Abstract
The Wada test has been considered the gold standard for later-alizing language and memory function in the presurgical workup of patients with epilepsy. It has further evolved in its applications in its superselective form with applicability to a plethora of cerebrovascular pathology. This chapter reviews historical manuscripts and provides a review of the approach with a critical analysis of its utility in the era of advanced noninvasive imaging modalities.
Key words
Wada test – epilepsy – sodium amobarbital25 Wada and Selective Wada Tests
25.1 Goals
Present the frequency, clinical indications, and methods of Wada testing and its associated complications.
Compare the literature on use of Wada and noninvasive approaches.
Analyze the validity of Wada testing for language determination and memory function.
Review the literature on posterior cerebral artery (PCA) and superselective Wada.
25.2 Case Example
25.2.1 History of Present Illness
A 53-year-old, left-handed man on aspirin with a history of traumatic brain injury presents for surgical consideration of his medically refractory complex partial epilepsy with secondary generalization since the age of 15 after a motor vehicle accident. The patient reports his seizures start with right eye deviation, head deviation to the right, ringing noises in his ears, “feeling funny,” and unusual odor perception. He continues to have bilateral upper extremity tremors as a side effect from his Depakote. He complains of residual weakness in his right leg and numbness that affects his right foot and palm after a stroke in 2000. A Wada test was recommended prior to a potential left temporal lobectomy.
Past medical history: Mitral valve prolapse, aortic stenosis, cerebrovascular accident, right-sided eye trauma (status postprosthesis).
Past surgical history: Appendectomy, right eye removed, C3-C5 fusion.
Family history: Noncontributory, no family history of seizures.
Social history: 30-pack-year smoking history, social alcohol usage, no drugs of abuse.
Review of systems: As per the history of present illness.
Neurological examination: Remarkable for a mild right facial droop, decreased hearing bilaterally, and mild right hemipa-resis (4 + /5). He has a noticeable tremor of the left greater than right on outstretched upper extremities.
Imaging studies: See Fig. 25.1.
25.2.2 Treatment Plan
The patient underwent selective catheterization and angiography of the bilateral internal carotid arteries (ICAs) followed by administration of 125 mg of sodium Amytal in the left ICA and 200 mg of sodium Amytal in the right ICA followed by language and memory testing and subsequent Mynx closure of right common femoral artery. Wada testing affirmed that the patient harbored a left hemisphere language representation and left memory dominance. After performance of the Wada test, a fronto-temporal grid was implanted with depth electrodes into the hippocampus. Surgical resection was subsequently performed after mapping the location of the seizure focus more definitively
25.2.3 Follow-up
The patient tolerated the Wada test without complication. He initially underwent placement of a frontotemporal grid with depth electrodes into the hippocampus and subsequent resection of the seizure focus. At 1-year follow-up evaluation, the patient has been seizure-free since his surgery.
25.3 Case Summary
What would you report as the most common complications associated with the Wada test?
The complication rate associated with angiography and has been reported to range from 0.3% to nearly 11% of patients. 1 , 2 , 3 , 4 , 5 Most complications are associated with the angiogram and not with the injection of amobarbital itself; thus, the main source of complications is thromboemboli. Other sources of morbidity include dissections and groin complications. As modern reports cite lower and lower rates of complications, one would expect a commensurate rate for the Wada test as well.
What patient factors would you consider when deciding on your recommendations for Wada testing?
Both patient’s age and medical comorbidities are important patient factors when deciding on Wada testing. Neurologic complications are significantly more common in patients 55 years of age or older and in patients with cardiovascular disease. 3 In the study by Loddenkemper et al, older age was a risk factor for stroke (47 years as compared with 32 years) and dissection (52 years as compared with 32 years), whereas younger age (21 years as compared with 32 years) was a risk factor for seizures. 4
In which cases may the Wada test be omitted prior to surgical resection?
Although decisions should be made on a case-by-case basis, the Wada test may possibly be omitted in the preoperative evaluation in a patient with right temporal lobe epilepsy if there is an evidence of typical left hemispheric language dominance from functional imaging. 1 Also, combined structural and functional imaging in conjunction with neuropsychological testing could be used as opposed to the Wada testing for patients at high risk of memory decline. 6 Some centers consider functional magnetic resonance imaging (flvIRI) to be a reasonable “triage test,” and Wada testing is indicated when flvIRI does not provide straightforward left lateralization. 7 As functional imaging improves and resultant ambiguity decreases, the use of the Wada test may become reserved for a narrower patient population.
Can the Wada test be more broadly applied?
Wada tests may also be performed superselectively to identify clinically relevant neurologic deficits. This procedure can be employed to detect eloquent cortex perfused by feeding arteries, and therefore prior to embolization, one can anticipate potential neurologic deficits. The following case demonstrates utilization of the superselective Wada.
A 43-year-old male who previously underwent craniotomy for resection of a left frontal glioma and subsequent radiation was found to have an anterior cerebral artery (ACA) pseudoaneurysm on follow-up imaging, confirmed angiographically (Fig. 25.2a). The patient underwent superselective Wada testing with 30 mg of intra-arterial sodium amobarbital infused into the right pericallosal artery resulting in no discernible neurologic changes (Fig. 25.2b). He thus underwent embolization of the pseudoaneurysm and parent vessel with Onyx 34 without complication (Fig. 25.2c). Imaging studies: See Fig. 25.2.
25.4 Level of Evidence
Given the patient’s refractory epilepsy, left-handedness and potential need for temporal lobectomy, a Wada test is a safe and effective test to facilitate determination of language and memory dominance (Class 4).
25.5 Landmark Papers
25.5.1 Original Wada Papers
Wada J. A new method for the determination of the side of cerebral speech dominance: a preliminary report of the intra-carotid injection of sodium Amytal in man. Med Biol 1949;14:221-222.
Any discussion of landmark papers on the Wada test must include the original work of Juhn A. Wada in his development of the intracarotid amobarbital procedure (IAP). 8 , 9 , 10 , 11 While studying seizure mechanisms and searching for a method to allow unilateral electroconvulsive shock therapy for psychosis during the course of several studies in 1948, Juhn Wada used intracarotid injection of sodium amobarbital and metrazol to investigate how epileptic discharge spreads between the hemispheres of the brain. 11 It was determined that this technique could be utilized to assess the lateralization of cerebral speech dominance as sodium amobarbital induced a temporary aphasia when the dominant cerebral hemisphere was injected. This technique was tested on 80 patients in Japan from 1948 to 1954 without any reported complications. The procedure described by Wada would become the standard test in the presurgical assessment for resection of an epileptic focus for the treatment of medically intractable epilepsy.
Perria L, Rosadini G, Rossi GF. Determination of side of cerebral dominance with amobarbital. Arch Neurol 1 961 ;4: 1 73-181.
In 1961, Perria et al set out to establish the validity of the IAP and to standardize results.12 Perria et al established conditions that must be satisfied before interpreting results from the method utilized by Wada. These conditions included: (1) the dose of amobarbital that produces an effect when injected into the carotid must not produce any effect when administered intravenously; (2) the action of the drug be confined to the hemisphere ipsilateral to the side of the intracarotid injection; and (3) the EEG and all the clinical phenomena are correlated. On the basis of these conditions, Perria et al looked for changes in EEG activity, speech production, plantar reflex, knee jerk, and emotional state. They reached the conclusion that speech disturbances combined with depressive-type emotional reactivity shows the drug is acting on the dominant hemisphere, whereas lack of speech deficits with euphoric-type emotional reactivity shows the drug is acting on the nondominant hemisphere. These clinical effects can only be analyzed when the EEG activity, reflexes, and motor power are also lateralized.
jack CR, Jr., Nichols DA, Sharbrough FW, Marsh WR, Petersen RC. Selective posterior cerebral artery Amytal test for evaluating memory function before surgery for temporal lobe seizure. Radiology 1988;168:787-793.
When the Wada test is intended for use prior to selective amygdalohippocampectomy, the reliability of the IAP has been questioned. In most patients, the ICA perfuses the uncus, amygdala, and anterior hippocampus, but not the posterior two-thirds of the hippocampus. 13 Due to this inadequate perfusion of mediobasal temporal lobe structures with the ICA method, in 1988, Jack et al injected sodium amobarbital selectively into the PCA to distribute the sodium amobarbital solely within the hippocampus for selective testing of memory function, depicting favorable procedures in 38 of 45 patients. 14 The significant correlation between performance during memory testing during the PCA-amobarbital procedure and pre- and postoperative results was significant only for left-sided operations and injections, which the authors suggest signifies that the left PCA-amobarbital procedure simulates the outcomes of resection on memory performance and verbal learning.
Urbach H, Klemm E, Linke DB, et al. Posterior cerebral artery Wada test: sodium Amytal distribution and functional deficits. Neuroradiology 2001;43:290-294.
In the study by Urbach et al, the authors sought to assess sodium amobarbital distribution in the PCA Wada test and to relate it to the neurological deficits that occurred during the test. 13 The PCA Wada test was performed in 14 patients with medically intractable temporal lobe epilepsy. Eighty mg of sodium amobarbital and 14.8 MBq 99mTc-hexamethylpropylene-amine oxime (HMPAO) (due to the lipophilic nature of HMPAO, the distribution of the radiotracer reflects that of sodium amobarbital) were simultaneously injected into the P2-segment of the PCA, and distribution of sodium amobarbital was determined with high-resolution single-photon emission computed tomography (SPECT). In all patients, SPECT demonstrated the HMPAO/sodium amobarbital combination was distributed throughout the parahippocampal gyrus, hippocampus, and occipital lobe (including the calcarine area), and in 11 cases was also seen in the thalamus. Selective amygdalohippocampectomy was subsequently carried out in nine of the 14 patients, none of whom showed a major postoperative decline in memory.
Rauch RA, Vinuela F, Dion J, et al. Preembolization functional evaluation in brain arteriovenous malformations: the superselec-tive Amytal test. AJNR American journal of neuroradiology 1992;13:303-308.
During the analysis of vascular anomalies such as aneurysms and arteriovenous malformations (AVMs), superselective angiography is useful in providing accurate architecture on angiography. 15 The combination of pretreatment Wada testing with arterial occlusion proves a helpful instrument, providing dynamic, functional, and anatomic data about the vascular territory of the vessel to be catheterized. In the endovascular treatment of an aneurysm located in eloquent cortex with possible speech and language involvement, a superselective Wada test can be used to determine the safety of vascular sacrifice. 16 Injection of sodium amobarbital or Hdocaine to detect feeding vessels to the spinal cord in primates 17 and in humans 18 has similarly been described.
Rauch et al reported on 109 superselective Wada tests that were performed with 30-mg injections of sodium amobarbital prior to embolization of an AVM to reproduce the subsequent injection of contrast and embolic material. 19 The vascular territory of the vessels studied included middle cerebral artery in 32 patients, anterior cerebral artery in 13 patients, and PCA in 18 patients. There were 23 positive tests (associated with changes in the neurologic examination or EEG) following sodium amobarbital injection. There were no reported adverse long-term effects of the 109 injections as the focal effects of the sodium amobarbital completely dissipated after 10 minutes. The authors conclude that determining positive tests can facilitate decision making as to which vessels can be embolized without inducing permanent neurologic deficits.
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