofibromas, and characteristic brain T2 hyperintense “unidentified bright objects” in the basal ganglia and cerebellum, rather than bilateral vestibular schwannomas and numerous meningiomas, which are hallmark features of type 2.
Schwannomatosis is characterized by multiple peripheral and spinal schwannomas without vestibular schwannomas and without the high prevalence of meningiomas; identification of bilateral vestibular schwannomas on internal auditory canal MRI essentially excludes pure schwannomatosis and supports neurofibromatosis type 2.
Multiple meningiomatosis may mimic the intracranial findings but generally lacks vestibular schwannomas and intramedullary ependymomas; careful inspection of the internal auditory canals and spinal cord on thin-slice MRI is critical to differentiate it from neurofibromatosis type 2.
Other intramedullary spinal tumors such as astrocytomas or solitary sporadic ependymomas tend to present as single lesions rather than multiple ependymomas combined with a background of extramedullary schwannomas and meningiomas along the neuroaxis.
Metastatic disease with multifocal spinal and intracranial lesions generally demonstrates different enhancement patterns, aggressive bone involvement, and a clinical history of systemic malignancy, in contrast to the dural-based and neurogenic distribution of tumors in neurofibromatosis type 2.
Leptomeningeal carcinomatosis or lymphoma can cause diffuse leptomeningeal enhancement but usually lacks discrete bilateral internal auditory canal schwannomas and tends to produce nodular or sheet-like enhancement rather than well-formed encapsulated nerve sheath tumors.
Imaging Protocols and Techniques
Imaging of neurofibromatosis type 2 should be systematic and encompass the entire neuroaxis, with tailored MRI protocols optimized for tumor detection, characterization, and longitudinal follow-up.
Baseline evaluation should include contrast-enhanced MRI of the brain with internal auditory canal protocol and contrast-enhanced whole-spine MRI to document the full extent of vestibular schwannomas, meningiomas, schwannomas, and ependymomas.
For the brain and cerebellopontine angle, recommended sequences include high-resolution T1-weighted and T2-weighted images, FLAIR, diffusion-weighted imaging, and post-gadolinium T1-weighted images with fat saturation in axial and coronal planes focused on the internal auditory canals.
Thin-slice (typically 0.5–1 mm) 3D T2-weighted steady-state sequences such as FIESTA, CISS, or DRIVE are highly valuable for delineating small intracanalicular vestibular schwannomas, cranial nerve anatomy, and relationships within the cerebellopontine angle cistern.
For spinal imaging, protocols should include sagittal and axial T1-weighted and T2-weighted sequences, with post-contrast T1-weighted images with fat suppression to highlight enhancing intradural extramedullary tumors and intramedullary lesions along the entire cervical, thoracic, and lumbar spine.
Slice thickness of 3 mm or less and coverage from the craniocervical junction through the sacrum are recommended to avoid missing small schwannomas in neural foramina or subtle intramedullary ependymomas.
CT of the temporal bones is useful for assessing bony internal auditory canal widening, skull base remodeling, and intracranial calcifications within meningiomas or non-tumoral foci that can provide supportive evidence of the syndrome.
MR neurography with high-resolution, fat-suppressed T2-weighted and diffusion-based sequences can be considered to evaluate peripheral nerve and plexus involvement, especially in symptomatic limbs or when planning surgical approaches.
Follow-up imaging is typically performed with contrast-enhanced brain MRI and internal auditory canal sequences at 6–12 month intervals, with spine MRI added when spinal tumors are present, to monitor tumor growth rates and treatment response.
Imaging pearls include consistently using the same scanner and protocol for longitudinal volume assessment of vestibular schwannomas, measuring maximal craniocaudal, anteroposterior, and transverse dimensions, and when possible calculating volumetric changes to guide intervention thresholds.
Common pitfalls include overlooking very small intracanalicular schwannomas when only routine brain MRI is performed without dedicated internal auditory canal thin sections, misclassifying multiple meningiomas without carefully assessing for vestibular schwannomas, and underestimating spinal tumor burden when imaging is limited to symptomatic levels.
Radiologists should explicitly report tumor number, size, location, relationship to critical neurovascular structures, associated mass effect, presence of cystic or hemorrhagic components, and any interval growth, as these details are central to multidisciplinary management in patients with neurofibromatosis type 2.
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