J Neurosurg Spine 20:142–147, 2014 ©AANS, 2014

Coexistence of multiple cavernous angiomas in the spinal cord and skin: a unique case of Cobb syndrome Case report Yuya Matsui, M.D.,1 Yohei Mineharu, M.D., Ph.D.,1 Takeshi Satow, M.D., Ph.D.,1 Noriyoshi Takebe, M.D.,1 Eiji Takeuchi, M.D., Ph.D., 2 and Masaaki Saiki, M.D., Ph.D.1 Departments of 1Neurosurgery and 2Diagnostic Pathology, Shiga Medical Center for Adults, Shiga, Japan Cobb syndrome is a rare, noninherited, neurocutaneous disease characterized by vascular abnormality of the spinal cord and is associated with vascular lesions in the skin at the same metamere. The majority of spinal vascular lesions are arteriovenous malformations, and skin lesions are mostly port-wine angiomas. The authors report the first case of multiple intramedullary cavernous angiomas (CAs) accompanied by skin CAs within the same metamere. A 42-year-old man presented with an acute onset of gait disturbance, low-back pain, and urinary incontinence. Magnetic resonance imaging of the thoracolumbar spine showed homogeneously enhanced lesions on a contrast-enhanced T1-weighted image and a hypointense area on a T2*-weighted image surrounding this enhanced lesion, between the T-12 and S-1 levels. Purple protruding skin lesions were detected on the left side of his gluteal region. The patient received a laminectomy followed by evacuation of a hematoma and partial removal of the tumor, which completely resolved his neurological symptoms. Pathological examinations showed that the spinal and skin lesions were CAs, suggesting that these vascular lesions developed congenitally. Cavernous angiomas associated with Cobb syndrome present with multiple lesions spanning more than 3 vertebral levels, making it difficult to completely resect these tumors. Although Cobb syndrome is an uncommon disease entity, it should be considered if a patient manifesting with neurological deficits has skin vascular lesions, including CAs. (http://thejns.org/doi/abs/10.3171/2013.11.SPINE13419)

Key Words      •      cavernous angioma      •      Cobb syndrome      •      cauda equina      •      oncology


obb syndrome is a rare, noninherited, neurocutaneous disease characterized by vascular abnormality of the spinal cord and is associated with vascular lesions in the skin at the same metamere. Cobb syndrome is accompanied by a wide variety of vascular pathologies,12 but most of the spinal lesions are arteriovenous malformations (AVMs), and only 5 cases have been reported in association with cavernous angiomas (CAs).2,5,6,13,23 Skin lesions in patients with Cobb syndrome are reported to be port-wine angiomas and biopsy of these lesions has rarely been performed. We report a unique case of spinal intramedullary CAs that were accompanied by cutaneous CAs of the same pathology.

Abbreviations used in this paper: AVM = arteriovenous malformation; CA = cavernous angioma.


Case Report History and Examination. A 42-year-old man presented with acute onset of gait disturbance and visited the outpatient clinic of a nearby hospital. Four weeks later he began to experience low-back pain and urinary incontinence, and was referred to our hospital. Neurological examinations showed bilateral lower-limb hyperesthesia and weakness of bilateral toe flexors (Grade 4/5). His deep tendon examination showed normal reflexes and symmetry. He had multiple verrucous purple skin lesions on the left side of his gluteal region (Fig. 1A). Magnetic resonance imaging of the thoracic and lumber spinal cord showed a well-demarcated mass at the conus medullaris accompanied by poorly defined multiple small lesions around the cauda equina between T-12 and S-1. On contrast-enhanced T1-weighted MR images, tumors showed J Neurosurg: Spine / Volume 20 / February 2014

Multiple cavernous angiomas in Cobb syndrome

Fig. 1.  Images showing characteristics of the skin lesions in the patient. A: Purple verrucous skin lesion in the gluteal region. Inset shows a higher magnification (×4). B: Photomicrograph showing typical features of CAs, including thin-walled vascular channels surrounded by fibrous tissues, without any evidence of neuronal or glial tissue. H & E, original magnification ×40.

weak homogeneous enhancement (Fig. 2A). A hypointense area on a T2*-weighted image indicated bleeding from the tumor (Fig. 2B). Spinal angiography revealed no pathological findings, such as an arteriovenous shunt. An FDG-PET study showed increased uptake in the lesion of the conus medullaris, with a standardized uptake value of 3.23 at the delayed phase, with no uptake for other lesions in the cauda equina and skin (Fig. 2C). Operative Course. To improve his symptoms, at least partially, we recommended resection of the tumors. Laminectomy was performed at T12–L1, and the dura was opened. The conus medullaris was surrounded by port-wine colored tumors originating from the fine vasculature on the spinal cord. Importantly, the origin of the cauda equina was involved by the tumor, and several bundles of nerve fibers of the spinal cord were also attached by different pieces of the tumor (Fig. 2D). Because the tumors were so adhesive that it was difficult to remove them completely without damaging the spinal cord, we cut 1 fiber of the cauda equina along with a block of the tumor for histopathological examination, under electrophysiological monitoring. A hematoma observed in the conus medullaris was evacuated as much as possible (Fig. 2E).

Histopathological Findings. Histopathological analysis showed thin-walled vascular channels surrounded by fibrous tissues without any evidence of neuronal or glial tissue (Fig. 2F). The patient was diagnosed with CAs with hemorrhagic manifestation. He had two purple lesions of the skin tumor in the sacral area (S1–5) and biopsy of the tumor also showed typical features of CA (Fig. 1B). Postoperative Course. After the operation, the patient demonstrated immediate improvement in motor weakness and sensory disturbance. Sensorimotor deficits were completely resolved within 1 week and urinary disturbance also disappeared within 6 months. Postoperative MRI showed a reduced size of the main tumor mass, which lost contrast enhancement, while other lesions remained unchanged (Fig. 3A and 3B). No differences were observed in MR images obtained 18 months after the J Neurosurg: Spine / Volume 20 / February 2014

operation (Fig. 3C and 3D). The patient experienced no neurological deterioration during an 18-month follow-up period.


Spinal CAs account for approximately 5% of those occurring in the CNS.7,13,18 Gross et al. reviewed 27 publications and analyzed 352 cases of intramedullary spinal cord CAs.7 They reported that the mean age at presentation was 42 years, without sex predominance. Thirtyeight percent of the cases were cervical, 57% thoracic, 4% lumbar, and 1% in an unspecified location, indicating that lumbar spinal cord CA is extremely rare (14 cases). Approximately 90% of CAs, either intramedullary or extramedullary, have been reported to be completely removed by surgery.7,11 However, it appears to be more difficult to completely resect CAs in the cauda equina without damaging nerve roots. Of 15 cases of CAs occurring in the cauda equina, 7 required surgical dissection of the nerve roots because of strong adhesion of the tumors to the nerve roots. Of these 7 cases, 4 developed neurological deficits.4,19 In our case, the origin of the cauda equina, as well as the conus medullaris, was encapsulated by adherent tumors that were difficult to dissect, and several pieces of tumor were attached to different nerve roots. Repetitive hemorrhage in and around CAs might induce inflammation, which causes adhesion of the tumor to its surrounding tissue. We left most parts of the tumors untouched because resection of these tumors was likely to result in severe neurological deficits, according to electrophysiological monitoring. A similar decision was made by Miyake et al., who left 4 pieces of a CA that was adherent to distinct nerve roots.19 In addition, the difficulty in resecting angioma appears to be different between multiple angiomas and solitary angiomas. Multiple angiomas in the cauda equina failed to be completely resected in previous reports,19,22 although solitary angiomas were safely resected.3 Therefore, partial removal of CAs could be a treatment option if tumors apparently adhere to the nerve roots and electrophysiological examinations indicate a 143

Y. Matsui et al.

Fig. 2.  Images showing characteristics of the spinal lesions in the patient.  A and B: Sagittal contrast-enhanced T1-weighted (A) and (B) noncontrast T2*-weighted MR images of the thoracolumbar spinal cord showed intramedullary spinal lesions at T12– S1.  C: A PET scan demonstrated increased uptake of FDG in the largest lesion at T12–L1 (arrow).  D and E: Intraoperative view of a CA around the conus medullaris before (D) and after (E) a hematoma in the CA was evacuated. The angioma was adherent to the spinal cord. F: Photomicrograph showing a CA. H & E, original magnification ×10.

high risk of neurological complications in dissecting the nerve root, although the first-line treatment for symptomatic spinal CAs is complete resection of the tumor.7,17 The annual risk of hemorrhage of intramedullary CAs has been reported to be 1.6%–4.5%.7,14 Although we detected no signs of rebleeding on MR images at the 18-month follow-up, because there is a higher risk of bleeding for symptomatic CAs compared with asymptomatic CAs,1 we need to maintain a rigorous follow-up of the patient (such as MRI examinations every 6 months). Increased uptake of FDG is not common in CAs, and FDG-PET has been reported to be useful for differentiating a lesion from a malignant tumor.8,9,21 However, the FDG-PET study in our patient showed increased uptake of the tracer in the largest tumor at the conus medullaris, making it difficult to exclude malignancy. Miyauchi et al. reported a patient with a CA who showed increased uptake of FDG, and they speculated that inflammation 144

might account for the increased uptake.20 In our case, the lesion with increased uptake of FDG showed CAs with intra- or peritumoral hemorrhage, which might reflect inflammation induced by the hemorrhage. Cobb syndrome is a rare clinical entity, which includes the combination of a vascular skin nevus and a spinal angioma present at identical dermatomal levels. Arteriovenous malformations are a main spinal vascular pathology of Cobb syndrome, but Johnson and Petrie suggested that Cobb syndrome is accompanied by a wide variety of vascular pathologies, including telangiectasic angioma, venous angioma, hemangioblastoma, and CA.12 A total of 47 AVMs10,15,23 and 6 CAs,2,5,6,13,24 including our case, have been reported to date. Six cases of CAs associated with Cobb syndrome are summarized in Table 1. The reason why CAs are less frequently observed in Cobb syndrome than AVMs or port-wine angiomas is unclear. We speculate that spinal CAs are less likely to J Neurosurg: Spine / Volume 20 / February 2014

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63, F

26, F

8, M

32, F

42, M

Kaito et al., 1989

Basappa, 1996

Wakabayashi et   al., 2000

Gatzonis et al.,  2010

present case


port-wine stain on rt side of   back at T2–6 & infraaxil  lary region multiple angiokeratomas in   the rt C4–T1, S3–4 &   the lt L3–4, S1–4 areas large skin nevi at the lt back,   rt arm & lt lateral abdominal   wall at T2–3, T5–6, T9–11 multiple protruded purple skin   lesions in the gluteal area cavernous an gioma

not examined


not examined

deep purple nevus involving not examined   the whole of the rt UE &   neck at C4–T2* port-wine stain at chest, back, not examined   lt arm & shoulder


Skin Lesions

T-1, T-4,   T-5, T-7,  T-8 T12–S1



laminectomy, partial re  moval of tumor

completely free


urinary disturbance, up  per back pain

UE & LE weakness, posi- good recovery   tive pathological reflex   in both LEs LE weakness flaccid paraplegia

laminectomy, subtotal re- LE weakness   moval of tumor


Neurological Findings

slight sensory disturbance in   left foot & pathological re  flex in both LEs intramedullary posterior longitudinal my- LE weakness numbness & hypesthesia,   elotomy, partial re  flaccid paraparesis, promi  moval of tumor   nent spasticity intramedullary laminectomy, partial re- LE weakness & hypesthe- completely free   moval of tumor   sia, urinary distur  bance, low-back pain

not described




C5–7, T1–3, intramedullary gradually improved w/o  T12–L1   surgical intervention





Spinal CAs

* The lesions may be associated with Klippel-Trenaunay-Weber syndrome. LE = lower extremity; UE = upper extremity.

25, M

Gourie-Devi &   Prakash, 1978

Authors & Year

Age at Onset (yrs), Sex

TABLE 1: Characteristics of patients with Cobb syndrome with spinal CAs reported in the literature

Multiple cavernous angiomas in Cobb syndrome


Y. Matsui et al. lished cases, and in our case, whereas most spinal CAs present with solitary lesions.7,17 Multiple lesions in Cobb syndrome could be associated with incomplete resection and worse neurological outcome in patients. None of the previous reports described pathological findings of both spinal and skin lesions. However, in the present case, pathological findings of the spinal and cutaneous tumors were the same, showing typical features of CA. This is the first report of pathologically confirmed multiple intramedullary lumbar spinal CAs associated with skin CAs within the same metameric region. Coexistence of identical pathology in spinal and skin lesions at the same metamere suggests that CAs in our patient developed congenitally. Abnormality may occur in the mesoderm and the adjacent neural crest, which share the same metameric origin, before migration of these cells.16 Broad distribution and multiple lesions observed in Cobb syndrome could be associated with the timing of the development of CAs. Acknowledgment We thank Dr. Masato Hojo for his assistance in obtaining MR images. Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Author contributions to the study and manuscript preparation include the following. Conception and design: Mineharu, Matsui, Saiki. Acquisition of data: all authors. Analysis and interpretation of data: Mineharu, Matsui, Satow, Takeuchi, Saiki. Drafting the article: Matsui. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Mineharu. Administrative/ technical/material support: Mineharu. Study supervision: Saiki. References

Fig. 3.  Sagittal postoperative MR images of the spinal lesions.  A and B: Contrast-enhanced T1-weighted (A) and noncontrast T2weighted (B) images of the thoracolumbar spinal cord showed reduced size of the main tumor mass, which lost contrast enhancement, while other lesions remained unchanged.  C and D: Contrast-enhanced T1-weighted (C) and noncontrast T2-weighted (D) images obtained at the 18-month follow-up after the operation showed no significant differences compared with the postoperative MR images (A and B).

cause symptoms compared with spinal AVMs, and might be underdiagnosed. Spinal CAs in previous reports were observed in the cervicothoracic spine in 5 cases,2,5,6,13,24 whereas the CAs in our case were observed mainly in the lumbar spinal region. Patients in the previous reports were treated by laminectomy with or without partial removal of the tumor in all cases except for 1, and complete or partial recovery of clinical symptoms was obtained in 3 patients. Given that permanent morbidity is 6%–12% in patients with spinal CAs,7,17 the long-term outcome of patients with this syndrome may not be as good compared with patients with spinal CAs alone. Notably, CAs associated with Cobb syndrome present with multiple lesions, which spanned more than 3 vertebral levels in all 5 pub146

  1.  Al-Holou WN, O’Lynnger TM, Pandey AS, Gemmete JJ, Thompson BG, Muraszko KM, et al: Natural history and imaging prevalence of cavernous malformations in children and young adults. Clinical article. J Neurosurg Pediatr 9:198–205, 2012   2.  Basappa: Cobb syndrome. J Assoc Physicians India 44:846, 1996 (Letter)   3.  Cecchi PC, Rizzo P, Faccioli F, Bontempini L, Schwarz A, Bricolo A: Intraneural cavernous malformation of the cauda equina. J Clin Neurosci 14:984–986, 2007   4.  Chun SW, Kim SJ, Lee TH, Koo HS: Intra-root cavernous angioma of the cauda equina: a case report and review of the literature. J Korean Neurosurg Soc 47:291–294, 2010   5.  Gatzonis S, Stranjalis G, Siatouni A, Boviatsis E, Sakas DE: Neurological picture. Multiple spinal intramedullary cavernomas with vascular skin nevus or ‘Cobb syndrome’: a case report. J Neurol Neurosurg Psychiatry 81:500–501, 2010 (Erratum in J Neurol Neurosurg Psychiatry 82:944, 2011)   6.  Gourie-Devi M, Prakash B: Vertebral and epidural hemangioma with paraplegia in Klippel-Trenaunay-Weber syndrome. Case report. J Neurosurg 48:814–817, 1978   7.  Gross BA, Du R, Popp AJ, Day AL: Intramedullary spinal cord cavernous malformations. Neurosurg Focus 29(3):E14, 2010   8.  Hatayama K, Watanabe H, Ahmed AR, Yanagawa T, Shinozaki T, Oriuchi N, et al: Evaluation of hemangioma by positron emission tomography: role in a multimodality approach. J Comput Assist Tomogr 27:70–77, 2003

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Multiple cavernous angiomas in Cobb syndrome   9.  Higashiyama S, Kawabe J, Hayashi T, Kurooka H, Oe A, Kotani J, et al: A case of cavernous hemangioma in which malignancy was preoperatively excluded by FDG-PET. Ann Nucl Med 22:327–330, 2008 10.  Jagła M, Szymońska I, Kruczek P: Sonographic findings in a neonate with Cobb syndrome. J Clin Ultrasound 41:258–260, 2013 11.  Jin YJ, Chung SB, Kim KJ, Kim HJ: Spinal intradural extramedullary cavernoma presenting with intracranial superficial hemosiderosis. J Korean Neurosurg Soc 49:377–380, 2011 12.  Johnson WD, Petrie MM: Variety of spinal vascular pathology seen in adult Cobb syndrome. Report of 2 cases. J Neurosurg Spine 10:430–435, 2009 13.  Kaito H, Kuwata T, Nohara T, Yokoyama J, Mochio S, Hashimoto N, et al: [Cobb syndrome (cutaneomeningospinal angiomatosis). The first case reported in Japan.] Nihon Naika Gakkai Zasshi 78:1758–1764, 1989 (Jpn) 14.  Kim KM, Chung CK, Huh W, Lee WJ, Park SB, Kim CH, et al: Clinical outcomes of conservative management of spinal cord cavernous angiomas. Acta Neurochir (Wien) 155:1209–1214, 2013 15.  Kivelev J, Ramsey CN, Dashti R, Porras M, Tyyninen O, Hernesniemi J: Cervical intradural extramedullary cavernoma presenting with isolated intramedullary hemorrhage. Case report. J Neurosurg Spine 8:88–91, 2008 16.  Krings T, Geibprasert S, Luo CB, Bhattacharya JJ, Alvarez H, Lasjaunias P: Segmental neurovascular syndromes in children. Neuroimaging Clin N Am 17:245–258, 2007 17.  Liang JT, Bao YH, Zhang HQ, Huo LR, Wang ZY, Ling F: Management and prognosis of symptomatic patients with intramedullary spinal cord cavernoma. Clinical article. J Neurosurg Spine 15:447–456, 2011 18.  Linfante I, Tari Capone F, Dabus G, Gonzalez-Arias S, Lau PE, Samaniego EA: Spinal arteriovenous malformation associated with spinal metameric syndrome: a treatable cause of long-term paraplegia? Case report. J Neurosurg Spine 16: 408–413, 2012

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19.  Miyake S, Uchihashi Y, Takaishi Y, Sakagami Y, Kohmura E: Multiple cavernous angiomas of the cauda equina. Case report. Neurol Med Chir (Tokyo) 47:178–181, 2007 20.  Miyauchi Y, Matsubara H, Okuwaki H, Kunimitsu T, Suzuki S, Matsumoto M: [A case of malignancy suspected by fluorodeoxyglucose positron emission tomography which was confirmed to be cavernous hemangioma of the rib.] Nihon Rinsho Geka Gakkai Zasshi 71:2279–2282, 2010 (Jpn) 21.  Nakamura H, Kawasaki N, Taguchi M, Kitamura H: Cavernous hemangioma of the rib diagnosed preoperatively by percutaneous needle biopsy. Gen Thorac Cardiovasc Surg 55: 134–137, 2007 22.  Roncaroli F, Scheithauer BW, Deen HG Jr: Multiple hemangiomas (hemangiomatosis) of the cauda equina and spinal cord. Case report. J Neurosurg 92 (2 Suppl):229–232, 2000 23.  Spiotta AM, Hussain MS, Masaryk TJ, Krishnaney AA: Combined endovascular and surgical resection of a giant lumbosacral arteriovenous malformation in a patient with Cobb syndrome. J Neurointerv Surg 3:293–296, 2011 24.  Wakabayashi Y, Isono M, Shimomura T, Tajima A, Terashi H, Asada Y, et al: Neurocutaneous vascular hamartomas mimicking Cobb syndrome. Case report. J Neurosurg 93 (1 Suppl):133–136, 2000

Manuscript submitted April 30, 2013. Accepted November 12, 2013. Please include this information when citing this paper: published online December 20, 2013; DOI: 10.3171/2013.11.SPINE13419. Address correspondence to: Yohei Mineharu, M.D., Ph.D., Di­­vision of Neuroendovascular Therapy, Institute of Biomedical Research and Innovation (IBRI), 2-2 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. email: [email protected] ac.jp.


Coexistence of multiple cavernous angiomas in the spinal cord and skin: a unique case of Cobb syndrome.

Cobb syndrome is a rare, noninherited, neurocutaneous disease characterized by vascular abnormality of the spinal cord and is associated with vascular...
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