BACKGROUND Single-session stereotactic radiosurgery (SRS) for large arteriovenous malformations (AVMs) ≥10 mL remains controversial, which is considered as the current size limitation. OBJECTIVE To reconsider the size limitation of SRS for AVMs by profoundly analyzing dose-volume relationship. METHODS Data on 610 consecutive patients with AVM treated with SRS using regular (18-22 Gy) or low (<18 Gy) prescription doses were retrospectively analyzed. AVMs were classified into 4 groups: small (<5 mL), medium (≥5 and <10 mL), medium-large (≥10 and <15 mL), and large (≥15 mL). The maximum volumes were 22.5 mL (regular-dose group) and 23.5 mL (low-dose group). RESULTS When treated with regular doses, the cumulative 6-yr obliteration rates for each of the 4 AVM groups were 86%, 80%, 87%, and 79%, respectively; the cumulative 10-yr significant neurological event (SNE) rates were 2.6%, 3.9%, 6.8%, and 5.3%, respectively. Regarding large AVMs, regular-dose SRS resulted in marginally better obliteration rate (6-yr cumulative rate, 79% vs 48%, P = .111) and significantly lower SNE (5-yr cumulative rate, 5% vs 31%, P = .038) and post-SRS hemorrhage rate (8-yr cumulative rate, 0% vs 54%, P = .002) compared to low-dose SRS. Multivariate analyses revealed that regular-dose SRS significantly contributed to increase in the obliteration rate and decrease in SNEs and hemorrhage. CONCLUSION The outcomes for large AVMs were generally favorable when treated with ablative doses. Single-session SRS could be acceptable for AVMs up to ≈20 mL if treated with ablative doses.

The efficacy of radiosurgery for neurofibromatosis type 2 (NF2)-associated vestibular schwannoma (VS) remains debatable. We retrospectively analyzed radiosurgical outcomes for NF2-associated VS compared to sporadic VS using our database of 422 consecutive VS patients. Twenty-five patients with 30 NF2-associated VSs with a mean follow-up of 121 months were identified. NF2-associated VSs exhibited excellent tumor control (10-year cumulative rate, 92% vs. 92% in sporadic VSs; p = 0.945) and worse overall survival (73% vs. 97%; p = 0.005), mainly due to tumor progression other than the treated VSs. The presence of NF2 was not associated with failed tumor control via multivariate Cox proportional hazard analyses. No difference in radiation-induced adverse events (RAEs) was confirmed between cohorts, and prescription dose (hazard ratio 8.30, 95% confidence interval 3.19–21.62, p < 0.001) was confirmed as a risk for cranial nerve injuries via multivariate analysis. Further analysis after propensity score matching using age, volume, and sex as covariates showed that NF2-associated VSs exhibited excellent local control (100% vs. 93%; p = 0.240) and worse overall survival (67% vs. 100%; p = 0.002) with no significant difference in RAEs. Excellent long-term tumor control and minimal invasiveness may make radiosurgery a favorable therapeutic option for NF2 patients with small to medium VS, preferably with non-functional hearing or deafness in combination with postoperative tumor growth or progressive non-operated tumors, or with functional hearing by patients’ wish.

OBJECTIVEIn Gamma Knife radiosurgery (GKS) for arteriovenous malformations (AVMs), CT angiography (CTA), MRI, and digital subtraction angiography (DSA) are generally used to define the nidus. Although the AVM angioarchitecture can be visualized with superior resolution using rotational angiography (RA), the efficacy of integrating RA into the GKS treatment planning process has not been elucidated.METHODSUsing data collected from 25 consecutive patients with AVMs who were treated with GKS at the authors’ institution, two neurosurgeons independently created treatment plans for each patient before and after RA integration. For all patients, MR angiography, contrasted T1 imaging, CTA, DSA, and RA were performed before treatment. The prescription isodose volume before (PIVB) and after (PIVA) RA integration was measured. For reference purposes, a reference target volume (RTV) for each nidus was determined by two other physicians independent of the planning surgeons, and the RTV covered by the PIV (RTVPIV) was established. The undertreated volume ratio (UVR), overtreated volume ratio (OVR), and Paddick’s conformal index (CI), which were calculated as RTVPIV/RTV, RTVPIV/PIV, and (RTVPIV)2/(RTV × PIV), respectively, were measured by each neurosurgeon before and after RA integration, and the surgeons’ values at each point were averaged. Wilcoxon signed-rank tests were used to compare the values obtained before and after RA integration. The percentage change from before to after RA integration was calculated for the average UVR (%ΔUVRave), OVR (%ΔOVRave), and CI (%ΔCIave) in each patient, as ([value after RA integration]/[value before RA integration] − 1) × 100. The relationships between prior histories and these percentage change values were examined using Wilcoxon signed-rank tests.RESULTSThe average values obtained by the two surgeons for the median UVR, OVR, and CI were 0.854, 0.445, and 0.367 before RA integration and 0.882, 0.478, and 0.463 after RA integration, respectively. All variables significantly improved after compared with before RA integration (UVR, p = 0.009; OVR, p < 0.001; CI, p < 0.001). Prior hemorrhage was significantly associated with larger %ΔOVRave (median 20.8% vs 7.2%; p = 0.023) and %ΔCIave (median 33.9% vs 13.8%; p = 0.014), but not %ΔUVRave (median 4.7% vs 4.0%; p = 0.449).CONCLUSIONSIntegrating RA into GKS treatment planning may permit better dose planning owing to clearer visualization of the nidus and, as such, may reduce undertreatment and waste irradiation. Further studies examining whether the observed RA-related improvement in dose planning also improves the radiosurgical outcome are needed.

Transient receptor potential vanilloid subfamily member 1 (TRPV1) is activated by capsaicin, acid, and heat and mediates pain through peripheral nerves. In the tongue, TRPV1 expression has been reported also in the epithelium. This indicates a possibility that sensation is first received by the epithelium. However, how nerves receive sensations from the epithelium remains unclear. To clarify the anatomical basis of this interaction, we performed immunohistochemical studies in the rodent tongue to detect TRPV1 and calcitonin gene-related peptide (CGRP), a neural marker. Strong expression of TRPV1 in the epithelium was observed and was restricted to the apex of the tongue. Double immunohistochemical staining revealed that CGRP-expressing nerve terminals were in close apposition to the strongly TRPV1-expressing epithelium of fungiform papilla in the apex of rodent tongues. These results suggest that the TRPV1-expressing epithelium monitors the oral environment and acquired information may then be conducted to the adjacent CGRP-expressing terminals.

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