1. Introduction
Spinal nerve sheath tumors (NSTs) are common intradural spinal tumors [
1,
2], usually arising from the dorsal sensory roots [
3]. They present a ubiquitarian localization in the spine, although a more common incidence in the cervical and lumbar tracts is reported [
4,
5,
6,
7]. The majority of these lesions (60%) are intradural extramedullary, 25% are purely extradural and a further 15% have both intradural and extradural components. Less than 1% are intramedullary [
3]. In 15% of cases, they extend laterally through the nerve root origin, assuming a dumbbell shape [
8], representing the most common spinal foraminal lesion. Local progression may lead to spinal cord compression, bony erosion and subsequent deformity.
NSTs include schwannomas, neurofibromas and malignant nerve sheath tumors (MNST). Spinal schwannomas originate from the Schwann cells, with an eccentric growth pattern [
9], whereas neurofibromas are mostly peripheral NSTs arising from the endoneurium and encasing the nerve root [
10]. Whenever they occur in the spine, both are benign and have a prevalence for transdural and foraminal extension in 15% of cases [
4]. MNST are rare yet aggressive soft tissue sarcomas of neural origin that may occasionally occur in the spine. Prognosis is poor, with a high rate of relapse and mortality (between 23% and 69%) [
11]. In order to obtain total resection with free margins, root sacrifice is routinely performed.
The gold-standard treatment for benign NSTs (WHO grade I schwannomas and neurofibromas) is radical resection with neurological function preservation. Recurrence occurs in up to one third of cases at 15 years [
12]. In contrast to pure intradural lumbar schwannoma, entire nerve root sacrifice for intra-foraminal and/or dumbbell NSTs is controversial regarding the risk of permanent motor dysfunction and neuropathic pain [
7,
13,
14,
15]. Even if histological studies have shown that the parent nerve progressively loses its function [
16], and several surgical series have reported a low incidence of permanent postoperative neurological deficits after root sacrifice [
17,
18,
19,
20], surgeons often opt for root preservation. Consequently, foraminal extension is associated with a higher risk of subtotal resection (STR) [
7,
20]. In contrast to peripheral nerve tumors, we assume that foraminal/dumbbell tumors lead to the chronic compression of the root against the stiff bony limits of the foramen, with progressive loss of nerve function. We therefore hypothesize that most of these involved roots are non- or poorly functional, with compensation by adjacent roots cranially and caudally, and could thus be sacrificed with no or very limited postoperative deficit. The sacrifice of the involved nerve root presents many advantages, permitting one to remove the tumor in total, in an “en bloc” fashion, making the surgery easier, faster, less hemorrhagic and more respectful of the principles of oncologic resection, thus reducing the risk of tumor recurrence [
21]. Nowadays, little is known about the predictive risk factors of postoperative deficit with root sacrificed [
13].
The aim of this study is therefore to report the neurological outcomes in a retrospective series of spinal dumbbell and intraforaminal benign NSTs treated with systematic nerve root amputation and to evaluate the predictive factors of postoperative deficit.
4. Discussion
Even if still controversial, amputation of a single rootlet is widely performed for intradural NSTs [
7,
12,
13,
14,
15,
16,
17,
19,
23,
24]. Immediate postoperative deficit is reported in 0% to 55% of cases for functional roots [
13,
14,
19,
23] and in 0% to 20% of cases for all the spinal levels [
7,
12,
15,
16,
17,
19]. In almost all cases, an improvement or complete recovery is observed at follow-up and it is rarely debilitating [
13,
23]. Moreover, complete nerve amputation is routinely performed in MNST surgery in order to obtain complete en bloc resection with free margins. Sacrifice of the parent nerve in benign foraminal dumbbell NSTs is less accepted, although no significant increase in long-term postoperative deficit was reported previously [
13,
14,
15,
18]. In our series, the appearance of a new motor deficit was observed in 35.7% of cases and a mild deficit persisted in 14.2%.
Intradural NSTs cause a gradual loss of function of the affected rootlets [
13,
14,
16,
18,
19], and it is compensated by the concomitant reinnervation of the dependent peripheral structures via the nerve endings of the roots [
23]. The same results can be expected for lesions extending through the neural foramen. Rather, compensation may be enhanced by progressive and chronic compression against the stiff bony limits of the neural foramen [
13]. Reinnervation of the relevant spinal nerve is especially facilitated in the cervical and lumbar plexus, which provide a rich anastomotic network [
13,
23]. Consequently, invasiveness of the spinal plexus may compromise functional outcomes.
Foraminal NSTs, compared to pure intradural lesions, tightly encase the entire spinal nerve, increasing root deformation and adhesion. This makes root preservation challenging, and sometimes more deleterious than sacrifice (longer operation time, increased blood loss and damage to spinal cord or to other rootlets/roots, etc.). Moreover, postoperative MD was associated with nerve sacrifice in only 50% of cases by Safaee et al. [
7]. Contrarily, peripheral NSTs do not have a distal anatomic network and nerve amputation is associated with a high risk of neurological impairment; therefore, enucleation is suggested.
In our series of 26 dumbbell NSTs, a global improvement in the neurological status was observed following complete nerve root amputation. We are not aware of previous larger series focused on this localization. As with Butenschoen et al. [
19], we did not observe a severe motor deficit at last follow up. In most of the patients, nerve sacrifice did not produce persistent MD and 80% of the patients with a preoperative deficit completely recovered postoperatively. All the patients (n = 5) who experienced new, immediate postoperative MD improved at FU. Three patients completely recovered, and in the last two (14.2%), MD improved to MRC ≥ 3. The immediate and persistent MD were an aggravation of pre-existing MD in 60% and 20% of cases, respectively (
Figure 3). We observed a high rate of new postoperative and pre-existing MD recovery accordingly with the current literature. Recovery of pre-existing and new postoperative deficits probably follows the same pathophysiologic mechanism [
13,
18,
23]. We hypothesize that the functional recovery and cross-innervation by adjacent nerves may be enhanced by the combination of nerve deafferentation and intensive physical therapy. Among the entire cohort, we analyzed the MD, SL and RP evolution. SL is frequently underappreciated. It may be disabling, especially if concomitant MD occurs at the extremities, and should not be neglected. Concerning the RP, at last follow-up, its prevalence consistently decreased compared to the preoperative status (42% vs. 23%). Among the six patients with persistent RP, four already suffered preoperatively, and in only two cases, neuropathic pain occurred following parent nerve sacrifice. In no cases was postoperative pain debilitating and it was always controlled by a step I WHO analgesic ladder. Finally, nerve root sacrifice does not seem to improve the risk of postoperative RP compared to previous series [
25].
We performed a univariate analysis of the entire cohort to identify the risk factors for postoperative RD and MD. Previous studies suggested the cervical location, histology, neurofibromatosis and symptomatic NSTs as negative predictive factors for intradural NSTs [
12,
13,
14,
19], but their role was not confirmed in foraminal lesions [
18]. Normal clinical findings were previously reported as a sign of complete functional compensation (of the affected nerve) by the adjacent spinal nerve, while radicular symptoms represented nerve sufferance without complete function resumption [
12,
14,
15,
19]. In our series, patients with persistent RD and MD tended to be older, with recent onset of RP and/or deficit. Moreover, they presented larger lesions, with major extraforaminal and paravertebral extension. Preoperative RP was the only factor significantly associated with immediate and persistent postoperative deficits in the entire cohort. Furthermore, subgroup analysis for functional nerve roots showed that all the patients with immediate and persistent postoperative motor deficits presented with preoperative radicular pain. Preoperative motor and/or sensory deficits seem to increase the risk of postoperative RD and MD (
Table 5 and
Table 6), although no significant difference was observed, probably because of the small sample size. RP, and not preoperative motor and/or sensory deficit, was revealed to be significantly predictive of a persistent deficit following nerve sacrifice. RP could be a more reliable and sensitive sign of nerve sufferance, without complete compensation by the surrounding nerves and residual functionality of the root [
12,
14,
15,
19]. Theoretically, a protracted medical history may indicate a higher chance of functional compensation. However, symptom duration, as a predictive factor, was not previously established. In our series, we found that patients with persistent postoperative MD had a more recent medical history compared to patients without a deficit (2 ± 0 months vs. 27.8 ± 23.4 months), even if the difference was not significant (
p = 0.15).
The data in our study suggested that paravertebral extension may affect the adjacent nerve roots and compromise compensation, especially in the lumbar spine with extension to the lumbar plexus. All persistent sensory and motor postoperative deficits occurred in lesions with paraspinal or vertebral body invasion, Sridhar class IV and V lesions, in our series. Similar results were reported by Butenschoen et al. [
18]. Moreover, patients who developed RD and MD both had larger lateral extension compared to untouched patients (
Table 5 and
Table 6). Finally, lesions with extension through multiple foramens showed a higher rate of persistent postoperative deficit compared to mono-foraminal NSTs in the entire cohort (50% vs. 14%,
p = 0.15) and in the functional root subgroup (33% vs. 9%,
p = 0.39). We hypothesize that the postoperative deficit may consequently be due to a combination of the compromised compensation via the compression of adjacent roots and the dissection of the paravertebral extension of the tumor, and not related to the sacrifice of the parent nerve root. Indeed, adjacent peripheric fibers adherent to the paravertebral portion are at risk of being accidentally sacrificed during the resection. We suggest that special attention is paid to these lesions, which may be considered more similar to peripheral NSTs.
Preoperative signs of denervation on the EMG are associated with a higher risk of postoperative deficit in previous reports [
12,
13,
14,
17]. In our study, only five patients had preoperative EMG. All the patients with signs of EMG denervation had at least a temporary postoperative RD (
p = 0.1), but this did not reach significance.
To determine parent nerve root sacrifice, intraoperative triggered electromyogram (tEMG) has been proposed to identify residual function [
5]. tEMG has high specificity (94.7%) and safe resection may be performed with a significant (80%) amplitude reduction [
5,
26]. However, the sensitivity is still low (37.5%) and it tends to overestimate residual motor function and detect subclinical responses. Safe resection occurred despite positive responses [
26]. tEMG is a useful intraoperative tool to detect residual functions, but due to its low sensitivity and the positive functional outcome reported with systematic nerve amputation, it should not preclude nerve sacrifice.
Concerning the GTR, the extension in multiple anatomical compartments, intradural, intraforaminal and paraspinal, may be technically challenging. It is significantly associated with a higher risk of STR in the literature [
7,
12]. The recurrence rate is not negligible and it occurred in up to 30% of spinal NSTs at 15 years [
12]. The risk of recurrence has been reported to be increased by four times in patients who undergo intralesional resection compared to en bloc removal [
21]. Moreover, it may be even higher in patients affected by neurofibromatosis and in MNST [
4]. GTR in dumbbell NSTs without nerve root sacrifice is achieved in 22% to 60%, while nerve root sacrifice increases the GTR rate up to 96% [
12,
18]. In our series, GTR was obtained in 84.6% of cases. In all the cases of STR, the intracanal and intraforaminal parts were completely resected and residue remained in the paraspinal region, and patients were stable at follow-up. No cases of recurrence were observed.
Different histopathologic entities were not significantly associated with postoperative deficit. Spinal neurofibromas are generally associated with a lower incidence of postoperative deficit [
13,
14]. A diffuse growth pattern compared to eccentric schwannomas is supposed to rapidly compromise nerve function and decrease the risk of postoperative deficit. In our series, we reported only two cases of neurofibroma and none of them developed a persistent motor deficit. Due to the rarity of these lesions, less is known about dumbbell neurofibromas, and no definitive evidence is available.