Letter to the Editor: Stereotactic injection of nondiffusible dyes

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  • 1 Neurosurgery Unit, NOCSAE Modena Hospital, Modena, Italy; and 
  • | 2 Treviso Hospital, University of Padova, Treviso, Italy
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TO THE EDITOR: We read with interest the paper by Margetis et al.3 (Margetis K, Rajappa P, Tsiouris AJ, et al: Intraoperative stereotactic injection of Indigo Carmine dye to mark ill-defined tumor margins: a prospective Phase I—II study. J Neurosurg 122:40–48, January 2015). Our group in Treviso used a very similar technique and published the results about 25 years ago.1,2 We similarly used nonspreading dyes to highlight the tumor borders before performing the craniotomy and consequently before brain shift could occur. Methylene blue was injected to label the tumor boundaries. The only differences were the use of a stereotactic frame, because the frameless navigation system was not available at that time, and the injection of the dye through a single bur hole. With this technique, the mass is encompassed in a cone, with its apex at the entry point and its base at the deepest face of the tumor. The colored tracks can be also helpful to reach the tumor, minimizing the damage to the normal brain tissue. Our series included 25 patients harboring not only WHO I–IV gliomas (19 cases), but also cavernomas and metastasis.

Of course, nowadays we would not recommend such a method to resect cavernomas, which are much better localized using neuronavigation. However, we agree with Margetis et al. when they say that stereotactic injection of nondiffusible dyes can be useful to better visualize tumor margins for improving the extent of removal, reducing damage to normal brain tissue, and avoiding inaccuracies due to brain shift. Moreover, this technique has very limited costs, which is of great interest for the large number of neurosurgical departments that cannot afford the expenses related to more updated and technologically advanced techniques to localize and intraoperatively outline brain tumors.

After the publication of our first 25 patients in 1990, we have been using dye injection until recent years in selected cases. The injection of nondiffusible dyes should be considered as a possible tool especially for deep-seated tumors and for low-grade gliomas, whose limits are often difficult to guess intraoperatively. Coupling this technique with cortical and subcortical neurophysiological mapping is likely to maximize the resection and better preserve functionally eloquent areas.

References

  • 1

    Longatti P, & Carteri A: Stereotactic location and delimitation of brain tumors in children. Technical note. Childs Nerv Syst 5:250251, 1989

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  • 2

    Longatti P, , Di Paola F, , Baratto V, , Zanata R, , Trincia G, & Carteri A: Stereotactic support in the excision of brain tumors. Technical note. J Neurosurg Sci 34:315318, 1990

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  • 3

    Margetis K, , Rajappa P, , Tsiouris AJ, , Greenfield JP, & Schwartz TH: Intraoperative stereotactic injection of Indigo Carmine dye to mark ill-defined tumor margins: a prospective Phase I-II study. J Neurosurg 122:4048, 2015

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  • Weill Cornell Medical College, New York, NY

Response

We thank Drs. Feletti and Longatti for bringing to our attention their work on the stereotactic injection of methylene blue for delineating the border of brain tumors prior to surgery.3,4 Their work predates our paper and clearly represents the first stereotactic injection of dye in the brain for these purposes. As such, they should be credited for proof of concept. The differences in the techniques (e.g., framed vs frameless stereotaxy, single vs multiple bur holes for dye injection, the use of preoperative CT vs MRI, and the use of brain cannula vs spinal needle) are not based on different fundamental concepts, but rather they represent technological advances that occurred between the two studies.

However, we wish to point out another key difference, which is that our study required approval from the FDA for an investigational new drug study emphasizing the safety of the pharmaceutical compound used. The use of methylene blue by the Treviso group hinders the generalizability of their method. Several reports1,2,5,6—with the first one being published 66 years ago7—have established the toxicity of methylene blue after intrathecal injection. In the light of these reports it would be problematic to use methylene blue for this technique. The use of methylene blue was eliminated from consideration very early in the planning phase of our study, which may explain why the Treviso study eluded our literature review. Ultimately, we are pleased to reiterate and confirm the utility of stereotactic injection of dyes for tumor delineation as a helpful adjunct in neuro-oncological surgery even in the age of intraoperative MRI scans.

References

  • 1

    Arieff AJ, & Pyzik SW: Quadriplegia after intrathecal injection of methylene blue. JAMA 173:794796, 1960

  • 2

    Evans JP, & Keegan HR: Danger in the use of intrathecal methylene blue. JAMA 174:856859, 1960

  • 3

    Longatti P, & Carteri A: Stereotactic location and delimitation of brain tumors in children. Childs Nerv Syst 5:250251, 1989

  • 4

    Longatti PL, , Di Paola F, , Baratto V, , Zanata R, , Trincia G, & Carteri A: Stereotactic support in the excision of brain tumors. Technical note. J Neurosurg Sci 34:315318, 1990

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    • Export Citation
  • 5

    Schultz P, & Schwarz GA: Radiculomyelopathy following intrathecal instillation of methylene blue. A hazard reaffirmed. Arch Neurol 22:240244, 1970

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  • 6

    Sharr MM, , Weller RO, & Brice JG: Spinal cord necrosis after intrathecal injection of methylene blue. J Neurol Neurosurg Psychiatry 41:384386, 1978

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    • Export Citation
  • 7

    Walker AE: Spontaneous ventricular rhinorrhea and otorrhoea. J Neuropathol Exp Neurol 8:1710183, 1949

  • 1

    Longatti P, & Carteri A: Stereotactic location and delimitation of brain tumors in children. Technical note. Childs Nerv Syst 5:250251, 1989

    • Search Google Scholar
    • Export Citation
  • 2

    Longatti P, , Di Paola F, , Baratto V, , Zanata R, , Trincia G, & Carteri A: Stereotactic support in the excision of brain tumors. Technical note. J Neurosurg Sci 34:315318, 1990

    • Search Google Scholar
    • Export Citation
  • 3

    Margetis K, , Rajappa P, , Tsiouris AJ, , Greenfield JP, & Schwartz TH: Intraoperative stereotactic injection of Indigo Carmine dye to mark ill-defined tumor margins: a prospective Phase I-II study. J Neurosurg 122:4048, 2015

    • Search Google Scholar
    • Export Citation
  • 1

    Arieff AJ, & Pyzik SW: Quadriplegia after intrathecal injection of methylene blue. JAMA 173:794796, 1960

  • 2

    Evans JP, & Keegan HR: Danger in the use of intrathecal methylene blue. JAMA 174:856859, 1960

  • 3

    Longatti P, & Carteri A: Stereotactic location and delimitation of brain tumors in children. Childs Nerv Syst 5:250251, 1989

  • 4

    Longatti PL, , Di Paola F, , Baratto V, , Zanata R, , Trincia G, & Carteri A: Stereotactic support in the excision of brain tumors. Technical note. J Neurosurg Sci 34:315318, 1990

    • Search Google Scholar
    • Export Citation
  • 5

    Schultz P, & Schwarz GA: Radiculomyelopathy following intrathecal instillation of methylene blue. A hazard reaffirmed. Arch Neurol 22:240244, 1970

    • Search Google Scholar
    • Export Citation
  • 6

    Sharr MM, , Weller RO, & Brice JG: Spinal cord necrosis after intrathecal injection of methylene blue. J Neurol Neurosurg Psychiatry 41:384386, 1978

    • Search Google Scholar
    • Export Citation
  • 7

    Walker AE: Spontaneous ventricular rhinorrhea and otorrhoea. J Neuropathol Exp Neurol 8:1710183, 1949

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