This chapter includes an accompanying lecture presentation that has been prepared by the author: .

Key Concepts

  • Wada testing involves brief anesthetization (i.e., several minutes) of one cerebral hemisphere to enable assessment of cognitive function within the contralateral, nonanesthetized hemisphere and provide a crude, reversible analog of the proposed resection.

  • Wada testing is used primarily before temporal lobe resection or ablation to determine hemispheric language dominance and hemispheric memory capacity.

  • Within several weeks before the procedure, patients should undergo neuropsychological evaluation (1) to establish baseline language and memory and (2) to familiarize the patient with Wada procedures.

  • Valid Wada testing requires adequate perfusion of the anesthetic, reliable indicators of hemianesthesia, and optimal patient cooperation.

  • Hemispheric memory performance asymmetries can be used to predict changes in postoperative verbal memory following dominant hemisphere temporal lobe resection.

  • With recent advances in neuroimaging, fMRI paradigms can be considered in place of Wada testing in certain situations.

  • It is recommended that patients who are at risk for postoperative amnesia undergo Wada testing rather than fMRI.

Depending on the location of the epileptogenic zone, resective (including ablative) epilepsy surgery frequently carries a risk for cognitive decline, and Wada testing is used to predict the nature and degree of this risk. The procedure remains unstandardized; thus the term Wada test refers not to a specific paradigm but rather to a class of procedures involving brief anesthetization of one cerebral hemisphere to enable assessment of cognitive function of the contralateral, nonanesthetized hemisphere. Accordingly, the procedure serves as a crude, reversible analog of the proposed resection.

Originally developed in the 1940s by Juhn Atsushi Wada of the University of British Columbia and Theodore Rasmussen to determine hemispheric language dominance, , the procedure remains the “gold standard” in this regard. However, both the role and use of Wada testing in the evaluation for epilepsy surgery have changed over time. Following several cases of amnesia and severe memory impairment after bilateral and unilateral temporal lobe resection, Wada testing was modified to include assessment of hemispheric memory function to identify patients at risk for postoperative amnesia. For the next few decades, virtually all surgical candidates underwent Wada testing as part of the presurgical evaluation. This intense use of the procedure generated an explosion of Wada-related research in the 1990s, providing a wealth of data regarding procedural issues, reliability, validity, safety, and utility, all of which influence current usage of the technique.

Procedures

Pre-Wada Procedures

Patients referred for Wada testing typically have pharmacologically refractory epilepsy, with seizures that arise from the temporal lobe, and thus these patients are at risk for language decline (if seizures arise from the dominant hemisphere) and memory decline. Therefore, Wada testing primarily involves assessment of language and memory during the period of hemianesthesia. A comprehensive neuropsychological evaluation, performed ideally within a few weeks before the procedure, provides the examiner with information regarding baseline language and memory, which aids interpretation of language and memory performance during the period of hemianesthesia. It is also helpful to familiarize patients with Wada procedures at the time of the neuropsychological evaluation. This increases the likelihood of cooperation and reduces anxiety, which, if significant, could interfere with the patient’s ability to comply with the procedure. On the day of the Wada procedure, an abbreviated practice session ensures that the patient understands the instructions, is not in a postictal state, and is functioning at his or her baseline level.

Scalp EEG leads may be applied to assist in monitoring the effect of hemianesthesia and, when needed, to ascertain the presence of seizure activity or whether the patient is in an awake or asleep state. Before the anesthetizing agent is administered, carotid angiography is performed to determine the presence or degree of cross-flow to the contralateral hemisphere, the extent of perfusion of the posterior cerebral artery (PCA), and potentially dangerous neurovascular patterns that would result in perfusion to the brainstem. The catheter that was used for angiography remains at the proximal segment of the internal carotid artery (ICA) in preparation for injection of the anesthetic agent.

eFigure 87.1, Example of the Wada protocol used at the Columbia Comprehensive Epilepsy Center. EEG, Electroencephalography; ICA, internal carotid artery.

Wada Procedure: Cognitive Testing

Despite variations, there are some basic commonalities in Wada procedures across most epilepsy surgery centers (see eFig. 87.1 for sample protocol). Wada procedures take place in a neuroradiology suite, with the patient lying supine on a procedural table. Before injection of the anesthetic (see later for agents and dosages), the patient is instructed to raise both arms, typically gripping the physician’s fingers for a baseline measure of grip strength. In some centers, the epileptogenic hemisphere is injected first because ipsilateral anesthetization yields the most critical information with respect to memory, that is, whether the contralateral hemisphere can support learning and memory. When it is determined that the hemianesthetic effect has taken hold several seconds after the initial injection (i.e., contralateral hemiplegia, unilateral EEG slowing), testing begins, and it proceeds at a relatively quick pace to ensure sufficient testing during this brief hemianesthetic interval. This consists of a combination of speech-language and memory testing conducted within 3 to 5 minutes. When the language-dominant hemisphere is injected, the patient typically exhibits an initial speech arrest, yet may be able to vocalize. Orally presented commands (e.g., point to your nose) serve to test speech comprehension and can also serve as auditory verbal memory stimuli (e.g., what did the examiner ask you to do?). However, most Wada memory items are dually encodable by verbal or visual means, typically consisting of either real (e.g., comb, watch) or pictured items. , Patients are asked to name and remember these items, thereby serving the dual purpose of testing both language (i.e., naming) and memory encoding (for later recall or recognition testing). Some centers also include unnamable visual stimuli for a “purer” test of visual memory. Although the memory component of the Wada test was intended to predict amnesia and not gradations in memory decline, “pure” verbal or visual stimuli have been used in attempts to predict “material-specific” memory decline (i.e., nonamnestic postoperative memory reduction limited to verbal or visual memory). The number of memory items presented varies among centers, generally ranging from 4 to 12. ,

Intermittently during the procedure, typically following presentation of two to three test items, the hemianesthetic effect is monitored by EEG and grip strength. After presentation of memory items, language is typically assessed further by repetition of phrases and sentences, comprehension questions, and possibly reading. With dominant hemisphere injection, recovery of speech and language is typically characterized by paraphasic speech errors before full return to baseline. The point at which the hemianesthetic effect is considered no longer adequate varies among centers (e.g., full return versus partial return). After full neurological recovery (i.e., baseline EEG, speech and motor function), memory is tested, either by free recall or, more often, by recognition memory testing using either multiple-choice arrays or forced-choice, yes/no recognition. The memory score is typically expressed as a fraction or percentage correct (e.g., 7/10 or 70%), with some centers reducing the score by a penalty for false-positive recognition responses and others adding a point as a handicap for performance after the language-dominant hemisphere injection. Another variation involves the inclusion of confidence ratings for each memory response. This provides information regarding the strength of the memory response and is incorporated into the memory asymmetry score (see the “Memory Asymmetry” section later in the chapter).

Interpretation of Wada Testing Results

Language

It is necessary for the surgical team to know whether the epileptogenic hemisphere supports language. This information may determine whether the patient requires cortical language mapping, the extent of the resection, and how the patient will be counseled regarding postoperative cognitive outcome.

Although most right-handed individuals are left-hemisphere dominant for language, the ability to predict hemispheric language dominance is reduced in patients with epilepsy because structural or functional lesions can cause intrahemispheric or interhemispheric reorganization. Although Wada testing is considered the gold standard for determining language dominance, the actual testing techniques are not standardized. Some centers determine hemispheric language representation based on qualitative observations, such as occurrence of speech arrest or presence of paraphasic errors, whereas others use more empirically based scoring methods with calculated laterality indexes. , There is some agreement that the absence of language disruption after both left and right hemisphere injections is not sufficient to conclude bilateral language representation because this could merely reflect inadequate perfusion of the anesthetic. Rather, it is generally accepted that the presence of paraphasic speech errors following both left and right injections is the most reliable indicator of bilateral language representation. , , Certainly, in the context of epilepsy, the rate of atypical language organization is higher than in the normal population. Interestingly, it appears that when language does shift, in whole or in part, to the right hemisphere, expressive and receptive functions are more likely to shift together, whether the shift-inducing pathology is in the left frontal or left temporal region.

Memory

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