Replacing the Wada Test: Is Functional MRI Up to the Task?
Abstracts & Commentary
Sources: Gaillard WD, et al. Language dominance in partial epilepsy patients identified with an fMRI reading task. Neurology. 2002;59:256-265; Abou-Khalil B, Schlaggar BL. Is it time to replace the Wada test? Neurology. 2002;59:160-161.
Gaillard and colleagues conducted a study to assess language dominance with fMRI. They compared the results of language lateralization by fMRI (30 subjects) with that obtained by intracarotid amobarbital test (IAT) in 21 patients who underwent both. Given that the preponderance of epilepsy patients who undergo evaluation for resective epilepsy surgery have their seizures originate from the temporal lobe, most language tasks have preferentially caused fMRI activation in frontal structures. However, Gaillard et al were most interested in the ability of fMRI to demonstrate temporal activation in their silent naming paradigm.
Of 30 patients with temporal lobe epilepsy studied with fMRI, 27 had convincing lateralization (25 left, 2 right), 1 had bilateral activation, and 2 were indeterminate (weak activation) by region of interest (ROI) analysis. Of the 27 with lateralizing fMRI, 26 had activation in the temporal lobe. Fifteen of 20 patients had completely concordant lateralization by fMRI and IAT. Lack of concordance occurred when one of the tests demonstrated lateralization while the other suggested bilateral language representation. No patients were fully discordant (ie, contralateral findings in one test vs the other). Finally, visual interpretation of the fMRI was comparable to more detailed ROI analysis.
Commentary
Introduced in 1949, the IAT was described by Juhn Wada to assess cerebral language dominance. Milner and colleagues at the Montreal Neurological Institute subsequently recommended its use to assess memory. The test is now the standard for lateralization of language and memory functions in epilepsy patients undergoing evaluation for excisional epilepsy surgery. IAT is useful not only to assess postoperative risk of language dysfunction and amnesia, but it also can be predictive of postoperative seizure control (Perrine K, et al. Epilepsia. 1995;36(9):851-856; Loring DW, et al. Neurology. 1994;44(12):2322-2324). The test is invasive and carries the potential for morbidity. While surveys of epilepsy centers report complication rates of 0-5% and about 60% of those centers report no complications, the overall risk of thromboembolism and stroke remains at 0.5-1% for transfemoral carotid angiography. The development of a noninvasive alternative of at least comparable sensitivity, specificity, and predictive value is obviously desirable. Gaillard et al furnish significant data toward using fMRI to achieve this goal.
In their editorial, Abou-Khalil and Schlaggar suggest "We are almost there," in replacing IAT with fMRI. Certainly, fMRI is superior to positron emission tomography (PET) in spatial resolution. Furthermore, as compared to PET, radionuclide exposure is not involved. Repetitive transcranial magnetic stimulation (rTMS) is the only other technique that has been rigorously studied as a replacement for the language lateralization provided by the Wada test. Unfortunately, the data for rTMS are not encouraging (Epstein CM, et al. Neurology. 2000; 55(7):1025-1027). While Neurology Alert remains optimistic about the ultimate prospects for replacement of IAT by fMRI, the most formidable hurdle to overcome is the creation of a battery of fMRI memory protocols. These will be useful in predicting the risks of amnesia from a unilateral mesial temporal resection. Once this is achieved, it will be time for a multi-institution trial that compares outcomes of epilepsy surgery for patients studied with IAT vs. fMRI. —Andy Dean
Dr. Dean is Assistant Professor of Neurology and Neuroscience, Director of the Epilepsy Monitoring Unit, Department of Neurology, New York Presbyterian Hospital—Cornell Campus.
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