Key-words:
Intraoperative neurophysiology - outcome - spinal cord tumors - surgery
Introduction
Intramedullary spinal cord tumors (IMSCT) comprise the least common types of spinal
neoplasms. They account for about 2%–4% of all central nervous system tumors and 20%–30%
of all spinal cord tumors.[[1]],[[2]],[[3]],[[4]],[[5]],[[6]],[[7]],[[8]],[[9]],[[10]] The most common type of IMSCT is ependymoma, followed by astrocytoma.[[11]],[[12]],[[13]],[[14]],[[15]],[[16]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]] Pain manifested as back pain, radicular pain, or neuropathic pain has been reported
to be the most common presenting symptom in patients with an IMSCT. Other common symptoms
include motor disturbances and sensory symptoms (dermatomal, saddle, or segmental).
Sphincter disturbances may occur as an early symptom.[[11]],[[12]],[[13]],[[14]],[[15]],[[16]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]]
Without treatment, IMSCT can lead to severe neurologic deterioration with serious
motor deficits, including paraplegia or even quadriplegia. The most important part
of the treatment is surgical resection. Radical resection has been associated with
increased long-term overall survival.[[23]],[[24]],[[25]],[[26]],[[27]],[[28]] However, surgery might cause damage to functional tissues, which leads to neurologic
complications.[[25]],[[26]]
To reduce the risk of iatrogenic complications, intraoperative neuromonitoring (IONM)
is a worldwide adopted measure.[[18]],[[19]],[[20]],[[21]],[[22]],[[23]],[[24]],[[25]],[[26]],[[27]],[[28]] Several different monitoring modalities are currently in use.[[8]],[[9]],[[10]] Although IONM is widely used, and many single-center studies have been conducted,
no high evidence study has clearly defined the added value, in terms of overall sensitivity
and specificity to detect or prevent neuronal injury of the different monitoring techniques
used in IMSCT surgery.[[16]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]],[[23]],[[24]],[[25]],[[26]],[[27]],[[28]]
Below, we describe the results of IMSCT submitted to surgery under IONM at a tertiary
institution. Clinical and radiological data, lesion features, timing of symptom onset,
and IONM findings were recorded. The IONM included continuous needle electromyography.
We evaluated the outcome according to the modified McCormick scale.
Methods
The study sample consisted of consecutive patients with IMSCT admitted to the Neurological
Institute of Curitiba (INC) Neurosurgical Ward from January 2007 to November 2016.
Patients enrolled in the study were then followed during treatment. We evaluated age,
gender, symptoms, histology, surgical data (IONM), and postoperative outcome.
Inclusion criteria
All patients undergoing microsurgery as a treatment strategy for IMSCT were eligible
for inclusion.
Criteria for surgery
Criteria used to indicate surgery were as follows: patients with intramedullary spinal
cord lesions, incidental or symptomatic. Patients in palliative care and/or with very
low functional status (Karnofsky score <40) were not considered candidates for surgery.
Signs and symptoms were described according to neurological impairments: pain, sensorial
disturbances, reflexes, motor strength, gait and balance disturbances, and sphincterian
changes. Patients were classified according to McCormick classification (ranging from
I to IV). Postoperatively, patients were then compared and considered with neurological
improvement, stability, or neurological impairment.
Sample
A total of 47 patients were surgically treated. Twenty-three were male (48.9%) and
24 were female (51.1%). The mean age was 42.77 years, ranging from 7 to 80 years.
The mean follow-up time was 42.7 months (ranging from 8 to 120 months). Survival analysis
was extracted from the INC registry of patient data.
Surgical approach
In all cases, the institutional routine is to perform laminotomy of target levels
and midline myelotomy with microsurgical technique. The surgical aim is to perform
maximal safe resection without neurological impairment.
Neuromonitoring evaluation
IOM was recorded continuously, from before patient positioning, at which point baseline
signals were obtained, until waking up from anesthesia. Our evaluation was limited
to continuous electromyography. We did not apply somatosensory evoked potential (SSEPs),
motor evoked potentials (MEPs), D-waves, or dorsal column mapping. Signals were obtained
from all four extremities.
Statistical analysis
Statistical analyses were performed using SPSS Statistics, IBM, Armonk, New York,
USA. We applied the Chi-square test when applicable. We considered statistically significant
data when P < 0.05.
Ethics
The study protocol was approved by the Institutional Ethics in Research Board.
Results
Location of tumors
Cervical tumors occurred in 23 patients (40.4%), while cervicothoracic in 3 (6.4%)
patients and thoracic in 25 (53.2%) patients. The extension of tumor was correspondent
to 2 levels or less in 37 (78%) subjects, while 3 or more in 10 subjects (22%).
Gross total resection was achieved in 40 patients (85%), while partial resection was
obtained in 7 patients (15%).
Histology
As described in [[Table 1]], the most common tumor was ependymoma, with 23 cases (48.9%), followed by hemangioblastomas
(6 cases, 12.8%) and astrocytomas (5 cases, 10.6%). We had also atypical pathological
specimens, such as chordoma and lymphoma. There were two cases of metastases, being
both of melanomas. We illustrate pre- and postoperative images of typical cases in
[[Figure 1]].
Table 1: Histological types
Figure 1: Pre- and postoperative images of typical cases. Above, pre- and postoperative magnetic
resonance of an ependymoma. Below, pre- and postoperative magnetic resonance of a
hemangioblastoma
Clinical presentation
The initial clinical presentation is presented in [[Table 2]]. The main symptoms were sensorial (29 cases, 62%), followed by pain (28%–60%) and
motor deficits (15 cases, 32%). Hyperreflexia, esfincterian, and gait symptoms completed
the main symptoms. Two patients were symptom free at the diagnosis.
Table 2: Initial symptoms in evaluated patients
Preoperative McCormick
Preoperative McCormick was I in 8 subjects (17%), II in 22 subjects (46.8%), III in
15 patients (32%), and IV in 2 other patients (4.2%).
Follow-up
The mean follow-up time was 42.7 months (ranging from 8 to 120 months). In the late
follow-up (1 year), neurological status was improved in 29 patients (62%), stable
in 6 (13%) patients, and worse in 12 (25%). Overall survival rate free of disease
was 90%, with three cases of postoperative complications (6%), being one case of pulmonary
thromboembolic event, and two cases of cerebrospinal fluid fistula. At the end of
the follow-up, we diagnosed one case of melanoma central nervous system dissemination
and one case of tumoral progression instead of surgery.
Intraoperative neuromonitoring parameters and correlation to outcome
We divided IONM parameters into three groups: a group without decrease in intraoperative
electromyography, a second group with decrease and recovery during surgery, and the
last group with decrease without recovery.
In the late follow-up (1 year), neurological status was improved in 29 patients (62%),
stable in 6 (13%) patients, and worse in 12 (25%). Among 47 patients, 24 (51%) did
not present intraoperative signal decrease, while 23 (49%) presented decrease, being
12 patients (25.5%) with recovery and 11 (23.5%) without recovery.
Among 29 patients with clinical improvement, 19 had no decrease in IONM (65%), while
10 had decrease (35%), being 9 with recovery and 1 without. Among 6 patients clinically
stable, 3 had no decrease in IONM (50%), while 3 had decrease (50%), being 0 with
recovery and 3 without. Among 12 patients clinically worse, 2 had no decrease in IONM
(8%), while 10 had decrease (92%), being 3 with recovery and 7 without [[Table 3]].
Table 3: Correlation of intraoperative neuromonitoring parameters and clinical outcome
[[Table 4]] illustrates parameters evaluated and postoperative functional outcome. Gender,
mean age, histology, anatomical localization, extension, preoperative McCormick, and
resection rate did not change the outcome. Factors involved in outcome included initial
motor symptoms presentation and intraoperative change in IONM. The worse outcome occurred
in male patients, above 40-year-old, with partial resection and McCormick III or IV.
Table 4: Factors related to postoperative outcome
Patients who presented with motor symptoms at initial diagnosis had a worse outcome
compared to patients with sensory impairment and pain (P = 0.026). Patients with a
change in electromyography (reduction in peak amplitude >50%, increase in peak latency
>10%, and total loss of waveform) had worse neurological outcomes compared to patients
who did not show changes in monitoring (P = 0.017). Patients who showed changes in
monitoring and returned to baseline potential during surgery had better neurological
outcomes compared to patients who did not return to baseline wave pattern (P = 0.001)
[[Table 4]].
Discussion
Intramedullary tumors account for 2%–4% of central nervous system tumors and 10% of
spinal tumors, with ependymomas and astrocytomas being the most frequent histological
types.[[1]],[[2]],[[3]],[[4]],[[5]],[[6]],[[7]],[[8]],[[9]],[[10]] These tumors are usually benign, slow growing and may extend to various segments
of the spinal cord and have few specific symptoms because they usually evolve insidiously.[[11]],[[12]],[[13]],[[14]],[[15]],[[16]] Even with the progress in surgical technique and intraoperative monitoring, postoperative
prognostic factors are conflicting in the literature.
Ependymomas are common in adults, while astrocytomas are far more common in children.[[10]] Most ependymomas have relatively demarcated borders, while astrocytomas are more
infiltrative and need to be resected until a white matter “interphase” appears.[[20]]
Microsurgical resection of IMSCTs is currently considered the primary treatment modality,
while radiotherapy and/or chemotherapy are reserved for recurrent or malignant tumors.[[3]],[[9]] The observation that the majority of IMSCTs are benign and consequently gross-total
removal might result in long-term survival further supports the need for safe resection.[[10]] The extent of resection has been correlated with progression-free survival and
lower recurrence rates.[[21]] Advances in microsurgery have contributed to safer resection ability. The most
common surgical complication is postoperative cerebrospinal fluid (CSF) leak which
occurs in about 5%–10% of surgeries.[[12]],[[14]]
However, despite all advances, surgery for IMSCTs is still very challenging and may
carry significant morbidity. The most significant risk associated with surgery for
IMSCTs is spinal cord injury and a resulting neurological deficit. Neurophysiological
monitoring is an important tool intended to eliminate or reduce this surgical risk.[[16]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]],[[23]],[[24]],[[25]],[[26]],[[27]],[[28]] To date, both SSEP and transcranial MEP monitoring techniques have been used. Continuous
electromyography and D-wave are also recommended, increasing the sensitivity and specificity
of intraoperative findings.[[16]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]],[[23]],[[24]],[[25]],[[26]],[[27]],[[28]]
No prospective randomized high evidence study has been performed to date to compare
clinical evolution after surgery with or without monitoring.[[6]],[[28]] A recent meta-analysis failed to find a strong support for IONM use in spinal surgery.[[23]] On the other hand, there was a slight tendency to support IONM in IMSCT surgery.[[23]] Thus, the use of IONM is still only supported series of low scientific evidence.
In addition, there are no studies comparing different modalities of IONM in IMSCT
and thus, there is no established superiority of one modality over the other.[[16]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]],[[23]],[[24]],[[25]],[[26]],[[27]],[[28]]
Even though, the routine neurosurgical practice has incorporated IONM and the advocated
advantages include detecting positioning disturbances, intraoperative disturbances
due to anesthetic and surgical intervention, and it adds information to a neurosurgeon
when deciding to continue resection or stopping it, avoiding further tissue damage.[[6]],[[7]],[[8]],[[9]],[[10]],[[11]],[[12]],[[13]],[[14]] Factors associated with improved outcomes for IMSCT include preoperative neurological
status, presence of a tumor dissection plane, tumor size, the use of neuromonitoring,
and postoperative radiation therapy.[[6]],[[11]],[[12]]
In our sample of 47 patients, histology was similar to most series in the literature,
prevailing ependymomas, astrocytomas, and hemangioblastomas. Symptoms were mainly
sensorial, pain, and motor symptoms. Surgical resection was the best treatment mainly
in oligosymptomatic patients with low preoperative McCormick classification (I and
II) and no worsening of IONM during surgery. Worst results were observed in patients
with preoperative motor symptoms, high McCormick classification (III and IV), and
with decrease in IONM sign and persistent decrease in the postoperative period.
There are some limitations of the study. At first, the small sample size does not
allow us to perform an individualized analysis concerning each histological type.
Then, we did not apply routinely SSEPs and MEPs and D-wave monitoring. We applied
exclusively continuous electromyography which might decrease the final power to identify
monitoring changes and thus interfere with optimal results. However, once there is
not still a consensus on the ideal monitoring setup, we believe that this fact may
interfere but not invalidate our results.
We believe that microsurgical resection of IMSCT is the gold standard treatment and
achieved with acceptable complications. Simultaneous use of IONM is for us mandatory,
mitigating positioning and manipulation problems and taken into account when deciding
surgical and resection extent goals. The ideal setup of which monitoring modalities
in each case is yet to be delimitated.
