Meningiomas are lesions that arise from arachnoidal cap cells, the outer part of the arachnoid layer and villi (1). They usually form dural attachments and are marked by meningothelial hyperplasia (1).

Spinal meningiomas are relatively rare, accounting for approximately 3% of all meningiomas of the central nervous system (CNS) (2) and 25-46% of all primary intraspinal neoplasms (2, 3). 90% of intradural extramedullary spinal tumors are either meningiomas or schwannomas and constitute nearly 25% of primary spinal neoplasia (3).

Spinal meningiomas mainly affect people in their fifth decade of life and are more frequent in women (given their estrogen receptors) (4). In case they occur in young patients, or if they cause multiple lesions, a genetic disorder like neurofibromatosis type 2 (NF2) or aggressive histological subtypes should be suspected (2, 4). Spinal meningiomas most commonly occur in the posterior, posterolateral, or lateral thoracic region, followed by the anterior cervical and lumbosacral regions. The main treatment is surgery, which can be performed in (a) a classical open microsurgical approach in the vast majority of cases, (b) a minimally invasive surgery (MIS), or (c) through an endoscopic intervention (5). The choice of the most appropriate surgical method could be challenging, especially in the case of aggressive meningiomas and in some difficult access tumors (e.g., location anterior to the spinal cord in the thoracic region). For instance, ventral/ventrolateral cervical meningiomas within the upper cervical region, may envelop the vertebral artery (6), and thus require precise presurgical calculations to adopt the safest approach.

The scientific knowledge regarding spinal meningiomas has evolved over the past twenty years. This evolution concerns multiple aspects, including clinical evaluation, molecular and radiological specificities, and microsurgical management techniques. Therefore, the main goal of this paper is to come up with an updated review of spinal meningiomas, with a particular focus on their clinical presentation, biological and imaging aspects, and neurosurgical strategies.

A review of the literature was carried out using PubMed/Medline and Scopus databases. The following keywords were used: “spinal meningioma” AND (“biology” OR “molecular” OR “genetic” OR “endocrine” OR “imaging” OR “grading” OR “prognosis” OR “surgery” OR “resection” OR “intraoperative monitoring” OR “adjuvant therapy” OR “recurrence” OR “psychology” OR “anxiety” AND “depression”). Original papers published in English and French were included in the analysis. The references of the selected papers were manually scanned in order to identify any additional references. To note, papers on intracranial meningiomas were also scanned and relevant papers were included since some research on spinal meningiomas stem from studies carried out on intracranial meningiomas.

Spinal meningiomas are typically solitary, well-circumcised, slow-growing, intradural extramedullary tumors ( Figure 1 ) (7) that usually respect the surrounding normal tissue (1). Hence, they are often perceived as noninvasive. However, they could be aggressive in some cases by seeding other parts of the CNS or the surgical site.

As stated above, meningiomas are more frequently seen at the thoracic level and tend to expand slowly without any clinical manifestation initially. Around 9% of cases are asymptomatic and report no complaints (8). At an advanced stage, meningiomas compromise spinal elements, resulting in various neurological symptoms and signs, such as pain, motor, and sensory disturbances, gait abnormality, and sphincter dysfunction. Complaints can vary from one person to another depending on the size of the meningioma and the exact site of the spinal compression (8). Clinical manifestations depend also on the initial size of the spinal canal as large constitutional ones can tolerate the development of large sized tumors while remaining asymptomatic.

The most frequent presentation is pain, ranging from 42% in some case series to as high as 87% in other reports (8, 9). Pain is more frequently described as local or radicular. Apart from pain, patients often report sensory and motor symptoms. Sensory manifestations can have many aspects, such as aching, burning, tingling, numbness, hypoesthesia, paresthesia, and anesthesia. These symptoms can be present in 16% to 84% of cases (4, 10). However, the most alarming sign for patients is motor deficit. It can start as a slight weakness and evolves later into a complete motor deficit. Motor symptoms are present in 33% to 93% of patients with spinal meningiomas (2, 4). Moreover, some patients could complain of gait and balance disturbances in 47% to 93% of cases (8, 11). Finally, sphincter dysfunction is reported in some series but less frequently than other symptoms. Sphincter dysfunction can be seen in 6 to 60% of patients seeking medical opinion (8, 11). A summary of the clinical manifestations is depicted in Table 1 .

Many histological subtypes of meningiomas have been described, among which meningothelial, fibroblastic, and transitional meningiomas are the most frequent ones. The histological analysis of meningiomas defines the histological type and grade of the tumor according to the 2021 World Health Organization (WHO) classification, as illustrated in Figure 2 (16). It classifies meningiomas into three grades, where each grade correlates with different potential for growth, metastatic spread, recurrence, and prognosis.

Many histologic subtypes are observed in both intracranial and spinal meningiomas. Meningothelial, metaplastic, psammomatous, transitional, atypical, and clear cell subtypes are the most common subtypes of intracranial meningiomas. As for spinal meningiomas, the psammomatous, meningothelial and transitional subtypes distinguish them, and they have a lower risk of recurrence than the intracranial ones for reasons yet to be determined.

The WHO divides meningiomas into three grades from 1 to 3 (benign, atypical and malignant, respectively) based on their malignancy degree (17). In the case of “mixed” tumors, the diagnosis of the dominant histological type (i.e., the type forming more than 50% of the tumor) is retained. However, the presence of a minority contingent with more aggressive potential should be reported.

Advances in molecular biology have greatly improved the understanding of the various mechanisms at the origin of meningiomas development. Molecular profiles of spinal meningiomas are similar to their intracranial counterparts (18). These alterations account for 3% of reported cases only. Chromosomal instability is a widespread molecular alteration that characterizes recurrent or poor prognosis meningiomas. Accumulation of cytogenetic aberrations is associated with higher-grade meningiomas and a higher risk of recurrence, which explains why high-grade meningiomas have more altered cytogenetic profiles than benign meningiomas (19). Table 2 summarizes the different gene mutations implicated in meningiomas and their prognosis.

Among the multiple mechanisms of oncogenesis, the increased cell proliferation was considered as the most important one. In brain tumors, the typical immunohistochemically marker Ki-67/MIB-1 for cell proliferation is more predictive of survival than the expression of proliferating cell nuclear antigens p53 and PCNA. In meningiomas, a high expression level of Ki-67 is directly associated with significant worse prognostic, especially with Ki-67 index higher than 4% (24). A close follow-up is recommended in this population.

Multiple reasons suggest the association between sexual hormones and the development of meningiomas. Meningiomas are more common in females, even more for spinal meningiomas than intracranial meningiomas, and are positively correlated with breast cancer (29, 30). Most meningiomas express progesterone and somatostatin receptors (31). Spinal meningiomas expressed more androgen receptors (AR+) and estrogen receptors (ER+) than intracranial meningiomas (30).

Many studies have investigated the impact of sex hormone medication, such as oral contraception or hormonal replacement therapy (HRT), on meningiomas development. Results were inconclusive still recently (32–34). A dose-dependent relationship between the incidence and growth of meningiomas and hormonal treatment with progestin cyproterone acetate (CPA) has recently been established (35). A similar but lower risk of meningiomas has been recently reported with the use of chlormadinone acetate and nomegestrol acetate as progestin treatments (35).

Concerning HRT in menopausal patients, evidence from epidemiological studies seem to favor an increased risk of meningiomas in treated patients although a recent study failed to show an increased growth of meningiomas in HRT treated vs. nontreated patients (36). Until larger studies are available, it seems wise to recommend avoiding HRT in patients with meningiomas (37).

Based on studies demonstrating the expression of hormonal receptors in meningiomas, therapies targeting these receptors have been tried but have failed to show an overall favorable clinical outcome in meningioma treatment (37).

To the best of our knowledge, there are no published data on spinal meningiomas in pregnant women. However, data arising from intracranial meningiomas research suggest that the latter may enlarge during pregnancy, as noted by Cushing and Eisenhardt (38). But the rarity of this condition does not allow to clearly define the risk and the need for surgery during pregnancy. Usually, urgent neurosurgery can be indicated during pregnancy in case of neurological symptoms such as motor deficit or visual impairment (39, 40). For asymptomatic meningiomas, a multidisciplinary approach is always useful to better evaluate the pros and cons of surgery during pregnancy and following management both for maternal and fetal health, the aim being, as far as possible, to organize the surgery away from childbirth (41).

More available neuroimaging modalities as MRI scans facilitated the discovery of incidental meningiomas. These lesions represent of 0.9% to 1.0% of the general population (48). Depending on the growth of the lesions, a follow-up plan is set for every individual patient. Presently, it is agreed that annual MRI scans are recommended in meningiomas of WHO grade 1 for five years. After that period, biannual MRIs can be performed.

During pregnancy, a close follow-up is recommended in patients known to have meningiomas (40).

Unlike intracranial meningiomas, spinal meningiomas do not generally invade the pia and rarely result in spinal cord edema, compared to small intracranial meningiomas that can cause significant vasogenic edema thus becoming symptomatic (49). Spinal meningiomas tend to manifest clinically once they exhibit a direct mass effect on the neural elements (50). For incidentally discovered meningiomas, clinical and radiographical observation is essential to select the best management strategy, even in the case of a documented tumor growing on serial imaging. Several factors should be considered in asymptomatic spinal meningioma before proposing tumor resection. Those factors include the patient’s age, comorbidities, and tumor size.

Spinal surgery has little margin for error. Therefore, all means must be deployed to preserve the functioning of the spinal pathways and reduce the postsurgical neurological deficit. For this purpose, intraoperative neurophysiological monitoring was first introduced in 1975 by Tamaki and Yamane and has been widely used by spinal surgeons to provide information regarding the extent of tissue manipulation, tissue resection, and preservation of spinal tracts function (2, 56).

Motor evoked potentials (MEP) and somatosensory evoked potentials (SEP) are the two main neuromonitoring tools used during surgery. MEP explore the integrity of the pyramidal tracts and are primarily used in the context of anterior and anterolateral spinal lesions. SEP examine the dorsal columns and are thus mainly used in the case of posterior and posterolateral spinal lesions. The two modalities are frequently combined and offer quick and valuable surgical feedback. Intraoperative SEP and/or MEP deterioration prompt rapid surgical intervention and prevent irreversible sensory and motor pathways damage.

MEP requires stimulation of the pyramidal tracts and response recording through surface electrodes placed over a muscle of interest (for instance, intrinsic hand muscles or tibialis anterior muscle) (63–66). Direct spinal stimulation could elicit muscle responses and has been used by several groups worldwide. However, it is now known that the obtained responses could not accurately reflect the functioning and integrity of central motor pathways. Although these motor responses translate the firing of lower motor neurons, they result from the activation of various spinal tracts, including antidromic activation of dorsal column axons that have collaterals with lower motor neurons (67). Therefore, brain stimulation is recommended to monitor the integrity of corticospinal (pyramidal) tracts (64).

Brain activation could be obtained by applying magnetic or electric stimulation to the scalp. For intraoperative monitoring, electric currents are by far more practical than the magnetic field. They are delivered to the brain through “corkscrew” needles, straight needles, or surface electrodes. The latter consists of electroencephalographic (EEG) cups that could be securely fixed on the scalp (before surgery) using collodium. Anodal stimulation was more efficient than cathodal stimulation in evoking MEP. Stimulating electrodes are placed at specific sites over the motor cortex, such as C3, C4, C1, C2, Cz - 1 cm, and Cz + 6 cm (according to the 10-20 international system of electrode placement). Several montages have been proposed, like hemispheric, interhemispheric, and midline (for review, please refer to 64); each has its advantages and inconveniences that fall outside the scope of this paper and will not be discussed here.

As for SEP, this technique requires stimulation of a peripheral nerve of the upper or lower limb and response recording through electrodes positioned over the primary sensory cortex (65). Recording electrodes consist of either EEG cup electrodes fixed to the scalp using collodium or subcutaneous needle electrodes. The latter provide rapid positioning but could increase the risk of local infection or subcutaneous hemorrhage.

Concerning stimulation, median and posterior tibial nerves are usually used; other peripheral nerves can also be stimulated in certain circumstances; for instance, the ulnar nerve is chosen in lower cervical interventions. The stimuli are rectangular, of 0.2 to 0.3 ms duration, and supramaximal intensity. The latter corresponds to two times the motor threshold or three times the sensory threshold (65).

For both techniques, qualified and experimented personnel is needed to accurately detect any changes in SEP or MEP response, distinguish it from any confounder, and warn the surgical team.

The literature regarding spinal meningiomas metastasis is lacking. However, according to data arising from intracranial meningiomas research, extracranial meningioma metastases (EMM) occur in 0.1% of intracranial meningiomas mainly encountered in atypical and anaplastic lesions. Most common sites of metastasis are the lungs and pleura but intraspinal and vertebral EMM also occur in a lesser percentage and are poorly described in the literature. There is no standard treatment protocol for EMM although their presence might worsen the prognosis of the concerned patients (68). EMM occurrence is independent of WHO grading and can be even present before tumor recurrence.

As stated previously, spinal meningiomas are benign tumors with a low recurrence rate independently of the histological grade of the cancer. In general, the recurrence rate in spinal meningiomas tend to be less than in intracranial meningiomas. The recurrence/progression of meningiomas after ten years can reach 13% (2, 69). The incidence was lower for convexity lesions (3%) than parasagittal (18%) and sphenoid ridge (34%) meningiomas. Multiple demographic, clinical and radiological factors have been associated with increased recurrence rates, such as patient age (recurrence rate higher in young patients (below 50)), tumor location (cervical), infiltrating meningioma, En plaque growth, extradural extension, arachnoid scarring, and partial resection (Simpson IV-V grades). Moreover, a recent series reported by Park et al. found that foraminal and thoracic location is associated with a higher recurrence rate (70).

In addition, histological types seem to influence the recurrence risk; for instance, spinal clear cell meningioma was found to have a greater recurrence rate (10).

The importance of dural attachment resection is controversial and contrasting results have been described. For instance, Nakamura et al. found that the recurrence rate was lower for Simpson Grade I than for Simpson Grade II resection (53). In contrast, a low recurrence rate can be found even without dural resection (71). In the same perspective, the add-on value of including the dural tail in the field of radiation therapy is still undetermined. Some data come from the domain of intracranial meningioma, where the radiation of the dural attachment was not found to be beneficial (i.e., it did not reduce the recurrence rate) in a large retrospective series recently reported by Piper etal. (72). A better understanding of the dural tail (or dural attachment) pathophysiology is needed to guide and improve the management of this cancer.

Spinal meningiomas are frequently associated with a favorable neurological and functional prognosis (4, 73, 74).

The patients who underwent surgical decompression experienced significant post-operative improvements in Patient Reported Outcomes as measured by the Brief Pain Index and MD Anderson Symptom Inventory (75). However, anterior or calcified lesions, recurrences, cases in which the arachnoid layer has been violated, tumors invading the spinal cord and/or the vascular structures do not have the same favorable outcome (74). Therefore, the preoperative functional and neurological evaluation using the Frankel and the McCormick scales should be carried out before and after surgery ( Tables 4 , 5 ). Complications are present due to neurological worsening that can be caused by the surgery itself. This includes spinal epidural hematoma, CSF leakage with or without deep or superficial infections, syringomyelia, and iatrogenic instability (4, 73, 76). In the event of early postoperative neurological deterioration, epidural hematoma should be suspected, and an emergent MRI obtained, in order to rule out this complication, the other possibility being spinal cord ischemia or edema. Epidural hematoma should be evacuated in an urgent manner to obtain rapid and total neurological recovery. In the absence of epidural hematoma and the presence of spinal cord edema, high-dose intravenous steroids should be administered. There are no exact percentages in the literature for these postoperative complications, but all publications agree on their rarity and (i.e., below 5% of cases). CSF leakage is treated by lumbar drainage for 4-5 days and usually resolves without surgical revision. Superficial and deep infections are rare and must be treated with antibiotic therapy and surgical revision when required. Syringomyelia is a late onset complication. If chronic neurological impairment is attributed to the development of the evolving syrinx, subarachnoidal shunting of the cavity through an intracystic catheter should be considered. This complication is usually of bad prognosis. Iatrogenic instability should be considered mainly when back pain remains an issue with the appearance of local kyphosis on control imaging. Instrumented fusion should be considered. It could be done through a minimally invasive navigated percutaneous approach.

Surgery remains the primary treatment modality for spinal meningiomas, although radiotherapy may be used as an adjuvant treatment in some cases.

Postoperative radiotherapy role is not well understood yet (14). Radiotherapy and radiosurgery are the two best substitutes for surgery in specific situations described in the literature (77–79).

Both therapeutic strategies are depicted in Table 6 . Patients with WHO grade 1 meningiomas do not necessarily need adjuvant treatment after resection that might be sufficient for short-term tumor control (80).

Upfront radiosurgery is usually not an option, given that small, non-compressive lesions usually require a close observation strategy, and large symptomatic lesions should undergo surgery. It may be used in fragile patients who cannot be operated. In addition, a 2-3 mm margin between the meningioma and the spinal cord is required for an effective tumoricidal dose (81). Thus, stereotactic body radiation therapy (SBRT) can be proposed for operated patients within a safe margin. The definitive SBRT dose consisted of delivering 21 Gray in three fractions. Five-year control rates with stereotactic therapy for meningiomas, varied between 70% and 100% (82). Adjuvant therapy can also be considered in WHO grade 3 meningiomas, given that these lesions are more aggressive and have a higher recurrence rate (83). Image-modulated radiation therapy (IMRT) and conventional fractionated radiation therapy have also been used to treat spinal meningioma, but SBRT is the preferred modality (77).

Chemotherapy is not used in the management of spinal meningiomas. In invasive atypical meningiomas (WHO grade 3), multiple agents have been used, including hydroxyurea, interferon α-2B, long-acting Sandostatin, and even multidrug sarcoma protocols (84). Chemotherapy can also have a role as a salvage therapy in cases of highly aggressive tumors.

When a spinal meningioma is diagnosed in children, a strictly follow-up must be adopted because of the high risk of developing other tumors, particularly in the context of NF2 (52). Complete surgical resection is the primary treatment modality of spinal meningiomas (85). Adjuvant radiotherapy should be recommended only for children with recurrence (85).

Neuropsychiatric symptoms could be observed in oncology wards, including neuro-oncology. They could result either from the direct effect of the tumoral processes affecting the CNS (such in the case of intracranial meningiomas) and/or secondary to the stressful events or the adjustment processes that arise from the announcement of potentially life-threatening conditions and the related workup, surgical interventions, prognosis, and follow-up (86–88). Although these manifestations might affect patients with meningiomas, as in those with other tumors, they remain overlooked and sometimes forgotten. The majority of the few available studies published on this matter focused on intracranial meningiomas and reported the frequent occurrence of fatigue, anxiety, and depression symptoms (89, 90), as well as the lack of effect of pharmacological therapies (Methylphenidate or Modafinil) on these symptoms, compared to placebo in the randomized clinical trials that recruited patients with primary brain tumors including meningiomas (91, 92).

Fewer data are available on this matter in spinal meningiomas and involve anxiety, depression, and quality of life. For instance, in one study that considered patients with intradural extramedullary spinal tumors (of which 31.8% were meningiomas), some (50%) or extreme (14.3%) problems with anxiety and depression according to a quality-of-life questionnaire (EQ-5D-3L) were reported before the surgical intervention; the rates started to decrease from less than 1-month following the surgery to 3-12 months later, but they increased back to baseline values after one-year follow-up (93). Moreover, in another study involving patients with intradural extramedullary spinal tumors, of which 4.2% had meningiomas, 22.9% met the diagnostic and statistical manual of mental disorder criteria (DSM IV-TR) of a psychiatric disorder. In comparison, 37.5% and 12.5% of patients had mild and moderate depression symptoms according to Beck Depression Inventory, respectively (94). Furthermore, in a third study that addressed the previous limitation by including a homogeneous cohort of patients with spinal meningiomas (n=84), some or extreme problems with anxiety and depression were reported by 31% and 3.6% of patients, respectively, according to a quality-of-life questionnaire (EQ-5D-3L; 95). Here, no significant differences in problems related to anxiety and depression were found in gender or neurological status.

These facts warrant more research to further understand this clinical population’s affective and cognitive outcomes. A thorough investigation of these variables would help to (a) understand such outcomes (depression and anxiety symptoms, fear of recurrence, fatigue, coping strategies) and their clinical predictors, (b) subsequently develop specific screening tools to quantify the symptoms and identify patients at risk, and (c) implement psycho-oncological interventions that could be ideally offered in a patient-tailored manner (psychoeducation, psychosocial support, pharmacotherapeutics or psychotherapies if justified) (96). Lastly, informal caregivers of patients with spinal meningiomas seem to be still forgotten (97), and future studies are needed to evaluate and help these “hidden patients” (98), which might contribute to its turn in improving patients’ outcomes.

Spinal meningiomas are intradural, slow-growing tumors, classified as a WHO grade 1 lesion in more than 70% of the cases. There is no histological difference between spinal and intracranial meningiomas.

Since intradural spinal tumors are not frequent, multicenter studies are required to fully understand and materialize the promise of targeted genetic therapies that will widen the treatment options in the future with a better clinical decision-making.

Observation should be implemented when suitable. Surgical treatment is the gold standard solution, with a principal goal of a GTR (Simpson grade I). If this GTR cannot be achieved, a SIMPSON II is advised, if possible, given the low recurrence rates. In cases of the ventral tumor where GTR is hardly achievable, small amounts of the tumor should be left. If interval growth is seen, the residual tumor can be observed and/or treated with adjuvant therapy, mainly SBRT.

Advances in surgical approaches, especially endoscopic and minimally invasive techniques, are still ongoing to minimize the risks with a better postoperative prognosis with a complete resection as a primary treatment modality.

Psycho-oncological interventions might be beneficial in patients presenting with spinal meningiomas. More research is needed to optimize screening and support patients and their informal caregivers.

SA and GL: Conceptualization and methodology. NS, IL, CA, BT, FN, JF, JM, MC, RB-N and YA: Data analysis, writing-original draft preparation. MC and SA: Review and editing. SA and GL: supervision. All authors contributed to the article and approved the submitted version.