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Cervical clear cell meningioma mimicking a vertebral metastasis
Case Report
Cervical clear cell meningioma mimicking a vertebral metastasis Toshiyuki Inoue1 MD, Kei Miyamoto1 MD PHD, Hirotaka Kodama1 MD PHD, Hideo Hosoe1 MD PHD, Kuniyasu Shimokawa2 MD PHD, Katsuji Shimizu1 MD DMSC 1 Department of Orthopaedic Surgery, 2 Department of Laboratory Medicine, Gifu University School of Medicine, Gifu, Japan
Summary Cervical vertebral involvement of clear cell meningioma is very rare. We report a case of clear cell meningioma in the cervical vertebral body in a 72-year old male. Seven years prior to this presentation, the patient underwent palliative surgery and posterior instrumentation for a cervical vertebral tumor at C5, which had been diagnosed as a metastatic renal cell carcinoma. On this admission, the patient presented with severe neck pain. Examination revealed hypesthesia on the left in a C6 nerve root distribution. Plain X-rays and MRI revealed an enlarging tumor in the C5 and C6 vertebral bodies. The tumor was resected via an anterior approach followed by fusion using a strut bone graft. Histological examination of the surgical specimen diagnosed a clear cell meningioma. Postoperatively, the patient achieved pain relief and resolution of the neurological deficit. At follow-up two years postoperatively, he remains asymptomatic. We emphasize that cervical clear cell meningioma with involvement of the vertebral bodies may mimic metastatic renal cell carcinoma. ª 2005 Elsevier Ltd. All rights reserved. Journal of Clinical Neuroscience (2005) 12(6), 685–687 0967-5868/$ - see front matter ª 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2004.08.019
Keywords: clear cell meningioma, cervical spine, surgery, vertebral metastasis Received 21 July 2004 Accepted 27 August 2004 Correspondence to: Dr. Kei Miyamoto, MD PhD, Department of Orthopaedic Surgery, Gifu University School of Medicine, 1-1 Yanagido, Gifu-City, Gifu-Prefecture, 501-1194, Japan. Tel.: +58 230 6333; Fax: +58 230 6334; E-mail: [email protected]
INTRODUCTION Although spinal meningiomas are comparatively common among spinal intradural tumors,1,2 vertebral body involvement by meningioma is rare.3,4 Surgical excision is often required3 to preserve spinal cord function. A rare case of clear cell meningioma involving the cervical vertebral body of a 72-year-old male is described. To our knowledge, this has not been reported previously.
CASE REPORT A 72-year old male with a 1 month history of severe neck pain and hypesthesia in his left forearm presented at our clinic in 2002. His previous medical history included similar numbness in 1995 when he also suffered motor weakness and loss of sensation in both
upper and lower extremities, bowel and bladder dysfunction and severe neck pain. A cervical plain X-ray at that time revealed radiolucency of the fifth cervical vertebral body (Fig. 1). A preliminary diagnosis of metastatic vertebral tumor was made, although general examination revealed no evidence of a malignant tumor in the other organs. In October 1995, posterior decompression with a laminectomy of C4 to C6, a biopsy of the tumor, and posterior fixation using Louque rods were performed as a palliative surgical solution. A diagnosis of metastatic renal cell carcinoma was made after histological examination of the surgical specimen. The patient’s postoperative course was uneventful and he returned to his normal daily activities. He did not return for regular postoperative appointments, had no radiotherapy and was lost to follow-up. On re-presentation, in February 2002, neurological examination disclosed normal deep tendon reflexes in the upper and lower extremities and absence of abnormal reflexes (Hoffmann, Trçmner, Wartenberg, Babinski). Motor testing revealed mild weakness of his left biceps muscle (4+/5). Sensory testing showed hypesthesia in the left C6 dermatome (6/10). His bowel and bladder function were intact. A cervical plain X-ray showed destruction of the C5 and C6 vertebral bodies (Fig. 2). An MRI scan showed an expanding tumor of the C5 and C6 vertebral bodies with low signal intensity on T1-weighted images (Fig. 3) and high signal intensity on a T2-weighted images. The C5 vertebral body was deformed and compressed and the spinal cord was compressed at this level. Prior to surgery, angiography demonstrated that the left thyrocervical trunk was the main artery feeding the tumor (Fig. 4) and this vessel was embolized to minimize intraoperative bleeding. Surgery Radical resection of the tumor at the C5 and C6 vertebral bodies was attempted via an anterior approach followed by a fusion using a strut fibular graft. At operation, the extraosseous extension of the tumor was identified and was found to ensheath the dura mater and was firmly attached to it. However, there was no evidence of invasion of the dura mater. The tumor was not well demarcated from the surrounding tissue and infiltrated soft tissue and bone. We considered the origin of the meningioma to be the dura mater adjacent to the C5 and C6 vertebral bodies. Despite preoperative embolization, there was substantial intraoperative bleeding (1810 ml) and autologous blood transfusion was required. A near-total resection of the tumor was achieved but further attempts at radical resection were aborted due to blood loss. Histopathological findings Histopathological examination of the tumor demonstrated a sheetlike proliferation of polygonal cells; the cytoplasm of the cells was clear and the tumor cells formed a somewhat lobular architectural pattern (Fig. 5). Periodic acid-Schiff (PAS) staining was strongly positive. Immunohistochemistry revealed neoplastic cells positive for epithelial membrane antigen. No staining for keratin or cytokeratin was observed. Thus, the tumor was diagnosed as a clear cell meningioma. Postoperative course Postoperatively, the patient was immobilized in a halo vest for 3 months. His postoperative course was uneventful. Neurological examination immediately after surgery demonstrated no new focal deficit, and his preoperative deficit gradually improved. His severe neck pain resolved. Currently, two years after surgery, cervical plain X-ray shows the grafted bone to be consolidated (Fig. 6) with no signs of tumor recurrence. 685
686 Inoue et al.
Fig. 1 Lateral cervical plain X-ray taken at first presentation in 1995. A discrete radiolucency in the 5th cervical vertebral body is seen. Fig. 3 Sagittal T1-weighted MRI of the cervical spine taken on admission in 2002. An enlarging low signal intensity tumor of the C5 and C6 vertebral bodies is seen. The height of the C5 vertebral body is reduced and the spinal cord is compressed at this level.
Fig. 2 Lateral cervical plain X-ray taken on admission in 2002. A destructive lesion accompanied by osteolysis is seen involving the C5 and C6 vertebral bodies.
DISCUSSION Clear cell meningioma was added to the WHO classification of tumors of the central nervous system in 1988.5,6 This tumor is composed of apposed polygonal cells with clear, glycogen-rich (PAS-positive, diatase-labile) cytoplasm; variable amounts of hyaline connective tissue intermingled with tumor cells is also a typical morphological feature. Although several cases of clear cell meningioma in the skull and brain are reported in the literature,5–9 clear cell meningioma in the spine is relatively rare.2,5,6,8–11 As Journal of Clinical Neuroscience (2005) 12(6)
Fig. 4 Anteroposterior angiogram prior to the second surgery in 2002. The left thyrocervical trunk was the main feeding artery for the tumor, and was subsequently embolized.
far as the authors are aware, clear cell meningioma involving the cervical vertebral bodies and presenting with neurological deficit has not been previously reported. Based on the intraoperative findings, we presume that this tumor arose from the dura mater, the usual origin of meningioma, and gradually invaded the vertebral body. ª 2005 Elsevier Ltd. All rights reserved.
Cervical clear cell meningioma 687
Fig. 5 Histopathological examination of the surgical specimen (hematoxylin and eosin, x40). A sheet-like proliferation of polygonal cells can be seen. The cytoplasm of the cells is clear and the tumor cells form a somewhat lobular architectural pattern.
Cytokeratin was also negative but PAS staining was positive. These findings confirmed the diagnosis of clear cell meningioma. Generally, the principle of surgical management of clear cell meningioma is complete removal.5,7,11 Carra et al.7 advocated complete surgical removal for clear cell meningioma of the lumbar spine as it is a potentially aggressive tumor which may recur. However, as demonstrated by our reported patient, surgery may involve significant intraoperative blood loss. Shi et al12 reported that preoperative embolization of hypervascular spinal tumors is safe and effective. Superselection or flow control is necessary to achieve effective devascularization while avoiding complications. We employed preoperative embolization but could not avoid significant blood loss and autologous blood transfusion. Although complete radical removal of the tumor was not accomplished in our patient, his short-term clinical course has been excellent, resulting in an improved quality of life. Followup over a long period will be required, as recurrence of meningioma is frequently reported.3,5,8,9 CONCLUSION A case of clear cell meningioma of the cervical vertebral body in a 72-year-old male has been described. To our knowledge, this has not been reported previously. This tumor may mimic metastatic renal cell carcinoma.
ACKNOWLEDGEMENT The authors thank Takatoshi Ohno MD (Department of Orthopaedic Surgery, Gifu University School of Medicine), Eiji Wada MD (Department of Orthopaedic Surgery, Hashima Municipal Hospital), and Shinichi Yoshimura MD (Department of Neurosurgery, Gifu University School of Medicine) for their contributions to this paper.
REFERENCES
Fig. 6 Lateral cervical plain X-ray taken 18 months after surgery. The grafted bone is consolidated and there are no signs of tumor recurrence.
From the histopathological examination of the specimen from the first operation, the tumor was diagnosed as a metastatic vertebral tumor, originating from a renal cell carcinoma. Seven years later, the patient presented with mild neurological symptoms and signs, seeking further treatment. After radical resection of the tumor, the diagnosis was changed to clear cell meningioma. In retrospect, the relatively slow growth of the C5 vertebral tumor in the 7-year follow-up period did not support the diagnosis of metastatic renal cell carcinoma. However, the histological findings of clear cell meningioma are often difficult to differentiate from clear cell renal cell carcinoma,9 as demonstrated by this case. Prinz et al.9 also reported that clear cell meningioma may mimic other tumors composed of clear cells, particularly metastatic renal cell carcinoma. Of assistance in the differential diagnosis, immunoreactivity for keratin is common in renal cell carcinoma but not in meningioma.4 In the present case, immunoreactivity for keratin was negative. ª 2005 Elsevier Ltd. All rights reserved.
1. Levy Jr WJ, Bay J, Dohn D. Spinal cord meningioma. J Neurosurg 1982; 57: 804–812. 2. Cohen-Gadol AA, Zikel OM, Koch CA, Scheithauer BW, Krauss WE. Spinal meningiomas in patients younger than 50 years of age: a 21-year experience. J Neurosurg 2003; 98(Suppl 3): 258–263. 3. Wu JK, Kasdom DL, Whitmore EL. Metastatic meningioma to cervical vertebra: A case report. Neurosurgery 1985; 17: 75–79. 4. Tominaga T, Koshu K, Narita N, Yoshimoto T. Metastatic meningioma to the second cervical vertebral body. A case report. Neurosurgery 1994; 34: 538–541. 5. Zorludemir S, Scheithauer BW, Hirose T, Van Houten C, Miller G, Meyer FB. Clear cell meningioma: A clinicopathologic study of a potentially aggressive variant of meningioma. Am J Surg Pathol 1995; 19: 493–505. 6. Matsui H, Kanamori M, Abe Y, Sakai T, Wakaki K. Multifocal clear cell meningioma in the spine: A case report. Neurosurg Rev 1998; 21: 171–173. 7. Prinz M, Patt S, Mitrovics T, et al. Clear cell meningioma: Report of a spinal case. Gen Diagn Pathol 1995/96; 141: 261–267. 8. Prinz M, Patt S, Mitrovics T, Cervos-Navarro J. Clear cell meningioma variant and clinical aggressiveness. Clin Neuropathol 1998; 17: 141–146. 9. Carra S, Drigo P, Gardiman M, Perilongo G, Rigobello L. Clear cell meningioma in a 22-month-old male. A case report and literature review. Pediatric Neurosurg 2001; 34: 264–267. 10. Alameda F, Lloreta J, Ferrer MD, Corominas JM, Galito E, Serrano S. Clear cell meningioma of the lumbo-sacral spine with chordoid features. Ultrastruct Pathol 1999; 23: 51–58. 11. Jallo GI, Kothbauer KF, Silvera VM, Epstein FJ. Intraspinal clear cell meningioma: Diagnosis and management: Report of two cases. Neurosurgery 2001; 48: 218–222. 12. Shi HB, Suh DC, Lee HK, et al. Preoperative transarterial embolization of spinal tumor: embolization techniques and results. AJNR Am J Neuroradiol 1999; 20: 2009–2015.
Journal of Clinical Neuroscience (2005) 12(6)
Cervical clear cell meningioma mimicking a vertebral metastasis Toshiyuki Inoue1 MD, Kei Miyamoto1 MD PHD, Hirotaka Kodama1 MD PHD, Hideo Hosoe1 MD PHD, Kuniyasu Shimokawa2 MD PHD, Katsuji Shimizu1 MD DMSC 1 Department of Orthopaedic Surgery, 2 Department of Laboratory Medicine, Gifu University School of Medicine, Gifu, Japan
Summary Cervical vertebral involvement of clear cell meningioma is very rare. We report a case of clear cell meningioma in the cervical vertebral body in a 72-year old male. Seven years prior to this presentation, the patient underwent palliative surgery and posterior instrumentation for a cervical vertebral tumor at C5, which had been diagnosed as a metastatic renal cell carcinoma. On this admission, the patient presented with severe neck pain. Examination revealed hypesthesia on the left in a C6 nerve root distribution. Plain X-rays and MRI revealed an enlarging tumor in the C5 and C6 vertebral bodies. The tumor was resected via an anterior approach followed by fusion using a strut bone graft. Histological examination of the surgical specimen diagnosed a clear cell meningioma. Postoperatively, the patient achieved pain relief and resolution of the neurological deficit. At follow-up two years postoperatively, he remains asymptomatic. We emphasize that cervical clear cell meningioma with involvement of the vertebral bodies may mimic metastatic renal cell carcinoma. ª 2005 Elsevier Ltd. All rights reserved. Journal of Clinical Neuroscience (2005) 12(6), 685–687 0967-5868/$ - see front matter ª 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2004.08.019
Keywords: clear cell meningioma, cervical spine, surgery, vertebral metastasis Received 21 July 2004 Accepted 27 August 2004 Correspondence to: Dr. Kei Miyamoto, MD PhD, Department of Orthopaedic Surgery, Gifu University School of Medicine, 1-1 Yanagido, Gifu-City, Gifu-Prefecture, 501-1194, Japan. Tel.: +58 230 6333; Fax: +58 230 6334; E-mail: [email protected]
INTRODUCTION Although spinal meningiomas are comparatively common among spinal intradural tumors,1,2 vertebral body involvement by meningioma is rare.3,4 Surgical excision is often required3 to preserve spinal cord function. A rare case of clear cell meningioma involving the cervical vertebral body of a 72-year-old male is described. To our knowledge, this has not been reported previously.
CASE REPORT A 72-year old male with a 1 month history of severe neck pain and hypesthesia in his left forearm presented at our clinic in 2002. His previous medical history included similar numbness in 1995 when he also suffered motor weakness and loss of sensation in both
upper and lower extremities, bowel and bladder dysfunction and severe neck pain. A cervical plain X-ray at that time revealed radiolucency of the fifth cervical vertebral body (Fig. 1). A preliminary diagnosis of metastatic vertebral tumor was made, although general examination revealed no evidence of a malignant tumor in the other organs. In October 1995, posterior decompression with a laminectomy of C4 to C6, a biopsy of the tumor, and posterior fixation using Louque rods were performed as a palliative surgical solution. A diagnosis of metastatic renal cell carcinoma was made after histological examination of the surgical specimen. The patient’s postoperative course was uneventful and he returned to his normal daily activities. He did not return for regular postoperative appointments, had no radiotherapy and was lost to follow-up. On re-presentation, in February 2002, neurological examination disclosed normal deep tendon reflexes in the upper and lower extremities and absence of abnormal reflexes (Hoffmann, Trçmner, Wartenberg, Babinski). Motor testing revealed mild weakness of his left biceps muscle (4+/5). Sensory testing showed hypesthesia in the left C6 dermatome (6/10). His bowel and bladder function were intact. A cervical plain X-ray showed destruction of the C5 and C6 vertebral bodies (Fig. 2). An MRI scan showed an expanding tumor of the C5 and C6 vertebral bodies with low signal intensity on T1-weighted images (Fig. 3) and high signal intensity on a T2-weighted images. The C5 vertebral body was deformed and compressed and the spinal cord was compressed at this level. Prior to surgery, angiography demonstrated that the left thyrocervical trunk was the main artery feeding the tumor (Fig. 4) and this vessel was embolized to minimize intraoperative bleeding. Surgery Radical resection of the tumor at the C5 and C6 vertebral bodies was attempted via an anterior approach followed by a fusion using a strut fibular graft. At operation, the extraosseous extension of the tumor was identified and was found to ensheath the dura mater and was firmly attached to it. However, there was no evidence of invasion of the dura mater. The tumor was not well demarcated from the surrounding tissue and infiltrated soft tissue and bone. We considered the origin of the meningioma to be the dura mater adjacent to the C5 and C6 vertebral bodies. Despite preoperative embolization, there was substantial intraoperative bleeding (1810 ml) and autologous blood transfusion was required. A near-total resection of the tumor was achieved but further attempts at radical resection were aborted due to blood loss. Histopathological findings Histopathological examination of the tumor demonstrated a sheetlike proliferation of polygonal cells; the cytoplasm of the cells was clear and the tumor cells formed a somewhat lobular architectural pattern (Fig. 5). Periodic acid-Schiff (PAS) staining was strongly positive. Immunohistochemistry revealed neoplastic cells positive for epithelial membrane antigen. No staining for keratin or cytokeratin was observed. Thus, the tumor was diagnosed as a clear cell meningioma. Postoperative course Postoperatively, the patient was immobilized in a halo vest for 3 months. His postoperative course was uneventful. Neurological examination immediately after surgery demonstrated no new focal deficit, and his preoperative deficit gradually improved. His severe neck pain resolved. Currently, two years after surgery, cervical plain X-ray shows the grafted bone to be consolidated (Fig. 6) with no signs of tumor recurrence. 685
686 Inoue et al.
Fig. 1 Lateral cervical plain X-ray taken at first presentation in 1995. A discrete radiolucency in the 5th cervical vertebral body is seen. Fig. 3 Sagittal T1-weighted MRI of the cervical spine taken on admission in 2002. An enlarging low signal intensity tumor of the C5 and C6 vertebral bodies is seen. The height of the C5 vertebral body is reduced and the spinal cord is compressed at this level.
Fig. 2 Lateral cervical plain X-ray taken on admission in 2002. A destructive lesion accompanied by osteolysis is seen involving the C5 and C6 vertebral bodies.
DISCUSSION Clear cell meningioma was added to the WHO classification of tumors of the central nervous system in 1988.5,6 This tumor is composed of apposed polygonal cells with clear, glycogen-rich (PAS-positive, diatase-labile) cytoplasm; variable amounts of hyaline connective tissue intermingled with tumor cells is also a typical morphological feature. Although several cases of clear cell meningioma in the skull and brain are reported in the literature,5–9 clear cell meningioma in the spine is relatively rare.2,5,6,8–11 As Journal of Clinical Neuroscience (2005) 12(6)
Fig. 4 Anteroposterior angiogram prior to the second surgery in 2002. The left thyrocervical trunk was the main feeding artery for the tumor, and was subsequently embolized.
far as the authors are aware, clear cell meningioma involving the cervical vertebral bodies and presenting with neurological deficit has not been previously reported. Based on the intraoperative findings, we presume that this tumor arose from the dura mater, the usual origin of meningioma, and gradually invaded the vertebral body. ª 2005 Elsevier Ltd. All rights reserved.
Cervical clear cell meningioma 687
Fig. 5 Histopathological examination of the surgical specimen (hematoxylin and eosin, x40). A sheet-like proliferation of polygonal cells can be seen. The cytoplasm of the cells is clear and the tumor cells form a somewhat lobular architectural pattern.
Cytokeratin was also negative but PAS staining was positive. These findings confirmed the diagnosis of clear cell meningioma. Generally, the principle of surgical management of clear cell meningioma is complete removal.5,7,11 Carra et al.7 advocated complete surgical removal for clear cell meningioma of the lumbar spine as it is a potentially aggressive tumor which may recur. However, as demonstrated by our reported patient, surgery may involve significant intraoperative blood loss. Shi et al12 reported that preoperative embolization of hypervascular spinal tumors is safe and effective. Superselection or flow control is necessary to achieve effective devascularization while avoiding complications. We employed preoperative embolization but could not avoid significant blood loss and autologous blood transfusion. Although complete radical removal of the tumor was not accomplished in our patient, his short-term clinical course has been excellent, resulting in an improved quality of life. Followup over a long period will be required, as recurrence of meningioma is frequently reported.3,5,8,9 CONCLUSION A case of clear cell meningioma of the cervical vertebral body in a 72-year-old male has been described. To our knowledge, this has not been reported previously. This tumor may mimic metastatic renal cell carcinoma.
ACKNOWLEDGEMENT The authors thank Takatoshi Ohno MD (Department of Orthopaedic Surgery, Gifu University School of Medicine), Eiji Wada MD (Department of Orthopaedic Surgery, Hashima Municipal Hospital), and Shinichi Yoshimura MD (Department of Neurosurgery, Gifu University School of Medicine) for their contributions to this paper.
REFERENCES
Fig. 6 Lateral cervical plain X-ray taken 18 months after surgery. The grafted bone is consolidated and there are no signs of tumor recurrence.
From the histopathological examination of the specimen from the first operation, the tumor was diagnosed as a metastatic vertebral tumor, originating from a renal cell carcinoma. Seven years later, the patient presented with mild neurological symptoms and signs, seeking further treatment. After radical resection of the tumor, the diagnosis was changed to clear cell meningioma. In retrospect, the relatively slow growth of the C5 vertebral tumor in the 7-year follow-up period did not support the diagnosis of metastatic renal cell carcinoma. However, the histological findings of clear cell meningioma are often difficult to differentiate from clear cell renal cell carcinoma,9 as demonstrated by this case. Prinz et al.9 also reported that clear cell meningioma may mimic other tumors composed of clear cells, particularly metastatic renal cell carcinoma. Of assistance in the differential diagnosis, immunoreactivity for keratin is common in renal cell carcinoma but not in meningioma.4 In the present case, immunoreactivity for keratin was negative. ª 2005 Elsevier Ltd. All rights reserved.
1. Levy Jr WJ, Bay J, Dohn D. Spinal cord meningioma. J Neurosurg 1982; 57: 804–812. 2. Cohen-Gadol AA, Zikel OM, Koch CA, Scheithauer BW, Krauss WE. Spinal meningiomas in patients younger than 50 years of age: a 21-year experience. J Neurosurg 2003; 98(Suppl 3): 258–263. 3. Wu JK, Kasdom DL, Whitmore EL. Metastatic meningioma to cervical vertebra: A case report. Neurosurgery 1985; 17: 75–79. 4. Tominaga T, Koshu K, Narita N, Yoshimoto T. Metastatic meningioma to the second cervical vertebral body. A case report. Neurosurgery 1994; 34: 538–541. 5. Zorludemir S, Scheithauer BW, Hirose T, Van Houten C, Miller G, Meyer FB. Clear cell meningioma: A clinicopathologic study of a potentially aggressive variant of meningioma. Am J Surg Pathol 1995; 19: 493–505. 6. Matsui H, Kanamori M, Abe Y, Sakai T, Wakaki K. Multifocal clear cell meningioma in the spine: A case report. Neurosurg Rev 1998; 21: 171–173. 7. Prinz M, Patt S, Mitrovics T, et al. Clear cell meningioma: Report of a spinal case. Gen Diagn Pathol 1995/96; 141: 261–267. 8. Prinz M, Patt S, Mitrovics T, Cervos-Navarro J. Clear cell meningioma variant and clinical aggressiveness. Clin Neuropathol 1998; 17: 141–146. 9. Carra S, Drigo P, Gardiman M, Perilongo G, Rigobello L. Clear cell meningioma in a 22-month-old male. A case report and literature review. Pediatric Neurosurg 2001; 34: 264–267. 10. Alameda F, Lloreta J, Ferrer MD, Corominas JM, Galito E, Serrano S. Clear cell meningioma of the lumbo-sacral spine with chordoid features. Ultrastruct Pathol 1999; 23: 51–58. 11. Jallo GI, Kothbauer KF, Silvera VM, Epstein FJ. Intraspinal clear cell meningioma: Diagnosis and management: Report of two cases. Neurosurgery 2001; 48: 218–222. 12. Shi HB, Suh DC, Lee HK, et al. Preoperative transarterial embolization of spinal tumor: embolization techniques and results. AJNR Am J Neuroradiol 1999; 20: 2009–2015.
Journal of Clinical Neuroscience (2005) 12(6)