The Neuroradiology Journal 20: 500-504, 2007
www. centauro. it
Childhood Spinal Glioblastoma Multiforme with Intracranial Dissemination. A Case Report S. BATTAGLIA, L. ALBINI RICCIOLI, F. BARTIROMO, E. GALASSI, A.F. MARLIANI, M. LEONARDI Neuroradiology Department, Bellaria Hospital; Bologna, Italy
Key words: spinal cord glioblastoma, MRI, leptomeningeal dissemination
SUMMARY – Primary spinal cord tumors in children are uncommon and account for approximately 5% of all pediatric central nervous system tumors. Intracranial metastases from primary spinal cord tumors have rarely been reported. Spinal cord glioblastoma in children mainly involves the thoracic region, whereas involvement of the medullaris conus with intracranial dissemination has been described in six cases. This paper describes a pediatric case of thoracic glioblastoma multiforme with intracranial dissemination in the early stage of the clinical course and discuss the clinical and neuroradiological manifestations, the possible patterns of dissemination and finally to consider the therapeutic implications.
Introduction
Case Report
Primary spinal cord tumors in children are uncommon and account for approximately 5% of all pediatric central nervous system (CNS) tumors 1. Most childhood intramedullary tumors are histologically astrocytomas (47-88%), followed in frequency by ependymomas (2437%) 2-6. This is in contrast with epidemiology of spinal cord tumors in the adult population, where ependymoma is the most common histological type 7. Intracranial metastases from primary spinal cord tumors have rarely been reported. Spinal cord glioblastoma in children mainly involves the thoracic region, whereas involvement of the medullaris conus with intracranial dissemination has been described in six cases 8. There seems to be a predilection for the second and third decades of life. The aim of this paper is to describe a pediatric case of thoracic glioblastoma multiforme with intracranial dissemination in the early stage of the clinical course and discuss the clinical and neuroradiological manifestations, the possible patterns of dissemination and finally to consider the therapeutic implications.
An 11-year-old boy was admitted to the emergency department with a rapid history of progressive paraparesis associated with tactile hypoesthesia in the lower limbs and bladder dysfunction. Magnetic resonance imaging (MRI) of the spinal cord revealed an intramedullary and exophytic mass extending from Th4 to Th5. The lesion showed inhomogeneous contrast enhancement after gadolinium injection (figure 1). Full neuraxis MRI did not disclose other lesions. The patient underwent thoracic laminotomy and gross total tumor excision. Pathological examination of the surgical specimens showed characteristic features and final histological diagnosis was consistent with glioblastoma multiforme. The postoperative course was uneventful with initial improvement and partial resolution of his neurological deficits and at the time of discharge he was able to walk with assistance. Postoperative radiotherapy to the whole spinal axis and chemotherapy with Temozolamide were administered, but three months later his neurological conditions deteriorated and he presented with symptoms of raised intracranial pressure and impaired
500
S. Battaglia
Childhood Spinal Glioblastoma Multiforme with Intracranial Dissemination
A
B
C
D
Figure 1 Spinal MRI pre-surgery. A) Sagittal T2-weighted thoracic spine image shows the tumor extending between Th4 and Th5. B-D) T1-weighted sagittal, coronal and axial views after gadolinium injection demonstrate a strong and inhomogeneous enhancement with necrotic core.
consciousness. Spinal high-field MRI (3 Tesla) showed diffuse leptomeningeal perimedullary and spinal root enhancement (figure 2), while brain MRI disclosed hydrocephalus due to diffuse leptomeningeal dissemination along the CSF subarachnoid spaces (figure 3), as documented by diffuse pericerebral and cerebellar leptomeningeal enhancement. The left hippocampus was also involved; the 5th, 7th, 8th, 9th and 10th cranial nerves also appeared encased by the tumor dissemination (figure 4). A CSF ventriculoperitoneal shunt was inserted with control of the hydrocephalus and resolution of the intracranial hypertension. However the patient’s neurological status and general conditions continued to deteriorate progressively and he died six months after the onset of symptoms. Discussion Primary spinal cord tumors in children are uncommon and account for approximately 5% of all pediatric CNS tumors 1. Glioblastoma
multiforme (GBM) of the spinal cord is a rare highly aggressive tumour with fewer than 200 cases of intramedullary spinal cord glioblastomas reported to date 9. The prognosis remains poor in most patients: generally a short period (few weeks) of non-specific symptoms is followed by a rapid neurological deterioration (as in our patient who became suddenly paraparetic) progressively leading to death within months despite aggressive surgical and oncological treatments. Initial, non specific, clinical symptoms may include back pain, leg weakness and sensory disturbances which are usually followed by severe motor deficits 10. Multiple examples of spinal cord malignancies causing hydrocephalus have been described in literature 10-11 . Hydrocephalus associated with spinal cord tumors may be determined by several mechanisms such as increased protein concentration in CSF, arachnoiditis, occlusion of the CSF channels in the subarachnoid spaces at the skull base and brain surface and spontaneous tumor bleeds 12. Leptomeningeal tumor spread through the subarachnoid pathways is an ad501
Childhood Spinal Glioblastoma Multiforme with Intracranial Dissemination
S. Battaglia
A
B
C
D
Figure 2 Spinal MRI 3 months after surgery. A) Sagittal T2-weighted; B,C) sagittal and D) axial T1-weighted views after contrast administration show diffuse leptomeningeal and spinal root enhancement. No recurrence of the primary tumor is evident.
A
B
C
D
Figure 3 Brain MRI 3 months after surgery. A) Sagittal and B-D) axial T1-weighted images confirm a leptomeningeal brain dissemination. B) The left hippocampus appears involved.
502
www. centauro. it
A
The Neuroradiology Journal 20: 500-504, 2007
B
C
D
Figure 4 Brain MRI 3 months after surgery. A) Coronal and B-D) axial T1-weighted sections: the 5th, 7th, 8th, 9th and 10th cranial nerves are also involved.
ditional cause of impaired CSF circulation and hydrocephalus 9-11, but the main factor responsible for the dissemination of GBM cells, either simply GBM exposure to CSF spaces or surgical manipulation with bleeding of the tumor mass, remains unsettled. In addition to the subarachnoid spaces, other sites of dissemination have been documented such as the ventricular system 13, cerebellum, hypothalamus, brain stem, thalamus 14 and septum pellucidum15. In our case metastases from the thoracic primary location were also demonstrated in the cerebellum, brain stem, hippocampus and cranial nerves
(V, VII, VIII, IX, X). Suggested treatment of spinal cord GBM includes tumor resection, high dose postoperative radiotherapy, that can exceed the radiation tolerance of the spinal cord 16, and an adjuvant combination of irradiation and chemotherapy 9,11. Despite the poor prognosis (a mean survival rate of 12 months is mostly reported10), an aggressive approach is recommended 9 and whole brain irradiation should be seriously considered postoperatively even in the absence of evident leptomeningeal dissemination at the time of initial neuroradiological examinations 13.
References 1 Oake C, Borg MF, Hanieh A et Al: Childhood glioblastoma multiforme of the spinal cord. Australasian Radiology 50, 360-363, 2006. 2 Farwell JR, Dohrmann GJ, Flamery JT: Central nervous system tumors in children. Cancer; 40: 3123-3132, 1977. 3 Reimer R, Onofrio BM: Astrocytomas of the spinal cord in children and adolescents. J Neurosurg; 63: 669-675, 1985. 4 Cooper PR, Epstein F: Radical resection of intramedullary spinal cord tumor in adults. J Neurosurg; 63: 491492, 1985. 5 Epstein F, Epstein N: Intramedullary tumors of the spinal cord. In: Section of Pediatric Neurosurgery of the American Association of Neurological Surgeons (eds). Pediatric Neurosurgery. Surgery of the Developing Nervous System. Grim & Straton: New York 1982: 529-533. 6 Garret PG, Simpson WJK: Ependymomas: results of radiation treatment. Int J Radiat Oncol Biol Phys; 9: 1121-1124, 1997. 7 Michalski JM, Garcia DM: Spinal canal. In: Perez CA, Brady LW (eds). Principles and Practice of Radiation Oncology, 3rd edn. Lippincott-Raven Publishers, Philadelphia 1997: 849-65. 8 Medhkour A, Chan M: Extremely rare glioblastoma multiforme of the conus medullaris with holocord and brain stem metastases, leading to cranial nerve deficit and respiratory failure: a case report and review of the literature. Surgical Neurology 63: 576-583, 2005. 9 Ciappetta P, Salvati M, Capoccia G et Al: Spinal gliob-
10 11 12 13 14 15 16
lastoma: report of seven cases and review of the literature. Neurosurgery 28: 302-6, 1991. Asano N, Kitamura K, Seo Y et Al: Spinal cord glioblastoma multiforme with intracranial dissemination. Neurol Med Chir (Tokyo) 30: 489- 94, 1990. Cohen AR, Wisoff JH, Allen JC et Al: Malignant astrocytomas of the spinal cord. J Neurosurg 70: 50-4, 1989. Schijimann E, Zuccaro G, Monges JA: Spinal tumors and hydrocephalus. Childs Brain 8: 401-405, 1981. Johnson D, Schwarz S: Intracranial metastases from malignant spinal cord astrocytoma. J Neurosurg; 66: 621- 5, 1987. Tashiro K, Tachibana S, Tsuru M: Spinal cord tumor with probable intracranial dissemination, presenting akinetic mutism. No To Shinkei; 28: 1311-8, 1976. Andrews A, Enriques L, Renaudin J et Al: Spinal. intramedullary glioblastoma with intracranial seeding. Arch Neurol 35: 244-5, 1978. Scarrow AM, Rajendran P, Welch W: Glioblastoma multiforme of the conus medullaris. Clin Neurol Neurosurg; 102: 166-7, 2000. Dr Stella Battaglia Neuroradiology Department - Bellaria Hospital Via Altura, 3 40139 Bologna - Italy Tel.: +39 051 6225536 - Fax: +39 051 3370942 E-mail: [email protected] [email protected]
503
The Neuroradiology Journal 20: 504, 2007
www. centauro. it
Errata Corrige
The Neuroradiology Journal - Vol. 20 Suppl. 1 - June 2007 Comunicazioni I SESSIONE • "NEUROFIBROMATOSI" • page 31 1
Poster III SESSIONE • "RM FUNZIONALE E DTI" • page 105 16.30-16.40
The Role of the Cerebellum in Visuospatial Tests in Children with Neurofibromatosis Type I. La valutazione del ruolo del cervelletto nei compiti di manipolazione visiva nei soggetti con neurofibromatosi Tipo 1 (NF1). D. Longo, G. Fariello, L.N. Delfino, A.P. Marsico, C. Digilio, R. Capolino, V. Di Ciommo, E. Genovese, O. Piscitelli
P. 33 • Diffusion Tensor Tractography of White Matter Pathways in Term Newborns: Comparative Study of Deterministic and Probabilistic Tractography Trattografia con tensore di diffusione della sostanza bianca nei neonati a termine: studio comparativo con tecnica deterministica e probabilistica S. Vennarini, M. Kavec, N. Gultasli, A. Aeby, U. Salvolini, D. Balériaux
COLLÈGE D’ENSEIGNEMENT POST-UNIVERSITAIRE DE RADIOLO-
COURS DU CEPUR - STRASBOURG IMAGERIE FONCTIONNELLE CÉRÉBRALE IRMf, spectroscopie, perfusion et diffusion Strasbourg, 28 et 29 mai 2008 organisé par S. KREMER, I.J. NAMER et J.L. DIETEMANN Avec la participation de M. BRAUN, S. RODRIGO, T. SCHUNCK Dans le service de Radiologie 2 • CHU de Strasbourg • Hôpital de Hautepierre Principes physiques, acquisition, post-traitement et applications cliniques. Neuroanatomie sulcale et fonctionnelle cérébrale. Cours magistraux et travaux pratiques (consoles d’acquisition et de post-traitement) Inscriptions limitées à 12 participants Renseignements et inscriptions: Professeur JL DIETEMANN • Service de Radiologie 2
Hôpitaux Universitaires de Strasbourg • Hôpital de Hautepierre • Avenue Molière • F-67098 Strasbourg Cedex Tél.: 03 88 12 78 89 • Fax: 03 88 12 71 18 • E-mail: [email protected] 504
www. centauro. it
Childhood Spinal Glioblastoma Multiforme with Intracranial Dissemination. A Case Report S. BATTAGLIA, L. ALBINI RICCIOLI, F. BARTIROMO, E. GALASSI, A.F. MARLIANI, M. LEONARDI Neuroradiology Department, Bellaria Hospital; Bologna, Italy
Key words: spinal cord glioblastoma, MRI, leptomeningeal dissemination
SUMMARY – Primary spinal cord tumors in children are uncommon and account for approximately 5% of all pediatric central nervous system tumors. Intracranial metastases from primary spinal cord tumors have rarely been reported. Spinal cord glioblastoma in children mainly involves the thoracic region, whereas involvement of the medullaris conus with intracranial dissemination has been described in six cases. This paper describes a pediatric case of thoracic glioblastoma multiforme with intracranial dissemination in the early stage of the clinical course and discuss the clinical and neuroradiological manifestations, the possible patterns of dissemination and finally to consider the therapeutic implications.
Introduction
Case Report
Primary spinal cord tumors in children are uncommon and account for approximately 5% of all pediatric central nervous system (CNS) tumors 1. Most childhood intramedullary tumors are histologically astrocytomas (47-88%), followed in frequency by ependymomas (2437%) 2-6. This is in contrast with epidemiology of spinal cord tumors in the adult population, where ependymoma is the most common histological type 7. Intracranial metastases from primary spinal cord tumors have rarely been reported. Spinal cord glioblastoma in children mainly involves the thoracic region, whereas involvement of the medullaris conus with intracranial dissemination has been described in six cases 8. There seems to be a predilection for the second and third decades of life. The aim of this paper is to describe a pediatric case of thoracic glioblastoma multiforme with intracranial dissemination in the early stage of the clinical course and discuss the clinical and neuroradiological manifestations, the possible patterns of dissemination and finally to consider the therapeutic implications.
An 11-year-old boy was admitted to the emergency department with a rapid history of progressive paraparesis associated with tactile hypoesthesia in the lower limbs and bladder dysfunction. Magnetic resonance imaging (MRI) of the spinal cord revealed an intramedullary and exophytic mass extending from Th4 to Th5. The lesion showed inhomogeneous contrast enhancement after gadolinium injection (figure 1). Full neuraxis MRI did not disclose other lesions. The patient underwent thoracic laminotomy and gross total tumor excision. Pathological examination of the surgical specimens showed characteristic features and final histological diagnosis was consistent with glioblastoma multiforme. The postoperative course was uneventful with initial improvement and partial resolution of his neurological deficits and at the time of discharge he was able to walk with assistance. Postoperative radiotherapy to the whole spinal axis and chemotherapy with Temozolamide were administered, but three months later his neurological conditions deteriorated and he presented with symptoms of raised intracranial pressure and impaired
500
S. Battaglia
Childhood Spinal Glioblastoma Multiforme with Intracranial Dissemination
A
B
C
D
Figure 1 Spinal MRI pre-surgery. A) Sagittal T2-weighted thoracic spine image shows the tumor extending between Th4 and Th5. B-D) T1-weighted sagittal, coronal and axial views after gadolinium injection demonstrate a strong and inhomogeneous enhancement with necrotic core.
consciousness. Spinal high-field MRI (3 Tesla) showed diffuse leptomeningeal perimedullary and spinal root enhancement (figure 2), while brain MRI disclosed hydrocephalus due to diffuse leptomeningeal dissemination along the CSF subarachnoid spaces (figure 3), as documented by diffuse pericerebral and cerebellar leptomeningeal enhancement. The left hippocampus was also involved; the 5th, 7th, 8th, 9th and 10th cranial nerves also appeared encased by the tumor dissemination (figure 4). A CSF ventriculoperitoneal shunt was inserted with control of the hydrocephalus and resolution of the intracranial hypertension. However the patient’s neurological status and general conditions continued to deteriorate progressively and he died six months after the onset of symptoms. Discussion Primary spinal cord tumors in children are uncommon and account for approximately 5% of all pediatric CNS tumors 1. Glioblastoma
multiforme (GBM) of the spinal cord is a rare highly aggressive tumour with fewer than 200 cases of intramedullary spinal cord glioblastomas reported to date 9. The prognosis remains poor in most patients: generally a short period (few weeks) of non-specific symptoms is followed by a rapid neurological deterioration (as in our patient who became suddenly paraparetic) progressively leading to death within months despite aggressive surgical and oncological treatments. Initial, non specific, clinical symptoms may include back pain, leg weakness and sensory disturbances which are usually followed by severe motor deficits 10. Multiple examples of spinal cord malignancies causing hydrocephalus have been described in literature 10-11 . Hydrocephalus associated with spinal cord tumors may be determined by several mechanisms such as increased protein concentration in CSF, arachnoiditis, occlusion of the CSF channels in the subarachnoid spaces at the skull base and brain surface and spontaneous tumor bleeds 12. Leptomeningeal tumor spread through the subarachnoid pathways is an ad501
Childhood Spinal Glioblastoma Multiforme with Intracranial Dissemination
S. Battaglia
A
B
C
D
Figure 2 Spinal MRI 3 months after surgery. A) Sagittal T2-weighted; B,C) sagittal and D) axial T1-weighted views after contrast administration show diffuse leptomeningeal and spinal root enhancement. No recurrence of the primary tumor is evident.
A
B
C
D
Figure 3 Brain MRI 3 months after surgery. A) Sagittal and B-D) axial T1-weighted images confirm a leptomeningeal brain dissemination. B) The left hippocampus appears involved.
502
www. centauro. it
A
The Neuroradiology Journal 20: 500-504, 2007
B
C
D
Figure 4 Brain MRI 3 months after surgery. A) Coronal and B-D) axial T1-weighted sections: the 5th, 7th, 8th, 9th and 10th cranial nerves are also involved.
ditional cause of impaired CSF circulation and hydrocephalus 9-11, but the main factor responsible for the dissemination of GBM cells, either simply GBM exposure to CSF spaces or surgical manipulation with bleeding of the tumor mass, remains unsettled. In addition to the subarachnoid spaces, other sites of dissemination have been documented such as the ventricular system 13, cerebellum, hypothalamus, brain stem, thalamus 14 and septum pellucidum15. In our case metastases from the thoracic primary location were also demonstrated in the cerebellum, brain stem, hippocampus and cranial nerves
(V, VII, VIII, IX, X). Suggested treatment of spinal cord GBM includes tumor resection, high dose postoperative radiotherapy, that can exceed the radiation tolerance of the spinal cord 16, and an adjuvant combination of irradiation and chemotherapy 9,11. Despite the poor prognosis (a mean survival rate of 12 months is mostly reported10), an aggressive approach is recommended 9 and whole brain irradiation should be seriously considered postoperatively even in the absence of evident leptomeningeal dissemination at the time of initial neuroradiological examinations 13.
References 1 Oake C, Borg MF, Hanieh A et Al: Childhood glioblastoma multiforme of the spinal cord. Australasian Radiology 50, 360-363, 2006. 2 Farwell JR, Dohrmann GJ, Flamery JT: Central nervous system tumors in children. Cancer; 40: 3123-3132, 1977. 3 Reimer R, Onofrio BM: Astrocytomas of the spinal cord in children and adolescents. J Neurosurg; 63: 669-675, 1985. 4 Cooper PR, Epstein F: Radical resection of intramedullary spinal cord tumor in adults. J Neurosurg; 63: 491492, 1985. 5 Epstein F, Epstein N: Intramedullary tumors of the spinal cord. In: Section of Pediatric Neurosurgery of the American Association of Neurological Surgeons (eds). Pediatric Neurosurgery. Surgery of the Developing Nervous System. Grim & Straton: New York 1982: 529-533. 6 Garret PG, Simpson WJK: Ependymomas: results of radiation treatment. Int J Radiat Oncol Biol Phys; 9: 1121-1124, 1997. 7 Michalski JM, Garcia DM: Spinal canal. In: Perez CA, Brady LW (eds). Principles and Practice of Radiation Oncology, 3rd edn. Lippincott-Raven Publishers, Philadelphia 1997: 849-65. 8 Medhkour A, Chan M: Extremely rare glioblastoma multiforme of the conus medullaris with holocord and brain stem metastases, leading to cranial nerve deficit and respiratory failure: a case report and review of the literature. Surgical Neurology 63: 576-583, 2005. 9 Ciappetta P, Salvati M, Capoccia G et Al: Spinal gliob-
10 11 12 13 14 15 16
lastoma: report of seven cases and review of the literature. Neurosurgery 28: 302-6, 1991. Asano N, Kitamura K, Seo Y et Al: Spinal cord glioblastoma multiforme with intracranial dissemination. Neurol Med Chir (Tokyo) 30: 489- 94, 1990. Cohen AR, Wisoff JH, Allen JC et Al: Malignant astrocytomas of the spinal cord. J Neurosurg 70: 50-4, 1989. Schijimann E, Zuccaro G, Monges JA: Spinal tumors and hydrocephalus. Childs Brain 8: 401-405, 1981. Johnson D, Schwarz S: Intracranial metastases from malignant spinal cord astrocytoma. J Neurosurg; 66: 621- 5, 1987. Tashiro K, Tachibana S, Tsuru M: Spinal cord tumor with probable intracranial dissemination, presenting akinetic mutism. No To Shinkei; 28: 1311-8, 1976. Andrews A, Enriques L, Renaudin J et Al: Spinal. intramedullary glioblastoma with intracranial seeding. Arch Neurol 35: 244-5, 1978. Scarrow AM, Rajendran P, Welch W: Glioblastoma multiforme of the conus medullaris. Clin Neurol Neurosurg; 102: 166-7, 2000. Dr Stella Battaglia Neuroradiology Department - Bellaria Hospital Via Altura, 3 40139 Bologna - Italy Tel.: +39 051 6225536 - Fax: +39 051 3370942 E-mail: [email protected] [email protected]
503
The Neuroradiology Journal 20: 504, 2007
www. centauro. it
Errata Corrige
The Neuroradiology Journal - Vol. 20 Suppl. 1 - June 2007 Comunicazioni I SESSIONE • "NEUROFIBROMATOSI" • page 31 1
Poster III SESSIONE • "RM FUNZIONALE E DTI" • page 105 16.30-16.40
The Role of the Cerebellum in Visuospatial Tests in Children with Neurofibromatosis Type I. La valutazione del ruolo del cervelletto nei compiti di manipolazione visiva nei soggetti con neurofibromatosi Tipo 1 (NF1). D. Longo, G. Fariello, L.N. Delfino, A.P. Marsico, C. Digilio, R. Capolino, V. Di Ciommo, E. Genovese, O. Piscitelli
P. 33 • Diffusion Tensor Tractography of White Matter Pathways in Term Newborns: Comparative Study of Deterministic and Probabilistic Tractography Trattografia con tensore di diffusione della sostanza bianca nei neonati a termine: studio comparativo con tecnica deterministica e probabilistica S. Vennarini, M. Kavec, N. Gultasli, A. Aeby, U. Salvolini, D. Balériaux
COLLÈGE D’ENSEIGNEMENT POST-UNIVERSITAIRE DE RADIOLO-
COURS DU CEPUR - STRASBOURG IMAGERIE FONCTIONNELLE CÉRÉBRALE IRMf, spectroscopie, perfusion et diffusion Strasbourg, 28 et 29 mai 2008 organisé par S. KREMER, I.J. NAMER et J.L. DIETEMANN Avec la participation de M. BRAUN, S. RODRIGO, T. SCHUNCK Dans le service de Radiologie 2 • CHU de Strasbourg • Hôpital de Hautepierre Principes physiques, acquisition, post-traitement et applications cliniques. Neuroanatomie sulcale et fonctionnelle cérébrale. Cours magistraux et travaux pratiques (consoles d’acquisition et de post-traitement) Inscriptions limitées à 12 participants Renseignements et inscriptions: Professeur JL DIETEMANN • Service de Radiologie 2
Hôpitaux Universitaires de Strasbourg • Hôpital de Hautepierre • Avenue Molière • F-67098 Strasbourg Cedex Tél.: 03 88 12 78 89 • Fax: 03 88 12 71 18 • E-mail: [email protected] 504
