Aetna considers magnetic source imaging (MSI) or magnetoencephalography (MEG) experimental and investigational because there is inadequate evidence in the medical literature documenting that the use of MSI or MEG is effective in influencing the management and improving outcomes of neurosurgical candidates (e.g., members with intractable seizures or brain tumors). There are insufficient data to indicate that the use of MSI or MEG would eliminate the need for intra-operative functional brain mapping. There is also insufficient evidence to support the use of MSI/MEG for all other indications, including the diagnosis and treatment of Alzheimer's disease, autism, cognitive and mental disorders, developmental dyslexia, multiple sclerosis, Parkinson's disease, schizophrenia, stroke rehabilitation, and traumatic brain injury.

See also CPB 648 - Pervasive Developmental Disorders.

Magnetic source imaging or magnetoencephalography is a non-invasive functional imaging technique in which the weak magnetic forces associated with the electrical activity of the brain are monitored externally on the scalp, i.e. MSI differs from a standard electroencephalography (EEG) in that it records the magnetic fields instead of the electrical activity. The principal advantage of MSI is that while the measurement of electrical activities is affected by surrounding brain structures, the magnetic fields are not. Thus, when coupled to a MRI, MSI allows a high-resolution functional/anatomical image.

Although the literature contains some information regarding the clinical use of MSI (e.g., pre-surgical evaluation of patients with refractory epilepsy and pre-surgical mapping of sensorimotor cortex in patients with intra-cranial tumors), there is insufficient scientific evidence regarding its effectiveness. Critical outcomes such as comparison of MSI with intra-operative methods and whether the use of MSI would change the management of patients are lacking. In other words, is the sensitivity and specificity of the technique adequate to identify those patients who are not surgical candidates or would the use of MSI eliminate time consuming intra-operative localization techniques? Well-designed studies (prospective, randomized, controlled trials with large sample size) are needed to validate the accuracy of MSI, e.g., by comparing it with other neurodiagnostic procedures such as scalp EEG. Furthermore, patient selection criteria for this procedure need to be better defined.

An assessment conducted by the BlueCross BlueShield Technology Evaluation Center (2003) concluded that there is insufficient evidence to render conclusions regarding the effect of MSI/MEG on health outcomes for either pre-surgical localization of seizure origin or pre-surgical functional mapping. 

An assessment of MEG from the Ontario Ministry of Health and Long Term Care Medical Advisory Secretariat (2006) found that studies are generally of poor quality, and were graded of low or very-low quality of evidence. Specifically with regard to the use of MEG in epilepsy, the assessment stated that it is unclear whether MEG has similar accuracy in localizing seizure foci as intacranial EEG.

Pataraia, et al. (2005) studied the functional organization of the inter-ictal spike complex in 30 patients with mesial temporal lobe epilepsy (MTLE) using combined MEG/EEG recordings. Spikes could be recorded in 14 patients (47%) during the 2- to 3-h MEG/EEG recording session. The MEG and EEG spikes were subjected to separate dipole analyses; the MEG spike dipole localizations were superimposed on MRI scans. All spike dipoles could be localized to the temporal lobe with a clear preponderance in the medial region. Based on dipole orientations in MEG, patients could be classified into 2 groups: (i) patients with anterior medial vertical (AMV) dipoles, suggesting epileptic activity in the mediobasal temporal lobe, and (ii) patients with anterior medial horizontal (AMH) dipoles, indicating involvement of the temporal pole and the anterior parts of the lateral temporal lobe. Whereas patients with AMV dipoles had strictly unitemporal inter-ictal and ictal EEG changes during prolonged video-EEG monitoring, half of patients with AMH dipoles showed evidence of bitemporal affection on inter-ictal and ictal EEG. Nine patients underwent epilepsy surgery so far. While all 5 patients with AMV dipoles became completely seizure-free post-operatively (Class Ia), 2 out of 4 patients with AMH dipoles experienced persistent auras (Class Ib). However, this difference was not statistically significant. These researchers concluded that combined MEG/EEG dipole modeling can identify subcompartments of the temporal lobe involved in epileptic activity and may be helpful to differentiate between subtypes of mesial temporal lobe epilepsy non-invasively. Thee results need to be confirmed in well-designed studies with larger sample sizes.

Papanicolaou, et al. (2005) predicted the replacement of the more invasive procedure with MEG in the near future for temporal lobe epilepsy cases, subsequent to the optimization of the conditions under which pre-operative MEG is performed. Furthermore, in a review on management of intractable epilepsy in infancy and childhood, Wirrell, et al. (2006) stated that “MEG has proven to be useful in mapping sensory cortex and may also be useful to define eloquent cortex. The author stated that in a recent study (Stefan, et al., 2003), magnetic source imaging proved most useful in the localization of extra-temporal foci. The usefulness of MEG in pediatric epilepsy surgery planning remains to be determined”. Available evidence lacks systematic comparisons to other diagnostic techniques. Furthermore, there are no data specifically documenting how MSI/MEG might alter surgical management (i.e., changing the surgical approach or reducing the time needed for intra-operative mapping).

Knowlton, et al. (2006) stated that non-invasive brain imaging tests can potentially supplement or even replace the use of intra-cranial EEG (ICEEG) in pre-surgical epilepsy evaluation. These investigators prospectively examined the agreement between MSI and ICEEG localization in epilepsy surgery candidates. Patients completing video monitoring with scalp EEG who had intractable partial epilepsy based on ictal electro-clinico-anatomical features were screened. A total of 49 enrolled patients (mean age of 27 years; ranging from 1 to 61 years) completed MSI and ICEEG studies. Decisions about ICEEG and surgery were made at a consensus conference where MSI could only influence ICEEG coverage by indicating supplemental coverage to that already planned by an original hypothesis. The positive predictive value of MSI for seizure localization was 82 to 90 %, depending on whether computed against ICEEG alone or in combination with surgical outcome. The kappa score of agreement for MSI with ICEEG was 0.2744 (p < 0.01).  These researchers found that MSI yields localizing information with a high positive predictive value in epilepsy surgery candidates who typically require ICEEG. This finding suggested that enough clinical validity exists for MSI to potentially replace ICEEG for seizure localization.  Moreover, the authors stated that future studies must ascertain if certain MSI results are more predictive of accurate epilepsy localization, and if so, what other criteria are sufficient to preclude the need for further confirmation by ICEEG. This type of weighting will have to be measured in the context of all other epilepsy localization test. Furthermore, how discordant results from multiple non-invasive tests should be handled in a single surgical decision-making score, either toward or away from surgical resection, will have to be determined from greater outcome evidence.

Rampp and Stefan (2007) stated that while MEG systems are still expensive and complex, the technique's characteristics offer promising possibilities for the investigation of epilepsy patients (e.g., for focus localization and pre-surgical functional mapping).

Lam, et al. (2008) conducted a systematic evidence review of evidence of the effectiveness of MEGI in the presurgical evaluation of localization-related epilepsies. The investigators identified studies correlating surgical outcome (seizure freedom) with MEG source localization and resection area. The investigators found these studies of MEG reported wide ranging sensitivities (range: 0.20-1.0), specificities (0.06-1.00), positive likelihood ratios (0.67-2.0), and negative likelihood ratios (0.40-2.13). Based upon the results of their systematic review of the literature, the investigators concluded that "there is insufficient evidence in the current literature to support the relationship between the use of MEG in surgical planning and seizure-free outcome after epilepsy surgery." The investigators stated that additional studies are needed.

In a review on interictal electromagnetic source imaging in focal epilepsy, Leijten and Huiskamp (2008) noted that whether MEG is superior to electroencephalography is still unresolved, because fair comparisons are lacking. Clinical studies have not yet adopted all technical possibilities. Localization accuracy seems high, but studies lack uniformity regarding methods, goals and outcome parameters. Therefore, the final place of electromagnetic source imaging in the pre-surgical work-up is still to be determined. The diagnostic potential is probably highest in extra-temporal epilepsies, and lowest in mesial temporal lobe epilepsy. The authors concluded that electromagnetic source imaging has evolved technically and can provide valuable localization information in the pre-surgical evaluation of patients with epilepsy. However, standardization of the technique is required before further clinical studies can better establish its role in pre-surgical evaluation of focal epilepsy.

A BlueCross BlueShield Association's technology assessment on MEG and MSI for the purpose of pre-surgical localization of epileptic lesions (2009) stated that "[t]he argument that MEG improves the diagnostic yield of IC-EEG is often made, but it is difficult to identify studies that can support this argument. Studies that compare IC-EEG to MEG do not inform this particular question. On the other hand, given the gravity of this particular situation, there are some possible arguments to be made on behalf of MEG. Given that current decisionmaking regarding who should receive surgery and what type of surgery is done with some uncertainty and lack of a true reference standard, an additional piece of information that is known to correlate with seizure focus could be arguably of some value in making difficult decisions. The diagnostic test is easy to perform and noninvasive. Also, IC-EEG and surgery are extremely invasive procedures that do not always provide diagnostic information. Information from MEG might influence a patient’s decision to undergo the risks of further testing or surgery if the outcome can be slightly better estimated. However, given that one possible outcome of use of MEG may result in avoidance of tests and procedures that may benefit the patient, it is not possible to rule out harm from use of the test. The net effect of the use of MEG on patient outcomes for this indication remains to be determined".

There is also insufficient evidence to support the use of MSI/MEG for other indications including the diagnosis and treatment of various neurological conditions/diseases such as Alzheimer's disease, autism, cognitive and mental disorders, developmental dyslexia, multiple sclerosis, Parkinson's disease, schizophrenia, stroke rehabilitation, and traumatic brain injury. Currently, there are reliable data from well designed clinical studies that report the test performance (sensitivity, specificity, positive and negative predictive values) and clinical utility of MSI/MEG for these indications.