4 Intramedullary spinal cord tumour

Expert comment Intraoperative neuromonitoring

Intra-operative potentials are recorded from the thenars, hypothenars, tibialis anterior, and flexor hallucis brevis, as these have strong pyramidal innervation. The sensitivity of motor-evoked potentials (MEPs) for post-operative motor deficit approaches 100% and is about 90% specific.

Recent guidelines provide level A evidence that intra-operative neurophysiology during spinal cord predicts an increased

risk of paraparesis, paraplegia, and quadriplegia. All twelve studies included in this analysis demonstrated that every incident of paraparesis, paraplegia, and quadriplegia was associated with changes in monitoring output and no paralysis occurred without changes in the monitoring output. The role of intra-operative monitoring in the prevention

of mild motor deficits was not studied [1].

Figure 4.2 Intra-operative photograph of a spinal cord ependymoma resection. The cord is split in the midline and the tumour resected using micro-instruments, with neurophysiological monitoring of both the sensory and the motor tracts.

After discussion in the spinal oncology MDT meeting and at length with the patient, a decision was made to attempt resection of this intramedullary cord lesion. After C4–6 laminectomies, a midline durotomy was carried out and, under the microscope, a midline myelotomy revealed a cavity containing tumour. A clear plane of dissection was identified between the tumour and the surrounding spinal cord, allowing complete macroscopic excision of the lesion (Figure 4.2). Intra-operative neurophysiological monitoring comprising motorand somatosensory-evoked potentials remained stable throughout the procedure.

Histopathological analysis revealed a WHO Grade 2 ependymoma. Postoperatively the patient had no new neurological deficit. She developed a CSF leak

Learning point Histopathology and World Health Organization grading of ependymomas

Histological characteristics of ependymomas typically include the presence of perivascular and ependymal rosettes (Figure 4.3), and positive immunohistochemical staining for glial fibrillary acidic protein (GFAP), CD56, and epithelial membrane antigen (EMA).

According to the 2007 WHO classification of tumours of the central nervous system, there are three grades of ependymal tumours [2]:

●Grade I: subependymoma and myxopapillary ependymoma.

●Grade 2: ependymoma without the malignant features that define Grade 3 (the most common type).

●Grade 3: anaplastic ependymoma, revealing malignant features of increased cellularity, brisk mitotic activity, microvascular proliferation, and pseudopalisading necrosis.

There are four recognized histological subtypes of ependymona—cellular, papillary, clear cell, and tanycytic. The subtypes generally apply to Grades 2 and 3 ependymomas.

A controversy in the grading of ependymomas arises in the distinction between Grades 2 and 3 [3]. Poor correlation with clinical progression and lack of biological usefulness in distinguishing Grades 2 and 3. The current grading system does not take account of factors such as location, segments involved, age, and clinical features.

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Case 4 Intramedullary spinal cord tumour

Surgical options for infiltrative tumours include biopsy, debulking, or subtotal resection. Biopsy only is an appropriate choice in patients not fit to tolerate extensive surgery, or when the diagnosis is uncertain and the lesion could represent non-malignant athology. The extent of resection in infiltrative tumours is guided by microscopy and intra-operative MEPs, somatosensory-evoked potentials (SSEPs) and occasionally D-wave (epidural) monitoring. Some papers suggest a role for intra-operative ultrasound in defining the margins of the tumour, its relation to the spinal cord, vascular relations, and its consistency [15]. Karikari et al. point out that the extent of resection is dependent on the plane of dissection, which is somewhat variable in the literature [14], with some series such as Garcés-Ambrossi et al. describing a fairly high rate (up to 40%) of gross total resection of spinal cord astrocytomas [10]. McGirt et al. point out that aggressive resection of astrocytoma can lead to substantial motor deficits and this risk needs to be balanced against the option of a more conservative resection, followed by radiotherapy [16]. Complete resection is, however, associated with a lower recurrence risk [17, 18]. While some papers show the degree of resection to be an independent risk factor in recurrence, it may be that those tumours that are easier to resect are also the ones that are benign. A series of 100 IMSCTs showed that 45% had an associated syrinx [19]. The authors suggested that the presence of a syrinx may be a favourable prognostic sign as it suggests displacement, rather than infiltration of the cord [19]. The presence of a syrinx may also facilitate resection by creating natural planes within the cord and improve outcome compared with cases without a syrinx [10].

Another area of controversy in the management of IMSCTs is the optimal timing of surgery. Since most authors advocate aiming for complete excision, it can be argued that early surgery on a small mass is desirable. However, in patients who are not functionally impaired by their neurological deficit and who have a slow growing tumour on serial imaging, the risks of surgery may not be acceptable. Since pre-operative neurological deficit is an established determinant of outcome, it is important to operate before neurological deficits that affect mobility and function appear. Whether surgery should be performed in an asymptomatic patient, or whether to risk the development of neurological deficits in time from an expanding tumour, is a difficult decision to make. Patients should be counselled about the risks and benefits of early or delayed surgery. Evolving neurological deficit is a definite indication for surgery.

It is known that intra-operative monitoring is effective in reducing neurological deficit. However, the interpretation of intra-operative monitoring is not a clear-cut matter. Various grading systems have been proposed to quantify loss of potentials intra-operatively. No widely-accepted system is available. Intra-operative monitoring is of limited value in patients with pre-operative neurological deficits. Differences in intra-operative monitoring waveforms in infiltrating versus well-defined tumours, especially towards the tumour margins, have not been defined.

Surgery for IMSCTs is high risk and the patient should be counselled about this. The main risks include infection, CSF leak [17], transient and permanent neurological deficits, and chronic pain post-operatively. Hydrocephalus can occur in about 1% of patients by an unknown mechanism [22]. IMSCTs are not uncommon in the over-60 age group, which can lead to some concerns about the suitability of these patients for surgical management. Reports in the literature on neurosurgery in elderly patients suggest that elective procedures in the absence of diffuse neurological disturbance does not lead to poor outcomes [23, 24, 25]. Neuropathic pain in IMSCTs is described preand post-operatively in the literature for neural and vascular tumours [26, 27, 28], and can be the cause of significant disability and depression

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Expert comment Resecting intramedullary tumours

A challenge in the surgical management of IMSCTs is how aggressively to resect tumours, especially those without a clear plane of dissection. Tumour histology has been found to influence ease of resection and ability to achieve complete resection [14]. For ependymomas and vascular tumours with well-defined margins, the gold standard is total resection. Astrocytoma and other infiltrative tumours, however, are more difficult to resect as there is no clear dissection plane and, here, the aim may not be complete resection, but rather subtotal resection without causing new neurological deficits.

Clinical tip Loss if motor-evoked potentials / somatosensory-evoked potentials signal intra-operatively

Diminishing signals are a warning that neurological deficit may occur and gives the surgeon an opportunity to react. Should signals be lost, stop surgery and assess for spontaneous recover of potentials. Irrigate the operative field with warm saline and increase the blood pressure to increase spinal cord perfusion [20]. Sala et al. reported that surgery may need to be stopped for up to 30 minutes in some cases, before potentials reappear and surgery can progress. If potentials fail to recover, it may be appropriate to perform the

operation as a two-stage procedure or even to abandon surgery completely [20, 21].

Expert comment Minimizing the risk of cerebrospinal fluid leak

Perfect primary closure is important, for example, by using a running 4/0 prolene or nylon suture (vicryl can tear the dura), supplemented with a dural patch and tissue adhesive. Lumbar drains

are seldom required, and should be reserved for troublesome persistent leaks.

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Expert comment Role for fixation

Young patients, with more than two levels of laminectomy and positive (kyphotic) balance, are more prone to delayed instability, and should be considered for prophylactic spinal fixation at the time of tumour resection

Learning point Cavernomas and haemangioblastomas

Cavernomas are thin-walled sinusoidal channels with no intervening neural tissue.

Haemangioblastomas are WHO Grade 1 tumours. They are composed of capillary channels with interstitial cells containing foamy cytoplasm. The cell types are endothelial cells, pericytes, and clear cells.

Challenging concepts in neurosurgery

for patients. Pain and spinal deformity are two long-term sequelae after surgery for IMSCTs, the latter being more common in children. A retrospective series of 52 IMSCTs in children showed that fusion or instrumentation at the time of tumour excision was associated with a significantly lower risk of post-operative deformity [29]. Removal of more than three laminae was associated with significantly increased risk of kyphotic deformity.

In terms of adjuvant treatment, radiotherapy is used variably. It can be used for all high-grade tumours, high-grade tumours with incomplete resection margins, and recurrence of high-grade tumours. There is currently no level 1 or 2 evidence investigating the role of adjuvant radiotherapy in IMSCTs, so the decision is made on a case-by-case basis. Typically, external beam radiotherapy has been reserved for recurrence, inoperable tumours, and palliatively [30]. Cyberknife radiotherapy has been attempted for IMSCTs, but there are no long-term outcome data on its effectiveness as yet. Chemotherapy can be considered in patients with progression of disease following radiotherapy, but data are limited [31, 32]. Vascular intramedullary tumours broadly comprising spinal cord cavernomas and haemangioblastomas, present specific challenges. They are benign, usually well-defined, and typically can be shelled out en bloc.

Evidence base Surgery for IMSCTs

The literature on IMSCTs is comprised of retrospective series, which represents NHS Class C evidence. Two of the larger series are:

●Raco et al. review the outcome of 202 IMSCTs. Sixty-one (30%) were cervical tumours (30%), sixty (29%) thoracic, and fifty-one (25%) cervicothoracic. Astrocytoma (eighty-six patients, 42%) and ependymoma (sixty-eight patients, 34%) were the main tumour types. Long-term functional outcome was determined by histology, degree of resection and pre-operative neurological status [8].

●Kucia et al. [17] review sixty-seven spinal ependymomas. Like Raco et al. [8], cervical and thoracic location predominated. Complete resection was achieved in fifty-five patients. The findings of note in this paper were that preand post-operative neurological outcome correlated significantly

(P < 0.001). Early post-operative neurological worsening was found at 3-month follow-up to have improved in a significant number. This series reported a high complication rate of 34%, mainly wound infections and cerebrospinal fluid leaks

Spinal cavernomas mainly affect the cervical and thoracic cord. A recent literature review suggests that just over a quarter of these have a co-existing cranial cavernoma and a tenth have a family history of cavernoma [33]. Mutations in the cerebral cavernous malformation (CCM) one, two, and three genes have been described in cavernoma development. Clinical features can be secondary to expansion and/or to recurrent haemorrhaging, and progressive deterioration follows an acute, stepwise, or progressive nature [27]. Gross et al. [33] discussed surgical management based upon whether the lesion is exophytic or deep, and whether it is symptomatic or not. They recommended intervention for symptomatic lesions and for accessible lesions, while recommending observation for deep and asymptomatic or mildly symptomatic lesions [33]. This approach is supported by a retrospective review of 96 intramedullary cavernomas, where 91% of operated cases were stabilized or improved, and none of the twelve conservatively-managed patients deteriorated [34]. Radiologically, cavernomas are commonly described as having a ‘popcorn’ appearance, due to the hyperdense vascular component surrounded by a hypodense haemosiderin ring on MRI with gradient echo sequencing. Operatively, this translates into the presence of a well-defined gliotic plane along the outside of the cavernoma.

Haemangioblastmas can be sporadic or occur in the setting of VHL disease, where they are more likely to be multiple. Mehta et al. reported on 218 spinal haemangioblastoma surgeries in 108 VHL patients, where 99.5% were completely resected and 96% improved clinically post-operatively [35]. Later decline was due to VHL disease progression unrelated to the operated cavernoma.

Learning point Von Hippel–Lindau disease

VHL disease is an autosomal dominant syndrome with a defect on chromosome 3 (3p25-p26), which is a tumour suppressor gene. VHL is associated with renal cell carcinoma, pheochromocytoma, hemangioblastomas of the CNS, retinal angiomas, epididymal cysts, endolymphatic sac tumours, and pancreatic cysts and solid lesions.

Clinical tip Pre-operative preparation of vascular intramedullary spinal cord tumours

Haemangioblastomas can cause massive intra-operative haemorrhage! Ensure there are blood products available and consider pre-operative endovascular embolization.