Radiologic findings of the head and spine in neurofibromatosis 1 (NF1) in Northern Finland

Eeva-Liisa Leisti

Department of Diagnostic Radiology, University of Oulu
Department of Clinical Genetics, University of Oulu
Oulu University Hospital, Oulu University Hospital

Abstract

Imaging of the head and spine with CT and/or MRI was performed on 125 Northern Finnish NF1 patients to evaluate the CNS lesions in patients of different ages and their role in diagnosis and follow-up.

Manifestations of NF1 in the head were more common in children than in adults. 77% of the children and 33% of the adults had T2 hyperintense brain lesions. Optic gliomas were present in 29% of the patients, in 44% of the children and 10% of the adults. 8% of the patients had other intracranial tumours. Spinal lesions were seen in 75% of the patients.

Hyperintense T2 lesions were most common in the age group of 5 to 9 years. During follow-up of the children, the lesions diminished in 25%, remained unchanged in 36%, showed mixed behaviour in 20% and disappeared in 10%. In 15% they increased in size and number. In one patient a malignant tumour developed at the site of a T2 lesion.

Optic gliomas were located intraorbitally and/or prechiasmally in 94%, chiasmally and/or at the hypothalamus in 58% and in other optic areas in 14% of the patients. 52% of the intraorbital gliomas were bilateral. The gliomas remained unchanged in 68% of the children and 50% of the adults. Other lesions included plexiform neurofibromas, sphenoid bone dysplasias and hydrops of the optic sheath. Optic glioma was more common in children with T 2 hyperintense brain lesions than without them.

The other brain tumours included six astrocytomas, including an affected mother and her son. In one patient the astrocytoma regressed spontaneously. Hydrocephalus was seen in 5% of the patients.

T2 hyperintense brain lesions were more common and numerous in macrocephaly; all macrocephalic children, but only 59% of the normocephalic children were affected. All children without T2 lesions were normocephalic. The brain measurements did not reveal any specific area to be responsible for macrocephaly.

Spinal postural changes and dural ectasias were more common in adults. The spinal cord was affected in two patients. Spinal neurofibromas were seen in 19% of the children and 55% of the adults. Even young children may have severe manifestations. In one family a rare familial type of spinal neurofibromatosis (FSNF) was observed in four adults with bilateral spinal neurofibromas at all levels of the spine.

Although both CT and MRI were valuable in CNS imaging, MRI proved to be the method of choice in detecting T2 hyperintense brain lesions, in evaluating the intracranial extent of optic gliomas and hydrops of the optic sheath and lesions of the spinal cord and nerves. MR imaging proved necessary for evaluating the extent of NF1 manifestations and helpful in the diagnosis, screening and follow-up of NF1 patients.

Dedication

To my family

Table of Contents
Acknowledgements
Abbreviations
1. Introduction
2. Review of the literature
2.1. Classification and diagnostic criteria of neurofibromatoses
2.2. Genetics and occurrence of neurofibromatoses
2.3. Role of radiologic imaging in NF1
2.3.1. CT and MRI in the diagnosis and follow-up of NF1
2.3.2. MR spectroscopic and diffusion studies and PET
2.4. NF1 as a clinical entity
2.4.1. Main diagnostic signs
2.4.2. Other somatic manifestations
2.4.3. Neuropsychologic manifestations
2.5. Brain manifestations in NF1
2.5.1. T2 hyperintense lesions of the brain
2.5.2. T1 hyperintense lesions of the brain
2.5.3. Brain tumours
2.5.4. Hydrocephalus
2.5.5. Other lesions of the brain
2.5.6. Vascular lesions of the head and neck
2.6. Manifestations of the optic pathways and orbits in NF1
2.6.1. Anatomy and imaging of the optic pathways
2.6.2. Optic pathway gliomas
2.6.3. Orbital plexiform neurofibromas
2.7. Bony lesions of the skull in NF1
2.8. Macrocephaly in NF1
2.8.1. Morphometric studies
2.8.2. Significance of macrocephaly
2.9. Spinal manifestations in NF1
2.9.1. Lesions of the bony spine
2.9.2. Dural ectasias and meningocele
2.9.3. Neurofibromas
2.9.4. Spinal nerve plexiform neurofibromas
2.9.5. Intramedullary tumours
2.9.6. Other spinal manifestations
2.9.7. Familial spinal neurofibromatosis (FSNF)
3. Aims of the study
4. Patients and methods
4.1. Patients
4.2. Radiologic methods
4.2.1. Computed tomography (CT)
4.2.2. Magnetic resonance imaging (MRI)
4.2.3. Plain X-rays, myelography and PEG
4.2.4. Cerebral measurements
4.2.5. Statistic methods
5. Results
5.1. General
5.1.1. CT and MRI of the head
5.1.2. CT and MRI of the spine
5.2. Imaging findings of the head and brain in NF1
5.2.1. General
5.2.2. T2 hyperintense lesions of the brain
5.2.3. Manifestations of the optic pathways and orbits
5.2.4. Other brain tumours
5.2.5. Other manifestations of the head
5.2.6. Macrocephaly
5.3. Imaging findings of the spine in NF1
5.3.1. General
5.3.2. Manifestations of the bony spine
5.3.3. Dural ectasias
5.3.4. Spinal neurofibromas
6. Discussion
6.1. General
6.2. Presence of CNS lesions in NF1
6.3. Brain manifestations in NF1
6.3.1. T2 hyperintense brain lesions: localization, appearance and development
6.3.2. Significance of T2 hyperintense brain lesions
6.3.3. Brain tumours
6.3.4. Other manifestations of the brain and head
6.4. Manifestations of the optic pathways and orbits in NF1
6.4.1. Optic gliomas
6.4.2. Other orbital findings
6.5. Macrocephaly in NF1: Nature and associations with other CNS manifestations
6.6. Spinal manifestations in NF1
6.6.1. Manifestations of the bony spine and CSF spaces
6.6.2. Spinal neurofibromas
6.6.3. Familial spinal neurofibromatosis (FSNF)
6.6.4. Other spinal manifestations
6.7. Role of radiologic imaging in the study and diagnosis of NF1
7. Summary and conclusions
References
List of Tables
1. Occurrence, localization and follow-up of T2 hyperintense brain lesions in NF1 in previous studies.
2. Occurrence, localization and follow-up of optic glioma in NF1 in previous studies.
3. Occurrence, localization and follow-up of spinal lesions in NF1 in previous studies.
4. Imaging abnormalities of the head in 124 patients with NF1, including 59 children (< 18 years of age) and 65 adults (18 years or older).
5. Appearance of T2 hyperintense lesions in NF1 patients examined with MRI, including 39 females and 53 males.
6. Localization of T2 lesions in 36 affected NF1 children according to sex.
7. Mean number of T2 hyperintense lesions per affected NF1 patient according to age and sex (n = 51).
8. NF1 patients affected with optic glioma according to sex and age at the time of initial CT/MRI imaging (n = 124).
9. Localization and extent of optic lesions in 36 NF1 patients with optic glioma according to age and sex. (F = female, M = male, ch = chiasm, ht = hypothalamus, o.n = optic nerve, o.tr. = optic tract)
10. Histologically verified brain tumours in six patients with NF1.
11. Comparison of mean brain measurements in 14 macrocephalic and 14 sex- and age-matched normocephalic children with NF1.
12. Spinal abnormalities seen in 76 NF1 patients examined with CT and/or MRI in children (< 18 years, n = 31) and adults (18 years or older, n = 45).
List of Figures
1. The brain measurements of MRI images in macrocephaly (see Table 13).
2. Typical T2 hyperintense lesions (thick arrows) bilaterally in the globus pallidus and a small lesion behind the trigonum of the right lateral ventricle on axial MRI scans of a 13-year-old girl with NF1. A plexiform neurofibroma on the left side frontally (thin arrow). – (a) T2-weighted image (SE, 2200/80, 5 mm); (b) proton density image (2200/15); (c) T1-weighted image (600/15). A = anterior, R = right.
3. Multiple T2 hyperintense lesions (arrows) in an 11-year-old boy with NF 1. There are diffuse cerebellar lesions, lesions in the pons and crus cerebelli (a,b), a lesion in the right globus pallidus (c) and sharply demarcated lesions anteriorly in the corpus callosum (c,d). – T2-weighted axial MR images (TSE, 3500/93, 5 mm).
4. Diffuse bilateral T2 hyperintense lesions (arrows) on hippocampal regions bilaterally (a,b) in a 27-year-old female patient with NF 1. – T2-weighted axial MR images (TSE, 3500/93, 5 mm).
5. Hyperintense lesions (arrows) bilaterally in globus pallidus on MRI (a) of a 7.6-year-old girl with NF1. Two years earlier, hypodense areas were seen in the same regions on CT (b) – (a) an axial proton-weighted MR image (FSE, 3500/14, 5 mm) and (b) a non-enhanced axial CT scan (10mm).
6. Reduction of T2 hyperintense lesions during three-year follow-up in a boy with NF1. Several lesions (thick arrows) are seen in both the cerebrum (a, b) and the cerebellum (c) on MR images taken at the age of 3.1 years. On control scans (d, e, f) taken three years later, only small lesions are seen in the cerebellum (thin arrows). A chiasmal tumour (arrow) is also seen (e). – Axial T2-weighted images (SE, 2200/80, 5 mm).
7. Variably behaving T2 hyperintense lesions (thick arrows) in a girl with NF 1 during follow-up for 3.7 years (a, b, c, d, e). A tumour (thin white arrow) diagnosed as glioblastoma multiforme developed in the frontal horn of the right lateral ventricle. – T2-weighted axial MR images at the ages of 3.0 (a), 5.2 (b), 5.3 (c), 6.3 (d) and 6.7 (e) years; TSE, 3500/93, 5 mm. The same patient also had a widespread optic glioma (Fig. 7). The intraventricular tumour seen on a non-enhanced T1-weighted axial image (f) (SE, 600/15).
8. A thickened and tortuous left optic nerve (arrow) (a,c) and an asymmetrically enlarged optic chiasm (asterix) (b) in a 3-year-old girl with NF1. – T1-weighted sagittal (a) and coronal (b) MR images (SE, 570/15, 5 mm) and a proton density axial image (2300/15) (c). S = superior, A = anterior, R = right.
9. An optic glioma affecting the intracanalicular (arrows) (a) and prechiasmal (arrows) (b) parts of the optic nerves of a 16-year-old boy with NF1. The chiasma (arrow) (c) is also affected. The prechiasmal parts of the nerves and the chiasm are slightly hyperdense. The intraorbital optic nerves (thin arrows) (d) appear thin. Bilateral papillary atrophy had been detected three years earlier. – Non-enhanced axial CT scans (4 mm).
10. An enhancing hypothalamic tumour (arrows) (a,b) compressing the third ventricle in a 3.2-year-old boy with NF 1. Two years after radiotherapy, no signs of the tumour were visible (c). – Non-enhanced (a) and enhanced (b, c) coronal T1-weighted images (SE, 690/15, 5 mm; Magnevist 3 ml i.v). The patient also had bilateral optic nerve glioma (Fig. 12) and multiple T2 hyperintense brain lesions.
11. A widespread optic glioma in a 20-year-old male NF1 patient. Tortuous, slightly thickened optic nerves (black arrows) up to the enlarged optic chiasm (white arrow) are seen (a, b, c). There is a diffuse T2-hyperintense lesion (asterix) (b) in the right optic tract at the site of the calcified area (black arrow) seen earlier on CT (d). None of the lesions enhanced with contrast, and they remained unchanged during MRI follow-up for three years. Thickening of the optic nerves (black arrows) had not progressed since the previous CT over 12 years earlier (d). – T2-weighted axial MR image (a) (FSE, 3500/ 88, 5 mm), proton density images (b, c) (3500/14), and enhanced CT images (d, e) (4 mm, Urografin 60% I/ ml 40 ml i.v.).
12. Bilateral optic thickening with an enhancing tumour of the right optic nerve (thick arrow) and ectatic dilatation of the left optic sheet (long arrow) (a) in a 2.9-year-old boy with NF 1. Enhancement of the right, 12 mm thick tortuous optic nerve is mostly peripheral (short arrows, b), whereas the left, 8 mm thick nerve is surrounded by a hypodense zone that corresponds to the ectatic optic sheath. The patient also had a thickened chiasm, a hypothalamic tumour (see fig. 10) and several T2 hyperintense brain lesions. – Axial non-enhanced (a) and enhanced (b) CT images (2mm; Ultravist 300 mg I / ml 30 ml i.v.).
13. Ectatic dilated optic sheaths (thick arrows) and thickening of the posterior part of the right intraorbital optic nerve (thin arrow) in a 5.4-year-old boy with NF 1. The finding remained unchanged during follow-up for two years. – T2-weighted axial MR image (TSE, 3500/ 93, 5 mm).
14. Thickening and tortuosity of the whole left optic nerve (thick black arrows), asymmetry of the bony orbits and edema of the upper right eyelid are seen on axial CT images (3 mm) (a, b) in a three-year-old boy with NF 1. On the right, the optic foramen and the superior orbital fissure were fused (asterix). On contrast-enhanced CT images (5 mm, Omnipaque 300 mg I/ ml) (c, d) enhancement of the prechiasmal optic nerves and the chiasm is seen (white arrows). The affision of the left optic nerve and chiasm (white arrows) is well demonstrated on enhanced T1-weighted MR images (SE, 600/15, 5 mm, Magnevist 4 ml i.v.) (f, g). The patient also had several T2 hyperintense brain lesions (Fig. 6).
15. Bilateral plexiform neurofibromas (arrows) lateral to the orbits in a 44-year-old female patient with NF 1. – T2-weighted axial MR image (TSE, 3500/ 95, 5 mm).
16. A spontaneously regressing pilocytic astrocytoma in a boy with NF 1. On a contrast-enhanced CT image (10 mm, Urografin 60% 50 ml i.v.) (a) of the boy at the age of 8.3 years, an enhancing mass lesion (short arrow) surrounded by edema is seen on the left side. Biopsy revealed a pilocytic astrocytoma. On the CT scan (b) at the age of 9.7 years, the left-sided lesion has almost disappeared, and there is a new mass lesion (long arrow) on the right (normal brain tissue at biopsy). Both lesions are nearly invisible on CT taken at the age of 11.3 years (c), and on T2-weighted (SE, 3500/95, 5 mm) MR images (d, e) at the age of 20 years, only small hyperintense areas on both sides, consistent with brain biopsy sites, are seen (arrows).
17. Development of a malignant tumour at the site of a previous T2 hyperintense lesion in a boy with NF 1. A the age of 6.6 years, only slight asymmetry of the lateral ventricles is seen on CT (a). On MR images at the ages of 12.3 and 16.5 years, diffuse hyperintensity (arrow) in the right trigonal area is visible (b, c), and dilatation of the lateral ventricles had developed. The patient also had diffuse hyperintensity around the cerebral aqueduct (Fig. 18). Six months later, MRI revealed a 5 cm tumour (black arrow) surrounded by edema (glioblastoma multiforme at operation) (d). – Enhanced CT image (8 mm, Omnipaque 300 mg I/ ml 30 ml i.v.) (a), T2-weighted MR image (SE, 3500/93, 5 mm) (b), T2-weighted MR images (SE, 4000/114, 4 mm) (c,d).
18. Hyperintensity (arrow) around the upper part of the aqueduct is seen on a T2-weighted image (TSE, 3500/93, 5 mm) (a) a boy aged 12.3 years. Dilated third and lateral ventricles are seen. Hydrocephalus is also seen in a T1-weighted sagittal image (b) (SE, 570/15, 5 mm), no tumorous lesions are seen around the aqueduct (arrow).
19. Dilated cervical CSF spaces (long arrows) and concavity of the posterior parts of the vertebral bodies (short arrows) in a symptom-free girl aged 10.8 years (a), and a male aged 37 years (b). The spinal cords were normal. In patient (b), thoracic kyphoscoliosis was also found. – T2-weighted sagittal MR images (SE, 2300/103, 3 mm).
20. Dilated lumbar spinal canal with a wide dural sac and concavity of the posterior parts of the vertebral bodies (arrows) are seen on a plain film (a) and myelography (b) at the age of 4.6 years in a boy with NF 1. The same finding is shown on a sagittal T2-weighted MR image (TSE, 2500/103, 4 mm) (c) of the same patient at the age of 16.7 years.
21. Multiple cervical intra- and extraspinal tumours in a 24-year-old male patient with NF1. Enhancing intramedullary tumours (white arrows) and subcutaneous tumours (black arrows) are seen on sagittal non-enhanced (a) and enhanced (b) T1-weighted MR images (SE, 500/15, 3 mm; Magnevist 15 ml i.v.). A large number of intra- and extraspinal tumours are also visible on a coronal T2-weighted image (2200/90) (c), and there is also a small hyperintense lesion in the cerebellum (arrow). Symmetric neurofibromas of the spinal nerves (arrows) on a T2-weighted coronal image (d).
22. a–c. Coronal T1 weighted non-enhanced MR images (SE, 500 /15, 3 mm) (a, b) of the cervical spine of four adult female patients (1–4) in the family with familial spinal neurofibromatosis show several bilateral extradural intraspinal neurofibromas (white arrows) compressing the spinal cord. Extraspinal tumours are also seen in all patients. Several small bilateral extraspinal neurofibromas (white arrows) are seen in the middle and lower parts of the thoracic spine in all of the four patients on T1-weighted MR images (c). Patient 2 also has a paraspinal mass on the right ( c 2.2).
22. d–e. T1-weighted coronal (d) and T2-weighted sagittal MR images (SE, 5000/105, 4 mm) (e) of the lumbar spine of the same patients show numerous bilateral extradural intra- and/or extraspinal tumours (black arrows) in all patients. There is a dumb-bell type of tumour (small white arrows) (d 3) and scalloping of the posterior parts of the vertebral bodies (e). – Not all tumours are marked.
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