Background

Management of Brain Tumors

Surgical management of brain tumors involves resecting the brain tumor and preserving essential brain function. "Mapping" of brain functions, such as body movement and language, is most accurately achieved with direct cortical stimulation (DCS), an intraoperative procedure that lengthens operating times and requires a wide surgical opening. Even if not completely accurate compared with DCS, preoperative techniques that map brain functions may aid in planning the extent of resection and the surgical approach. Although DCS is still usually performed to confirm the brain locations associated with specific functions, preoperative mapping techniques may provide useful information that improves patient outcomes.

Noninvasive Mapping Techniques

The most commonly used tool for the noninvasive localization of brain functions is functional magnetic resonance imaging (fMRI). Functional MRI identifies regions of the brain where there are changes in localized cortical blood oxygenation, which correlate with the neuronal activity associated with a specific motor or speech task being performed as the image is obtained. The accuracy and precision of fMRI depend on the patient's ability to perform the isolated motor task, such as moving the single assigned muscle without moving others. This may be difficult in patients in whom brain tumors have caused partial or complete paresis. The reliability of fMRI in mapping language areas has been questioned. Guissani et al (2010) reviewed several studies comparing fMRI with DCS of language areas and found large variability in the sensitivity and specificity rates of fMRI.¹ Reviewers also pointed out a major conceptual point in how fMRI and DCS "map" language areas: fMRI identifies regional oxygenation changes, which show that a particular region of the brain is involved in the capacity of interest, whereas DCS locates specific areas in which the activity of interest is disrupted. Regions of the brain involved in a certain activity may not necessarily be required for that activity and could theoretically be safely resected.

Magnetoencephalography (MEG) is also used to map brain activity. In this procedure, electromagnetic recorders are attached to the scalp. Unlike electroencephalography, MEG records magnetic fields generated by electric currents in the brain, rather than the electric currents themselves. Magnetic fields tend to be less distorted by the skull and scalp than electric currents, yielding an improved spatial resolution. MEG is conducted in a magnetically shielded room to screen out environmental electric or magnetic noises that could interfere with the MEG recording. (See evidence review 6.01.21 for additional information on MEG and magnetic resonance imaging.)

Navigated transcranial magnetic stimulation (nTMS) is a noninvasive imaging method for evaluating eloquent brain areas. Transcranial magnetic pulses are delivered to the patient as a navigation system calculates the strength, location, and direction of the stimulating magnetic field. The locations of these pulses are registered to a magnetic resonance image of the patient's brain. Surface electromyography electrodes are attached to various limb muscles of the patient. Moving the magnetic stimulation source to various parts of the brain causes electromyography electrodes to respond, indicating the part of the cortex involved in particular muscle movements. For evaluation of language areas, magnetic stimulation areas that disrupt specific speech tasks are thought to identify parts of the brain involved in speech function. Navigated TMS can be considered a noninvasive alternative to DCS, in which electrodes are directly applied to the surface of the cortex during craniotomy. Navigated TMS is being evaluated as an alternative to other noninvasive cortical mapping techniques (eg, fMRI, MEG) for presurgical identification of cortical areas involved in motor and language functions.Navigated TMS, used for cortical language area mapping, is also being investigated in combination with diffusion tensor imaging tractography for subcortical white matter tract mapping.

Regulatory Status

In 2009, the eXimia Navigated Brain Stimulation System (Nexstim) was cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process for noninvasive mapping of the primary motor cortex of the brain to its cortical gyrus for preprocedural planning.

Similarly, in May 2012, the Nexstim Navigated Brain Stimulation System 4 and Navigated Brain Stimulation System 4 with NexSpeech® were cleared for marketing by the FDA through the 510(k) process for noninvasive mapping of the primary motor cortex and for localization of cortical areas that do not contain speech function for preprocedural planning.

Related Policies

• Intraoperative Neurophysiologic Monitoring (Policy #114 in the Surgery Section)

For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.

FIDE SNP:

For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

[RATIONALE: This policy was created in 2014 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through May 27, 2020.

Evidence reviews assess whether a medical test is clinically useful. A useful test provides information to make a clinical management decision that improves the net health outcome. That is, the balance of benefits and harms is better when the test is used to manage the condition than when another test or no test is used to manage the condition.

The first step in assessing a medical test is to formulate the clinical context and purpose of the test. The test must be technically reliable, clinically valid, and clinically useful for that purpose. Evidence reviews assess the evidence on whether a test is clinically valid and clinically useful. Technical reliability is outside the scope of these reviews, and credible information on technical reliability is available from other sources.

Preoperative Localization of Eloquent Areas of the Brain
Clinical Context and Test Purpose

The purpose of navigated transcranial magnetic stimulation (nTMS) in patients who have brain lesions is to aid in the localization of eloquent areas of the brain to reduce damage to verbal and motor functions during surgery.

The question addressed in this evidence review is: Does nTMS improve health outcomes in patients who have brain lesions and are about to undergo surgery that could harm eloquent areas of the brain?

The following PICO was used to select literature to inform this review.

Patients

The relevant population of interest is individuals who have brain lesions and are undergoing surgery that could harm eloquent areas of the brain (e.g., those controlling motor or language function).

Interventions

The intervention of interest is navigated transcranial magnetic stimulation (nTMS), a noninvasive imaging method for evaluating eloquent brain areas.

Navigated TMS is performed during preoperative surgical planning in a specialty setting (ie, neurosurgery).

Comparators

Several tools are used for the noninvasive localization of brain functions. They include functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). Whether noninvasive presurgical tools are used, direct cortical stimulation (DCS) is usually performed during surgery to confirm the brain locations associated with specific functions.

Outcomes

The outcomes of interest are a surgical improvement in survival or in functional measures such as speaking and walking or in a reduction in morbidity.

Technically Reliable

Assessment of technical reliability focuses on specific tests and operators and requires a review of unpublished and often proprietary information. Review of specific tests, operators, and unpublished data are outside the scope of this evidence review, and alternative sources exist. This evidence review focuses on the clinical validity and clinical utility.

Clinically Valid

A test must detect the presence or absence of a condition, the risk of developing a condition in the future, or treatment response (beneficial or adverse).

Review of Evidence

Most studies of nTMS are small case series evaluating patients with brain tumors,^1,2,3, cavernous angiomas,^4, arteriovenous malformations,^5, or other brain lesions; case series are not ideal studies to ascertain diagnostic characteristics. A number of small nTMS studies have also evaluated healthy volunteers but they do not add substantially to the evidence base.^4,6,7,8,9, Studies comparing nTMS with DCS, MEG, and/or fMRI and/or using DCS as the reference standard are described next.

Distance Between Navigated Transcranial Magnetic Stimulation and Direct Cortical Stimulation Hotspots

Several small studies have evaluated the accuracy of nTMS by measuring the distance between nTMS "hotspots" (the point at which stimulation produced the largest electromyographic response in the target muscles) during preoperative cortical mapping and the gold standard of intraoperative DCS hotspots.

Picht et al (2011) evaluated 17 patients with brain tumors using nTMS and DCS.^10, Both techniques were used to elicit hotspots. Target muscles were selected based on the needs of each patient concerning tumor location and clinical findings. Intraoperative DCS locations were chosen independently of nTMS, and the surgeon was unaware of the nTMS hotspots. For 37 muscles in 17 patients, nTMS and DCS data were both available. Mean distance between nTMS and DCS hotspots was 7.83 mm (standard error, 1.18) for the abductor pollicis brevis muscle (95% confidence interval, 5.31 to 10.36 mm) and 7.07 mm (standard error, 0.88) for the tibialis anterior muscle. When DCS was performed during surgery, there were large variations in the numbers of stimulation points, and the distance between nTMS and DCS was much smaller when a larger number of points were stimulated.

Forster et al (2011) performed a similar study in 11 patients.^11,Functional MRI also was performed in this study. The distance between corresponding nTMS and DCS hotspots was 10.49 mm (standard deviation [SD], 5.67). The distance between the centroid of fMRI activation and DCS hotspots was 15.03 mm (SD=7.59). However, it was unclear whether hotspots elicited by 1 device could be elicited by the other and vice versa. In at least 2 excluded patients, hotspots were elicited by DCS but not by nTMS.

Tarapore et al (2012) evaluated the distance between nTMS and DCS hotspots.^12, Among 24 patients who underwent nTMS, 18 of whom also underwent DCS, 8 motor sites in 5 patients corresponded. The median distance between nTMS and DCS hotspots was 2.13 mm (standard error of the mean, 0.29). In the craniotomy field where DCS mapping was performed, DCS elicited the same motor sites as nTMS. The study also evaluated MEG; the median distance between MEG motor sites and DCS sites was 12.1 mm (8.2).

Mangravati et al (2013) evaluated the distance between nTMS and DCS hotspots in 7 patients.^1, It is unclear how many hotspots were compared or how many potential comparisons were unavailable due to a failureof either device to find a particular hotspot. It appears that the mean distance between hotspots was based on locations of hotspots for 3 different muscles. The overall mean difference between nTMS and DCS was 8.47 mm, which was less than the mean difference between the fMRI centroid of activation and DCS hotspots (12.9 mm).

Krieg et al (2012) compared nTMS with DCS in 14 patients.^13, Interpreting this study is difficult because the navigation device employed appeared to differ from the U.S. Food and Drug Administration-approved device. Additionally, the comparison of nTMS to DCS used a different methodology. Both nTMS and DCS were used to map the whole volume of the motor cortex, and a mean difference between the borders of the mapped motor cortex was calculated. The mean distance between the 2 methods was 4.4 mm (SD=3.4).

Language Mapping

A study by Picht et al (2013) evaluated the accuracy of nTMS in identifying language areas.^14, Twenty patients underwent evaluation of language areas over the whole left hemisphere, which was divided into 37 regions. DCS was performed only in areas accessible in the craniotomy site. Data for both methods were available in 160 regions for the 20 patients. Using DCS as the reference standard, there were 46 true-positive, 83 false-positive, 26 true-negative, and 5 false-negative findings. Considering the analysis as 160 independent data points for each brain region, nTMS had a sensitivity of 90%, a specificity of 24%, positive predictive value (PPV) of 36%, and negative predictive value of 84%. An analysis of regions considered to be in the classic Broca area (involved in speech production) showed a sensitivity of 100%, a specificity of 13%, PPV of 57%, and negative predictive factor of 100%. This study, which found a high rate of false-positives, raises concerns about the utility of nTMS for identifying language areas. Even if nTMS were used to rule out areas in which language areas are unlikely, the sensitivity of 90% might result in some language areas not appropriately identified.

Tarapore et al (2013) also evaluated the use of nTMS and MEG to identify language areas (n=12).^15, A total of 183 regions were evaluated with both nTMS and DCS. In these 183 regions, using DCS as the reference standard, there were 9 true-positives, 4 false-positives, 169 true-negatives, and 1 false-negative, translating to a sensitivity of 90%, a specificity of 98%, PPV of 69%, and negative predictive factor of 99%.

Section Summary: Clinically Valid

The studies assessing the distance between nTMS and DCS hotspots appear to show that stimulation sites eliciting responses from both techniques tended to be mapped within 10 mm of each other. This distance tends to be less than the distance between fMRI centers of activation and DCS hotspots. It is difficult to assess the clinical significance of these data for presurgical planning. The available studies of the diagnostic accuracy nTMS evaluating language areas have shown a sensitivity of 90% and variable specificity in 2 studies (range, 24%-98%). The PPVs were relatively low in both of the studies (range, 57%-69%). Even if nTMS were used to rule out areas in which language areas are unlikely, the sensitivity of 90% might result in some language areas not appropriately identified.

Clinically Useful

A test is clinically useful if the use of the results informs management decisions that improve the net health outcome of care. The net health outcome can be improved if patients receive correct therapy, or more effective therapy, or avoid unnecessary therapy, or avoid unnecessary testing.

Review of Evidence
Direct Evidence

Direct evidence of clinical utility is provided by studies that have compared health outcomes for patients managed with and without the test. Because these are intervention studies, the preferred evidence would be from randomized controlled trials (RCTs).

The ideal study to determine whether nTMS improves health outcomes in patients being considered for surgical resection of brain tumors would be an RCT comparing nTMS with strategies that do not use nTMS. There are challenges in the design and interpretation of such studies. Given that results of diagnostic workups of brain tumor patients may determine which patients undergo surgery, the counseling given to patients, and the type of surgery performed, it would be difficult to compare outcomes for groups of patients with qualitatively different outcomes. For example, it is difficult to compare the health outcomes of a patient who ends up not having surgery, who conceivably has a shorter overall lifespan but a short period of very high quality of life, with a patient who undergoes surgery and has some moderate postoperative disability but a much longer lifespan.

No RCTs were identified. However, controlled observational studies are available. Several studies have matched patients who underwent presurgical nTMS with similar historical controls who did not. Hendrix et al (2017) reported on 20 consecutive patients with malignant brain tumors and lesions in language-eloquent areas who underwent preoperative nTMS and matched them to patients treated in the pre-nTMS era.^16, Patients were matched on tumor location, tumor and edema volume, preoperative language deficits, and histopathology. The primary efficacy outcome was not specified. Patients underwent clinical language assessments before and after surgery at postoperative day 1 and weeks 1, 6, and 12 post surgery. Language performance status was characterized as no language deficit (grade 0), mild deficit (grade 1), medium deficit (grade 2); and severe deficit (grade 3). The complication rates, gross resection rates, and residual tumor volumes on fMRI did not differ significantly between groups. The group that had presurgical nTMS had shorter surgery durations than patients treated pre-nTMS (mean, 104 minutes and 135 minutes, respectively, p=0.039) and a shorter inpatient stay (mean, 9.9 days vs 15 days, p=0.001). Language deficits did not differ between groups preoperatively, or at postoperative day 1, week 1, or week 12. For example, at week 12, 15 patients in the nTMS group and 14 patients in the pre-TMS group had a grade 0 deficit (p=0.551). There was a statistically significant difference at week 6 (p=0.048); the p-value was not adjusted for multiple comparisons (ie, assessment at multiple time points). Groups might have differed in other ways that affected outcomes and procedures might have changed over time in ways that affected surgical duration, complication rates, and inpatient stays.

Krieg et al (2014) enrolled 100 consecutive patients who underwent nTMS preoperative mapping and identified 100 historical controls who were matched by tumor location, preoperative paresis, and histology.^17, Most patients had glioblastoma (37%), brain metastasis (24%), or astrocytoma (29%). Data analysis was performed blinded to group assignment. The primary efficacy outcome was not specified. Median follow-up was 7.1 months (range, 0.2-27.2 months) in the nTMS group and 6.2 months (range, 0.1-79.4 months) in controls. Incidence of residual tumor by postoperative fMRI was lower in the nTMS group (22%) compared with controls (42%; odds ratio, 0.38; 95% confidence interval, 0.21 to 0.71). The incidence of new surgery-related transient or permanent paresis did not differ between groups. However, "when also including neurological improvement [undefined] in the analysis," more patients in the nTMS group improved (12% nTMS vs 1% controls), and similar proportions of patients worsened (13% nTMS vs 18% controls) or remained unchanged (75% nTMS vs 81% controls; p=0.006). Limitations of this study included the use of historical controls, uncertain outcome assessments (eg, "neurological improvement" was not defined), and uncertain validity of statistical analyses because the primary outcome was not specified and there was no correction for multiple testing.

A second study by Krieg et al (2015) had some overlap in enrolled patients^18, It prospectively enrolled 70 patients who underwent nTMS and matched them with a historical control group of 70 patients who did not have preoperative nTMS. All patients had motor eloquently located supratentorial high-grade gliomas and all underwent craniotomy by the same surgeons. As in the Krieg et al (2014) study, patients were matched by tumor location, preoperative paresis, and histology; the primary outcome was not specified. Outcome assessment was blinded. Craniotomy size was 25.3 cm² (SD=9.7) in the nTMS group and 30.8 cm² (SD=13.2) in the non-nTMS group; the size difference was statistically significant (p=0.006). There were no statistically significant differences between groups in rates of surgery-related paresis, rates of surgery-related complications on MRI, or degrees of motor impairment during follow-up. Median overall survival (OS) was 15.7 months (SD=10.9) in the nTMS group and 11.9 months (SD=10.3) in the non-nTMS group, which did not differ significantly between groups (p=0.131). Mean survival at 3, 6, and, 9 months was significantly higher in the nTMS group than in the non-nTMS group but did not differ statistically between groups at 12 months.

Frey et al (2014) enrolled 250 consecutive patients who underwent nTMS preoperative mapping and identified 115 historical controls who met the same eligibility criteria.^19, Criteria included being evaluated for surgery for a tumor in a motor eloquent area and without seizures more than once a week or cranial implants. Fifty-one percent of the nTMS group and 48% of controls had World Health Organization grade II, III, or IV gliomas; remaining patients had brain metastases from other primary cancers or other lesions. Intraoperative motor cortical stimulation to confirm nTMS findings was performed in 66% of the nTMS group. The Medical Research Council scale and Karnofsky Performance Status were used to assess muscle strength and performance status, respectively. Outcomes were assessed at postoperative day 7 and then at 3 month intervals. At the 3 month follow-up, 6.1% of the nTMS group and 8.5% of controls had new postoperative motor deficits (not significantly different); changes in performance status postoperatively also were similar between groups. Other outcomes were reported for patients with glioma only (128 nTMS patients, 55 controls). Based on postoperative MRI, gross total resection was achieved in 59% of nTMS patients and 42% of controls (p<0.05). At mean follow-up of 22 months (range, 6-62 months) in the nTMS group and 25 months (range, 9-57 months) in controls, mean progression-free survival (PFS) was similar between groups (mean PFS, 15.5 months [range, 3-51 months] for nTMS vs 12.4 months [range, 3-38 months] for controls; not significantly different).In the subgroup of patients with low-grade (grade II) glioma (38 nTMS patients, 18 controls), mean PFS was longer in the nTMS group (mean PFS, 22.4 months; range, 11-50 months) than in the control group (15.4 months; range, 6-42 months; p<0.05), and new postoperative motor deficits were similar (7.5% vs 9.5%, respectively; not significantly different). OS did not differ statistically between treatment groups.

One nonrandomized study used concurrent controls. Sollmann et al (2015) matched 25 prospectively enrolled patients who underwent preoperative nTMS but whose results were not available to the surgeon during the procedure (group 1) to 25 patients who underwent preoperative nTMS whose results were available to the surgeon (group 2).^9, All patients had language eloquently located brain lesions within the left hemisphere. Primary outcomes were not specified. Three months postsurgery, 21 patients in group 1 had no or mild language impairment, and 4 patients had moderate-to-severe language deficits. In group 2, 23 patients had no or mild language impairment, and 2 patients had moderate-to-severe deficits. The difference between groups in postoperative language deficits was statistically significant (p=0.015). Other outcomes, including duration of surgery, postoperative Karnofsky Performance Status scores, the percentage of residual tumor, and peri- and postoperative complication rates did not differ significantly between groups.

Picht et al (2012) assessed whether a change in management occurred as a result of knowledge of nTMS findings.^20, In this study, surgeons first made a plan based on all known information without nTMS findings. After being informed of nTMS findings, the surgical plan was reformulated if necessary. Among 73 patients with brain tumors in or near the motor cortex, nTMS was judged to have changed the surgical indication in 2.7%, changed the planned extent of resection in 8.2%, modified the approach in 16.4%, added awareness of high-risk areas in 27.4%, added knowledge not used in 23.3%, and only confirmed the expected anatomy in 21.9%. The first 3 surgical categories, judged to have been altered because of nTMS findings, were summed to determine "objective benefit" of 27.4%.

Chain of Evidence

Indirect evidence on clinical utility rests on clinical validity. If the evidence is insufficient to demonstrate test performance, no inferences can be made about clinical utility. Current evidence on clinical validity does not permit construction of a chain of evidence to support the use of nTMS for presurgical mapping of eloquent areas of the brain.

Section Summary: Clinically Useful

No RCTs have compared health outcomes in patients who did and did not have presurgical nTMS before brain surgery. There is direct evidence from several nonrandomized comparative studies of patients undergoing nTMS, mainly compared with historical controls. Findings were mixed; outcomes were not consistently better in patients who underwent presurgical nTMS. Complication rates did not differ significantly between groups. In 2 of 3 studies, residual tumor volume did not differ between groups. Two studies reported survival rates. In both, OS did not differ significantly between groups. One of the studies found significantly higher mean survival rates in the nTMS group at 3, 6, and 9 months postsurgery but not at 12 months. One of 2 studies, reporting postoperative language deficits, found significantly fewer deficits in the group that received presurgical nTMS. Limitations of all studies discussed in this section include the single-center settings (because nTMS is an operator-dependent technology, applicability may be limited), lack of randomization and/or use of historical controls (surgeon technique and practice likely improved over time), selective outcomes reporting (survival outcomes in glioma patients only), and uncertain validity of statistical analyses (primary outcome not identified and no correction for multiple testing).Additionally, studies either matched patients to controls on a few variables or used controls who met similar eligibility criteria. These techniques may not adequately control for differences in patient groups that may affect outcomes.

Summary of Evidence

For individuals who have brain lesion(s) undergoing preoperative evaluation for localization of eloquent areas of the brain who receive nTMS, the evidence includes controlled observational studies and case series. Relevant outcomes are overall survival, test accuracy, morbid events, and functional outcomes. Several small studies have evaluated the distance between nTMS hotspots and direct cortical stimulation hotspots for the same muscle. Although the average distance in most studies is 10 mm or less, this does not take into account the error margin in this average distance or whether hotspots are missed. It is difficult to verify nTMS hotspots fully because only exposed cortical areas can be verified with direct cortical stimulation. Limited studies of nTMS evaluating language areas have shown high false-positive rates (low specificity) and sensitivity that may be insufficient for clinical use. Several controlled observational studies have compared outcomes in patients undergoing nTMS with those (generally pre-TMS historical controls) who did not undergo nTMS. Findings of the studies were mixed; outcomes were not consistently better in patients who underwent presurgical nTMS. For example, overall survival did not differ significantly between groups in 2 studies and 1 reporting postoperative language deficits found significantly fewer deficits in the group that had presurgical nTMS. The controlled observational studies had various methodologic limitations and, being nonrandomized, might not have adequately controlled for differences in patient groups, which could have biased outcomes. The evidence is insufficient to determine the effects of the technology on health outcomes.

SUPPLEMENTAL INFORMATION
Clinical Input From Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

In response to requests, input was received from 1 physician specialty society (2 reviewers) and 2 academic medical centers while this policy was under review in 2013. Most reviewers considered navigated transcranial magnetic stimulation to be investigational.

Practice Guidelines and Position Statements

No guidelines or statements were identified.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 1.

Table 1. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT02741193a	Validation of Presurgical Motor Mapping With Transcranial Magnetic Stimulation (TMS) in Patients With Epilepsy	14	Jun 2021

NCT: national clinical trial.
^a Denotes industry-sponsored or cosponsored trial.]
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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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Index:
Navigated Transcranial Magnetic Stimulation
Transcranial Magnetic Stimulation, Navigated
nTMS
Nexstim® Navigated Brain Stimulation (NBS) System
Nexstim

References:
1. Mangraviti A, Casali C, Cordella R, et al. Practical assessment of preoperative functional mapping techniques: navigated transcranial magnetic stimulation and functional magnetic resonance imaging. Neurol Sci. Sep 2013; 34(9): 1551-7. PMID 23266868

2. Opitz A, Zafar N, Bockermann V, et al. Validating computationally predicted TMS stimulation areas using direct electrical stimulation in patients with brain tumors near precentral regions. Neuroimage Clin. 2014; 4: 500-7. PMID 24818076

3. Rizzo V, Terranova C, Conti A, et al. Preoperative functional mapping for rolandic brain tumor surgery. Neurosci Lett. Nov 07 2014; 583: 136-41. PMID 25224631

4. Forster MT, Limbart M, Seifert V, et al. Test-retest reliability of navigated transcranial magnetic stimulation of the motor cortex. Neurosurgery. Mar 2014; 10 Suppl 1: 51-5; discussion 55-6. PMID 23842557

5. Kato N, Schilt S, Schneider H, et al. Functional brain mapping of patients with arteriovenous malformations using navigated transcranial magnetic stimulation: first experience in ten patients. Acta Neurochir (Wien). May 2014; 156(5): 885-95. PMID 24639144

6. Weiss C, Nettekoven C, Rehme AK, et al. Mapping the hand, foot and face representations in the primary motor cortex - retest reliability of neuronavigated TMS versus functional MRI. Neuroimage. Feb 01 2013; 66: 531-42. PMID 23116812

7. Schmidt S, Bathe-Peters R, Fleischmann R, et al. Nonphysiological factors in navigated TMS studies; confounding covariates and valid intracortical estimates. Hum Brain Mapp. Jan 2015; 36(1): 40-9. PMID 25168635

8. Sollmann N, Ille S, Boeckh-Behrens T, et al. Mapping of cortical language function by functional magnetic resonance imaging and repetitive navigated transcranial magnetic stimulation in 40 healthy subjects. Acta Neurochir (Wien). Jul 2016; 158(7): 1303-16. PMID 27138329

9. Sollmann N, Tanigawa N, Tussis L, et al. Cortical regions involved in semantic processing investigated by repetitive navigated transcranial magnetic stimulation and object naming. Neuropsychologia. Apr 2015; 70: 185-95. PMID 25731903

10. Picht T, Schmidt S, Brandt S, et al. Preoperative functional mapping for rolandic brain tumor surgery: comparison of navigated transcranial magnetic stimulation to direct cortical stimulation. Neurosurgery. Sep 2011; 69(3): 581-8; discussion 588. PMID 21430587

11. Forster MT, Hattingen E, Senft C, et al. Navigated transcranial magnetic stimulation and functional magnetic resonance imaging: advanced adjuncts in preoperative planning for central region tumors. Neurosurgery. May 2011; 68(5): 1317-24; discussion 1324-5. PMID 21273929

12. Tarapore PE, Tate MC, Findlay AM, et al. Preoperative multimodal motor mapping: a comparison of magnetoencephalography imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation. J Neurosurg. Aug 2012; 117(2): 354-62. PMID 22702484

13. Krieg SM, Shiban E, Buchmann N, et al. Utility of presurgical navigated transcranial magnetic brain stimulation for the resection of tumors in eloquent motor areas. J Neurosurg. May 2012; 116(5): 994-1001. PMID 22304452

14. Picht T, Krieg SM, Sollmann N, et al. A comparison of language mapping by preoperative navigated transcranial magnetic stimulation and direct cortical stimulation during awake surgery. Neurosurgery. May 2013; 72(5): 808-19. PMID 23385773

15. Tarapore PE, Findlay AM, Honma SM, et al. Language mapping with navigated repetitive TMS: proof of technique and validation. Neuroimage. Nov 15 2013; 82: 260-72. PMID 23702420

16. Hendrix P, Senger S, Simgen A, et al. Preoperative rTMS Language Mapping in Speech-Eloquent Brain Lesions Resected Under General Anesthesia: A Pair-Matched Cohort Study. World Neurosurg. Apr 2017; 100: 425-433. PMID 28109861

17. Krieg SM, Sabih J, Bulubasova L, et al. Preoperative motor mapping by navigated transcranial magnetic brain stimulation improves outcome for motor eloquent lesions. Neuro-oncology. Sep 2014; 16(9): 1274-82. PMID 24516237

18. Krieg SM, Sollmann N, Obermueller T, et al. Changing the clinical course of glioma patients by preoperative motor mapping with navigated transcranial magnetic brain stimulation. BMC Cancer. Apr 08 2015; 15: 231. PMID 25884404

19. Frey D, Schilt S, Strack V, et al. Navigated transcranial magnetic stimulation improves the treatment outcome in patients with brain tumors in motor eloquent locations. Neuro-oncology. Oct 2014; 16(10): 1365-72. PMID 24923875

20. Picht T, Schulz J, Hanna M, et al. Assessment of the influence of navigated transcranial magnetic stimulation on surgical planning for tumors in or near the motor cortex. Neurosurgery. May 2012; 70(5): 1248-56; discussion 1256-7. PMID 22127045

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

64999