5-Aminolevulinic Acid and Indocyanine Green: Fluorescence-Guided Resection of Spinal Cord Intramedullary Tumors

8 5-Aminolevulinic Acid and Indocyanine Green: Fluorescence-Guided Resection of Spinal Cord Intramedullary Tumors


Toshiki Endo, Tomoo Inoue, and Teiji Tominaga


Abstract
During surgery for intramedullary spinal cord tumors, it is important to detect the boundaries between the lesion and the normal spinal cord. Better visualization of the border will increase the likelihood for the maximum degree of resection without damaging the surrounding spinal cord. For this purpose, we describe here the utility of 5-aminolevulinic acid (5-ALA) and indocyanine green (ICG) videoangiography during intramedullary spinal cord tumor surgery. In astrocytic and ependymal tumors, 5-ALA induces red fluorescence in tumors, which helps surgeons delineate lesions from the surrounding spinal cord, especially with ependymomas. ICG videoangiography is useful for removing hypervascular tumors including hemangioblastomas. By locating feeders as well as drainers, ICG helps surgeons better understand the angioarchitectures around the tumors and perform reliable surgical resections. In cavernous angioma surgery, ICG videoangiography highlights lesions as an avascular area. Both 5-ALA and ICG are useful surgical adjuncts during intramedullary spinal cord tumor surgery. With appropriate use of fluorescence-guided surgery in spinal cord surgery, neurosurgeons are more likely to achieve both maximum tumor removal and preservation of spinal cord functions.


Keywords: 5-aminolevulinic acid, endoscope, indocyanine green, intramedullary tumor, spinal cord tumors, neuromonitoring


8.1 Introduction


In spinal cord tumor surgery, the goal is to achieve both maximum tumor resection and functional preservation. In this chapter, we describe the utility of fluorescence-guided resection in spinal cord intramedullary tumor surgery. Specifically, we describe the application of 5-aminolevulinic acid (5-ALA) during spinal cord ependymoma and astrocytoma surgery. We also present clinical cases (hemangioblastoma and cavernous angioma) in which indocyanine green (ICG) videoangiography was utilized.


8.2 Protocols


8.2.1 5-Aminolevulinic Acid


Patients were orally administered 5-ALA (20 mg/kg body-weight; Cosmo Bio Co., Ltd, Tokyo, Japan) 2 hours before the induction of anesthesia. For intraoperative detection of 5-ALA fluorescence, an operative microscope (Carl Zeiss Co., Oberkochen, Germany), which can switch from conventional white light to violet–blue excitation light, was used. To avoid potential skin phototoxicity, all patients were protected from light sources for 24 hours after 5-ALA administration.


8.2.2 Indocyanine Green


For intraoperative ICG videoangiography, 0.3 mg/kg of ICG (Santen, Tokyo, Japan), diluted with 3.0 mL of saline, followed by 10 mL of saline were injected intravenously. A Pentero operating microscope (Carl Zeiss Co.) was used to excite and visualize ICG.


8.3 5-Aminolevulinic Acid in Ependymoma Surgery


8.3.1 Overview


Spinal cord ependymoma is the most common intramedullary tumor and accounts for 35 to 40% of such tumors.1 Once gross total resection is achieved, intramedullary ependymoma is potentially curable with an excellent prognosis and a low recurrence rate.2,3 The most important tip for gross total resection of intramedullary ependymoma is to find the cleavage plane between the tumor and the normal spinal cord parenchyma.4 This is often difficult at the rostral and caudal ends of the tumor cavity or in the anterior medial fissure.5 The former portion is connected to the cavity and central canal, and the plane is often unclear. Small branches from the anterior spinal artery frequently feed the tumors. Care must be taken to preserve the anterior commissure and the anterior spinal vasculature since gliosis on the ventral side of the tumor can be severe due to repeated hemorrhage. In the following section, we describe each step of the surgical procedure for 5-ALA fluorescence-guided resection of ependymoma.


8.3.2 Surgical Procedure


To separate the posterior median sulcus and approach the tumor, patients were usually positioned prone. At our facility, we routinely monitor motor evoked potentials (MEPs) and somatosensory evoked potentials (SSEPs) in all spinal cord tumor operations. SSEPs were elicited from the posterior tibial and ulnar nerves (pulse duration 0.20 ms, frequency 4.7 Hz, and intensity 10–30 mA). Transcranial stimulation was applied for MEPs under the following conditions: biphasic 5 train stimuli; pulse duration = 0.5 ms; pulse interval = 2 ms; and intensity = 150–200 mA (MS-120B, Nihon Koden, Tokyo, Japan). Evoked muscles included the biceps, hypothenar, tibialis anterior, and gastrocnemius. The surgical procedure began after the neuromonitoring team completed their setup and confirmed responses.



8.3.3 Representative Cases


Following dissection of the posterior median sulcus, we encountered gray tumors in the midline (image Fig. 8.1c). As shown in image Fig. 8.1, strong fluorescence was apparent in the tumor (image Fig. 8.1d). As we reported previously, spinal cord ependymoma tumors frequently reveal strong 5-ALA-induced fluorescence.5 In our case series, seven of nine cases showed strong fluorescence, which was dependent on MIB-1 labeling indexes.


In one case, we were unable to dissect a yellow tissue of the tumor at the ventrocaudal end (image Fig. 8.1e). Observation using violet–blue excitation light showed no 5-ALA fluorescence (image Fig. 8.1f). Therefore, we did not think it was necessary to proceed with further radical dissection of the ventral spinal cord, and we closed the case.


Preoperatively, his postoperative neurological recovery was remarkable. The last follow-up was 5 years after the surgery. The patient was free from tumor recurrence, and could walk and run without assistance.


In another case (image Fig. 8.2; Video 8.1), 5-ALA-induced protoporphyrin IX (PpIX) fluorescence was observed at the caudal border of the tumor (image Fig. 8.2e). We thus resected this portion and encountered yellowish tissue (image Fig. 8.2g). We did not remove the yellowish tissue since it exhibited no fluorescence (image Fig. 8.2h). Importantly, postoperative histological evaluations confirmed the findings of PpIX fluorescence. Tumor cells were evident where 5-ALA fluorescence was positive at the tumor border (image Fig. 8.2f). Following fluorescence-guided resection, this patient experienced postoperative neurological recovery and a long-term recurrence-free period.


8.3.4 Summary


As the representative cases indicate, tumor fluorescence derived from 5-ALA enabled neurosurgeons to identify the tumor during resection and to better identify the resection border. 5-ALA fluorescence-guided surgery (FGS) was easy and did not require the interruption of surgery.5 Moreover, this technique was useful for differentiating tumors from nontumor tissues, thus facilitating complete resections of intramedullary ependymomas without permanent neurological deterioration.


8.4 5-Aminolevulinic Acid in Astrocytoma Surgery


8.4.1 Overview


In general, the prognosis of spinal cord high-grade astrocytoma remains poor. According to previous reports, estimated median survival ranges from 10 to 72 months and 9 to 13.1 months in anaplastic astrocytoma and glioblastoma, respectively.6,7,8 Among various prognostic factors, the extent of surgical resection might improve patient outcomes. For instance, McGirt et al reported the beneficial effects of radical resection in increasing overall survival in high-grade astrocytoma cases.7 However, pursuing radical tumor resection can sometimes be harmful, since a clear cleavage plane between the tumor and the normal spinal cord does not exist in most cases of spinal cord astrocytoma.9


In treating spinal cord astrocytoma, we believe that treatment protocols should rely on histological grades. Therefore, when the preoperative diagnosis included astrocytoma, open biopsy or partial resections were indicated to determine the pathological diagnosis. Based on the diagnosis and histological grade, decisions were made for further surgical intervention and/or postoperative adjuvant chemotherapy and radiotherapy. In the following section, we describe our findings with 5-ALA FGS in spinal cord astrocytoma surgery.


Feb 12, 2020 | Posted by in NEUROSURGERY | Comments Off on 5-Aminolevulinic Acid and Indocyanine Green: Fluorescence-Guided Resection of Spinal Cord Intramedullary Tumors
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