Neuropsychological Evaluation and WADA Testing in Epilepsy

By William J. McMullen, Jr. Ph.D., ABCN, ABPP

Neuropsychological evaluation involves standardized testing of various cognitive functions to establish areas of cognitive strength and weakness. Neuropsychologists have developed tests of various cognitive skills (e.g., attention, memory, language function, etc.) and administered these tests to a large number of individuals free of neurological disorder. A subject’s performance on such tests is compared to the performance earned by a normative sample to determine the subject’s relative skill level in certain areas. Significant (negative) deviation from normal performance can identify areas of cognitive weakness that have real functional implications, but that are difficult to detect on standard neurological assessment or interview. In the hands of skilled neuropsychologists these tests have proven helpful in evaluating a wide array of neurological conditions, including stroke, dementia, learning disorder, head injury, epilepsy, and other neurological disorders.

Together with magnetic resonance imaging (MRI) and electroencephalography (EEG), neuropsychological evaluation has become a key component in the presurgical evaluation of patients undergoing surgery to address medically refractory seizures. As when working with patient populations outside of epilepsy, results of neuropsychological evaluation can be used to educate patients and families regarding areas of cognitive strength and weakness, to document any impairment that contributes to significant limitations in occupational functioning for legal purposes, or to guide rehabilitation efforts or establish academic goals. But perhaps most important in the context of the presurgical epilepsy evaluation is the role that neuropsychology plays in assisting the treatment team in gauging the potential risks and benefits of surgical resection to address an epileptogenic focus.

Predictors of Cognitive and Seizure Outcome

In addressing the potential risks and benefits of surgical resection for epilepsy, two of the most important issues that the treatment team considers are the likelihood of elimination or dramatic reduction in seizures and the likelihood of cognitive decline. Langfit and colleagues (2007 (Ref 1) demonstrated that quality of life following temporal lobectomy is dependent on seizure outcome and the presence of memory decline. Those individuals who were seizure-free following surgery, whether or not they experienced memory decline, reported improved quality of life. Those who were not seizure-free and who also experienced memory decline reported worsened quality of life. Thus prognosis for both seizure outcome and cognitive outcome is important in gauging whether to proceed with surgery to address refractory epilepsy.

Factors that have been shown to predict good seizure outcome following temporal lobectomy for medically refractory epilepsy include the presence of MRI abnormalities( Ref 2), extent of resection (Ref 3) and the Wada Memory Asymmetry score (Ref 4) (WMA). Factors that have been shown to predict the presence or absence of cognitive decline following temporal lobe resection include age at onset of seizures (Ref 5), side of surgery, preoperative neuropsychological test performance (Ref 6), presence or absence of MRI abnormalities (mesial temporal sclerosis), and the WMA (Ref 7).

One can glean from the above that factors predicting significantly localized, functionally inadequate tissue in the epileptogenic zone also predict good seizure outcome, provided the epileptogenic zone is adequately removed. Prognosis for cognitive outcome is a bit more complex; earlier onset of seizures predicts better cognitive outcome primarily because this is correlated with reorganization of functional tissue outside the epileptogenic zone. Other factors including preoperative neuropsychological test performance and the Wada memory asymmetry score relate to the function of the to-be-resected area. Better preoperative neuropsychological scores on tests known to be subserved by the epileptogenic zone predict greater postoperative decline in those same skills. Wada memory test results that suggest the epileptogenic zone is impaired relative to the contralateral temporal lobe predict favorable outcome.

Ultimately, what appears to matter in predicting cognitive outcome following surgery is whether the tissue to be resected is functionally adequate. Resection of functionally adequate tissue is known to result in a decline in cognitive skills, while resection of nonfunctional tissue is not likely to result in significant cognitive change.

The Neuropsychological Evaluation in Epilepsy

Many individuals with intractable epilepsy are known to exhibit neurocognitive deficits, with the nature and degree of deficit depending on the epilepsy syndrome. Individuals with language-dominant TLE are known to frequently demonstrate impairments in confrontation naming (Ref 8. 9), and verbal memory. Additionally, the long-term consequences of refractory temporal lobe seizures are known to include a gradual decline in intellectual functions (Ref 10). Neuropsychological evaluation of an individual with epilepsy seeks to determine whether any such patterns of neurocognitive disorder are present and consistent with their known epilepsy syndrome. This is of assistance in establishing whether EEG, MRI, and neuropsychological testing are consistent in suggesting a specific pattern of neurological dysfunction. Additionally, test performance is examined in light of known preoperative predictors of postoperative cognitive change; better preoperative performance on tests of skills subserved by the known epileptogenic temporal lobe predicts a higher likelihood of postoperative decline in those skills. This has been demonstrated most clearly with confrontation naming (Ref 11) and verbal memory (Ref 12) performance in patients undergoing language-dominant temporal lobe resection.

The Wada Test (Intracarotid Amobarbital Procedure)

The Wada test was developed by Juhn Wada¹³ to establish speech dominance prior to temporal lobe resection. It has since become useful in evaluating the integrity of bilateral memory structures as well. The procedure involves anesthetizing one cerebral hemisphere at a time, using a short-acting barbiturate administered by an interventional neuroradiologist into the internal carotid artery. The neuropsychologist then administers tests of memory and language during and following sedation to determine whether medication induced language or memory deficits. Using this method, it is possible to identify language laterality (left, right, or both) and to establish whether both mesial temporal structures support memory function.

It has been known since the case of H. M., reported by Scoville and Milner in 1957¹⁴, that removal of bilateral mesial temporal structures results in catastrophic anterograde memory impairment. A number of cases in the 1950s and 1960s, prior to the development of modern neuroimaging, reported that unilateral resection could cause the same catastrophic amnestic disorder. In these cases, the contralateral mesial temporal structures were later found to be functionally inadequate and in some cases atrophic. It was to prevent such cases, of catastrophic amnesia that the Wada test was adapted to assess the integrity of bilateral memory structures as well as to establish language lateralization.

In recent years, the Wada Memory Asymmetry Score (WMA) has been identified as an important predictor of both seizure and cognitive outcome following unilateral temporal lobectomy. This score is derived by subtracting the two adjusted memory recognition scores from each hemisphere studied. If the resulting difference score is in the expected direction (e.g., the hemisphere contralateral to the seizure focus shows stronger memory than the epileptogenic temporal lobe), this is a favorable predictor^15,4,7 of both seizure outcome and cognitive outcome.

Integration of Data

Final integration of neuropsychological and Wada test data is key to predicting the likelihood of postoperative cognitive change. By interpreting preoperative neuropsychological test performance in light of known language lateralization and Wada memory performance, the neuropsychologist is able to provide the treatment team with needed input regarding relative risk for neurocognitive decline following unilateral temporal lobectomy. This information is becoming ever more useful as non-resective approaches to treating refractory epilepsy are on the horizon and may provide better alternatives to those individuals deemed at risk for postoperative cognitive decline (e.g., implanted neurostimulators, etc.).

References

1. Langfitt., J., Westerveld, M., Hamberger, M., Walczak, T., Cicchetti, D., Berg, A., Vickrey, B., Barr, W., Sperling, M., Masur, D., & Spencer, S. (2007). Worsening of quality of life after epilepsy surgery; effects of seizures and memory decline. Neurology, 68, 1988–1994.


2. Garcia, P., Laxer, K., Barbaro, N., & Dillon, W. (1994). Prognostic value of qualitative magnetic resonance imaging hippocampal abnormalities in patients undergoing temporal lobectomy for medically refractory seizures. Epilepsia, 35(3), 520–524.


3. Wyler, A., Hermann, B., & Somes, G. (1995). Extent of medial temporal resection on outcome from anterior temporal lobectomy: A randomized prospective study. Neurosurgery, 37(5), 982–991.


4. Perrine, K., Westerveld, M., Sass, K., Devinsky, O., Dogali, M., Spencer, D., Luciano, D., & Nelson, P. (1995). Wada memory disparities predict seizure laterality and postoperative seizure control. Epilepsia, 36(9), 851–856.


5. Hermann, B., Seidenberg, M., Haltiner, A., & Wyler, A. (1995). Relationship of age at onset, chronological age, and adequacy of preoperative performance to verbal memory change after anterior temporal lobectomy. Epilepsia, 36(2), 137–145.


6. Chelune, G., Naugle, R., Luders, H., & Awad, I., (1991). Prediction of cognitive change as a function of preoperative ability status among temporal lobectomy patients seen at 6-month follow-up. Neurology, 41(3), 399–404.


7. Lee, G., Park, Y., Westerveld, M., Hempel, A., Blackburn, L., & Loring, D. (2003). Wada memory performance predicts seizure outcome after epilepsy surgery in children. Epilepsia, 44(7), 936–943.


8. Schefft, B., Testa, S., Dulay, M., Privitera, M., Yeh, H (2003). Preoperative assessment of confrontation naming ability and interictal paraphasia production in unilateral temporal lobe epilepsy. Epilepsy & Behavior Volume 4, Issue 2, April 2003, Pages 161-168.


9. Busch, R., Frazier, T., Haggerty, K., Kubu, C. (2005). Utility of the Boston Naming Test in Predicting Ultimate Side of Surgery in Patients with Medically Intractable Temporal Lobe Epilepsy. Epilepsia, Volume 46, Issue 11, pages 1773–1779, November 2005.
   
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11. Hermann BP, Wyler AR, VanderZwagg R. et al. (1991). Predictors of neuropsychological change following anterior temporal lobectomy: the role of regression to the mean. J Epilepsy ; 4: 139-48.


12. Chelune GJ, Naugle RI, Liiders H, Iwad I. (1991). Prediction of cognitive change as a function of preoperative ability status among temporal lobectomy patients seen at 6-month follow-up. Neurology 41: 399-404.


13. Wada, J. (1949). A New Method for determination of the side of cerebral speech dominance. A preliminary report on the intracarotid injection of Sodium Amytal in man. Igaku to Seibutsugaku; 14, 221-222.


14. Scoville, W., Milner, B. (1957). “Loss of recent memory after bilateral hippocampal lesions”. Journal of Neurology, Neurosurgery and Psychiatry 20 (1): 11–21.


15. Sabsevitz, D., Swanson, S., Morris, G., Mueller, W., & Seidenberg, M. (2001). Memory outcome after left anterior temporal lobectomy in patients with expected and reversed Wada memory asymmetry scores. Epilepsia, 42(11), 1408–1415.

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