Spinal cord hemangioblastoma treatment

Spinal cord hemangioblastoma treatment

Although radiosurgery has been used to treat multiple hemangioblastoma, particularly in the cerebellum, complete microsurgical removal is the treatment of choice for spinal cord hemangioblastoma 1).

Partial resection or biopsy may cause postoperative bleeding and should therefore not be performed. Bleeding during dissection, due to the vascularity of HBs, increases the risk of adverse events.

minimally invasive approach for the resection of selected spinal hemangioblastomas is safe and allows complete tumor resection with good clinical results in experienced hands 2).


They are almost always associated with a syrinx or significant edema.

Cases associated with edema and syrinx are more space-occupying than those only with solid part of the tumor. Consequently, the mass effect producing neurological symptoms derives from the cyst rather than the tumor itself. On the removal of hemangioblastomas in association with a syrinx, the syrinx is spontaneously opened and always stops growing and usually regresses in size. Thus, the additional opening of the syrinx or surgical removal of the syrinx is not necessary 3).

Preceding Embolization

Although some investigators recommend preoperative embolization, 4) 5) in the series of Harati et al. it was usually not necessary to achieve complete resection 6). This is in concordance to several other series so that preoperative embolization is generally not recommended 7) 8) 9) 10) 11). To prevent intraoperative bleeding in selected cases, temporary artery occlusion was performed. This technique is described in detail by Clark et al.12).

Fluorescent dye

As vascular tumors, intramedullary hemangioblastomas are associated with significant intraoperative blood loss, making them particularly challenging clinical entities. The use of intraoperative indocyanine green or other fluorescent dyes has previously been described to avoid breaching the tumor capsule, but improved surgical outcomes may result from identifying and ligating the feeder arteries and arterialized draining veins.

Molina et al. presented a written and media illustration of a technique for intraoperative indocyanine green use in the en bloc resection of intramedullary hemangioblastoma 13).

Radiosurgery

Cyberknife radiosurgery has proven to be safe in the treatment of spinal HBs 14). However, as radiographic regression was achieved in only 22%, microsurgical resection remains the gold standard for spinal HBs that are clearly symptomatic or have developed radiographic progression in size, spinal cord edema, or syrinx 15) 16) 17).

References

1)

Samii M, Klekamp J. Surgical results of 100 intramedullary tumors in relation to accompanying syringomyelia. Neurosurgery. 1994 Nov;35(5):865-73; discussion 873. PubMed PMID: 7838335.
2)

Krüger MT, Steiert C, Gläsker S, Klingler JH. Minimally invasive resection of spinal hemangioblastoma: feasibility and clinical results in a series of 18 patients. J Neurosurg Spine. 2019 Aug 9:1-10. doi: 10.3171/2019.5.SPINE1975. [Epub ahead of print] PubMed PMID: 31398701.
3)

Na JH, Kim HS, Eoh W, Kim JH, Kim JS, Kim ES. Spinal cord hemangioblastoma : diagnosis and clinical outcome after surgical treatment. J Korean Neurosurg Soc. 2007 Dec;42(6):436-40. doi: 10.3340/jkns.2007.42.6.436. Epub 2007 Dec 20. PubMed PMID: 19096585; PubMed Central PMCID: PMC2588179.
4)

Montano N, Doglietto F, Pedicelli A, Albanese A, Lauretti L, Pallini R. Embolization of hemangioblastomas. J Neurosurg. 2008. 108: 1063-4
5)

Yang Y, Wang D, Jiang H, Sha C, Yuan Q, Liu J. [Treatment of spinal cord hemangioblastoma by microoperations combined with embolization]. Zhonghua Yi Xue Za Zhi. 2008. 88: 1309-12
6)

Harati A, Satopää J, Mahler L, Billon-Grand R, Elsharkawy A, Niemelä M, Hernesniemi J. Early microsurgical treatment for spinal hemangioblastomas improves outcome in patients with von Hippel-Lindau disease. Surg Neurol Int. 2012;3:6. doi: 10.4103/2152-7806.92170. Epub 2012 Jan 21. PubMed PMID: 22347675; PubMed Central PMCID: PMC3279991.
7)

Cornelius JF, Saint-Maurice JP, Bresson D, George B, Houdart E. Hemorrhage after particle embolization of hemangioblastomas: Comparison of outcomes in spinal and cerebellar lesions. J Neurosurg. 2007. 106: 994-8
8)

Mandigo CE, Ogden AT, Angevine PD, McCormick PC. Operative management of spinal hemangioblastoma. Neurosurgery. 2009. 65: 1166-77
9)

Mehta GU, Asthagiri AR, Bakhtian KD, Auh S, Oldfield EH, Lonser RR. Functional outcome after resection of spinal cord hemangioblastomas associated with von Hippel-Lindau disease. J Neurosurg Spine. 2010. 12: 233-42
10)

Oppenlander ME, Spetzler RF. Advances in spinal hemangioblastoma surgery. World Neurosurg. 2010. 74: 116-7
11)

Pietilä TA, Stendel R, Schilling A, Krznaric I, Brock M. Surgical treatment of spinal hemangioblastomas. Acta Neurochir (Wien). 2000. 142: 879-86
12)

Clark AJ, Lu DC, Richardson RM, Tihan T, Parsa AT, Chou D. Surgical technique of temporary arterial occlusion in the operative management of spinal hemangioblastomas. World Neurosurg. 2010. 74: 200-5
13)

Molina CA, Pennington Z, Ahmed AK, Westbroek E, Goodwin ML, Tamargo R, Sciubba DM. Use of Intraoperative Indocyanine Green Angiography for Feeder Vessel Ligation and En Bloc Resection of Intramedullary Hemangioblastoma. Oper Neurosurg (Hagerstown). 2019 Apr 1. pii: opz053. doi: 10.1093/ons/opz053. [Epub ahead of print] PubMed PMID: 31220325.
14)

Moss JM, Choi CY, Adler JR, Soltys SG, Gibbs IC, Chang SD. Stereotactic radiosurgical treatment of cranial and spinal hemangioblastomas. Neurosurgery. 2009. 65: 79-85
15)

Ammerman JM, Lonser RR, Dambrosia J, Butman JA, Oldfield EH. Long-term natural history of hemangioblastomas in patients with von Hippel-Lindau disease: Implications for treatment. J Neurosurg. 2006. 105: 248-55
16)

Conway JE, Chou D, Clatterbuck RE, Brem H, Long DM, Rigamonti D. Hemangioblastomas of the central nervous system in von Hippel-Lindau syndrome and sporadic disease. Neurosurgery. 2001. 48: 55-62
17)

Samii M, Klekamp J. Surgical results of 100 intramedullary tumors in relation to accompanying syringomyelia. Neurosurgery. 1994. 35: 865-73

Lactotroph adenoma radiosurgery

Lactotroph adenoma radiosurgery

Lactotroph adenoma radiosurgery also serves as an option for those refractory to medical and surgical therapy 1).

GKRS plays a significant role in the treatment of non-functioning [NFA] and hormonal-active [HAA] pituitary adenoma. It affords high rate of tumor control and offers low risk of collateral neurological or endocrine axis injury. A study showed that control of tumor growth was achieved in 90% patients, shrinkage of tumor in 54% and arrest of progression in 36% cases after GKRS treatment. The biochemical remission rate in GH secreting adenoma was 57%, ACTH adenoma was 67% and prolactinoma was 40%. Age less than 50 years and tumor volume less than 5cm3 were associated with a favourable radiosurgical outcome 2).

Case series

retrospective study included lactotroph adenoma treated with SRS between 1997 and 2016 at ten institutions. Patients’ clinical and treatment parameters were investigated. Patients were considered to be in endocrine remission when they had a normal level of prolactin (PRL) without requiring dopamine agonist medications. Endocrine control was defined as endocrine remission or a controlled PRL level ≤ 30 ng/ml with dopamine agonist therapy. Other outcomes were evaluated including new-onset hormone deficiency, tumor recurrence, and new neurological complications.

The study cohort comprised 289 patients. The endocrine remission rates were 28%, 41%, and 54% at 3, 5, and 8 years after SRS, respectively. Following SRS, 25% of patients (72/289) had new hormone deficiency. Sixty-three percent of the patients (127/201) with available data attained endocrine control. Three percent of patients (9/269) had a new visual complication after SRS. Five percent of the patients (13/285) were recorded as having tumor progression. A pretreatment PRL level ≤ 270 ng/ml was a predictor of endocrine remission (p = 0.005, adjusted HR 0.487). An increasing margin dose resulted in better endocrine control after SRS (p = 0.033, adjusted OR 1.087).

In patients with medically refractory prolactinomas or a residual/recurrent prolactinoma, SRS affords remarkable therapeutic effects in endocrine remission, endocrine control, and tumor control. New-onset hypopituitarism is the most common adverse event 3).

2015

Radiotherapy as an alternative and adjuvant treatment for prolactinomas has been performed at the Department of Radiation Oncology, Prince of Wales Cancer Centre, Sydney, New South Wales, Australia, with the linear accelerator since 1990.

In a retrospective review of 13 patients managed with stereotactic radiosurgery (SRS) and 5 managed with fractionated stereotactic radiotherapy (FSRT), as well as 5 managed with conventional radiotherapy, at the Prince of Wales Hospital. Patients with a histopathologically diagnosed prolactinoma were eligible. Those patients who had a confirmed pathological diagnosis of prolactinoma following surgical intervention, a prolactin level elevated above 500 μg/L, or a prolactin level persistently elevated above 200 μg/L with exclusion of other causes were represented in this review.

At the end of documented follow-up (SRS median 6 years, FSRT median 2 years), no SRS patients showed an increase in tumour volume. After FSRT, 1 patient showed an increase in size, 2 showed a decrease in size and 2 patients showed no change. Prolactin levels trended towards improvement after SRS and FSRT, but no patients achieved the remission level of <20 μg/L. Seven of 13 patients in the SRS group achieved a level of <500 μg/L, whereas no patients reached this target after FSRT.

A reduction in prolactin level is frequent after SRS and FSRT for prolactinomas; however, true biochemical remission is uncommon. Tumour volume control in this series was excellent, but this may be related to the natural history of the disease. Morbidity and mortality after stereotactic radiation were very low in this series 4).


Cohen-Inbar et al., reviewed the outcome of patients with medically and surgically refractory prolactinomas treated with Gamma Knife radiosurgery (GKRS) during a 22 years follow-up period.

They reviewed the patient database at the University of Virginia Gamma Knife center during a 25-year period (1989-2014), identifying 38 patients having neurosurgical, radiological and endocrine follow-up.

Median age at GKRS treatment was 43 years. Median follow-up was 42.3 months (range 6-207.9). 55.3 % (n = 21) were taking a dopamine agonist at time of GKRS. 63.2 % (n = 24) had cavernous sinus tumor invasion. Endocrine remission (normal serum prolactin off of a dopamine agonist) was achieved in 50 % (n = 19). GKRS induced hypopituitarism occurred in 30.3 % (n = 10). Cavernous sinus involvement was shown to be a significant negative prognosticator of endocrine remission. Taking a dopamine agonist drug at the time of GKRS showed a tendency to decrease the probability for endocrine remission.

GKRS for refractory prolactinomas can lead to endocrine remission in many patients. Hypopituitarism is the most common side effect of GKRS 5).

2013

evaluated the efficacy of Gamma knife stereotactic radiosurgery (GKSR) as an adjunctive management modality for patients with drug resistant or intolerant cavernous sinus invasive prolactinomas. Twenty-two patients with cavernous sinus invasive prolactinoma underwent GKSR between 1994 and 2009. Thirteen patients were dopamine agonist (DA) resistant. Six patients were intolerant to DA. Three patients chose GKSR as their initial treatment modality in hopes they might avoid life long suppression medication. The median tumor volume was 3.0 cm3 (range 0.3–11.6). The marginal tumor dose (median= 15 Gy, range 12–25 Gy) prescribed was based on the dose delivered to the optic apparatus. The median follow-up interval was 36 months (range, 12–185). Endocrine normalization was defined as a normal serum prolactin level off DA (cure) or on DA. Endocrine improvement was defined asa decreased but still elevated serum prolactin level. Endocrine deterioration was defined as an increased serum prolactin level. Endocrine normalization was achieved in six(27.3%) patients. Twelve (54.5%) patients had endocrine improvement. Four patients (18.2%) developed delayed increased prolactin. Imaging-defined local tumor control was achieved in 19 (86.4%) patients, 12 of whom had tumor regression. Three patients had a delayed tumor progression and required additional management. One patient developed a new pituitary axis deficiency after GKSR. Invasive prolactinomas continue to pose management challenges. GKSR is a non invasive adjunctive option that may reduce prolactin levels in patients who are resistant to or intolerant of suppression medication. In a minority of cases, patients may no longer require long term suppression therapy 6).

2006

Twenty-three patients were included in analysis of endocrine outcomes (median and average follow-up of 55 and 58 mo, respectively) and 28 patients were included in analysis of imaging outcomes (median and average follow-up of 48 and 52 mo, respectively). Twenty-six percent of patients achieved a normal serum prolactin (remission) with an average time of 24.5 months. Remission was significantly associated with being off of a dopamine agonist at the time of GKRS and a tumor volume less than 3.0 cm3 (P < 0.05 for both). Long-term image-based volumetric control was achieved in 89% of patients. Complications included new pituitary hormone deficiencies in 28% of patients and cranial nerve palsy in two patients (7%).

Clinical remission in 26% of treated patients is a modest result. However, because the GKRS treated tumors were refractory to other therapies and because complication rates were low, GKRS should be part of the armamentarium for treating refractory prolactinomas. Patients with tumors smaller than 3.0 cm3 and who are not receiving dopamine agonist at the time of treatment will likely benefit most 7).

2000

Twenty patients with prolactinomas were followed after GKS. Five patients were treated successfully; their prolactin (PRL) levels dropped into the normal range and dopaminergic drugs could be discontinued. Two spontaneous pregnancies were observed and 11 patients experienced improvement. Improvement was defined as normal PRL levels with the continued possibility of reduced medical treatment or a substantially reduced medical treatment dose with some degree of hyperprolactinemia maintained. The treatment failed in three patients who experienced no improvement. Patients treated with dopaminergic drugs during GKS did significantly less well in comparison with the untreated group when a cumulative distribution function (Kaplan-Meier estimate) was used. CONCLUSIONS:

The results of GKS for prolactinomas in this investigation are better than the results published by others. This may be an effect of case selection because there were no “salvage cases” in our group of patients. Because a dopamine agonist seemed to induce radioprotection in this series, it is suggested that GKS be performed during an intermission in drug therapy when the dopamine agonist is discontinued 8).

References

1)

Wong A, Eloy JA, Couldwell WT, Liu JK. Update on prolactinomas. Part 2: Treatment and management strategies. J Clin Neurosci. 2015 Oct;22(10):1568-74. doi: 10.1016/j.jocn.2015.03.059. Epub 2015 Aug 1. Review. PubMed PMID: 26243714.
2)

Narayan V, Mohammed N, Bir SC, Savardekar AR, Patra DP, Bollam P, Nanda A. Long term Outcome of Non-functioning and Hormonal-active Pituitary Adenoma after Gamma Knife Radio Surgery. World Neurosurg. 2018 Mar 21. pii: S1878-8750(18)30576-X. doi: 10.1016/j.wneu.2018.03.094. [Epub ahead of print] PubMed PMID: 29574220.
3)

Hung YC, Lee CC, Yang HC, Mohammed N, Kearns KN, Nabeel AM, Abdel Karim K, Emad Eldin RM, El-Shehaby AMN, Reda WA, Tawadros SR, Liscak R, Jezkova J, Lunsford LD, Kano H, Sisterson ND, Martínez Álvarez R, Martínez Moreno NE, Kondziolka D, Golfinos JG, Grills I, Thompson A, Borghei-Razavi H, Maiti TK, Barnett GH, McInerney J, Zacharia BE, Xu Z, Sheehan JP. The benefit and risk of stereotactic radiosurgery for prolactinomas: an international multicenter cohort study. J Neurosurg. 2019 Aug 2:1-10. doi: 10.3171/2019.4.JNS183443. [Epub ahead of print] PubMed PMID: 31374549.
4)

Wilson PJ, Williams JR, Smee RI. Single-centre experience of stereotactic radiosurgery and fractionated stereotactic radiotherapy for prolactinomas with the linear accelerator. J Med Imaging Radiat Oncol. 2015 Jun;59(3):371-8. doi: 10.1111/1754-9485.12257. Epub 2014 Nov 20. PubMed PMID: 25410143.
5)

Cohen-Inbar O, Xu Z, Schlesinger D, Vance ML, Sheehan JP. Gamma Knife radiosurgery for medically and surgically refractory prolactinomas: long-term results. Pituitary. 2015 Dec;18(6):820-30. doi: 10.1007/s11102-015-0658-1. PubMed PMID: 25962347.
6)

Liu X, Kano H, Kondziolka D, Park KJ, Iyer A, Shin S, Niranjan A, Flickinger JC, Lunsford LD. Gamma knife stereotactic radiosurgery for drug resistant or intolerant invasive prolactinomas. Pituitary. 2013 Mar;16(1):68-75. PubMed PMID: 22302560.
7)

Pouratian N, Sheehan J, Jagannathan J, Laws ER Jr, Steiner L, Vance ML. Gamma knife radiosurgery for medically and surgically refractory prolactinomas. Neurosurgery. 2006 Aug;59(2):255-66; discussion 255-66. PubMed PMID: 16883166.
8)

Landolt AM, Lomax N. Gamma knife radiosurgery for prolactinomas. J Neurosurg. 2000 Dec;93 Suppl 3:14-8. PubMed PMID: 11143231.

Gamma knife radiosurgery for trigeminal neuralgia mechanism

Gamma knife radiosurgery for trigeminal neuralgia mechanism

Gamma Knife radiosurgery for trigeminal neuralgia (GKRS) is a noninvasive surgical treatment option. The long-term microstructural consequences of radiosurgery and their association with pain relief remain unclear.

Studies focusing on the electrophysiology properties of partially demyelinated trigeminal nerves submitted to radiosurgery are vital to truly advance our current knowledge in the field 1).

To better understand this topic, Shih-Ping Hung et al., used diffusion tensor imaging (DTI) to characterize the effects of GKRS on trigeminal nerve microstructure over multiple posttreatment time points.

Ninety-two sets of 3-T anatomical and diffusion weighted MR images from 55 patients with TN treated by GKRS were divided within 6-, 12-, and 24-month posttreatment time points into responder and nonresponder subgroups (≥ 75% and < 75% reduction in posttreatment pain intensity, respectively). Within each subgroup, posttreatment pain intensity was then assessed against pretreatment levels and followed by DTI metric analyses, contrasting treated and contralateral control nerves to identify specific biomarkers of successful pain relief.

GKRS resulted in successful pain relief that was accompanied by asynchronous reductions in fractional anisotropy (FA), which maximized 24 months after treatment. While GKRS responders demonstrated significantly reduced FA within the radiosurgery target 12 and 24 months posttreatment (p < 0.05 and p < 0.01, respectively), nonresponders had statistically indistinguishable DTI metrics between nerve types at each time point.

Ultimately, this study serves as the first step toward an improved understanding of the long-term microstructural effect of radiosurgery on TN. Given that FA reductions remained specific to responders and were absent in nonresponders up to 24 months posttreatment, FA changes have the potential of serving as temporally consistent biomarkers of optimal pain relief following radiosurgical treatment for classic TN 2).


Histopathology examination of the trigeminal nerve in humans after radiosurgery is rarely performed and has produced controversial results.

There is evidence of histological damage of the trigeminal nerve fibers after radiosurgery therapy. Whether or not the presence and degree of nerve damage correlate with the degree of clinical benefit and side effects are not revealed and need to be explored in future studies 3).

Existing studies leave important doubts as to optimal treatment doses or the therapeutic target, long-term recurrence, and do not help identify which subgroups of patients could most benefit from this technique 4).

References

1)

Gorgulho A. Radiation mechanisms of pain control in classical trigeminal neuralgia. Surg Neurol Int. 2012;3(Suppl 1):S17-25. doi: 10.4103/2152-7806.91606. Epub 2012 Jan 14. PubMed PMID: 22826806; PubMed Central PMCID: PMC3400477.
2)

Shih-Ping Hung P, Tohyama S, Zhang JY, Hodaie M. Temporal disconnection between pain relief and trigeminal nerve microstructural changes after Gamma Knife radiosurgery for trigeminal neuralgia. J Neurosurg. 2019 Jul 12:1-9. doi: 10.3171/2019.4.JNS19380. [Epub ahead of print] PubMed PMID: 31299654.
3)

Al-Otaibi F, Alhindi H, Alhebshi A, Albloushi M, Baeesa S, Hodaie M. Histopathological effects of radiosurgery on a human trigeminal nerve. Surg Neurol Int. 2014 Jan 18;4(Suppl 6):S462-7. doi: 10.4103/2152-7806.125463. eCollection 2013. PubMed PMID: 24605252.
4)

Varela-Lema L, Lopez-Garcia M, Maceira-Rozas M, Munoz-Garzon V. Linear Accelerator Stereotactic Radiosurgery for Trigeminal Neuralgia. Pain Physician. 2015 Jan-Feb;18(1):15-27. PubMed PMID: 25675056.
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