Clinical applications

Epilepsy

Approximately 50 million people worldwide suffer from epilepsy. This disorder is characterized by unprovoked, recurring seizures. Depending on the involved brain areas and systems, their semiology is highly variable, including staring, simple and complex movement patterns, changes of perception, unconsciousness, collapsing and tonic-clonic seizures (“grand mal”). Seizures can have a severe impact on patients’ lives by increasing morbidity and mortality. However, by far the biggest consequence of epilepsy, is the deterioration of their quality of life even by a few, seemingly harmless seizures. In addition, depending on the location of epileptic activity in the brain it may interfere with cognitive functions (Elger et al., 2004; Cornaggia et al., 2006).

Approximately 60-70% of all newly diagnosed epilepsy patients become seizure free with the first antiepileptic drug (AED). However, chances decrease to 5-10%  and less to become seizure free with the second or further AED for the remaining patients (Kwan and Brode, 2000). Even if a reduction of seizure frequency and severity can be achieved, adverse reactions to the medication may limit success of pharmacological therapy.

In cases of pharmacoresistant epilepsies, i.e. AED therapy is not effective or has adverse reactions, epilepsy surgery may be considered a therapy option, next to further AED therapy, vagal nerve stimulation (Rychlicki et al. 2006, Renfroe et al. 2002) and diets (Groesbeck et al. 2006). In patients with temporal lobe epilepsy for example, approximately 50% of surgically treated patients became seizure free, whereas medically treated patients had a chance of only 6% according to a randomized controlled trial (Wiebe et al., 2001).

An essential prerequisite for epilepsy surgery is the unambiguous localization of the epileptogenic zone, defined as the brain region which is essential for seizure generation, i.e. the ‘causa sine qua non’, resection or disconnection of which results in seizure freedom. Functionally distinct, is the irritative zone, which generates interictal epileptic discharges, e.g. spikes and sharp waves, in the time intervals between seizures. The epileptogenic and the irritative zone are distinct in concept, but may be overlapping or even be identical in reality. This “epileptic focus” may be very circumscribed and well localized in focal epilepsies, but can also have a more complex architecture with more than one seizure generating area and propagation pathways, which may be better described as an “epileptic network”.

A wide spectrum of diagnostic methods is applied to localize this epileptic network and estimate its relationship to essential functional areas. For example, next to the structural MRI, long-term video-EEG, SPECT and PET, MEG may be used to register ictal and inter-ictal patterns. Source analysis of the recorded brain activity may provide a focal localization. In practice, recording ictal data is a logistical problem, due to the limited time a patient is able to  remain still in the MEG.  Therefore, most focal localizations are derived from inter-ictal spike data and thus reflect the irritative zone. Nevertheless, these results can be used effectively in the presurgical evaluation and planning, as well as contributing crucial information that will enable a successful surgery (Stefan et al. 2004; Mäkela et al. 2007; Funke et al. 2009). An advantage of MEG in this regard is the very high sensitivity to a small neuronal population in the neocortical areas (Goldenholz et al. 2009). MEG and EEG provide complementary information as some spikes may only be visible to the MEG or only visible to the EEG, however, the majority of spikes are seen in both modalities, as demonstrated by Iwasaki and colleagues (Iwasaki et al. 2005).

MEG is therefore a valuable method for the presurgical evaluation of patients with pharmaco resistant epilepsy, which may provide information that would not have been available without it.

References:

Ben Renfroe, J., and Wheless, J.W. (2002). Earlier use of adjunctive vagus nerve stimulation therapy for refractory epilepsy. Neurology 59, S26-S30.
Cornaggia, C.M., Beghi, M., Provenzi, M., and Beghi, E. (2006). Correlation between cognition and behavior in epilepsy. Epilepsia 47, 34-39.
Elger, C.E., Helmstaedter, C., and Kurthen, M. (2004). Chronic epilepsy and cognition. Lancet Neurol 3, 663-672.
Funke, M., Constantino, T., Van Orman, C., and Rodin, E. (2009). Magnetoencephalography and Magnetic Source Imaging in Epilepsy. Clinical Eeg and Neuroscience 40, 271-280.
Groesbeck, D.K., Bluml, R.M., and Kossoff, E.H. (2006). Long-term use of the ketogenic diet in the treatment of epilepsy. Dev Med Child Neurol 48, 978-981.
Goldenholz, D.M., Ahlfors, S.P., Hamalainen, M.S., Sharon, D., Ishitobi, M., Vaina, L.M., and Stufflebeam, S.M. (2009). Mapping the Signal-To-Noise-Ratios of Cortical Sources in Magnetoencephalography and Electroencephalography. Human Brain Mapping 30, 1077-1086.
Iwasaki, M., Pestana, E., Burgess, R.C., Luders, H.O., Shamoto, T., and Nakasato, T. (2005). Detection of epileptiform activity by human interpreters: Blinded comparison between electroencephalography and magnetoencephalography. Epilepsia 46, 59-68.
Kwan, P., and Brodie, M.J. (2000). Early identification of refractory epilepsy. New Engl J Med 342, 314-319.
Makela, L.P., Forss, N., Jaaskelainen, J., Kirveskari, E., Korvenoja, A., and Paetau, R. (2006). Magnetoencephalography in neurosurgery. Neurosurgery 59, 493-510.
Rychticki, F., Zamponi, N., Trignani, R., Ricciuti, R.A., Iacoangeli, M., and Scerrati, M. (2006). Vagus nerve stimulation: Clinical experience in drug-resistant pediatric epileptic patients. Seizure-Eur J Epilep 15, 483-490.
Stefan, H., Hummel, C., Scheler, G., Genow, A., Druschky, K., Tilz, C., Kaltenhauser, M., Hopfengartner, R., Buchfelder, M., and Romstock, J. (2003). Magnetic brain source imaging of focal epileptic activity: a synopsis of 455 cases. Brain 126, 2396-2405.
Wiebe, S., Blume, W.T., Girvin, J.P., Eliasziw, M., and T, E.E.S. (2001). A randomized, controlled trial of surgery for temporal-lobe epilepsy. New Engl J Med 345, 311-318.
Zijlmans, M., Huiskamp, G.M., Leijten, F.S.S., van der Meij, W.M., Wieneke, G., and van Huffelen, A.C. (2002). Modality-specific spike identification in simultaneous magnetoencephalography/electroencephalography - A methodological approach. Journal of Clinical Neurophysiology 19, 183-191.

Functional mapping

In addition to the localization of pathological brain activity, MEG is also frequently used in clinical settings for mapping of essential functional areas. Such information can then be used preoperatively to determine whether the removal of e.g. a tumor, arteriovenous malformation (AVM) or epileptic focus is viable without causing a functional deficit. The surgical strategy can be optimized and tailored to the individual patient to plan the best surgical route to minimize complications and to achieve the best possible outcome.

A typical example for this application is the localization of somatosensory areas. Pulses of air are used to stimulate the patient’s fingers, face, and toes while evoked brain activity responses are recorded and processed using source localization analysis. Similar techniques with different stimuli can be applied to locate  essential functional areas for hearing and vision. The results are mapped to the individual patient’s MRI and can also be used for intraoperative neuronavigation.

MEG therefore provides non-invasive means for functional mapping during preoperative evaluation, in contrast to intraoperative awake surgical mapping (Duffau et al. 2003), a time-consuming procedure, demanding for both the patient and the surgical team. Another alternative for localizing functional areas is fMRI, but this method may yield false results in patients with altered perfusion,  due to tumors (Sakatani et al. 2007), stroke lesion (Murata et al. 2006), as well as in patients with abnormal areas of brain activity such as epilepsy (Benke et al. 2006). Evoked responses in MEG however remain undistorted by such influences.

MEG functional mapping, as part of the clinical routine,  has proven to yield good results, which complement other methods, such as intraoperative electrical stimulation and/or the WADA-test for epilepsy patients (Frye et al. 2009).

References:

Benke, T., Koylu, B., Visani, P., Karner, E., Brenneis, C., Bartha, L., Trinka, E., Trieb, T., Felber, S., Bauer, G., et al. (2006). Language lateralization in temporal lobe epilepsy: A comparison between fMRI and the wada test. Epilepsia 47, 1308-1319.
Duffau, H., Capelle, L., Denvil, D., Sichez, N., Gatignol, P., Taillandier, S.T.L., Lopes, M., Mitchell, M.C., Roche, S., Muller, J.C., et al. (2003). Usefulness of intraoperative electrical subcortical mapping during surgery for low-grade gliomas located within eloquent brain regions: functional results in a consecutive series of 103 patients. J Neurosurg 98, 764-778.
Frye, R.E., Rezaie, R., and Papanicolaou, A.C. (2009). Functional neuroimaging of language using magnetoencephalography. Phys Life Rev 6, 1-10.

Murata, Y., Sakatani, K., Hoshino, T., Fujiwara, N., Kano, T., Nakamura, S., and Katayama, Y. (2006). Effects of cerebral ischemia on evoked cerebral blood oxygenation responses and BOLD contrast functional MRI in stroke patients. Stroke 37, 2514-2520.

Sakatani, K., Murata, Y., Fujiwara, N., Hoshino, T., Nakamura, S., Kano, T., and Katayama, Y. (2007). Comparison of blood-oxygen-level-dependent functional magnetic resonance imaging and near-infrared spectroscopy recording during functional brain activation in patients with stroke and brain tumors. J Biomed Opt 12, 062110.