Neurofibromatosis type 2: The role of imaging

Transcription

1 Neurofibromatosis type 2: The role of imaging Poster No.: C-1225 Congress: ECR 2012 Type: Educational Exhibit Authors: I. F. Uri, J. Chandra, P. Pretorius; Oxford/UK Keywords: Neoplasia, MR-Angiography, MR, CT, Neuroradiology spine, Neuroradiology brain DOI: /ecr2012/C-1225 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 31

2 Learning objectives Provide background information about neurofibromatosis type 2 (NF2) including genetics, mode of inheritance, clinical features and natural history Become familiar with the criteria used to make the diagnosis and the role of imaging in the diagnosis Understand the imaging protocols used in the diagnosis and follow up of NF2 and the role of imaging in managing these patients Become familiar with the wide range of imaging appearances encountered in cranial and spinal imaging in patients with NF2 Background NF2 is an autosomal dominant disease but approximately 50% of patients represent new mutations with no family history of the disease. The disease is caused by mutations of the NF2 gene on chromosome 22q. 2. It is characterized by neoplastic and dysplastic disorders of Schwann cells (schwannomas and schwannosis), meningeal cells (meningiomas and meningoangiomatosis), and glial cells (gliomas and glial microhamartomas). Further features include posterior lens opacities and cerebral calcifications. It is a disease associated with significant morbidity and mortality. Bilateral vestibular schwannomas are pathognomonic. Despite the similarity in terminology, the disease is a completely separate entity from NF1 which is a distinct neuro-cutaneous disorder resulting from a defect of a separate gene located on chromosome 17. In fact, neurofibromas are relatively rare in NF2. It affects approximately 1 in 25,000 live births, with wide phenotypic variability in age of onset and severity of symptoms, and nearly 100% penetrance by the age of 60. Page 2 of 31

3 Due to the complexity of the cases, the management of NF2 patients requires a large multidisciplinary team approach. Patients should be treated by specialists experienced in the management of NF2, including: neurosurgery, neurology, clinical genetics, radiology, ophthalmology, audiology, otolaryngology, plastic surgery, clinical psychology and clinical nurse specialists MISME is a useful mnenomic for remembering the main pathological features of the disease: MISME: Multiple Inherited Schwannomas, Meningiomas, Ependymomas ROLE OF IMAGING 1. Diagnosis Bilateral vestibular schwannomas (VS) are pathognomonic of NF2. It is present in 90-95% of NF2 patients at clinical presentation. Diagnostic criteria have been developed to allow clinical diagnosis of the condition in the minority of patients who do not have bilateral VS. The most commonly used is the Manchester Diagnostic Criteria, see Table 1. Table 3: Table 1: Manchester Diagnostic Criteria Page 3 of 31

4 References: Data source from : Evans DGR, Baser ME, O'Reilly B, et al. Management of the patient and family with neurofibromatosis 2: a consensus conference statement. Br J Neurosurg 2005; 19: Findings on neuroimaging studies can often raise the possibility of NF2 in cases where it has not been clinically suspected, for example a meningioma in a young patient or multiple meningiomas in any patient should prompt close inspection of the IAMs and investigation for any of the other diagnostic features of the disease. 2. Disease monitoring Once a diagnosis of NF2 has been made, routine surveillance scans are advised to monitor tumour progression. In our institution we perform the following surveillance strategy for NF2 patients: MRI brain 1-yearly MRI spine 3-yearly 3. Screening Early diagnosis can improve the clinical outcome of patients; this has led to development of criteria to identify people with NF2 prior to development of symptoms, see Table 2. Table 2: Table 2: Asymptomatic Population at Risk of Developing NF2 References: Data source from : Evans DGR, Baser ME, O'Reilly B, et al. Management of the patient and family with neurofibromatosis 2: a consensus conference statement. Br J Neurosurg 2005; 19: In the UK, current imaging recommendations for pre-symptomatic screening of children: Page 4 of 31

5 (a) Cranial and spinal MRI at the age of years, or earlier if there are specific symptoms (b) Follow-up scanning at regular intervals (2-3 years) 4. Surgical planning Goal of treatment is to preserve neurological function for as long as possible. (a) Vestibular schwannomas: Tumour size and growth rate do NOT predict hearing status, complete surgical resection is curative but timing of surgery remains controversial. This is due to the high operative risks (deafness, facial palsy or lower cranial nerve palsies), and these risks should be balanced against the natural history of the tumours. Conventional management strategies are either conservative or surgical resection if tumour size is 2-3cm and serviceable hearing is lost already, or rapid tumour growth identified. Patients with tumour larger than 3cm but maintained serviceable hearing should bear in mind that operative morbidity is higher with increased tumour size. An auditory brain stem implant can be performed at the same time as surgical resection of a VS to restore some useful hearing. This makes future MRI scanning more difficult due to significant artefact in the posterior fossa. Stereotactic radiosurgery is an alternative treatment option for patients with schwannomas measuring less than 3cm in diameter. The role of this treatment in NF2 is not currently well-defined. (b) Meningiomas: Cranial and spinal meningiomas can be resected. Meningiomas arising from the optic nerve sheath can not be resected without compromising vision and are rarely operated on. As in the case of schwannomas, stereotactic radiosurgery is an alternative treatment option for meningiomas 3cm in diameter in surgically inaccessible locations. (c) Ependymomas: Page 5 of 31

6 It is important to distinguish between the small - often multiple - very slowly growing enhancing intramedullary lesions commonly seen in NF2 and the more conventional appearing large heterogeneous ependymomas which are relatively rare. The former need no treatment apart from very occasional drainage of associated intramedullary cyst while the latter may require conventional neurooncological management with surgery, +/radiotherapy, +/- chemotherapy. 5. Eligibility for Avastin (Bevacizumab) Anti-VEGF monoclonal antibody - new systemic immunotherapy for a wide range of tumours. Evidence is emerging of radiological regression of VS and hearing improvement in some NF2 patients treated with Avastin. There is also anecdotal evidence of good clinical responses of other schwannomas including spinal schwannomas in NF2. The long term safety profile is unknown and concerns regarding wound healing limits its use in patients who are going to be considered for surgery in the near future. Very limited national funding is currently available for Avastin in this clinical setting and eligibility criteria are being developed. Imaging findings OR Procedure details Imaging protocol: Standardised imaging protocols are important to allow valid comparison on followup scans. As a time saving compromise, we obtain all sequences post gadolinium (Gd) adminstration (Table 1). This has the additional benefit of increased enhancement and therefore conspicuity of the tumours on the heavily T2 weighted sequences (FIESTA, CISS, B FFE) used in the posterior fossa due to the increased susceptibility effect on these gradient echo sequences. Page 6 of 31

7 Table 1: Table 1: Imaging Protocol Intracranial pathology: 1. Vestibular schwannoma (VS) Bilateral VS is the hallmark of NF2. Although benign and slow growing, their anatomical location lead to significant potential morbidity including deafness, facial nerve palsy and the effects of brain stem compression. VS arise in the internal auditory meatus (IAM) or its orifice, the porous acousticus Small VS can be located entirely within the IAM- intracanalicular, see Figure 1, and demonstrate uniform avid contrast enhancement Any patient with a single VS warrants close inspection of the contralateral IAM to exclude a second small VS that could be easily overlooked and point to a diagnosis of NF2 Page 7 of 31

8 Fig. 1: Figure 1: Bilateral VS within IAMs (arrow head) demonstrating uniform avid contrast enhancement Larger VS can widen the IAM and commonly extend into the cerebellopontine angle (CPA), see Figure 2. Page 8 of 31

9 Fig. 2: Figure 2: Upper row: The axial T2W images demonstrate bilateral VS extending into the CPA that are heterogeneously high signal (white arrows). Lower row: The high resolution axial T1W FS images demonstrate the masses filling both IAMs and extending into the CP angles. Patients with NF2 often have other intracranial tumours. In this case a small meningioma (black arrow) is seen at the petrous apex touching the right VS, there is a tiny right intracochlear schwannoma (white arrow) and there is a right trigeminal schwannoma (white arrowhead) arrising from the cisternal portion of the nerve. Larger schwannomas can demonstrate a more heterogeneous enhancement pattern, and develop cystic degeneration and haemorrhage. Intralabrynthine schwannomas are also a common feature in NF2 and can occur in the cochlea Figure 3 or vestibule. As the VS enlarges it can compress adjacent structures such as the middle cerebellar peduncles and pons, see Figure 3. Obstruction of the fourth ventricle will result in hydrocephalus. Page 9 of 31

10 Fig. 3: Figure 3: Large bilateral VS (star) with an intralabrynthine extension (curved arrow). Compression of the pons (straight arrow) and cerebellum is evident. Following radiosurgery (gamma knife) treatment of VS, the majority of tumours demonstrate central necrosis on T1W imaging, see Figure 4. This effect can be seen as early as one month after treatment. The majority of patients respond with a reduction in tumour volume, or stability. 10 % will demonstrate initial swelling after treatment but only a small proportion will demonstrate a significant increase in size after 2 years. Page 10 of 31

11 Fig. 4: Figure 4: One year following Gamma Knife therapy to the right-sided VS (arrow), the tumour developed central cystic degeneration. 2. Other cranial nerve schwannomas Schwannomas can also affect cranial nerves III to XII and demonstrate similar signal characteristics to VS. Examples of oculomotor nerve schwannomas are demonstrated in Figure 5 and Figure 6. Page 11 of 31

12 Fig. 5: Figure 5: Left large VS (star), a left oculomotor schwannoma (white arrow). Did you spot the left optic nerve sheath meningioma (white arrowhead)? Page 12 of 31

13 Fig. 6: Figure 6: Can you see the two schwannomas and two meningiomas on this image? Star= Vestibular schwannoma Long arrow= Occulomotor schwannoma Short arrows= meningiomas Trigeminal nerve schwannomasare the second most common cranial nerve schwannoma after VS. It can occur anywhere along its intra- or extracranial course but are most commonly identified in the following locations: Cisternal segment, see Figure 2 (white arrow head) Page 13 of 31

14 Meckel's cave at the petrous apex, where the trigeminal nerve ganglion lies, see Figure 7 and Figure 8 Following its division into the 3 branches via the cavernous sinus, see Figure 9. When the schwannomas become very large and touch each other, it can be difficult to distinguish their exact anatomical origin. Extracranial course Figure 10 Page 14 of 31

15 Fig. 7: Figure 7: A tiny enhancing nodule within the Meckel's cave (arrow)and small enhancing vestivular schwannoma (arrow head) Fig. 8: Figure 8: Small bilateral VS (curved arrows) and an avidly enhancing mass occupying but not expanding the right Meckel's cave (straight arrow), a typical appearance of a small trigeminal nerve schwannoma. Page 15 of 31

16 Fig. 9: Figure 9: When the schwannomas become very large and touch each other, it can be difficult to distinguish their exact anatomical origin. This patient has multiple bilateral schwannomas (stars) affecting the trigeminal and vestibular nerves demonstrated in the upper row of post gadolinium images. These are difficult to distinguish from each other. On the lower row, the axial T1W and post gad T1W fat saturation(fs)images demonstrate a large enhancing mass below the skull base encasing and displacing the internal jugular vein and internal carotid artery (white arrows). The vessel encasement is more suggestive of a meningioma rather than a schwannoma of one of the lower cranial nerves. Both of these types of tumour can grow through the jugular foramen and be difficult to distinguish radiologically. In the foramen magnum an intradural mass, either a meningioma or schwannoma (white arrowhead) pushes and compresses the medulla to the right. Page 16 of 31

17 Fig. 10: Figure 10: Large schwannoma within the right pterygoid muscles (star), presumably from the mandibular branch of the trigeminal nerve. Dennervation atrophy can occur in the muscles innervated by the affected cranial nerve, see Figure 11. Knowledge of the muscular innervation is key in detecting these changes eg the CN V supplies the muscles of mastication. Page 17 of 31

18 Fig. 11: Figure 11: Post gad T1W axial image demonstrates dennervation atrophy of the right temporalis muscle as a consequence to the large right trigeminal schwannoma (white arrowhead). A left VS (asterisk) and posterior fossa meningioma (white arrow) are noted. Facial nerve schwannomas within the IAM are impossible to distinguish from vestibular schwannomas unless very small at the time of presentation. They can be more clearly identified later in their petrous course or below the skull base as the nerve exits the stylomastoid foramen, see Figure 12. Page 18 of 31

19 Fig. 12: Figure 12: This post gad T1W FS image just below the skull base demonstrates an enhancing mass immediately below the left stylomastoid foramen (white arrow), in keeping with a facial nerve schwannoma. The white arrowhead in the right jugular bulb depicts a schwannoma of one of the lower cranial nerves. A subcutaneous schwannoma is noted in the scalp (black asterisk). Lower cranial nerve (IX-XI) schwannomas are demonstrated in the cerebello-medullary angle, the jugular foramen or below the skull base (Figure 12). Page 19 of 31

20 3. Intracranial meningiomas Meningiomas in NF2 are indistinguishable from sporadic meningiomas in imaging characteristics. They are typically avidly enhancing, well circumscribed extra-axial durally based or intraventricular mass lesions. Partially intraosseous skull base lesions e.g. sphenpoid winn meningiomas also occur in NF2. Multiple meningiomas are common, and the lesions can be large and cause occlusion of dural venous sinuses (Figure 13 and Figure 14). Fig. 13: Figure 13: Multiple meningiomas. This patient has blindness secondary to raised intra-cranial pressure (ICP). Page 20 of 31

21 Fig. 14: Figure 14: MRV showing multiple venous sinus occlusion secondary to meningiomas in figure 13. Patients with NF2 can get optic nerve sheath meningiomas, see Figure 5 (arrow head) and Figure 15. This is in contrast with NF1 patients who develop optic pathway gliomas. Intraventricular meningiomas are more common in NF2 than sporadic (16% v 5%), see Figure 13. Page 21 of 31

22 Fig. 15: Figure 15: Small right optic nerve meningioma (arrow). They arise from the tela choroidea or arachnoidal cell rest within the choroid plexus stroma. Meningiomas can demonstrate a more atypical appearance for example, the lesion in Figure 16 which has a large juxtatumoural cyst end a relatively small enhancing component. The clue is identification of a rim of displaced cortex confirming the extraaxial nature of the mass. Page 22 of 31

23 Fig. 16: Figure 16: Small typical (arrow) and large atypical cystic meningomas. Be aware that sporadic meningiomas are extremely rare in childhood - accounting for 2% of all brain tumours at this age. If detected, always consider a diagnosis of NF2. The patient in Figure 16 presented at the age of 17 with a predominantly cystic meningioma, multiple small meningiomas and bilateral small VS. 4. Meningioangiomatosis This is a rare lesion that can occur in NF2 or sporadically. Characterised by intracortical meningovascular fibroblastic proliferation and leptomeningeal calcification. On imaging there is leptomeningeal/cortical calcification on CT and MRI, avid leptomeningeal/cortical (gyriform) enhancement and sometimes adjacent oedema, atrophy, or cystic change, see Figure 17. Page 23 of 31

24 Fig. 17: Figure 17: NF2 patient with meningioangiomatosis. Spinal pathology: 1.Intramedullary tumours These tumours are usually ependymomas but astrocytomas can also occur. There are two distinct types of ependymoma in NF2 patients associated with differing prognosis: Better prognosis - Figure 18. Small (usually <1cm) Page 24 of 31

25 Well-defined centrally placed tumours Homogeneous contrast enhancing tumours No surrounding cord signal change (although may develop peritumoural cyst) Often involve craniocervical junction or upper cord Worse prognosis Less well defined, heterogeneous and extending over multiple vertebral levels. Heterogeneous contrast enhancement Associated signal change in cord Fig. 18: Figure 18: Large intramedullary mass expanding the upper cord (arrows). Did you spot the VS adjacent to the pons (curved arrow)? Page 25 of 31

26 Patients with mutliple small enhancing intramedullary tumours as described above are likely to have asymptomatic non-progressive ependymomas that will not require surgery. If a peritumoural cyst develops and is symptomatic they can be aspirated. 2. Extramedullary tumours: Intradural tumours Schwannomas Schwannomas (Figure 19, Figure 20 and Figure 21) usually arise in the dorsal sensory nerve roots of the spinal cord Asymptomatic or present with compressive symptoms or pain Well circumscribed, heterogeneous, intermediate signal T1, hyperintense T2, enhance, frequently multiple Meningioma Spinal meningiomas, more broad based, may be calcified. Can be difficult to distinguish from intradural schwannomas Extradural tumour: Spinal nerve or peripheral schwannoma Most commonly these are schwannomas but they can be difficult to distinguish from other more rarer peripheral nerve sheath tumours, such as neurofibomas, plexiform neurofibromas and plexiform schwannomas. Malignant transformation of peripheral nerve sheath tumours very rarely occur in NF2 (Figure 19). Page 26 of 31

27 Fig. 19: Figure 19: Multiple intra and extradural tumours and peripheral schwannomas. Page 27 of 31

28 Fig. 20: Figure 20: Multiple cauda equina intradural schwannomas (round lesions). Page 28 of 31

29 Fig. 21: Figure 21: Subtle intradural schwannomas (arrows). Conclusion Neurofibromatosis type 2 is a rare and complex disorder that should be managed by specialists in a tertiary centre. However since the diagnosis is often made on imaging, and sometimes unexpectedly, all radiologists who report cranial and spinal imaging studies should be aware of the common manifestations. Personal Information References Page 29 of 31

30 Evans DGR, Baser ME, O'Reilly B, et al. Management of the patient and family with neurofibromatosis 2: a consensus conference statement. Br J Neurosurg 2005; 19: Rennie ATM, Side L, Kerr RSC, Anslow P, Pretorius P. Intramedullary tumours in patients with neurofibromatosis type 2: MRI features associated with a favourable prognosis. Clinical Radiology (2) : Plotkin SR, Stemmer-Rachamimov AO, Barker FG, 2nd, Halpin C, Padera TP, Tyrrell A, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009; 361(4): Mautner VF, Nguyen R, Kutta H, Fuensterer C, Bokemeyer C, Hagel C, et al. Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2. Neuro Oncol. 2010;12(1):14-8. Mathieu D, Kondziolka D, Flickinger JC, Niranjan A, Williamson R, Martin JJ, et al. Stereotactic radiosurgery for vestibular schwannomas in patients with neurofibromatosis type 2: an analysis of tumor control, complications, and hearing preservation rates. Neurosurgery. 2007;60(3): Evans DGR, Moran A, King A, Saeed S, Gurusinghe N, Ramsden R. Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought. Otol Neurotol 2005; 26: Baser ME, Mautner VF, Parry DM, Evans DGR. Methodological issues in longitudinal studies: vestibular schwannoma growth rates in neurofibromatosis 2. J Med Genet 2005; 42: Ruggieri M, Iannetti P, Polizzi A, et al. Earliest clinical manifestations and natural history of neurofibromatosis type 2 (NF2) in childhood: a study of 24 patients. Neuropediatrics 2005; 36: Mautner VF, Lindenau M, Baser ME, et al. The neuroimaging and clinical spectrum of neurofibromatosis 2. Neurosurgery 1996; 38: Page 30 of 31

31 Evans DG, Watson C, King A, Wallace AJ, Baser ME. Multiple meningiomas: differential involvement of the NF2 gene in children and adults. J Med Genet 2005; 42: Samii M, Matthies C, Tatagiba M. Management of vestibular schwannomas (acoustic neuromas): auditory and facial nerve function after resection of 120 vestibular schwannomas in patients with neurofibromatosis 2. Neurosurgery 1997; 40: Patronas NJ, Courcoutsakis N, Bromley CM, Katzman GL, MacCollin M, Parry DM. Intramedullary and spinal canal tumors in patients with neurofibromatosis 2: MR imaging findings and correlation with genotype. Radiology 2001; 218: Lee M, Rezai AR, Freed D, Epstein FJ. Intramedullary spinal cord tumors in neurofibromatosis. Neurosurgery 1996; 38: Hagel C, Lindenau M, Lamszus K, Kluwe L, Stavrou D, Mautner VF. Polyneuropathy in neurofibromatosis 2: clinical findings, molecular genetics and neuropathological alterations in sural nerve biopsy specimens. Acta Neuropathol 2002; 104: Iwata A, Kunimoto M, Inoue K. Schwann cell proliferation as the cause of peripheral neuropathy in neurofibromatosis-2. J Neurol Sci 1998; 156: Page 31 of 31