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@0W�Ѓ�@�L[��@�sj�������՜.��+,��D��՜.��+,��\���M 	�0.zCaolan80	2�9��>	��G���"4VL�d��8D��b�j�L����Hemangioblastoma of the filum terminale resected with the aid of intraoperative indocyanine green angiography in a patient affected by von Hippel Lindau disease
Annette Puzzolante, Andrea Prontera, Giacomo Pavesi
Neurosurgery, Nuovo Ospedale Civile Sant Agostino Estense, Modena, Italy


Corresponding Author:
Giacomo Pavesi, MD
Neurochirurgia, NOCSAE Baggiovara, Modena, Italy
tel: 0039 059 3961471   fax: 0039 059 3962408   mobile: 3485844804
e-mail: g.pavesi@ausl.mo.it


keywords: von Hippel-Lindau; filum terminale; hemangioblastoma; indocyanine green videoangiography.


Cover letter
All Authors agree that the paper submitted tro the Editors of Journal of Spine and Neurosurgery deserves attention because of the relative rarity of the tumor treated location and because of the increasing, but still early, experience with indocyanine green videoangiography as a new technological adjunct for these vascular lesions. The paper has included  2 figures and 1 table.
All authors have no conflict of interest.
A Puzzolante, A Prontera, G Pavesi


Introduction
Hemangioblastomas are benign vascular tumours that occur sporadically or as part of von Hippel-Lindau (VHL) syndrome. In order of frequency, central nervous system (CNS) hemangioblastoma originates in cerebellum, spinal cord and brainstem [1]. Regarding spinal involvement, these lesions represent 1.6-2.1% of all spinal cord tumors and the majority of them are localized intramedullary. Hemangioblastomas of the filum terminale are rare. Although spinal hemangioblastomas are more VHL-related rather than sporadic, the few cases of hemangioblastoma of the filum terminale reported in the literature concern patients without VHL diagnosis. 
The use of indocyanine green (ICG) is well established in neurovascular field; recently, this fluorescent tracer has been showed to have an increasing role in CNS tumor resection [2,3].
We report the case of an hemangioblastoma of the filum terminale, resected with the aid of intraoperative indocyanine green angiography, arising in a patient with VHL disease.

Case report
A 22 years-old woman affected by VHL disease (tested by genetic molecular analysis) previously operated for bilateral pheochromocitomas and for cerebellar and dorsal spinal cord hemangioblastomas, harboured other multiple cerebellar and spinal localizations. She returned to our attention for hypoesthesia to the left big toe, without weakness nor sphincteric disorders. MRI showed a mild growth of a lumbar hemangioblastoma at L2-L3 level, occupying the whole intradural space, displacing laterally and anteriorly the adjacent nerve roots (Fig.1 A-B). The patient was submitted to microsurgical treatment through a L2 laminectomy. Intraoperative indocyanine green angiography was obtained after tumour exposure, in order to distinguish arterial vascularization from arterialized veins, before starting the microvascular dissection (Fig.2). Then the filum was cut above and below the lesion. After tumour resection, the �ICG-videoangiography images confirmed the radical excision of the nodule. No blood transfusion was required. Histological examination confirmed the diagnosis of hemangioblasoma. Patient was discharged after an uneventful postoperative course. A four months post-operative control MRI confirmed the total removal of the tumour (Fig.1 C).

Discussion
Epidemiology
In order of frequency, CNS hemangioblastoma originates in cerebellum, spinal cord and brainstem1. VHL is a neoplastic multisistemic autosomal-dominant syndrome, particularly predisposing to develop CNS hemangioblastomas. In the context of a multidisciplinary clinical surveillance these lesions can be successfully removed with a favourable impact on quality of life and survival of VHL-patients [4,5]. 
Hemangioblastoma may also arise as  sporadic case  in patients without VHL disease. Sporadic hemangioblastomas account for about 2/3 while VHL-related hemangioblastomas account for 1/3 of all hemangioblastomas [6,7].
Primary tumours of the spinal cord represent 4.5% of all CNS primary tumours with meningiomas, ependymomas and schwannomas being the most common histological types8. Spinal cord hemangioblastomas, mainly intramedullary located, comprise between 1.6  and 2.1% of all spinal cord tumours and usually occur in the cervical or thoracic spine; only 21-28% of spinal cord hemangioblastomas are located intradural-extramedullary and 9-13% of these arising at the cauda equina [6,8]. Acquired tumours arising at the filum terminale encompass a wide range of histopathological types:  ependymoma and astrocytoma are the most common, hemangioblastoma has been rarely reported (Table 1). Therefore, hemangioblastoma localizations in the cauda equina and particularly in the filum terminale are uncommon tumours. 
Epidemiological data show a discrepancy between the incidence of spinal hemangioblastomas and the incidence of filum terminale hemangioblastomas in relation with VHL association. Actually, spinal hemangioblastomas are more prevalent in VHL-affected patients rather than in sporadic cases [7,9]. Despite this, regarding the lesions of filum terminale, our patient represents the only VHL-affected patient among the reported cases; Ortega-Martinez et al. reviewed the literature and reported ten cases of hemangioblastomas arising in the filum terminale, but none of these cases was related to VHL syndrome [10-19]. Biondi et al reported other two cases of hemangioblastomas of the filum terminale in patients without VHL disease, but complete genetic molecular analysis was not performed [20].  Similarly, three successive cases of filum terminale hemangioblastomas were reported as sporadic cases [21-23].  On the other hand,  since the majority of extramedullary spinal hemangioblastomas occurs in VHL affected patients, VHL disease should be considered also in patients with a single hemangioblastoma at the filum terminale [24]. 

Treatment
IGC angiography is assuming an important role in neurosurgery as demonstrated by the increasing literature about its use in the treatment of vascular malformations. Recently, it has also been used to assess peripheral vascularization during hemangioblastomas resection [25-28]. Since hemangioblastomas are highly vascular soft and fragile tumours, they require a meticulous surgical planning in order to achieve a safe radical removal. In our experience preoperative embolization was never adopted, since their arterial feeders are often tiny fragile vessels preventing a safe endovascular selective navigation. Microsurgical technique and bipolar coagulation of the feeders all around the lesion are mandatory. However, in several cases intraoperative distinction of feeders and arterialized draining veins may be not straightforward. In order to avoid early closure of tumoral vascular drainage, that may be associated with lesion engorgement and subsequent intraoperative bleeding, in the present case, �indocyanine green was injected intravenously after the tumour was exposed. The ICG-videoangiography provided a fine dynamic map of the tumoral vascularization allowing a precise distinction between feeding and draining vessels (Fig.2). Thus, the task of tumour devascularization was performed with more precision and safety, since during spinal intradural surgery it is mandatory to identify tumour vessels from functional vascularization [29,30].
The hemangioblastoma was cut en bloc from both extremities of the filum and ICG angiography showed the complete removal of the lesion at the end of surgery.

Conclusions
Hemangioblastoma of the filum terminale is a rare entity and VHL syndrome should be investigated in patients with spinal hemangioblastoma, particularly extramedullary. ICG-videoangiography allows neurosurgeons to distinguish feeders and draining vessels in order to perform a safe devascularization before tumoral removal, thus reducing intraoperative blood loss and enhancing clearness of surgery.

REFERENCES
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5. Mehta GU, Asthagiri AR, Bakhtian KD, Auh S, Oldfield EH, Linser RR (2010) Functional outcome after resection of spinal cord hemangioblastomas associated with von Hippel-Lindau disease.  HYPERLINK ""J Neurosurg Spine 12(3):233-42.
6. Browne TR, Adams RD, Roberson GH (1976) Hemangioblastoma of the spinal cord. Review and report of five cases. Arch Neurol 33:435 41.
7. Conway JE, Chou D, Clatterbuck RE, Brem H, Long DM, Rigamonti D (2001) Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease. Neurosurgery 48:55 63.
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10. Ortega-Martinez M, Cabezudo J, Fernandez-Portales I, Pineda-Palomo M, Rodriguez-Sanchez JA, Bernal-Garcia LM (2007) Multiple filum terminale hemangioblastomas symptomatic during pregnancy. J Neurosurg Spine 7:254-8.
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Table 1 - Cases of filum terminale hemangioblastomas: literature review
Case
NoAuthor & yearAge (yrs)SexVHLLesion level1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16Wyburn-Mason, 1943 [11] 
Norstrom et al. 1961 [12] 
Sloof et al. 1964[13] 
Wolbers et al. 1985 [14] 
Silverman et al. 1986 [15] 
Tibbs et al. 1999[16] 
Arbelaez et al. 1999 [17] 
Farneti et al. 2001 [18] 
Biondi et al. 2005 [20] 
Biondi et al. 2005 [20] 
Nadkarni et al. 2006 [19]  
Ortega-Martinez et al. 2007[10]
Ciappetta et al. 2007 [21]  
Wong et al. 2007 [22] 
Sergides et al. 2009 [23] 
Present case25
NR
51
36
66
35
73
57
61
NR
52
41
62
64
75
22F
NR
M
M
M
M
M
M
M
M
M
F
F
M
M
FNR
NR
no
no
NR
no
no
no
no
no
no
no
no
no
no
yesL2-S2
NR
L4-S1
L1
L2
L2-L3
L1-L2
L4
L3
NR
L2-L3
L3 & S1
L2-L3
L4
L3
L2-L3
NR: not reported






FIGURE Legends
Figure 1: pre-operative post-contrast T1-weighted MRI showing an enhancing hemangioblastoma that occupies totally the lumbar canal in axial scan (A), at L2-L3 level in sagittal scan (B); post-operative MRI scan confirming total hemangioblastoma removal (C).

Figure 2: intraoperative view (A); early phase of ICG-videoangiography (B); late phase of ICG-videoangiography (C). ICG shows dynamically the early filling of tumour feeding vessels and the direction of the drainage veins.



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