Preoperative Neuropsychological Testing for Deep Brain Stimulation: The Right Action Perhaps for the Wrong Reason

Many, if not most centers implanting Deep Brain Stimulation (DBS) leads conduct neuropsychological testing prior to surgery. The reasonable question is why? Perhaps it is because neuropsychological testing was used in Randomized Control Trials (RCTs) of DBS. However, just importing inclusion/exclusion criteria from RCTs into general practice is problematic and often counterproductive (Montgomery Jr. E.B., Twenty Things to Know About Deep Brain Stimulation, Oxford University Press, 2015). Perhaps such testing is “standard” in these types of surgeries; borrowing from the long tradition of pre-operative neuropsychological testing for epilepsy surgery. It is reasonable to ask how is “standard” in this case different from just habit; however, one should not confuse habit for knowledge.

Lack of predictive value

The question of whether or not to conduct pre-operative neuropsychological testing preparatory to DBS surgery is reasonable, given that no study has demonstrated that neuropsychological status is a reliable predictor of post-operative outcomes. If the benefit to be gained is some prediction of outcome, then it hardly seems that pre-operative neuropsychological testing is justified due to cost and risk. Note, the risk of neuropsychological testing cannot be dismissed. What do the clinicians do in a case where there is evidence of mild cognitive impairment? Do clinicians then raise the issue of possible progression to Alzheimer’s disease? Does one decline to offer DBS surgery, although there is no evidence supporting the decision to do so? What if these abnormal test results are false positives? These are not insignificant concerns.

Note the claim that neuropsychological test performance is not prognostic of post-operative outcome is not to say that pre- and post-operative neuropsychological functions are not a concern. Rather, the lack of prognostic value may well be methodological, then an absence of data of the appropriate kind and quantity. As Carl Sagan said “the absence of evidence is not evidence of absence”. Then how is it possible, with all the clinical trials of DBS, that one does not know whether neuropsychological testing is predictive of post-operative outcome.

One possible explanation is that the neuropsychological screening of patients in DBS clinical trials excluded patients with significant pre-existing neuropsychological abnormalities. Upon review of several recent DBS and neuropsychological peer-reviewed studies, the inclusion criteria included patients without neurocognitive and mood deficits (Aono, M., Iga, J., Ueno, S., Agawa, M., Tsuda, T., & Ohmori, T. (2014). Neuropsychological and psychiatric assessments following bilateral brain stimulation of the subthalamic nucleus in Japanese patients with Parkinson’s disease. Journal of Clinical Neuroscience, 21, 1595 – 1598.; Borden, A., Wallon, D., Lefaucher, R., Derrey, S., Fetter, D., Verin, M., & Maltête, D. (2014). Does early verbal fluency decline after STN implantation predict long-term cognitive outcome after STN-DBS in Parkinson’s disease. Journal of the Neurological Sciences, 346, 299-302.; and Houvenaghel, J. F., Le Jeune, F., Dondaine, T., Esquevin, A., Robert, G. H., Péron, J., … & Sauleau, P. (2015). Reduced verbal fluency following subthalamic deep brains stimulation: A frontal-related cognitive deficit?. PLOS One). This results in a floor effect. The consequence is that there is relatively little variance in the neuropsychological outcomes and consequently one cannot parse out the variance over the variance in the pre-operative testing. Thus, if pre-operative neuropsychological status was predictive of outcome, one would not know it. Certainly, there is the exception of verbal fluency that does appear to worsen in many patients following DBS lead implantation. However, the effect is mild to moderate. Whether or not pre-existing deficits in verbal fluency places the patient at a greater risk for worsening of verbal fluency is unknown.

Identification of concerns

There certainly are neuropsychological concerns regarding DBS, but it is more likely that the benefit is detecting them early and constructing appropriate pre-operative treatment and/or post-operative surveillance. For example, depression is not an absolute contraindication to DBS, unless the patient has or will be in definite need for Electroconvulsive Therapy. However, identifying a patient with depression pre-operatively allows proactive intervention by assuring that mental health professionals are aware that the patient will undergo DBS and are prepared to intervene if necessary. Often times, mental health care professionals encourage patients to treat the depression prior to DBS depending on the severity of the depressive symptoms.

Impulsivity also can be a major problem identified in patients with Parkinson’s disease. Again, it is unclear whether impulsivity is a contraindication to DBS or if it is a post-operative outcome to recognize and then intervene following surgery. It is important to note that even successful DBS can cause a severe disruption of the psycho-social circumstances around the patient (Schüpbach M, Gargiulo M, Welter ML, Mallet L, Béhar C, Houeto JL, Maltête D, Mesnage V, Agid Y. Neurosurgery in Parkinson disease: a distressed mind in a repaired body? Neurology. 2006 Jun 27;66(12):1811-6. PubMed PMID: 16801642).

The realistic expectations of patients, family members and caregivers is critical to successful DBS outcomes. Unrealistic positive expectations can lead to serious disappointments. Unrealistic negative expectations can lead to a failure to get definitive help. Verbal fluency and impulsivity may be symptomatic of significant medical, psychological and sociological problems that deserve investigation and treatment in their own right.

One could argue that formal neuropsychological testing lacks sufficient positive and negative predictive values when detecting problems like depression, impulsivity and unrealistic expectations. Alternatively, the predictive value of neuropsychological testing is no better than the seasoned experience and judgment of physicians and nurses. However, in our experience (EBM), this is not likely or consistently the case. Interviews by expert neuropsychologists of the patients, family members and caregivers in addition to the formal testing often uncovers problems of depression, impulsivity and unrealistic expectations missed by the treating physicians and nurses.

Understanding post-operative changes

Slowly progressing declines in neuropsychological functions often go unnoticed even while advancing to a severe degree. For that reason, family members, caregivers, and healthcare professionals who have been involved in the patient’s care over long periods of time may not notice the degree of impairments, depression, and impulsivity. A fresh look by an expert neuropsychologist may recognize these problems missed by those chronically involved in the patient’s care.

The slow progressive change can often go unnoticed until a spotlight is placed on the patient, and then the extent of the problem(s) is finally realized. DBS surgery is quite a spotlight. Unfortunately, there is a tendency to jump to the conclusion that DBS surgery caused the neuropsychological problems. In actuality, they are often times present before DBS, but were unrecognized post-operatively. In those patients with pre-operative testing as a baseline, a repeat neuropsychological evaluation can help determine whether there actually was a significant change. That knowledge benefits all involved in the patient’s care.

Advising all when the patient has significant cognitive problems

Advising patients with a cognitive impairment whether to undergo DBS surgery is problematic. The lack of studies capable of determining the prognostic value of neuropsychological testing, as described above, is a significant handicap. One cannot even say that DBS meaningfully worsens cognitive functioning and thus, one cannot extrapolate to say that those with pre-existing cognitive problems are at greater risk.

The situation above places physicians and healthcare professionals at risk for ethical problems. No physician or healthcare professional wants to be responsible for worsening a patient in their care. This can lead to an Omission bias where there is the false notion that errors of commission are worse than errors of omission. While this may be psychologically true for physicians and healthcare professionals, it makes little difference to patients, family members and caregivers who suffer with either the continued disability and pain of the disease being treated or the suffering as a consequence of DBS surgery. Physicians and healthcare professionals defaulting to the Omission bias are guilty of patronizing the patient and violating the ethical principle of autonomy.

One approach to resolving these issues, at least for some patients, is to determine what is the “rate limiting” factor for the patient’s quality of life. If the cognitive problems are severe enough that the patient’s quality of life would not be substantially improved with DBS, even as the problems due to the disease for which the DBS is administered improves, the patient will have gained little and therefore the risk and suffering associated with DBS surgery is not justified. However, determining if the cognitive problems are the rate limiting effect requires some ability to prognosticate the impact of the cognitive problems on the quality of life. Neuropsychologists and Speech Language Pathologists experienced with patients with dementia can help in those determinations.

Greenville Neuromodulation Center’s Recommendation

Pre-operative neuropsychological testing is valuable and warranted even if the reasons are not what may have been originally expected. Neuropsychologists assessing DBS candidates conduct a battery of neuropsychological assessments, including measures of intelligence, fine motor functions, frontal executive tasks including attention, concentration, and problem solving, language and verbal fluency, verbal memory and learning, visual memory, dementia rating, and quality of life. Pre-operative neuropsychological testing is highly recommended for patients being considered for DBS.