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Multiple inherited Schwannomas, meningiomas, and ependymomas (MISME): A case report on rare case of neurofibromatosis type 2 tumors
Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 10 (2017) 40–43
Contents lists available at ScienceDirect
Interdisciplinary Neurosurgery: Advanced Techniques and Case Management journal homepage: www.inat-journal.com
Technical Notes & Surgical Techniques
Multiple inherited Schwannomas, meningiomas, and ependymomas (MISME): A case report on rare case of neurofibromatosis type 2 tumors Ahmad Faried, MD, PhD a,⁎, Guata Naibaho, MD a, Rully Hanafi Dahlan, MD, MSc b, Roland Sidabutar, MD, MSc a, Sevline Estethia Ompusunggu, MD, MSc b, Muhammad Zafrullah Arifin, MD, PhD a a b
Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, Indonesia Subdivision of Neurospine, Peripheral Nerve and Pain, Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, Indonesia
a r t i c l e
i n f o
Article history: Received 23 May 2017 Revised 31 May 2017 Accepted 11 June 2017 Available online xxxx Keywords: Neurofibromatosis type 2 MISME syndrome Rare case report
a b s t r a c t Neurofibromatosis type 2 (NF-2) is an autosomal dominant inheritance, chromosome 22q12 mutations in peripher and central nervous systems. Several literatures have discussed rare cases of triple NF-2 tumor, known as multiple inherited Schwannomas, meningiomas and ependymomas or MISME. Incidence of MISME reported from many country, but never been reported from Indonesia. Hopefully the MISME presence can be more revealed in our country and adding the evidence in world literature. A 15-year-old boy presented to our center with a progressive bilateral hearing loss for 2 years and started to experience weakness of both lower extremities since 1.5 years. Patient underwent both craniotomy intracranial and spinal tumor removal. Histopathological result showed Schwannomas, meningiomas and ependymoma. Diagnosis of MISME was made and had been treated with excellent clinical outcome. We are reporting a rare case of MISME syndrome, which is an extremely exceptional case in our center due to rare occurrence of MISME and the need to confirm NF-2 diagnosis using molecular investigations. © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction
2. Case report
Neurofibromatosis (NF) is a syndrome of autosomal dominant inheritance and characterized by the neural crest benign tumors development. Mutations in the NF type 2 (NF-2) gene are found in the majority of benign nervous system tumors. NF-2 is rare with an incidence of 1:37,000 [1]. It is marked by bilateral vestibular Schwannoma alongside Schwannoma of other craniospinal and peripheral nerve, craniospinal meningiomas and ependymomas of the spinal cord. NF-2, also referred as MISME syndrome for multiple inherited Schwannomas, meningiomas and ependymomas, is caused by mutations of a tumor-suppressor gene, the “Merlin” on chromosome 22q122 [1]. MISME is rare disorder, estimated 1 in 33,000 incidence and 1 in 60,000 prevalence [2]. Male and female are approximately equally affected. This syndrome is commonly seen in 2nd and 3rd decades, mostly between 16–24 years old. Almost 50% of cases are familial, other 50% are sporadic in nature as result of new mutations [2]. However, the incidence of MISME never been reported from Indonesia. Hopefully our case could add the evidence of MISME in world literature.
A 15 years old boy presented with progressive bilateral hearing loss for 2 years and weakness of both lower extremities since 1.5 years ago (Fig. 1A). Neurological examination revealed weak muscle strength of 2/5 and 3/5 in his left and right lower limb. His audiometry results presented severe sensorineural hearing loss (SNHL) of right ear and moderate on left ear. The brain magnetic resonance imaging (MRI) showed isointense well-defined mass on T1/T2 and postcontrast enhancement. These masses resided in bilateral cerebellopontine angles affecting acoustic nerves, causing enlargement of internal meatus canal (Fig. 1B). Spine MRI showed a dumbbell shaped mass at vertebral thoracal (VT) 8 level and enhanced with contrast; lesion VT 9–11 which also significantly compressed the spinal cord, presenting syrinx on VT 5–7 and VT 11–12 (Fig. 1C). Craniotomy tumor removal (CTR) with standard lateral suboccipital approach was performed (Fig. 2A–B) and we found two grayish solid mass (Fig. 2C–D) defined borders totally removed. Histopathological result revealed encapsulated of pure Schwann cells growing around the nerve. It contained blood vessels and had areas of sheets in intertwining fascicles (Antoni A) and looser arrangements (Antoni B) (Fig. 2E–F). Two months after CTR, we performed laminectomy tumor removal and posterior stabilization. The spinal tumors were found in 3 different places: 1.5 cm diameter mass alongside the left radix, well circumscribed, white colored and soft to hard in consistency (Fig. 3A–B) at level VT 8; a tumor directly
⁎ Corresponding author at: Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Jl. Pasteur No. 38, Bandung 40161, West Java, Indonesia. E-mail address: [email protected] (A. Faried).
http://dx.doi.org/10.1016/j.inat.2017.06.002 2214-7519/© 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
A. Faried et al. / Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 10 (2017) 40–43
41
Fig. 1. (A) Clinical feature of the patient. (B) Brain MRI of mass lesions exhibiting isointense signal to gray matter on T1/T2 and postcontrast enhancement at bilateral CPA affecting acoustic nerves and enlargement of the internal meatus canal. (C) MRI of thoracolumbar spine showed a dumbbell shaped mass at VT 8 level, an enhanced with contrast lesion VT 9–11 which also significantly compressed the spinal cord, and presenting syrinx on the VT 5–7 and VT 11–12.
aside to the first tumor which only separated by the duramater with same feature (Fig. 3C–D); and intramedullary tumor at level VT 9–11 (Fig. 3E–F), which was softer than the first and second tumors, white colored but not well circumscribed. Informed consent was obtained from the patient family. Histopathological results showed meningiomas
(Fig. 3G; upper and middle panel) and ependymoma (Fig. 3G; lower panel). Diagnosis of MISME was made; rehabilitated for his hearing loss and weakness of both lower extremities after the surgery. We've been following the patient for 1 year with improved clinical outcome.
Fig. 2. (A–B) CTR for the cranial tumor. (C–D) Two white solid masses with defined borders found during the cranial operation and the tumors were totally removed; (E–F) Sheets in intertwining fascicles in both solid masses for Antoni A and looser arrangements for Antoni B.
42
A. Faried et al. / Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 10 (2017) 40–43
Fig. 3. (A–B) Laminectomy tumor removal and posterior stabilization At VT 8, there was a mass alongside the left radix, well circumscribed, white colored and soft to hard consistency. (C– D) Second tumor was directly aside to the first tumor, only separated by duramater. (E–F) Third tumor was found intramedullary at VT 9–11. (G) Pathology anatomy results reveal of fibroblastic meningioma (upper), meningotheliomatous meningioma (middle) and ependymoma (lower) for the 3rd spine tumor, respectively.
3. Discussion In 1995, Mautner et al. published a case series of NF-2 [1]; 96% (46 patients, 43 bilateral and 3 unilaterals) had Schwannomas, 90% (43) had spinal tumors, 63% (30) had posterior subcapsular cataracts, 58% (28) had meningiomas and trigeminal Schwannomas were found in 29% (14) patients. The occurrence of various tumors in NF-2 includes the followings [2]: 1. Schwannomas: almost N 90% NF-2 cases will develop bilateral 8th nerve Schwannomas. The Schwannomas occurrence from other cranial nerves such as trigeminal, oculomotor, trochlear and abducens nerves have been described previously. 2. Spinal Schwannomas: the most common type of NF-2 spinal tumor is Schwannomas. Most common site is cervico thoracic region, originating from dorsal root. 3. Meningiomas: 50–75% of NF-2 patients develop meningiomas, most commonly in supratentorial with fibroblastic type. In spinal cord, it mostly seen in thoracic region. 4. Ependymomas: it mostly seen in intramedullary of conus medullaris or cervical region. 5. Astrocytomas: majority are low grade, seen in the brain. 6. Ocular lesions: 90% of NF-2 patients have ocular lesions. Posterior subcapsular lenticular cataract is important clue for diagnosis. Other lesions occurrence like retinal hamartomas, epiretinal membranes, orbital meningiomas and corneal abnormalities can be seen. MISME syndrome is synonymous with NF-2. The average age of NF-2 is 18–24 years, ranges from birth to 70 years old. NF-2 patients have 90– 95% chances to develop bilateral vestibular Schwannomas and 70% of various spinal neoplasms. The presence of multiple and different intraspinal tumors suggests NF-2 [1]. At least two thirds of patients develop spinal tumors, with Schwannomas as the most common spinal tumors. Intramedullary spinal tumors (IMSTs), such as ependymoma, occur in 5–33%. Although multiple tumors are often present, they remain asymptomatic in many individuals. Halliday et al. examined the clinical and pathological features of 86 spinal nerve sheath tumors (SNSTs) of 65 patients removed surgically, as well as 5 autopsy specimens [3]. Seven of 86 patients met the NF-2 criteria. These tumors were intradural, extramedullary arising from dorsal nerve roots. With one exception, all SNSTs both surgically treated and autopsied patients were Schwannomas, mostly occurring at cervical
or thoracic. One patient demonstrated a “mixed-type”. However, we did not conduct molecular investigation in this patient due to time and cost limitation. Ependymomas are relatively rare, 4–6% of primary central nervous system neoplasms. About one-third of all ependymomas arises within the spinal canal and represents the most common (40–60%) IMSTs in adults. Rodriguez et al. identified 16 reported NF-2 patients and IMSTs, eight were classified as ependymoma, in addition to three astrocytomas and three glioma [4]. Lee et al., in 1996, described 9 patients with NF (three NF-1, five NF-2 and 1 with “uncertain type”). Ependymoma was associated with NF-2 in 4/5 patients. The IMSTs incidence in NF-1 and NF-2 population as 19% overall. The literatures support presumption that solitary IMSTs in NF-1 will most likely be astrocytoma; NF-2 patient with IMSTs most likely have ependymoma [5]. Birch et al., at the same year, examined 7 ependymomas IMSTs from unrelated patients who did not have NF-2. It showed that 71% of patients with sporadic intramedullary ependymoma had NF-2 gene. 4. Conclusions MISME syndrome is a very rare case and the occurrence in our center is extremely rare and NF-2 final diagnosis must be confirmed by molecular investigation. Our case adding the evidence of MISME in world literature. Authors' contributions AF, GN, RFD, RS, SEO and MZ had examined, treated, observed, and followed up the subject of this research. All authors participated in writing the manuscript. All authors has read and approved of the final manuscript. Consent Informed consent was obtained from the patient for publication of this case report and any accompanying images. His family was present at the time. Competing interests The authors declare that they have no competing interests.
A. Faried et al. / Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 10 (2017) 40–43
Disclosure of funding None. References [1] V.F. Mautner, M. Tatagiba, M. Lindenau, C. Fünsterer, S.M. Pulst, M.E. Baser, L. Kluwe, F.E. Zanella, Spinal tumors in patients with neurofibromatosis type 2: MR imaging study of frequency, multiplicity and variety, AJR Am. J. Roentgenol. 165 (4) (1995) 951–955.
43
[2] D.S. Sekhar, I.B. Syamkumar, B.H. Srinivas, S. Vandanapu, A. Vimala, Triple tumors in MISME syndrome-a rare case report and review of literature, IOSR J. Dent. Med. Sci. 14 (8) (2015) 75–78. [3] A.L. Halliday, R.A. Sobel, R.L. Martuza, Benign spinal nerve sheath tumors: their occurrence sporadically and in neurofibromatosis types 1 and 2, J. Neurosurg. 74 (2) (1991) 248–253. [4] H.A. Rodriguez, M. Berthrong, Multiple primary intracranial tumors in von Recklinghausen's neurofibromatosis, Arch. Neurol. (Chicago) 14 (1966) 467–475. [5] M. Lee, A.R. Rezai, D. Freed, F.J. Epstein, Intramedullary spinal cord tumors in neurofibromatosis, Neurosurgery 38 (1) (1996) 32–37.
Contents lists available at ScienceDirect
Interdisciplinary Neurosurgery: Advanced Techniques and Case Management journal homepage: www.inat-journal.com
Technical Notes & Surgical Techniques
Multiple inherited Schwannomas, meningiomas, and ependymomas (MISME): A case report on rare case of neurofibromatosis type 2 tumors Ahmad Faried, MD, PhD a,⁎, Guata Naibaho, MD a, Rully Hanafi Dahlan, MD, MSc b, Roland Sidabutar, MD, MSc a, Sevline Estethia Ompusunggu, MD, MSc b, Muhammad Zafrullah Arifin, MD, PhD a a b
Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, Indonesia Subdivision of Neurospine, Peripheral Nerve and Pain, Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung, Indonesia
a r t i c l e
i n f o
Article history: Received 23 May 2017 Revised 31 May 2017 Accepted 11 June 2017 Available online xxxx Keywords: Neurofibromatosis type 2 MISME syndrome Rare case report
a b s t r a c t Neurofibromatosis type 2 (NF-2) is an autosomal dominant inheritance, chromosome 22q12 mutations in peripher and central nervous systems. Several literatures have discussed rare cases of triple NF-2 tumor, known as multiple inherited Schwannomas, meningiomas and ependymomas or MISME. Incidence of MISME reported from many country, but never been reported from Indonesia. Hopefully the MISME presence can be more revealed in our country and adding the evidence in world literature. A 15-year-old boy presented to our center with a progressive bilateral hearing loss for 2 years and started to experience weakness of both lower extremities since 1.5 years. Patient underwent both craniotomy intracranial and spinal tumor removal. Histopathological result showed Schwannomas, meningiomas and ependymoma. Diagnosis of MISME was made and had been treated with excellent clinical outcome. We are reporting a rare case of MISME syndrome, which is an extremely exceptional case in our center due to rare occurrence of MISME and the need to confirm NF-2 diagnosis using molecular investigations. © 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction
2. Case report
Neurofibromatosis (NF) is a syndrome of autosomal dominant inheritance and characterized by the neural crest benign tumors development. Mutations in the NF type 2 (NF-2) gene are found in the majority of benign nervous system tumors. NF-2 is rare with an incidence of 1:37,000 [1]. It is marked by bilateral vestibular Schwannoma alongside Schwannoma of other craniospinal and peripheral nerve, craniospinal meningiomas and ependymomas of the spinal cord. NF-2, also referred as MISME syndrome for multiple inherited Schwannomas, meningiomas and ependymomas, is caused by mutations of a tumor-suppressor gene, the “Merlin” on chromosome 22q122 [1]. MISME is rare disorder, estimated 1 in 33,000 incidence and 1 in 60,000 prevalence [2]. Male and female are approximately equally affected. This syndrome is commonly seen in 2nd and 3rd decades, mostly between 16–24 years old. Almost 50% of cases are familial, other 50% are sporadic in nature as result of new mutations [2]. However, the incidence of MISME never been reported from Indonesia. Hopefully our case could add the evidence of MISME in world literature.
A 15 years old boy presented with progressive bilateral hearing loss for 2 years and weakness of both lower extremities since 1.5 years ago (Fig. 1A). Neurological examination revealed weak muscle strength of 2/5 and 3/5 in his left and right lower limb. His audiometry results presented severe sensorineural hearing loss (SNHL) of right ear and moderate on left ear. The brain magnetic resonance imaging (MRI) showed isointense well-defined mass on T1/T2 and postcontrast enhancement. These masses resided in bilateral cerebellopontine angles affecting acoustic nerves, causing enlargement of internal meatus canal (Fig. 1B). Spine MRI showed a dumbbell shaped mass at vertebral thoracal (VT) 8 level and enhanced with contrast; lesion VT 9–11 which also significantly compressed the spinal cord, presenting syrinx on VT 5–7 and VT 11–12 (Fig. 1C). Craniotomy tumor removal (CTR) with standard lateral suboccipital approach was performed (Fig. 2A–B) and we found two grayish solid mass (Fig. 2C–D) defined borders totally removed. Histopathological result revealed encapsulated of pure Schwann cells growing around the nerve. It contained blood vessels and had areas of sheets in intertwining fascicles (Antoni A) and looser arrangements (Antoni B) (Fig. 2E–F). Two months after CTR, we performed laminectomy tumor removal and posterior stabilization. The spinal tumors were found in 3 different places: 1.5 cm diameter mass alongside the left radix, well circumscribed, white colored and soft to hard in consistency (Fig. 3A–B) at level VT 8; a tumor directly
⁎ Corresponding author at: Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Jl. Pasteur No. 38, Bandung 40161, West Java, Indonesia. E-mail address: [email protected] (A. Faried).
http://dx.doi.org/10.1016/j.inat.2017.06.002 2214-7519/© 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
A. Faried et al. / Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 10 (2017) 40–43
41
Fig. 1. (A) Clinical feature of the patient. (B) Brain MRI of mass lesions exhibiting isointense signal to gray matter on T1/T2 and postcontrast enhancement at bilateral CPA affecting acoustic nerves and enlargement of the internal meatus canal. (C) MRI of thoracolumbar spine showed a dumbbell shaped mass at VT 8 level, an enhanced with contrast lesion VT 9–11 which also significantly compressed the spinal cord, and presenting syrinx on the VT 5–7 and VT 11–12.
aside to the first tumor which only separated by the duramater with same feature (Fig. 3C–D); and intramedullary tumor at level VT 9–11 (Fig. 3E–F), which was softer than the first and second tumors, white colored but not well circumscribed. Informed consent was obtained from the patient family. Histopathological results showed meningiomas
(Fig. 3G; upper and middle panel) and ependymoma (Fig. 3G; lower panel). Diagnosis of MISME was made; rehabilitated for his hearing loss and weakness of both lower extremities after the surgery. We've been following the patient for 1 year with improved clinical outcome.
Fig. 2. (A–B) CTR for the cranial tumor. (C–D) Two white solid masses with defined borders found during the cranial operation and the tumors were totally removed; (E–F) Sheets in intertwining fascicles in both solid masses for Antoni A and looser arrangements for Antoni B.
42
A. Faried et al. / Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 10 (2017) 40–43
Fig. 3. (A–B) Laminectomy tumor removal and posterior stabilization At VT 8, there was a mass alongside the left radix, well circumscribed, white colored and soft to hard consistency. (C– D) Second tumor was directly aside to the first tumor, only separated by duramater. (E–F) Third tumor was found intramedullary at VT 9–11. (G) Pathology anatomy results reveal of fibroblastic meningioma (upper), meningotheliomatous meningioma (middle) and ependymoma (lower) for the 3rd spine tumor, respectively.
3. Discussion In 1995, Mautner et al. published a case series of NF-2 [1]; 96% (46 patients, 43 bilateral and 3 unilaterals) had Schwannomas, 90% (43) had spinal tumors, 63% (30) had posterior subcapsular cataracts, 58% (28) had meningiomas and trigeminal Schwannomas were found in 29% (14) patients. The occurrence of various tumors in NF-2 includes the followings [2]: 1. Schwannomas: almost N 90% NF-2 cases will develop bilateral 8th nerve Schwannomas. The Schwannomas occurrence from other cranial nerves such as trigeminal, oculomotor, trochlear and abducens nerves have been described previously. 2. Spinal Schwannomas: the most common type of NF-2 spinal tumor is Schwannomas. Most common site is cervico thoracic region, originating from dorsal root. 3. Meningiomas: 50–75% of NF-2 patients develop meningiomas, most commonly in supratentorial with fibroblastic type. In spinal cord, it mostly seen in thoracic region. 4. Ependymomas: it mostly seen in intramedullary of conus medullaris or cervical region. 5. Astrocytomas: majority are low grade, seen in the brain. 6. Ocular lesions: 90% of NF-2 patients have ocular lesions. Posterior subcapsular lenticular cataract is important clue for diagnosis. Other lesions occurrence like retinal hamartomas, epiretinal membranes, orbital meningiomas and corneal abnormalities can be seen. MISME syndrome is synonymous with NF-2. The average age of NF-2 is 18–24 years, ranges from birth to 70 years old. NF-2 patients have 90– 95% chances to develop bilateral vestibular Schwannomas and 70% of various spinal neoplasms. The presence of multiple and different intraspinal tumors suggests NF-2 [1]. At least two thirds of patients develop spinal tumors, with Schwannomas as the most common spinal tumors. Intramedullary spinal tumors (IMSTs), such as ependymoma, occur in 5–33%. Although multiple tumors are often present, they remain asymptomatic in many individuals. Halliday et al. examined the clinical and pathological features of 86 spinal nerve sheath tumors (SNSTs) of 65 patients removed surgically, as well as 5 autopsy specimens [3]. Seven of 86 patients met the NF-2 criteria. These tumors were intradural, extramedullary arising from dorsal nerve roots. With one exception, all SNSTs both surgically treated and autopsied patients were Schwannomas, mostly occurring at cervical
or thoracic. One patient demonstrated a “mixed-type”. However, we did not conduct molecular investigation in this patient due to time and cost limitation. Ependymomas are relatively rare, 4–6% of primary central nervous system neoplasms. About one-third of all ependymomas arises within the spinal canal and represents the most common (40–60%) IMSTs in adults. Rodriguez et al. identified 16 reported NF-2 patients and IMSTs, eight were classified as ependymoma, in addition to three astrocytomas and three glioma [4]. Lee et al., in 1996, described 9 patients with NF (three NF-1, five NF-2 and 1 with “uncertain type”). Ependymoma was associated with NF-2 in 4/5 patients. The IMSTs incidence in NF-1 and NF-2 population as 19% overall. The literatures support presumption that solitary IMSTs in NF-1 will most likely be astrocytoma; NF-2 patient with IMSTs most likely have ependymoma [5]. Birch et al., at the same year, examined 7 ependymomas IMSTs from unrelated patients who did not have NF-2. It showed that 71% of patients with sporadic intramedullary ependymoma had NF-2 gene. 4. Conclusions MISME syndrome is a very rare case and the occurrence in our center is extremely rare and NF-2 final diagnosis must be confirmed by molecular investigation. Our case adding the evidence of MISME in world literature. Authors' contributions AF, GN, RFD, RS, SEO and MZ had examined, treated, observed, and followed up the subject of this research. All authors participated in writing the manuscript. All authors has read and approved of the final manuscript. Consent Informed consent was obtained from the patient for publication of this case report and any accompanying images. His family was present at the time. Competing interests The authors declare that they have no competing interests.
A. Faried et al. / Interdisciplinary Neurosurgery: Advanced Techniques and Case Management 10 (2017) 40–43
Disclosure of funding None. References [1] V.F. Mautner, M. Tatagiba, M. Lindenau, C. Fünsterer, S.M. Pulst, M.E. Baser, L. Kluwe, F.E. Zanella, Spinal tumors in patients with neurofibromatosis type 2: MR imaging study of frequency, multiplicity and variety, AJR Am. J. Roentgenol. 165 (4) (1995) 951–955.
43
[2] D.S. Sekhar, I.B. Syamkumar, B.H. Srinivas, S. Vandanapu, A. Vimala, Triple tumors in MISME syndrome-a rare case report and review of literature, IOSR J. Dent. Med. Sci. 14 (8) (2015) 75–78. [3] A.L. Halliday, R.A. Sobel, R.L. Martuza, Benign spinal nerve sheath tumors: their occurrence sporadically and in neurofibromatosis types 1 and 2, J. Neurosurg. 74 (2) (1991) 248–253. [4] H.A. Rodriguez, M. Berthrong, Multiple primary intracranial tumors in von Recklinghausen's neurofibromatosis, Arch. Neurol. (Chicago) 14 (1966) 467–475. [5] M. Lee, A.R. Rezai, D. Freed, F.J. Epstein, Intramedullary spinal cord tumors in neurofibromatosis, Neurosurgery 38 (1) (1996) 32–37.