Clinical manifestations

Presentation and course

Intradural, extramedullary tumors generally cause a chronic compression syndrome. Symptomatology is due to displacement of the spinal cord and adjacent nerve roots and due to associated venous engorgement. Slow growth, over months or years, allows the cord to be gradually displaced and deformed. This produces an atrophic-appearing cord with remarkable preserved neurologic function given the degree of cord compression.

Back pain is the most common initial symptom. It usually precedes neurologic findings by months or years. The pain may be worse at night and is often described as an ache, a pressure sensation, and/or dull. Radicular pain is uncommon with spinal meningiomas. Motor symptoms usually begin in legs. Stiffness and spasticity lead gradually to weakness. Paraparesis is initially symptomatic on climbing stairs and trying to use proximal muscle groups. Sensory deficits nearly always appear after the motor disturbances. They depend on the affected tract, which is typically influenced by the ventral versus dorsal origin of the meningioma. Compression of the anterolateral tracts will produce a decline in pain and temperature sensation. A sensory level will appear, giving a valuable guide to the probable spinal cord level of compression. When posterior columns are displaced, position sense will be affected leading to an unsteady gait. Sphincter disturbances can occur at a late stage or they may be the initial complaint in tumors arising at the level of the conus.

Meningiomas at a high cervical level or the foramen magnum may produce quadriparesis, lower cranial nerve involvement, dysphagia, and respiratory disturbances. Horner syndrome, due to interference with the cervical sympathetic chain, may occur. Interestingly, disturbances in facial sensation may be present due to compression of the descending sensory root of the trigeminal nerve.

The duration of clinical symptomatology is usually of medium range. Of 174 spinal meningiomas reported by Solerno, 117 patients had a clinical history ranging from 6 months to 3 years (73). In the modern MRI era, this prodrome should be shortened if a high index of suspicion is practiced by community physicians and neurologists. Additionally, scans obtained for other complaints or in the trauma setting may reveal spinal meningiomas incidentally.

Prognosis and complications

The neurologic morbidity of the surgical removal of tumor is directly related to the preoperative neurologic status. Patients with little or no disability preoperatively are at little risk to sustain an injury, whereas patients with more advanced neurologic dysfunction have a greater chance of remaining impaired following surgery. Long-term neurologic recovery is usually excellent (47; 48).

Other complications are generally related to wound healing and perioperative fistulas. A joint neurologic and plastic surgery approach was developed to reduce the morbidity of wound closure following extensive and complicated laminectomy (80; 79).

Spinal meningiomas are almost always amenable to surgical resection and usually do not recur following radical resection. Long-term follow-ups following operations found a very low recurrence rate ranging from 5.6% to 8% (47; 53; 73).

Clinical vignette

A 33-year-old Caucasian woman presented with several months of back pain, progressive numbness, and weakness in the lower extremities. She also reported urinary urgency but denied bladder or bowel incontinence. Neurologic examination demonstrated mild spastic paraparesis with a sensory level at T10 level. An MRI scan with and without contrast of her thoracolumbar spine showed an extramedullary, intradural lesion at T7-8 level with diffuse contrast enhancement and moderate effacement of spinal cord. She underwent urgent decompressive surgery with laminectomy and resection of the lesion. Histopathology was consistent with a meningoepithelial meningioma. Postoperatively, she made good recovery with no residual neurologic deficits. She continued to do well several years after her surgery with no evidence of recurrence.

Biological basis

Etiology and pathogenesis

Prior radiation therapy has a well-established role in promoting growth of cranial meningiomas. This phenomenon falls into 2 categories: (1) those cases in which radiation was administered in high doses for the treatment of an intracranial growth, and (2) those in which low doses of scalp radiation were given (04; 72; 62). Because radiation therapy was primarily aimed to the scalp, these reported cases were primarily cranial and not spinal meningiomas. One case of cervical meningioma that developed 9 years after the radiation therapy for Hodgkin lymphoma was reported (52). Chemotherapy has also been implicated in the pathogenesis of meningioma, although a true causal relationship has not been established. One case of spinal meningioma was reported that occurred in a patient with essential thrombocythemia who had been on hydroxyurea therapy for 10 years. Paradoxically, hydroxyurea is often employed for the treatment of unresectable meningiomas (31). Head injury has been suggested as playing at least a statistically significant role in the development of cranial meningioma (81). A similar phenomenon in the spine has not been described.

Meningiomas arise from the endothelium which lines the leptomeningeal spaces. Meningiomas are firmly attached to the dura and appear to be arising from it. Those tumors are probably derived from sequestered clumps of arachnoidal cells that occur within normal dura. In the spinal canal, there are nests of arachnoidal cells at the junction of the arachnoid and the dura where they encase the nerve roots on their passage towards the intervertebral foramina (35).

Genetics. The sporadic loss of genetic material from the long arm of chromosome 22 is thought to be critical for the initial development of meningioma in older adults (78). The locus is separate from the neurofibromatosis type 2 gene on chromosome 22 and is between the myoglobin and the c-sis proto-oncogene locus. It is likely to be a tumor suppressor gene. Progression of a meningioma to a higher grade probably requires other chromosomal changes.

The growth rate of meningiomas can be measured using a bromodeoxyuridine labeling index that will measure S phase fraction of cells. In intracranial meningiomas, a labeling index of 5% was associated with increased incidence of recurrence and an index of greater than 1% with a faster growth rate (36).

In younger patients, germline mutations in the NF2 gene are frequently seen in patients with multiple meningiomas (59). Furthermore, germline mutations in SMARCE1 predispose to the clear cell variant of meningioma in young patients. Amongst intracranial meningiomas, some of those without NF2 mutation exhibit mutations of either AKT or SMO. SMO mutations most frequently occur in the olfactory groove and AKT at the skull base (10). It is unknown whether these mutations are commonly present in spinal meningiomas.

Pathology. In its simplest forms, the tumor is seen as a pinkish round or oval mass with a smooth, granular, or lobulated surface. The texture is usually firm but sometimes may be sufficiently friable to be removed with suction. Calcium deposits (psammoma bodies) are common, and cystic degeneration, hemorrhage, and lipid changes may occur.

The microscopic appearance of meningiomas was classified into 3 basic types: (1) syncytial, (2) transitional, and (3) fibroblastic (64).

Meningiomas are rarely anaplastic or malignant with mitotic figures and necrosis. Spinal meningiomas and midline skull base meningiomas are predominantly meningothelial meningiomas. Analysis of the increasingly available data on genetic and topographic characteristics of meningothelial meningiomas suggests that they may represent a unique entity, contrary to the prevailing belief that all benign meningiomas are identical tumors (46).

Briefly, the majority of meningioma variants are grade I, with the choroid and clear cell variants being classified as grade II (atypical) and the papillary and rhabdoid variants considered grade III (anaplastic) (45). The 2016 World Health Organization classification of meningiomas states that either evidence of brain invasion, 4 to 19 mitoses per 10 high powered fields, or any 3 of the following 5 histological features are sufficient for the diagnosis of an atypical (grade II) meningioma: spontaneous necrosis, sheeting (loss of whirling or fascicular architecture), prominent nucleoli, high cellularity, and small cells (49). Greater than 20 mitoses per high power field is considered anaplastic. In a series of nearly 200 patients, 91.5% of spinal meningiomas were grade 1, with 8.5% of patients having higher grade lesions (44). There has been a drive towards incorporating molecular characteristics into the prognostication for meningiomas (24). Recent work evaluating the epigenetic landscape of meningiomas has also provided valuable prognostic information. It is uncertain if this holds true for spinal meningiomas.

Pathophysiology. The meningeal attachment may be broad, rendering the tumor sessile, or narrower than the tumor's maximal diameter. Vascular supply usually comes from this attachment; thus, the dura is often thickened and vascular. About 7% to 10% of meningiomas are intradural and extradural and about 5% are entirely extradural (54). Spinal (as opposed to intracranial) meningiomas do not involve bone. This is probably due to an enlarged spinal epidural space filled with fat, venous plexuses, and nerve roots.

Spinal meningiomas are most frequently found in the thoracic area (57; 63; 40).

In a metaanalysis of 705 spinal meningiomas, 80.9% were found in the thoracic spine, 16.8% in the cervical area, and 2.3% near the conus and the lumbar spine (57). The lumbosacral canal may allow a slow-growing tumor to reach large size (28). There is no clear explanation for the predilection of meningiomas for the thoracic canal. Simultaneous occurrence of multiple meningiomas in different neuraxial compartments is uncommon but rarely reported even without underlying neurofibromatosis. Bhatoe reported a young patient with multiple meningiomas, 2 intraspinal and several intracranially, which were histologically different (07).

Meningiomas have been associated with pregnancy and menstruation (08), obesity (05), and breast cancer (69), raising the possibility that these tumors are hormonally reactive and, therefore, may respond to hormonal manipulation. Several studies have shown that progesterone receptors are present in a high percentage of cranial meningiomas and are more common than estrogen receptors. Several laboratory studies have shown that meningiomas in tissue culture had their growth suppressed by either progesterone (33) or progesterone antagonists such as RU486 (58). Other researchers suggested that progesterone receptors may play a role in the production of edema around cranial meningiomas (06). These drugs have not demonstrated any meaningful benefit when evaluated in clinical trials of intracranial meningiomas.

Epidemiology

Spinal meningiomas account for only 1.2% to 12% of all CNS meningiomas (76). The annual incidence of primary spinal neoplasms ranges from 0.8 to 2.5 per 100,000 population (29). In hospital neurosurgical practice, intraspinal neoplasms generally account for approximately 15% of all primary tumors of the central nervous system. A large series of 1322 primary intraspinal tumors, reported from the Mayo Clinic, recorded an incidence of 29% schwannomas, 25.5% meningiomas, 22% gliomas, and almost 12% sarcomas (71). Meningiomas in the spinal canal are far less frequent than those within the cranial cavity (25; 71; 64).

The majority of spinal meningiomas present in the older population, with a peak in the sixth decade. Meningiomas are rare in children and young adults. In this age group there is an increase of malignant variants when compared to adults and a higher association with neurofibromatosis (20; 55). Familial occurrence of meningiomas, usually multiple, is found largely in the context of von Recklinghausen disease (aka, neurofibromatosis I) (22).

Spinal meningiomas have a female preponderance of up to 90% (57; 73; 63; 40), although males have a higher mortality with these tumors (76). These tumors are most commonly found in the thoracic spine, potentially because this is the largest region of the spinal cord, although site is not associated with mortality.

Differential diagnosis

The most common differential diagnosis for an intradural-extramedullary spinal lesion is between a meningioma and a schwannoma or neurofibroma (48). Spinal schwannomas arise indiscriminately from any of the spinal nerves and almost invariably from the sensory roots. Therefore, there is a high incidence of radicular pain as the presenting symptom. When schwannomas are part of von Recklinghausen disease, the affected portion of the nerve is commonly diffusely swollen in spindle fashion with irregular enlargements. Because schwannomas arise from the nerve, they tend to grow laterally and enlarge the intervertebral foramen, occasionally forming a further mass outside the spinal canal (ie, a dumbbell tumor). These hourglass or dumbbell tumors occur most commonly in the cervical or thoracic regions. Dural metastases should also be considered on the differential diagnosis. Breast cancer and prostate cancer have the highest incidence of dural metastases amongst the solid tumors. Sarcoidosis may also rarely present as an intradural extramedullary mass which can easily be confused with meningioma on neuroimaging studies (34).

Diagnostic workup

Plain films are insensitive in evaluating patients with suspected intradural pathology. Even secondary bony changes such as erosion or foraminal widening are better demonstrated with computed tomography (75). Plain films are better, however, for diagnosis of instability and quantification of scoliosis and kyphosis.

Magnetic resonance imaging is the diagnostic procedure of choice for primary spinal tumors (74; 56). More than 95% of meningiomas enhance homogeneously and brightly following gadolinium injection and have sharply defined margins.

In cross-sectional images, one can visualize the dural base of the tumor vis-à-vis the compressed cord. Spinal meningioma may occasionally be associated with diffuse leptomeningeal enhancement (50). "Dural tail sign" is as common in spinal meningiomas as in cranial meningiomas (02). Occasionally, spinal meningiomas can be calcified and ossified, which is important for surgical planning, as these tumors are generally more difficult to resect, are associated with higher rates of neurologic injury, and can require a wider laminectomy margin (39). Ossified/calcified meningiomas are easily identified on plain x-rays and CT scans, and typically appear as hypointense lesions on both T1- and T2-weighted MRI scans.

MRI features can be helpful in differentiation of spinal meningioma from schwannoma. Diagnosis of schwannoma is more likely when a spinal intradural extramedullary tumour shows hyperintensity on T2W images or intense enhancement without dural tail sign. Otherwise, meningioma is more probable (19). Coexisting spinal meningioma and schwannoma have been reported in neurofibromatosis (13).

Management

Spinal meningiomas are typically managed surgically (01), and despite the challenge presented by lesions ventral to the cord or at the craniovertebral junction, the vast majority of patients have significant postoperative improvement (09; 12; 70; 42; 43; 15; 16). Generally speaking, the indications for surgery include axial pain that is worse with recumbent position, motor weakness, sensory disturbance, radiculopathy, loss of bowel/bladder function, myelopathy, gait impairment, or malignant appearance/growing tumor (11).

Surgical intervention should be considered in most cases, even in older patients with significant neurologic deficits. In a multicenter retrospective study, 102 patients aged 70 years or older with paraplegia or severe paraparesis underwent operation for spinal meningiomas at 5 French neurosurgical centers between 1990 and 2007. Complete tumor removal was obtained in 93 patients. There was no surgical mortality, and morbidity was 9%. Three months after surgery, 7 of the patients were unchanged, 87 patients had improved, and 8 were not evaluated. One year after surgery, 7 of the 100 surviving patients were clinically unchanged and 93 had improved. Of those who had improved, 49 patients experienced complete recovery. Advanced age is not a contraindication to surgery, even in patients with severe preoperative neurologic deficits; and quality of life can be improved in most cases (65).

Another single institution series of patients treated from 1976 to 2011 found a functional improvement at follow-up in 86.7% of cases, whereas 6.4% of patients remained stable, and 6.9% worsened (60). A low functional grade before surgery was associated with less postoperative improvement. Anterolateral meningiomas were the most represented (42.2%). A gross total resection (ie, Simpson grade I and II) was achieved in nearly 99% of patients, and a macroscopically complete removal without dural resection or coagulation (Simpson grade III) was performed in the remaining 1%. Negative prognostic factors from this study include anterior or anterolateral axial implant, long-lasting symptom duration, WHO grade II or III tumors, a Simpson grade II or III resection, symptomatology that includes sphincter involvement, and a poor functional grade at onset (61). These authors found surgical complications in 7 of 173 cases (4.04%). A total of 4 patients (2 postoperative spinal epidural hematoma, 1 syringomyelia, and 1 adverse reaction to dural sealant) required an additional surgery to address the complication. The remaining underwent conservative treatment (3 patients with CSF leakage resolved with lumbar drainage).

Regarding the operative procedure, usually a subperiosteal dissection of the paraspinal muscles is performed followed by a limited laminectomy over the tumor. If necessary, transdural ultrasonography can be utilized in addition to neuroradiology to further define the location of the tumor vis-à-vis the bone removal (26). The spinal cord is viewed in both sagittal and transverse sections. The rostral and caudal limits of the tumor are immediately obvious. Meningiomas are commonly homogeneously hyperechogenic compared to adjacent tissues, so the tumor mass may be completely visualized.

The dura is then opened in the standard fashion and retracted laterally. Spinal meningiomas have an anterolateral dural attachment and, therefore, the lateral edge will be visualized. Occasionally, the tumor is anteriorly based and not seen initially without lateral retraction of the spinal cord. In such a situation, it should be remembered that only minimal and intermittent retraction of the cord is allowed. The bony opening should be generous at the involved side and the microscope positioned in an angle that allows the most lateral view.

The dural attachment can be vaporized and detached with regular bipolar technique or with the CO2 laser. There should not be an attempt to remove the tumor in 1 piece. Rather, following coagulation of the dural vascular supply, bits and pieces should be removed using microdissecting scissors, a CO2 laser, and an ultrasonic surgical aspirator (15; 16; 11). The tumor usually has a rich vascular supply and early interruption is necessary for adequate visualization and tumor decompression (11). The surgical specimen should be sent for pathology and then the dura is extensively cauterized with the gap reapproximated with polypropylene sutures. Finally, fibrin and synthetic collagen can be added to seal the primary dural repair and minimize the changes of a CSF leak. If concern for spinal instability is present, a laminoplasty or instrumentation can be added for structural support.

Routinely monitor motor-evoked potentials (21) and somatosensory-evoked potentials during the surgery. Following initial laminectomy, rostral and caudal epidural electrodes are placed. The electrode proximal to the stimulus serves as a control and the distal one is for monitoring the operation. For anesthesia, a combination of propofol and narcotics is usually employed with a standard endotracheal intubation. Some basic principles apply for both somatosensory-evoked potentials and motor-evoked potentials. First, information needs to be immediately available and utilized by the surgeon to modify the operative dissection. Second, data should be continuously updated and communicated to the surgeon. Third, criteria for significant changes should be set and tailored for each patient according to the pathology and the baseline potentials.

For motor-evoked potentials, transcortical electrical stimulation (21) and epidural recordings are a reliable intraoperative technique that monitor the upper motor neuron. It has the disadvantage of not differentiating between left and right. Most surgeons do not push dissection beyond a 50% fall in motor-evoked potential amplitude. If and when such a decline occurred we would stop manipulating the cord in this area and wait for the recovery of potentials.

It has been advocated that an attempt should be made, whenever possible, to excise the dural attachment of spinal meningiomas. Nevertheless, a Simpson grade I resection can be riskier, and 1 series found that a Simpson grade II removal (coagulation of the dural attachment after gross total resection of the tumor) is an acceptable, safe alternative with very low long-term recurrence rates (38). Accordingly, most surgeons believe that simple coagulation of the dural attachment is sufficient for low recurrence rates (27; 23). Some authors have argued for a dura preservation technique to reduce the risk of CSF leakage, in which the meningioma together with the inner layer of the dura is removed and the outer layer is preserved, and the small case series have reported similar recurrence rates to previously published series (67; 68).

If there is recurrence and it is accessible, repeat surgical excision should be attempted. External beam irradiation should be used after subtotal resection or after recurrence of a totally resected meningioma. The Cyberknife® Radiosurgery System for benign spinal tumors may be an acceptable therapeutic option for some patients following subtotal resection or recurrent tumor (66).

Prognostic factors for poor functional recovery following surgery include tumor size occupying greater than 75% of the spinal canal, T2 hyperintense signal change in the spinal cord, and poor preop modified McCormick grade of functional status (51). Interestingly, there is no evidence that cross-sectional area of remaining cord had a relationship with function before or after surgery, suggesting that persistent cord atrophy after decompression may not indict insufficient cord recovery after decompression (18). Tumor calcification, which can reliably be detected with a CT scan, has been associated with longer operation times, more blood loss, and a significantly lower rate of neurologic improvement after surgery (41).

Operative complications range from 0% to 15% in the literature, with CSF leak, wound infections and dehiscence, and transient deterioration of neurologic status being the most common surgical complication (51). Medical complications include pulmonary embolism and urinary tract infection. Permanent neurologic deficit was seen in about 5% of patients (77).

It is possible that if systemic therapies prove to be of benefit for intracranial meningiomas in the future that this benefit could translate to spinal meningiomas as well. At this time there are no established systemic therapies for meningioma treatment.

Outcomes

Kilinc and colleagues reported functional outcomes after microsurgical resection in a cohort of 119 patients (37). After a mean follow-up of 25.4 ± 37.1 months, the rates of overall complication, tumor recurrence, and poor functional outcome were 9.2%, 7.6%, and 5%, respectively. Age, revision surgery, and tumor recurrence were identified as independent predictors of poor functional outcome. Obesity had an impact on the complication rate, whereas extent of resection and tumor calcification affected the rate of tumor recurrence (37).

For patients with high grade (grade 2 or 3) spinal meningiomas, adjuvant radiotherapy may improve recurrence rates.

Special considerations

Pregnancy

Meningioma tends to grow during pregnancy. Few cases of spinal meningioma presenting during second or third trimester pregnancy as new-onset paraplegia have been described in literature (03). Both hormonal and hemodynamic changes during pregnancy play a part (14).

Anesthesia

No special precautions are necessary during induction. Neuromonitoring can be performed to help ensure a safe resection is performed and motor responses are not lost during the operation. If there is evidence of cord compressions, some surgeons elect to elevate blood pressure/mean arterial pressure to ensure cord perfusion during the surgery.