Patients, tumors, and clinics
Detailed demographic and clinical data are summarized in Table 1.
Of all operated tumors, 148 (72%) were peripheral (each 72% NF2 ≙ 96 and SWNT ≙ 52 cases) and 57 (each 28%, ≙ 37 NF2 and ≙ 20 SWNT cases) of intraspinal location. In both NF2 and SWNT, peripheral nerve schwannomas were most often located in the facial/cervical area (n = 52 ≙ 35%) followed in descending order in the lower extremity (n = 39 ≙ 26%), upper extremity (n = 34 ≙ 23%), and lastly the torso (n = 23 ≙ 16%).
7/18 NF2 and 1/23 SWNT patients were identified to be mosaic cases with positive tumor DNA analysis and in 1/18 NF2 and 15/23 SWNT patients no mutation could be detected neither in blood nor in tumor DNA.
In the majority of tumors (n = 174 ≙ 85%), total resection was achieved, whereas only in 29 tumors (≙ 15%) partial resection could be accomplished due to the risk of a persisting functional loss, e. g. because of fragile or impaired feedback of electrophysiological monitoring.
Most of the patients suffered from persisting and medication resistant pain in both entities (total: n = 173, 84%; NF2: n = 105/133 ≙ 79%; SWNT: n = 68/72 ≙ 94%) followed by sensory (total: n = 80, 39%; NF2: n = 56/133 ≙ 42%; SWNT: n = 24/72 ≙ 33%) and motor (total: n = 68, 34%; NF2: 48/130 ≙ 37%; SWNT: n = 20/72 ≙ 28%) deficits before surgery.
Therefore, pain was the most common indication for surgery for both NF2 (48%) and SWNT (63%) associated schwannomas. This was followed by focal neurological deficits (29%) and growth progression (23%) in NF2-associated schwannomas and by growth progression (21%) and focal neurological deficits (15%) in SWNT-associated schwannomas. Only one SWNT-related schwannoma was operated on due to a radiological suspicion of a beginning malignant transformation, which could histologically not be confirmed.
Motor function could be improved in 15% (n = 20)/8% (n = 6) maintained in 81% (n = 105)/83% (n = 59) and worsened in 3% (n = 4)/8% (n = 6) after surgery in NF2-/SWNT-associated tumors. Postoperative sensory function improved in 11% (n = 14)/10% (n = 7), remained stable in 86% (n = 114)/87% (n = 62) and decreased in 16% (n = 5)/3% (n = 2) of NF2-/SWNT-related cases. Lastly, pain intensity improved in 75% (n = 99)/92% (n = 65), was maintained in 24% (n = 32)/7% (n = 5), and worsened in 1% (n = 1)/1% (n = 1) of NF2-/SWNT-associated tumors.
Overall, the complication rate was low, 202 cases had uneventful peri- and postoperative course (99%), and only in 3 cases (1%) complications were observed (two minor postoperative hematomas and one wound infection).
Association of mutations and location of NF2-related schwannomas and parameters
Distributions of the motor (MRC), sensory (SRS), and pain (VRS) rating scores were similar in the groups “NF2 mosaic” and “NF2 non-mosaic” and in the groups “NF2 associated spinal” and “NF2 peripheral”, as assessed by visual inspection. Median scores for MRC, SRS, and VRS were statistically significantly (p < 0.05) different in all comparison groups.
Detailed values are outlined in Table 2. Mosaic NF2 cases seem to have a better preoperative but worse postoperative motor and sensible function and more pain before and after surgery than tumors in non-mosaic NF2 patients. But only the higher preoperative VRS rank scores in mosaic NF2 patients were statistically significant (p = 0.017).
Peripheral schwannomas showed significant better pre- and postoperative motor (p < 0.001, p = 0.011), and preoperative sensory function (p = 0.032) and less pain after surgery (p = 0.032) compared to intraspinal NF2-associated tumors. A tendency towards better postoperative sensory function but higher preoperative pain intensity scores were seen in peripheral NF2-associated tumors (p > 0.05).
Association of mutations and location of SWNT-related schwannomas and parameters
Distributions of the motor (MRC), sensory (SRS), and pain (VRS) rating scores were similar in the groups “SWNT mutations” and “SWNT non-mutations” and in the groups “SWNT associated spinal” and “SWNT peripheral”, as assessed by visual inspection. Median scores for MRC, SRS, and VRS were statistically significantly (p < 0.05) different in all comparison groups. Schwannomas of SWNT patients carrying mutations showed more impaired pre-and postoperative MCR and SRS scales (category ≤ 4) and fewer cases with better pain scores before and after surgery compared to those cases without mutations.
Detailed values are outlined in Table 3. In summary, tumors exhibiting no mutation showed significant better pre- and postoperative motor (p = 0.019, p = 0.004) and sensory function (p = 0.001, p = 0.003) and less pain intensity (p = 0.007, p = 0.001). Peripheral SWNT-associated tumors tended to display better motor but worse sensory pre- and postoperative function as well as less pain intensity after surgery (p > 0.05) compared to intraspinal lesions. Significant worse preoperative pain intensity scores were seen in peripheral SWNT-associated tumors (p = 0.029).
Location category distribution of NF2- and SWNT-related schwannomas and association to parameters
In NF2-associated PNS, the median values for “preoperative MCR” (H (3) = 24.487, p < 0.001), “postoperative MCR” (H (4) = 18.877, p = 0.001), “preoperative SRS” (H (4) = 24.343, p < 0.001), “postoperative SRS” (H (4) = 21.787, p < 0.001) and “preoperative VRS” (H (4) = 17.499, p = 0.002) were statistically significantly different between the categories.
No significance was seen in median values for “postoperative VRS” scores (p = 0.051) in NF2 cases and for all categories in SWNT-related PNS (p > 0.05).
In SWNT-related tumors, a non-significant tendency was seen for worse preoperative motor and sensory function. Intraspinal lesions seem to cause more pain before and all extremity schwannomas have less pain after surgery than other localizations.
Subsequently, pairwise comparisons were performed using Dunn’s (1964) procedure with a Bonferroni correction for multiple comparisons. This post hoc analysis revealed statistically significant group differences only in NF2- and but not in SWNT-related tumors. For the NF2-associated cases, group differences are illustrated and highlighted in Fig. 1 (* adjusted p-values).
All other comparisons showed no statistically significant difference in the mentioned categories. In NF2-associated schwannomas with the same median values, intraspinal tumors exhibited a higher and therefore better preoperative MRC score compared to upper extremity (p = 0.001) cases but lower and thus worse postoperative SRS scores compared to tumors located at the torso (p = 0.023). In turn, the latter showed a higher SRS score preoperatively than those schwannomas located in the upper extremity (p = 0.012).
Comparison between NF2- and SWNT-related schwannomas and association to parameters
Distributions of the pre-and postoperative MRC, SRS, and VRS scores were similar in the groups “NF2-associated” and “SWNT-associated”, as assessed by visual inspection. Median scores for preoperative SRS and VRS as well as Age at time of surgery and Resection amount were statistically significantly (p < 0.05) different between “NF2-associated” and “SWNT-associated” schwannomas. NF2-associated tumors exhibited more cases with affected sensory category levels (0–4) before surgery and partial resection amounts compared to SWNT-related cases. Detailed values are outlined in Table 4.
Of the 201 tumors analyzed in the SRS category, the postoperative SRS category was higher in 21 tumors and lower in 20 tumors, and 162 unchanged in preoperative scores.
Of the 203 tumors analyzed in the VRS category, the postoperative VRS category was higher in 2 tumors, lower in 164 tumors, and 37 tumors unchanged to preoperative scores. There was no statistically significant difference in preoperative MRC, postoperative MRC, and SRS as well as VRS scoring between the two groups.