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Cranial Nerve Surgery Disease:Intraoperative Neurological Monitoring of Neurosurgery

Intraoperative monitoring is inevitable to prevent deficiency phenomenon

In the recent cranial nerve surgery operation, none of appearance or degradation of postoperative neurological deficit is permitted. Therefore, Intraoperative Neurological Monitoring of Neurosurgery becomes necessary. Also, intraoperative mapping is necessary for conducting neurological monitoring of neurosurgery or for identifying the functional region in operative field. In currently conducting neurological monitoring or mapping of neurosurgery, the followings are listed up.

Intraoperative Mapping
Intraoperative Monitoring

Among above, this paper will explain in detail about motor evoked potential (MEP) monitoring, especially about the simple transcranial MEP monitoring, which is commonly conducting for preventing the postoperative motor paralysis appearance or degradation. Also, Cortico-Cortical Evoked Potentials (CCEP), which is begun performing at some facility, and language monitoring is possible under full anesthesia, is explained here.

Motor-evoked potential (MEP) monitoring

Motor evoked potential is the method of direct stimulation to motive field or pyramidal system on subcortical/brain stem/spinal cord, and the method of stimulate to transcranial motive field by high voltage. As for derived region, recording by four limb electromyograms is common, but the other method is to derive D-wave by implementing epidural electrode in cervical spine.

  1. Direct stimulation of motor evoked potential (DMEP) monitoring

    Implement epidural electrode clipping cerebral sulcus which is suspicious as center channel, stimulate contralateral median nerve, deviate somatosensory evoked potential from brain surface, identify center channel by N19 or P20 phase alteration, stimulate motive field with 10-20mA train 5, and identifying pyramidal system with 5-10mA stimulation.

    Authors are conducting mapping/monitoring of pyramidal system by direct stimulation to brain stem or spinal cord. 1) Direct stimulation of motor evoked potential is primary conducting as MEP monitoring for intra-axial tumor. In authors experience, both sensitivity and specificity is 100% so that this is high-accuracy monitoring. But, for the craniotomy with no motive field exposure, it is necessary to slide in subdural electrode so that there is a risk for damaging of brain surface blood vessel, and there is a difficulty for deviation. Furthermore, DMEP usually deviates MEP from upper limbs so that lower limb monitoring is generally difficult.

  2. Transcranial MEP (TCMEP) monitoring

    Transcranial motor-evoked potential (MEP) monitoring is relatively easy and less-invasively to predict and prevent postoperative Limb Movement Paralysis and are performed broadly at the surgery for brain tumor, cerebrovascular disease, spinal cord in Cranial Nerve Surgery region. On the other hand, transcranial MEP monitoring are considered as less trustworthy than

    Authors consistently perform amplitude evaluation so that to increase Transcranial MEP sensitivity and specificity, MEP amplitude compensation by compound muscle action potential (CMAP) has been conducted since 2003. This time, CMAP compensation method and its expediency, significance of transcranial MEP monitoring at spine cord surgery, and decision of cut off value at MEP monitoring, are explained by disease base.

    Transcranial MEP monitoring method

    Stimulation electrode, CS electrode, is set fundamentally at 2cm back of C3, C4. Stimulating electrode is set at positive pole, and in case of craniotomy, negative pole is set at midline (Cz). Deriving electrode is used to use plate electrode but now disposal NCS electrode (NIHON KOHDEN Corporation) is used. Deriving electrode is used at 4 positions (Left, right, APB, AH) for craniotomy, 5 positions (left, right, APB, AH, patient side BB) for cervical spine surgery, and 5 positions (patient side BB, AH both side, TA, AD, IP). Simulation is made at 200 to 600V (200 to 300V for craniotomy, 300 to 400V for cervical spine), train 5, duration 0.2msec, inter-pulse interval 2 msec. It is recommended to set Stimulation voltage at 20% more than threshold voltage, but there is a fundamental issue in neurophysiology that the amplitude evaluation shall be made at maximum stimulation. To evaluate the amplitude correctly, we have set voltage a little bit higher value.

    About stimulated part by transcranial stimulation

    Discussion has been made for long time about which part is stimulated or about whether the nearest part of motor area is really stimulated by the electrode implemented on sculpt in Transcranial MEP. There is a report that transcranial stimulation is not appropriate for the monitoring of the tent surgery, since, nearest part of brain stem is stimulated since latent time of MEP waveform. 2) But this was the result of 900V singular stimulation so that the voltage is greatly exceeded currently doing stimulation voltage. Authors have reported that with decreasing stimulation voltage, stimulated part is coming closer to motor area at positive electrode side. 4) Also, normally 5 consecutive train stimulations are necessary for deviating MEP, and this stimulation takes 9 msec. It is still unknown in which point in this 9 msec, motor area is ignited. In the first place, it is unable to presume the stimulated area with latent time. Many clinical result including ours clearly indicates that transcranial MEP is clinically useful for craniotomy.

    Peripheral nerve stimulation CMAP correction

    Normally stimulation electrode is implemented on affected side median nerve and apply singular supramaximal stimulus (20 – 50mA) 2 seconds prior (used to be 2 seconds later) to transcranial stimulation, deviate CMAP from affected side APB, then compensate with dividing transcranial stimulation amplitude by CMAP amplitude. 3) In the currently using Neuromaster (MEE-12XX NIHON KOHDEN Corporation), it is programmed in a way that CMAP corrected amplitude relative value is displayed automatically. (Fig.1)

    Fig.1 Display of Neuromaster (NIHON KOHDEN Corporation)
    Amplitude relative value CMAP corrected is automatically calculated and displayed.

    Determination of Cut-Off value by Receiver Operating Characteristic(ROC) Analysis

    Cut-Off value of interoperative MEP monitoring, in other words, amplitude decline rate which derives motor paralysis newly after the surgery has no consensus opinion. This time we have tried to determine cut-off value on MEP monitoring with using ROC analysis. ROC analysis itself is developed during World War II for Rader system to find enemy airplane, but nowadays it is used to evaluate the accuracy of image diagnosis, or to determine cut-off value at clinical examination. 5) MEP monitoring is also one of clinical examination so that it can be considered adequate for using ROC analysis for the determination of abnormal value. In ROC analysis, sensitivity is set on vertical axis, and plot false positive rate (1 thru specificity) on horizontal axis and draw ROC curve, then tale the closest point to top-left is set as cut-off value. We had conducted ROC analysis, for the 156 cases of craniotomy which has no paralysis below MMT2/5 in prior to the surgery, and 2nd group of 233 cases of intra spinal surgery transcranial MEP. 5) In transcranial stimulation MEP at craniotomy, sensitivity is 91.7% at cut-off value for 69.6% amplitude decline with no peripheral nerve stimulation CMAP, specificity 95.8%, and with CMAP correction, cut-off value is 70.7%, sensitivity 91.7% and specificity 96.5% (Fig.2). In transcranial MEP at spine cord surgery, with no CMAP correction, they are 83.3%, 100%, 97.4% accordingly, and with CMAP correction, they are 83.1%, 100% and 97.4% accordingly.

    Fig.2 ROC curve of transcranial MEP monitoring at Craniotomy
    TPF, Sensitivity; FPF, 1-specificity

    Fig.3 ROC curve of transcranial MEP monitoring at Spinal Cord Surgery
    TPF, Sensitivity; FPF. 1 - Specificity

    Transcranial MEP in Cerebral Aneurysm Clipping surgery

    In Cerebral Aneurysm Clipping surgery, MEP monitoring by motor field sirect stimulation is used to be conducted 6). This method is considered the sensitivity is higher than Cranial stimulation, but disadvantage is that it is impossible to expose by the motor field of most posterior frontal lobe in normal Pterional approach, and it may take time and has a risk for bleeding to identify motor field with slipping electrode under dura mater, and also, it is difficult, although they are tried, to stimulate motor field on limb at interhemispheric fissure with subdural electrode.
    Because of the advancement of equipment and technics, it becomes common to conduct simple and easy transcranial MEP monitoring at brain aneurysm surgery operation. When we have conducted ROC analysis at 105 cases of transcranial MEP monitoring, 69.6% of amplitude decline is cut-off value and sensitivity is 100% for without peripheral nerve stimulation CMAP correction, in specificity 95.0%, with CMAP correction 670.7% is cut-off value and sensitivity 100%, and specificity is 93.6% so that transcranial MEP is a trustworthy monitoring method for Cerebral Aneurysm Clipping surgery.

    Transcranial MEP monitoring at brain tumor resection

    On the other hand, open brain tumor resection, especially at cerebral hemisphere glioma surgery, perform craniotomy having enough space including motor field, it is common to perform MEP monitoring by motor field direct stimulation or pyramidal stimulation after identifying central channel by cortex SEP 7). ROC result of 45 cases of motor field direct stimulation MEP monitoring, without CMAP correction, cut-off value is 86.3%, sensitivity 100%, and specificity is also 100%. With CMAP correction, cut-off is 83.5%, sensitivity 100% and specificity is 100%. We combine transcranial MEP with cerebral hemisphere glioma surgery as the supplemental method. Also, we are performing transcranial MEP monitoring for less MEP necessity surgery like temporal lobe tumors or meningioma, but sensitivity of transcranial MEP monitoring result in 36 cases of brain tumor surgery is as low as 83.0% even with CMAP correction.


    Transcranial MEP monitoring for spinal cord surgery is extremely sensitive monitoring method with 100% sensitivity regardless with/without CMAP correction. In the actual spinal cord surgery, we have experienced many cases that in case any direct invasion reaches at spinal cord or nerves, MEP amplitude decline or lost is immediately detected so that it is cured by the time of surgery completion and no symptom reappears after surgery. Because transcranial MEP is too sensitive for spinal cord surgery, it may be distantly respected.
    We have reviewed whether postoperative nerve disease can be predicted by transcranial monitoring at the surgery of compression spinal nerve disorder, focusing on the sensitivity and the specificity of transcranial MEP monitoring at spinal cord surgery 8). At the surgery of compression spinal nerve disorder, Japan Orthopedic Association (JOA) scores of before surgery, a day after surgery, one week after, one month after, 3 months after, 6 months after, and one year after surgery, are evaluated by the third person and calculated recovery rate by Hirabayashi method 9). Using the maximum value of recovery rate of JOA score, we have sorted out to 4 groups. They are; excellent (E) (recovery rate ≧50%), good (G) (recovery rate 0< and 50%>), no change (N) (recovery rate = 0%), worsening (W) (recovery rate < 0%). We have compared with intraoperative MEP relative amplitude value for the attention item in each group.
    As the result, among 202 decompression cases of compression spinal nerve disorder, E group, with recovery rate after surgery of JOA score is more than 50%, is 115 cases. These attention item’s relative amplitude value under CMAP correction is 1.8 ± 1.5 (mean ± standard deviation), and they are significantly exceeded from other 3 groups (G, N, W group) averaged relative amplitude value (P=0.0150). On the other hand, in case when no CMAP correction is performed, relative amplitude value of E group is 2.6±2.8 (mean ± standard deviation) so that there is no significant difference with the average of other 3 groups (P=0.1504). (Chart 1)

    Chart 1: Postoperative JOA score recovery rate and MEP amplitude at compression spinal nerve disorder

    On the other hand, recovery of JOA score recognized E+G group’s ratio with/without CMAP correction are shown in chart 2, by 10% step of attention item relative amplitude value climb rate 0 through 100%. (Chart 2) With performing CMAP correction, cases recognized more than 20% amplitude increase are all group E or group G, JOA score recovery is indicated. On the other hand, in case no CMAP correction is performed, there is a case which no JOA score recovery is recognized even though amplitude increase rate exceeds 100%.

    Chart 2: MEP amplitude increase rate and of JOA score recovery rate in compression spinal nerve disorder

Cortico-Cortical Evoked Potentials (CCEP)

Bedside mapping by chronic subdural electrode indwelling for preserving language faculty, or intraoperative language Mapping or monitoring by awake craniotomy has been performed at intra-axial tumor resection like glioma. In chronic subdural electrode indwelling, gradual mapping at bedside is possible, but it has a disadvantage of the necessity of two times, at electrode indwelling and at resection, of general anesthesia surgery, and unavailable monitoring at resection surgery.

On the other hand, for awake craniotomy, intravenous anesthetic Propofol is authorized in 1995 in Japan. Surgical operation conducted by Dr. Tomokatsu Hori, who is the author’s mentor, in 1996 at related hospital of Tottori University is Japan’s first operation. After that, awake craniotomy is commonly spread throughout Japan in accordance with the guideline in over 20 years, besides, period of alertness has certain limitation by facility, or there is a case where patient needs to be returned to full anesthesia status due to epilepsy seizure or anesthesia management. Nevertheless, it has to admit that this is the greatly invasive mapping/monitoring.

Cortico-Cortical Evoked Potentials (CCEP) starts to use for preserving language center and arcuate fasciculus at seizure surgery since 2005. 10) CCEP is a recordable language mapping/monitoring, which can conduct under awake or full anesthesia status, for alogia patient. Recently, it becomes common for glioma surgery. 11). CCEP derives evoked potential which is mainly transferred through arcuate fasciculus, a part of superior longitudinal fasciculus, from the other nerve with stimulating either motor speech center (Broca) of superior frontal gyrus or sensory speech center (Wernicke) of superior temporal gyrus. CCEP can relatively easily record in less invasively and in short period using multichannel evoked electromyograph like Neuromaster (NIHON KOHDEN) and stimulation equipment which is possible for alternate stimulation. Fig.4 shows CCEP waveform being taken at resection surgery for left temporal lobe metastatic brain tumor which this facility recently started.

Regarding the language faculty, other than the dorsal stream communication channel of so called Wernicke - superior longitudinal fasciculus – Broca, ventral stream, like frontal aslant tract (FAT) connecting superior frontal gyrus with Broca, or inferior frontooccipital fasciculus (IFOF) forming a network in temporal lobe, are involved. 12). Regarding FAT or IFOF, monitoring by CCEP is considered as possible so that much accurate language monitoring is realized in the future. CCEP is currently used in combination with awake craniotomy in many facilities, but for future, it is expected to become possible that the high accuracy intraoperative language mapping or monitoring.

Fig.4 Cortico-Cortical Evoked Potentials (CCEP)
Left superior temporal gyrus (Welnicke) stimulation. Right hand side indicates the N1 stimulation amplitude in color (Green: small to Yellow to Red: Large)

Continue making effort to eliminate postoperative sorrow.

Amplitude correction for transcranial MEP by peripheral nerve stimulation CMAP is the method we have developed for eliminating mainly the effect of muscle relaxant agent. 3). CMAP correction is considered to become common for future, with clarifying its effectiveness. For calculation of threshold value which causes postoperative paralysis to calculate MEP sensitivity and specificity, ROC analysis is used. 5). ROC analysis is theoretically corresponded to MEP analytical method where maximum specificity thing becomes a threshold for producing postoperative paralysis, among sensitivity maximum amplitude decline rate. 13). However, to decide the threshold of newly producing paralysis after surgery, or to calculate sensitivity, it is necessary to experience regretful cases where paralysis is appeared after surgery. With the advancement of operational technology at cranial nerve surgery, cases of postoperative motion paralysis become less, and in the future, this will reduce further. And, we shall continue to make effort to make unfortunate cases to zero. For this purpose, many case analyses is necessary to make decision on MEP monitoring amplitude analysis, especially for paralysis producing threshold. Also, multi-facility collaboration research is necessary, including retrospective review.


At the decompression for compression spinal nerve disorder, nerve symptoms recovery by depressurization is predictable by transcranial MEP monitoring, until the time of peripheral nerve CMAP correction. 6). Regarding the recovery of nerve symptom and amplitude increase at MEP monitoring, there ae still many different opinions, but, by means of increasing the accuracy of MEP by CMAP correction or by means of MEP amplitude increase, possibility of predicting intraoperatively the recovery of postoperative motor nerve symptom is indicated. 14).


Cortico-Cortical Evoked Potentials (CCEP) is possible to conduct under awake status or full anesthesia status. It is a recordable language mapping/monitoring even for alogia patient, and in future it is expected to conduct high accuracy language mapping/monitoring under full anesthesia, without conducting awake craniotomy.

1. Tanaka S, Takanashi J, Fujii K, Ujiie H, Hori T: Motor-evoked potential mapping and monitoring by direct brain stem stimulation. Technical note. J Neurosurg 107(5): 1053-1057, 2007
2. Yamamoto T, Katayama Y, Fukaya S, et al.: Comparison of the descending spinal cord evoked potentials with direct motor cortex stimulation and with transcranial brain stimulation. Clin Electroencephalogr 40:162-166, 1998.
3. Tanaka S, Kobayashi I, Sagiuchi T, et al.: Compensation of intraoperative transcranial motor-evoked potential monitoring by compound muscle action potential after peripheral nerve stimulation. J Clin Neurophysiol 22:271-274, 2005.
4. Jyunko Takanashi, Sou Tanaka: Effectiveness of Transcranial High-voltage MEP as Cranial Nerve Surgery Intraoperative Monitoring. Clinical Neurophysiology
5. Metz CE, Goodenough DJ, Rossmann K: Evaluation of receiver operating characteristic curve data in terms of information theory, with applications in radiography. Radiology 109:297-303, 1973.
6. Suzuki K, Kodama N, Sasaki T, et al.: Intraoperative monitoring of blood flow insufficiency in the anterior choroidal artery during aneurysm surgery. J Neurosurg 98:507-514, 2003.
7. Neuloh G, Pechstein U, Schramm J: Motor tract monitoring during insular glioma surgery. J Neurosurg 106:582-592, 2007.
8. Tanaka S, Hirao J, Oka H, et al.: Intraoperative monitoring in decompression of compressive spinal and spinal nerve diseases by transcranial motor-evoked potential: The law of twenty percent. J Clinical Neurosci 2015 doi: 10.1016/j.joen.2015.03.011
9. Japanese Orthopaedic Association: [Japanese Orthopaedic Association scoring system for cervical myelopathy (17-2 version and 100 version)]. Nippon Seikeigeka Gakkai Zasshi 68:490–503, 1994 (Japanese with English translation).
10. Matsumoto R, Kinoshita M, Taki J, et al.: In vivo epileptogenicity of focal cortical dysplasia: a direct cortical paired stimulation study. Epilepsia 46: 1744-1749, 2005.
11. Yamao Y, Matsumoto R, Kunieda T, et al.: Intraoperative dorsal language network mapping by using single-pulse electrical stimulation. Human Brain Mapping 35: 4345-4361, 2014.
12. Fujii M, Maesawa S, Ishiai S, et al.: Neural basis of language: an overview of an evolving model. Neurol Med Chir (Tokyo) 56: 379-386, 2016.
13. Tanaka S, Tashiro T, Gomi A, et al.: Sensitivity and specificity in transcranial motor-evoked potential monitoring during neurosurgical operations. Surg Neurol Int 2:111-118, 2011.
14. Voulgaris S, Karagiorgiadis D, Alexiou GA, et al.: Continuous intraoperative electromyographic and transcranial motor evoked potential recordings in spinal stenosis surgery. J Clin Neurosci 17: 274-276, 2010.NI).