Monday, July 25, 2016

Risk Involved in Advancing Microelectrodes with Tips Withdrawn

Erwin B. Montgomery Jr. MD

Professional Newlsetter

Vol. 2, No. 7

July 25, 2016

We recently learned that some intraoperative neurophysiologists and neurosurgeons utilize the large indifferent or reference electrical contact for macrostimulation during targeting of the Deep Brain Stimulation (DBS) lead.  Such macrostimulation may be useful to infer the regional anatomy and physiology of the electrode location and to, perhaps, anticipate post-operative clinical response. Those interested in a fuller discussion of these benefits might consult Montgomery Jr. E.B., Intraoperative Neurophysiological Monitoring for Deep Brain Stimulation: Principles, Practice and Cases, Oxford University Press, 2015. 

There is a problem with some microelectrodes in that the sharp recording tip may extend many millimeters beyond the indifferent or reference electrode on the outer cannula of the microelectrode.  Thus, advancing the indifferent or reference electrode to the desired depth also means advancing the extended sharp tip, perhaps to a depth that could injure important structures.

Apparently, some intraoperative neurophysiologists and neurosurgeons will withdraw or retract the sharp tip into the outer cannula and then continue to advance the microelectrode until the indifferent or reference electrical contact is at the desired depth.  However, this results in the open end of the cannula moving through brain tissue.  The concern is that this will result in the “coring out” of tissue similar to what occurs during procedures such as stereotactic biopsies.  Advancing the electrode with the tip withdrawn could lead to an increased risk of intracranial hemorrhage.

We examined this possibility by passing a standard DBS microelectrode through fresh cow brain.  The sharp tip was extended and then the electrode was inserted.  Once the tip of the outer cannula was well into the brain, the sharp tip was retracted and the electrode moved through the brain until the electrode emerged.  The tip of the electrode was inspected for brain tissue fragments and none were found.  When the sharp tip was extended, tissue fragments were extruded, indicating these fragments were within the outer cannula.  These results were repeated on a second pass.

While these observations warrant further examination, neurosurgeons and intraoperative neurophysiologists must at least consider the potential operative risk associated with advancing the electrode with the tip withdrawn. Both this incremental risk and the benefits referenced above must be included in the risk-to-benefit analysis of the procedure.  It is important to note that this issue is not evidence of a design or manufacturing problem.  Rather, the risk is only attendant on the use of these types of microelectrodes in this particular manner.

At least in the United States, if an FDA-approved microelectrode in used in a manner that is not warranted by the FDA-approved manufacturer labeling or manual, it is considered an “off-label” use of an FDA-approved device. Advancing the electrode with the tip withdrawn could be considered an example of this.  Physician discretion in such “off-label” use is well respected by the FDA; however, the FDA expects the physician to use due diligence.1

Unfortunately, there is no data currently available to determine the magnitude of the incremental risk associated with advancing a DBS microelectrode with the tip withdrawn.  As discussed in the last professional newsletter (“Is It a Sin If One Does Not Get Caught?”, Vol. 2 No. 6, June 25, 2016) the risk is already so low as to make detection of even a doubling or more of the risk unlikely.  Nevertheless, this is not license and does not obviate the responsibility of physicians to be reasonable and responsible.

1 It is important to note that this author does not speak for the FDA and is not an attorney providing legal opinion.

Friday, July 1, 2016

Is It a Sin If One Does Not Get Caught?

Erwin B. Montgomery Jr. MD
Medical Director

Greenville Neuromodulation Center

Professional Newsletter

Vol. 2, No. 6

June 25, 2016

Person A – If you use this method you can double the risk of problems.

Person B – We rarely have problems.

Person A – How would you know? And you still are doubling the risk.

               Fortunately, the major risks associated with Deep Brain Stimulation lead implantation surgery are relatively rare.  For example, while post-operative scanning may reveal an intracerebral hemorrhage rate of nearly 10%, only approximately 2% result in a clinically significant hemorrhage.  The problem is that such rare events make surveillance and judgments difficult.  Statistical analysis and judgment depends on the Theory of Large Numbers.  The Central Tendency of a data set, such as the mean or median of the sample, stabilizes as the number of observations increases.  Prior to some critical number of observations, one cannot “trust” measures of Central Tendency.

               Consider the situation where the risk of significant hemorrhage with optimal methods is 1%.  This means that with each surgery, the risk is 1% or 0.01.  Assuming that the risk for each subsequent patient is independent, then the cumulative risk of witnessing a significant hemorrhage is n * 0.01, where n is the number of persons having surgery.  For example, the average risk for a significant hemorrhage occurring after 10 subjects is only 10%, or 0.1.  However, this number is misleading.  An individual patient cannot have a 10% significant hemorrhage.  Even if 49 patients were observed, the probability of having seen a significant hemorrhage in one patient still is less than 50%, or 0.5.  Even this assumes that the sample from which patients are drawn is representative of the population at risk.

               Next, consider the situation where a surgeon adopts a method that increases the risk of significant hemorrhage to 2%, or 0.02.  On average, it would take at least 25 subjects to have a 50% chance of detecting a single significant hemorrhage, and again more than 50 subjects to detect the excess hemorrhage over what would be expected under optimal conditions.

               The scenarios described above are  best-case, or idealized, situations.   Decision-making  becomes even more problematic when the actual occurrence is a stochastic process.  Thus, in one group of 50 patients, no hemorrhages are encountered.  In the next group of 50, 2 patients with significant hemorrhages are encountered.  Though the overall risk is unchanged,  the physician’s experience is very different.  If one wants to have confidence in the rate of significant hemorrhages, typically a much larger number of patients is required to conform to the Theory of Large Numbers that underlies statistical judgments.

The great danger is that the physician will make judgments based only on the group of 50 patients that he or she experiences.  If it is the first group, then the physician likely will underestimate the risk.  If it is the second group, there is the chance of overestimating the risk.  The scenario just described is also idealized by assuming complete knowledge of all the patients.  It is not clear if patients are followed in such a manner as to have complete knowledge.

The risk that it may not be possible to know
               As can be seen, judgments based on small numbers are very difficult.  One cannot have confidence in the various measures upon which physicians and healthcare professionals depend.  Yet the patient is in front of the physician and healthcare professional, and the latter are obliged to help.  The responsibilities and interactions between the patient, physician and healthcare professional can be understood in terms of the ethical principles of beneficence, autonomy, non-malfeasance (meant as not harming rather than suggesting incompetence), and justice. 

The obligation to beneficence is fundamental to medicine in the presumption that persons become physicians and healthcare professionals just to help.  The issue of non-malfeasance is more difficult.  In the general sense, malfeasance is unavoidable.  It harms the patient to make an incision in the scalp, yet we counterbalance that necessary harm with the benefit hoped to be obtained.  It is an age-old problem of trying to strike a balance between necessary harm and the greater hope of benefit.  One approach to the situation is the Principle of Double Effect, which explains how an action causing harm may be justified when it is inseparable from the good effect that is desired. One of the clearest explications of this was described by Thomas Aquinas (1225 - 1275) in his work Summa Theologica. According to this principle, a key determinant in balancing harm versus good is the intention of the physician and healthcare professional.  The intentions relate not only to the good, but also to the harm; thus the harm must be minimized.

               As we, physicians and healthcare professionals, must intend to minimize harm, how do we gauge our efforts?  What is the basis for our accountability?  Is it based on actuarial experience, that is, how many patients we may have harmed with the judgment based on more harm than is standard?  In this case, accountability is retrospective.  Given the difficulty of ascertaining harm, holding strictly to a retrospective accountability may risk allowing us a “get out of jail free” card.

               Alternatively, should not accountability be prospective?  Clearly, the large majority of physicians and healthcare professionals implicitly display prospective accountability by their judicious considerations prior to causing harm in order to obtain benefit.  But the question is how to construct the prospective accountability?  What is the basis for determining that certain methods should or should not be used?  As discussed above, subsequent demonstrations of harm are not likely helpful in a great many decisions physicians and healthcare professionals must make.

Obligation to use reason
               Much of the argument against “cookbook” medicine is based on the skepticism that any “recipe” could address the variability among patients.  Most every physician and healthcare professional recognizes the necessity of individualizing the care of a particular patient.  Thus, by necessity, physicians and healthcare professionals must exercise reason, even if reasoning is not valued by Evidence-Based Medicine.  Indeed, courts of law have been defining standards of medical care, not by what similarly- situated physicians would do, but rather based on what reasonable physicians would do.

               That same obligation to use reason is inherent in virtually every decision.  Fortunately, many of these issues have already been settled by consensus or consilience.  Nevertheless, the individual physician and healthcare professional are expected to use their own reasoning.  It is no less the case in the decisions about what methods to use for DBS lead implantation surgery.  The use of microelectrode recordings clearly increases the risk of hemorrhage, even if that increased risk does not show up in clinical trials.  To appreciate how this must be so, consider making the contrary statement that it does not matter how many times you puncture the brain in terms of risk.  To maintain this position, one would have to argue that the second microelectrode penetration somehow has less risk and the next one, if necessary, has even less risk.  This clearly does not make sense.  Thus, the obligation is to minimize the risks while maintaining the benefit.  This is also true of the type of microelectrodes used and how they are used.  In the absence of unobtainable data, one has to reason using principles and physics.

Monday, May 23, 2016

A Calling to be Better than Ourselves

Erwin B. Montgomery Jr. MD

Greenville Neuromodulation Center

Professional Newsletter

Vol 2 No. 5

May 23, 2016

Dear Dr. Montgomery:

I did not refer the patient [to you].  I don’t need your help.  Here is your evaluation and recommendations back.

Dr. X


The patient sought a second opinion, as is any patients’ right.  The patient asked that the evaluation and recommendations be sent to Dr. X, which any physician so asked would be obligated to do.  The paradox is that Dr. Montgomery agreed with the diagnosis set forth by Dr. X and only offered one additional consideration in the treatment.  Clearly, the description of the event may be out of context and there could be mitigating circumstances, but it is hard to envision circumstances that would justify the aforementioned response.  Apart from not being collegial, it is not in the patient’s best interest.  Most physicians and healthcare professionals would likely agree.  So the question for our profession is how are such incidences handled, not just for this specific case, but also how to prevent future occurrences?  Essentially, the question is one of accountability.

This author has yet to meet any physician and/or healthcare professional whose first intention was not to help patients.  Physicians and healthcare professionals are intelligent, hardworking, and likely would find better financial remuneration in fields other than medicine; furthermore, the practice environment is difficult. A very large percentage of physicians would not recommend others to enter the practice of medicine. However, we know that there are other motivations that can affect intentions. 

Nevertheless, we cannot default to assuming that every medical professional holds themselves accountable and this is sufficient.  Experience with human experimentation demonstrates this will not work.  Many physicians and clinical scientists opposed mandating Institutional Review Boards to govern human research consequent to the Belmont report in 1978 (Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Department of Health, Education and Welfare [DHEW] [30 September 1978]). Washington, DC: United States Government Printing Office).   Many of these physicians and clinical scientists held that good ethical practice is just what good clinicians do.  The numerous scandals of unethical research, continuing to this day, demonstrates the incredulity of such claims.

This is NOT to say that these physicians and clinical scientists, and by extension medical professionals, intended unethical behavior.  Rather, it is reasonable that many physicians and healthcare professionals may not appreciate the ethical complexities that are exacerbated by the many conflicts of interest that are imposed on medical professionals.  Accountability is part of the ethical practice of medicine.  The purpose of this newsletter is to explore some of the issues surrounding accountability.  Further, if we consider patients’ rights on par with civil rights, we cannot take solace even if 99% of patients have their rights respected for by physicians who hold themselves accountable.

The remarkable extent of authority in contrast to the extent of accountability

            It is hard to point to any profession that allows their practitioners such authority with so little accountability.  Airline pilots are frequently observed for their flying skills, both in real situations and in simulations of circumstances that are hoped never to occur in reality.  They face mandatory retirement at age 65 in many countries.  Air traffic controllers are required to retire at 56 years.   Among the reasons is the risk of sudden medical problems at these ages, which may place the passengers at an unacceptable risk.  Yet, there is nothing comparable for physicians and healthcare professionals.  While US Supreme Court justices have lifetime appointments, their decisions are held in the public eye and at least in some fashion, the justices are held accountable.

With respect to accountability, courts of law are evolving in the standards by which physicians and healthcare professionals are held accountable.  Courts of law are departing from definitions of malpractice as departures from standards of care that are determined by the conduct of similarly situated medical professionals to what a reasonable medical professional would do.  This evolution is a direct consequence of the realization that the prior standards established by peer practice could be self-severing thus shielding medical professionals from accountability.  This author has seen peer review conferences where less than the best professional conduct was deemed standard in order to avoid other medical professionals from being held to the best standard of professional conduct in the future.

Malpractice and accountability

            In 2000, the Institute of Medicine reported that medical errors cause between 44,000 and 98,000 deaths every year in American hospitals (Kohn LT, Corrigan JM, Donaldson MS, eds. To err is human: building a safer health system. Washington, D.C.: National Academy Press, 2000).  While the percentages that were preventable is open for debate, it is a serious problem (Brennan TA. The Institute of Medicine report on medical errors--could it do harm? N Engl J Med. 2000 Apr 13;342(15):1123-5. PubMed PMID: 10760315).  In 2016, medical errors were estimated to be the third leading cause of death in the United States (Martin A Makary, Michael Daniel, Medical error—the third leading cause of death in the US, BMJ 2016; 353 doi: (Published 03 May 2016) Cite this as: BMJ 2016;353:i2139).  Yet, only 1 in 7 adverse effects result in a malpractice claim (Oyebode F. Clinical errors and medical negligence. Med Princ Pract. 2013;22(4):323-33. doi: 10.1159/000346296. Epub 2013 Jan 18. Review. PubMed PMID: 23343656) and thus, the deterrence of the threat of malpractice accusations as a means of accountability would appear inadequate.  Further, deterrence, in the risk of a medical malpractice claim, is only effective if those whose actions are the subject find the deterrence credible.  This author once asked a chair of a department whether the chair was concerned about the physician members of the department being sued because of poor practice.  The reply was “our patients don’t sue”.  Further, rightly or wrongly, most medical professionals view the application of malpractice claims as capricious and consequently, despite the discomfort at the possibility of being sued for malpractice, it is ineffective in establishing any meaningful accountability.

            The threats of disciplinary actions by state medical boards are most likely in the same situation as medical malpractice claims.  In the state of Texas, 28.7% of revocations of medical licenses were due to incompetency or negligence in the years of 1989-1998 (Cardarelli R, Licciardone JC. Factors associated with high-severity disciplinary action by a state medical board: a Texas study of medical license revocation. J Am Osteopath Assoc. 2006 Mar;106(3):153-6. PubMed PMID: 16585383).  This rate would seem incongruent with the frequency of medical errors as described above.  Also, medical malpractice claims, as well as a large number of state medical board actions, require an aggrieved party to make a claim and thus, will likely underestimate the extent of the problems, further undermining any use in the interest of accountability.


            Self-policing within the medical disciplines has been advocated as a means of accountability.  An archetype is the Morbidity and Mortality Conference whose intended purpose is to review cases that went wrong.  This certainly should provide an opportunity for accountability, but studies have shown that the issue of errors in reasoning is rarely addressed (Gore D.C., National survey of surgical morbidity and mortality conferences. The American Journal of Surgery Volume 191, Issue 5, Pages 708–714, May 2006 DOI:; Orlander JD, Fincke BG. Morbidity and mortality conference: a survey of academic internal medicine departments. J Gen Intern Med. 2003;18:656-658; Pierluissi E, Fischer MA, Campbell AR, et al. Discussion of medical errors in morbidity and mortality conferences. JAMA. 2003;290:2838-2842) despite that most governments provide legal protection against self-incrimination. 

This author knows of situations where a physician, concerned about the conduct of a surgeon, explicitly followed the instructions of the departmental chair only to find themselves removed from any position to observe the surgeon’s subsequent behaviors and further was subjected to retaliation by constructive dismissal.  In another situation of unprofessional conduct of a physician in a private practice, another physician attempted to enlist the help of the local medical society to find an informal and less threatening means to address the conduct after direct attempts to personally discuss the situation failed.  The medical society said they had no means and referred the concerned physician to the state medical board who stated they would only intervene if a formal complaint was lodged after speaking to the board’s attorney.  Such actions would only escalate the tension and cause the physician of concern to become defensive.  Making an opportunity to seek accountability into a “nuclear option” effectively takes such interventions off the table.

Too few to fail

One could argue that in a free capitalist market, the consumer, in this case the patient, could “vote with their feet” and find a physician or healthcare professional they find accountable.  One could argue to let the “free hand of the market” force accountability.  However, for any free market to be effective, there must be transparency and choice.   In this case, consumers (patients) cannot force transparency because of their lack of knowledge compared to the provider.  Further, there is really little choice.  Whatever choice patients may have had, has been lost by HMOs and PPO’s that severely limit the patient’s choice.

Whatever choice, by which to enforce accountability, is further eroded by the shortage of physicians generally.  It is estimated that the shortage of neurologists from what is needed will grow from 11% (from 2012) to 19% by 2025 (Dall TM, Storm MV, Chakrabarti R, Drogan O, Keran CM, Donofrio PD, Henderson VW, Kaminski HJ, Stevens JC, Vidic TR. Supply and demand analysis of the current and future US neurology workforce. Neurology. 2013 Jul 30;81(5):470-8. doi: 10.1212/WNL.0b013e318294b1cf. Epub 2013 Apr 17. PubMed PMID: 23596071; PubMed Central PMCID: PMC3776531).  The concern is that a healthcare provider system will not risk alienating a neurologist (or any other physician and healthcare professional) by insisting on higher standards of accountability.

Ethical principles and moral theory

            From a number of ethical and moral perspectives, physicians and healthcare professionals have a responsibility to hold themselves, and each other, accountable.  Such accountability is inherent in the ethical principle of autonomy, meaning respect for the patient.  Similarly, accountability is inherent in the ethical principle of justice, whether that principle of justice is informed by libertarian or Kantian (deontological) morality.  The Kantian notion of morality holds that each person (patient) is an end unto themselves and not a means by which others achieve their ends.  Libertarian moral theory holds the maximum freedom is the greatest good.  Libertarianism avoids anarchy by mutually agreed contracts, either implicit or explicit, where benefits and obligations are freely traded with a set of constraints that enforce good faith and fair dealing.  Clearly, this is a call for accountability.

            In many ways, patients (or their legal representatives) have a contract with their physician and healthcare professional. It may be explicit between them or a surrogate can intervene on behalf of the patient, such as the insurer, government or society.  For example, the government, such as state medical boards, require physicians to treat every patient to the standards of practice and it is not necessary for any patient to negotiate such treatment with the medical professional.  Further, there is a contract between the government and medical professionals representing an exchange of goods and obligations.  The government grants medical professionals a form of monopoly.  Only those licensed by the government can enjoy the goods that come from providing professional medical care.  In exchange, medical professionals are expected to act in the patient’s best interest.  The state holds the physician accountable.

            Physicians and many healthcare professionals have an additional obligation of beneficence to the patient.  It is highly unlikely that any physician or healthcare professional paid for their education and training on their own.  It is society that provides the opportunity for individuals to become physicians and healthcare professionals.  This implies an obligation to reciprocate by caring for patients as patients deserve.

A matter of personal choice

            All the ethical principles and moral theories, in themselves, cannot compel the best efforts of medical professionals.  As discussed, there is very little in the way of effective outside enforcement of accountability.  Consequently, the only real recourse is internal accountability.  In other words, it is up to each physician and healthcare professional to hold themselves accountable.  Thus, we come back around to the issue of personal motivation.  Hopefully the motivations will have a perspective that is outwardly directed to the benefit of patients.  There would be much to gain by such a perspective.  One can learn a great deal about themselves in the process.  It is striking that Mohandas (Mahatma) Gandhi entitled his autobiography describing his efforts on behalf of his fellow citizens, The Story of My Experiments with Truth (1948).

Thursday, May 5, 2016

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

Emily R. Friedrich, B.A.
Remote Specialist

Erwin B. Montgomery Jr. MD
Medical Director

Greenville Neuromodulation Center
Volume 2, Issue 4

                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.

Monday, March 21, 2016

Deep Brain Stimulation is a Screw, Not a Nail

Erwin B. Montgomery Jr. M.D.
Medical Director
Greenville Neuromodulation Center
Professional Newsletter
Volume 2 Issue 3
March 15, 2016

Professor – Abraham Maslow said “When all you have is a hammer, the whole world looks like a nail”
Student – What if the world is a screw?

Deep Brain Stimulation (DBS) is arguably the most effective treatment for many neurological and psychiatric disorders.  In disorders in which DBS has been applied, DBS is better than pharmaceutical or biologic treatments as DBS succeeds where the others fail.  So why is DBS only offered to a small percentage of those patients who need DBS?  Perhaps, it is because DBS is seen as a nail (conceptually equivalent to pharmacological or a biologic therapy) when in reality, DBS is a screw (different and more relevant than pharmaceuticals or biologics).

Perhaps we are in the midst of a Kuhnian paradigm shift, but not realizing it because of Kuhn’s observation of incommensurability (Thomas Kuhn The Structure of Scientific Revolutions, University of Chicago Press, 1962).  Kuhn reasonably argued that thinkers in one paradigm cannot appreciate the concepts of the alternative paradigm.  It is not an exaggeration to say that pharmacological approaches have dominated non-surgical medical disciplines, especially neurology.  Non-surgical physicians have little qualms about prescribing medications, including those that are potentially highly toxic, but it seems altogether different and foreign to prescribe electricity, as in the case of DBS. 

Even when physicians prescribe electricity, it is done as though electricity was the same as a pharmaceutical.  When DBS is not sufficient, physicians prescribe more electricity, and when there are side effects less electricity is prescribed.  The notion of levodopa equivalents in pharmacological therapies for Parkinson’s disease that subsume all the various dopamine replacement based therapies under a single concept, DBS has the erroneous notion of Total Electrical Energy Delivered (TEED).  It is as though all the variations of DBS stimulation parameters can be considered from a single mechanistic perspective.  DBS is far more complicated and dynamic.  DBS is altogether different.
As Albus Dumbledore said “Oh, by the way. When in doubt, I find retracing my steps to be a wise place to begin. Good luck.” (The movie “Harry Potter and the Prisoner of Azkaban”, 2004).  Perhaps the first real insight into the mechanisms by which the nervous system produced behavior was the notion of “animal electricity” based on the observations of Luigi Galvani (1737 – 1798, C.E.) who applied electricity to nerves and muscles.  Until that time, Galen’s notion of the four humors dominated without experimental evidence but by reasoning from Aristotle’s four elements.  It may have Galvani’s nephew who applied electricity to the exposed nerves of decapitated humans and causing them to move; thus inspiring Mary Shelly to write “Frankenstein”.
Even with the development of the Neuron Doctrine in the mid to late 1800’s and the identification of the neuron as the fundamental unit of neuroanatomy and (mistakenly) the fundamental unit of function, the widespread but not universally accepted notion was that neurons communicated electrically.  It was not until the 1940’s that chemical neurotransmission became ascendant.  Even though electric or gap junction, purely electrical transmission, was demonstrated in invertebrates in the late 1950’s and in vertebrates, including human, much later; chemical neurotransmission, perhaps fortified by the remarkable abilities of neuropharmacology, still dominates thinking.  The adverse effects of this mode of thinking are addressed later.
The first major implication of the dominance of chemical neurotransmission is that neurophysiology is thought synonymous with neurochemistry.  In 1921, Otto Loewi (1873 – 1961, C.E.) published his work demonstrating that the application of an extract (chemical) from the heart of one frog would slow the heart rate when applied to the heart of another frog.  Later, the chemical acetylcholine was found to be the active ingredient in the frog heart extract.  The extract slowed the heart just as did electrical stimulation of the vagus nerve.  The implication was that the effects of the electrical stimulation of the vagus nerve were mediated by, or due to, release of acetylcholine.  This inference was based on the syllogistic deductive argument that (major premise) slowing the heart is accomplished by applying acetylcholine; (minor premise) electrical activity in the vagus nerve slows the heart; thus, (conclusion) electrical activity in the vagus nerve is applying acetylcholine.
The classic example of a syllogistic deduction is: (major premise) All men are mortal; (minor premise) Socrates is a man; thus (conclusion) Socrates is a mortal.  Mortal (major term) and Socrates (minor term) are linking the bridging term “men/man”.  Thus, these three terms link in two premises to produce the conclusion.  But what if Socrates was a very special man unlike all other men?  The syllogistic deduction would not hold.  If “man” in the case of Socrates, in the second premise, is different than “men”, in the first premise, there is no single bridging term.  The result is the Fallacy of Four Terms.
The syllogistic deduction above relating electrical activity in the vagus nerve to the application of acetylcholine would fail, which is a consequence of the Fallacy of Four Terms, if the slowing of the heart with the application of acetylcholine was different than slowing the heart with electrical stimulation of the vagus nerve.  The difference can be seen in the time course of the effects.  The application of pharmacological amounts of acetylcholine slows the heart over a long period of time, requiring for its termination the degradation of acetylcholine by the enzyme acetylcholinesterase.  Slowing the heart and restoring the heart rate occurs over a matter of seconds with electrical stimulation of the vagus nerve.  What is different is the time scales over which the effects occurs, in other words, the dynamics of the effects.
To be sure, neuropharmacologists might argue that the pharmacological administration of acetylcholine is not the manner by which acetylcholine normally slows the heart rate.  Rather, they might argue that acetylcholine is released in very small doses over very short time scales. But that proves the point, because what is it that controls the timing and amount of acetylcholine?  There is nothing in the molecule of acetylcholine that would necessarily lead to its being released in small doses over very short time periods.  It is the precise control of the electrical activity of the vagus nerve that controls the effects of acetylcholine.  The conflation of acetylcholine with the physiology of the vagus nerve would be like saying that electrons are the fundamental unit of function of the computer.  While it is true most computers could not function without electrons, merely dumping electrons into a computer will not produce a working computer.
DBS in Parkinson’s disease is effective even when flooding the brain with industrial quantities of dopamine (either by the pro-drug levodopa or effectively by dopamine agonists).  Even localized application of dopamine by fetal dopamine implants fail to normalize function, most likely because the fetal dopamine derived neurons are disconnected from the normal electronics of the brain.  Thus, it is at least a logical error to equate the actions of DBS with those of dopamine agents.  Then why do physicians use DBS like dopamine agents?  Why do physicians view the dynamics of DBS like they do the dynamics of dopamine replacement, that is too little or too much.  DBS is far more complicated.  While the complexity of DBS is a challenge, it also is an opportunity, unless physicians “dumb down” DBS as though it was a drug.

An alternative paradigm or theory we at Greenville Neuromodulation Center (GNC) are working on, space permitting only a brief description, is that behavior depends on an orchestration of motor unit recruitment and de-recruitment over multiple time scales simultaneously.  The basal ganglia-thalamic-cortical system drives this orchestration because the system is organized as a large network of loosely coupled reentrant nonlinear discrete oscillators over a large bandwidth of frequencies.  The nonlinearities afford the network the properties of a chaotic system, while the integration of a very large number of neurons confers properties of Complex Systems.  The dynamics include stochastic resonance and stochastic coherence, among others.  Further, noncommensurate frequencies within the basal ganglia-thalamic-cortical oscillators allows multiple channels of information operating at different time scales allows encoding of different channels of information simultaneously.  DBS is a noisy oscillator that interacts with the oscillators within the basal ganglia-thalamic-cortical system.  Much work on this theory remains to be done.

Sunday, February 21, 2016

Helpful Hints at the Time of DBS Lead Implantation

Erwin B. Montgomery Jr. MD
Medical Director

Greenville Neuromodulation Center

Volume 2 Number 2

February 15, 2016

It is the little things that usually get you and they are the hardest to anticipate.

                While I am not a neurosurgeon, it appears to me that Deep Brain Stimulation (DBS) lead implantation surgery has a lot of moving parts, any one of which can go wrong.  One of the best descriptions of the surgery I heard was from Dr. Kathryn Holloway who described it as “fussy”.  As a neurologist, both in and out of the operating room, I can see how the little things can go wrong and what that ultimately means postoperatively; which fortunately is relatively uncommon.  But dealing with some of the postoperative problems, I have been able to compile a “wish list” of things I wish would have been done during surgery or soon thereafter.  This list is described as hints and admittedly, the helpful part is for the DBS programmer afterward.

The need for certainty
                There are hundreds of potential combinations of DBS electrode configurations, stimulation parameters, and pulse trains.  The combination of electrode configurations will increase dramatically as segmented DBS leads become commercially available and the ability to apply different stimulation currents over multiple contacts simultaneously.  Each combination takes time to implement and assess.  Difficulties settling quickly on the optimal combination can be frustrating.  Looming over the costs of time, effort and frustration, is the temptation to default back to medications.  However, just defaulting back to the medications will surely fail, as the failure of medication is the reason for the patient having DBS.
                It is unlikely that every conceivable combination will be tested and thus, eliminated as a possibility.  Consequently, every DBS programmer is confronted with the decision of when to give up on the programming of a patient who fails to reach satisfactory results without compromising on what constitutes “satisfactory.”  It is a slippery slope to re-define “satisfactory” in terms of what it means for the programmer, rather than for the patient.  Certainly, as the number of combinations tried increases, the probability of there being a combination that will produce a satisfactory response becomes less. 
With an increasing number of failed combinations, the programmer begins to construct a probability of there actually being a good combination.  In terms of Bayes Theorem, this estimate would be a posterior probability.  However, the posterior probability based on the programming experience with a particular patient must be weighted based on the prior probability.  In this case, the prior probability is the likelihood that the DBS lead is in a location that is capable of providing a satisfactory response.  Every programmer does a type of Bayesian analysis, even if only implicitly.  If the programmer has confidence that the DBS lead is well placed, then the prior probabilities will be high and thus increase the possibility of finding a combination that will provide a satisfactory response.  If however, the programmer has confidence that the DBS lead is not well placed, then the prior probability will be low.  In either case, the programmer can arrive at a point of equanimity about how hard to pursue the DBS programming.  The problem comes when the DBS programmer has no confidence one way or the other.  The risk is giving up too soon with the DBS or continuing programming well past the point of diminishing returns.
The confidence of prior probabilities, as described above, depends greatly on the efforts in the operating room.  Certainly, there are enormous pressures to complete the surgery as quickly as possible, for many reasons.  However, the necessary confidence of the prior probability may require some additional effort.  Perhaps, another microelectrode recording trajectory may help provide that confidence.  Although one tries to assure that the optimal trajectory has been found prior to implanting the DBS lead, additional testing through the DBS lead and perhaps DBS testing in an additional tract may be necessary to achieve confidence.  However, this first requires that the neurosurgeon appreciate the importance of confidence on the part of the post-operative DBS programmer.

The tyranny of partial benefit
                What does the treating physician do when the patient achieves only 50% of the reasonably expected benefit, for example experiencing only a 30% improvement in the Unified Parkinson Disease Rating Scales when most clinical trials demonstrate an average on the order of 60%?  Prior to the DBS lead implantation surgery, the patient balances the risks of the DBS lead implantation surgery against an improvement of 60%.  Now the patient, family members, caregivers, physicians and healthcare professionals are faced with the issue of revising the DBS lead.  The same risks associated with the first DBS surgery are confronted by the second surgery, but the benefit reduces from an improvement of 60% over the condition prior to the first surgery, to only an improvement of 30% compared to the state prior to the second surgery. 
The risk-to-benefit ratio is significantly different for the second or revision surgery compared to the initial surgery.  For some patients, the risk-to-benefit ratio for the revision surgery may not justify the second surgery.  The consequence is that the patient is forced to accept only the partial benefit, hence the tyranny.  Obviously, this situation is to be avoided and sometimes extra measures are needed to ensure optimal DBS lead placement.

Immediate post-operative imaging
                Even after nearly 20 years of working in the operating room and the post-operative DBS clinics, I continue to learn.  Fortunately, things generally go very well, but occasionally not.  In those circumstances, one clearly needs to learn what did not go right.  A significant factor in DBS leads not optimally placed is intra-operative brain shift.  The brain has a specific gravity greater than cerebrospinal fluid, which means the brain will sink to the lowest point within the skull.  That lowest point will differ between being supine, such as having a targeting MRI, and the semi-recumbent position in the operating room.  Brain shift due to the brain sinking will be exacerbated if there is more room within the skull for the brain to sink, such as in elderly patients.
                In my experience, one of the most frequent causes of misplaced DBS leads results from marked brain shift associated with intracranial air, particularly when a tension pneumocephalus is produced.  The tension pneumocephalus often results in DBS lead placement anteriorly due to posterior shift of the brain.  However, the cerebrum pivots on the brainstem so that posterior displacement also can produce a torsion that will result on the DBS lead being placed too medially or laterally dependent on the trajectory, relative to the axis of rotation.  The risk for tension pneumocephalus can be reduced by a scrupulous surgical technique, such as copious irrigation when the intra-dural cavity is exposed and the use of agents, such as fibrin glue, to seal the burr hole.
                As intra-cranial air is reabsorbed, the only way to know if there was significant brain shift due to intracranial air is if a MRI or CT scan is obtained very soon after surgery.  If three months later the DBS programmer is confronted with a difficult patient and imaging performed then shows poorly placed leads, it will not be possible to know whether a tension pneumocephalus or some other factor was involved unless scans are done very soon after surgery.  One will not learn from the failure and therefore will not be in a position to reduce the probability of a future failure.

Low tech to the rescue
                An acute loss of DBS efficacy can have serious consequences.  This is particularly true for disorders, such a Parkinson’s disease, where other treatments, medications for example, have been reduced.  In patients with Parkinson’s disease, DBS in the vicinity of the subthalamic nucleus results in an approximately 50% reduction in anti-Parkinson medications.  Thus, if the DBS fails, the patient only has a fraction of the medications previously need for some level of control.  It is not infrequent that such a patient comes into the emergency room often in the evenings, nights and weekends.
                One potential cause of acute loss of DBS efficacy is DBS lead migration.  If the patient had a routine AP and lateral skull x-ray post-operatively at a time when the patient was benefiting from DBS, an easy test would be to simply obtain another set of skull x-rays.  Comparison of the skull x-rays may readily demonstrate a lead migration without having to call in the MRI tech.  Also, the skull x-ray, performed with a chest x-ray may also demonstrate hardware failures such as a fracture of the DBS lead or extension of an uncoupling of the connectors.

                One could obtain a skull x-ray very soon after DBS lead implantation.  However, if there is substantial intra-cranial air, the skull x-ray may be unhelpful as the lead may migrate over the next one to two weeks that it takes for the intra-cranial air to be absorbed.  Further, obtaining the skull x-rays as soon as the patient demonstrates a satisfactory response allows the inference that the DBS lead is in good position.  Thus, if the skull x-ray at the time of DBS failure shows that the DBS lead has not migrated, then one can turn attention to other potential causes of acute DBS failure.

Monday, January 25, 2016

Predicting DBS Lead Implantation Success from Microsubthalamotomy

Erwin B. Montgomery Jr. MD
Medical Director
Greenville Neuromodulation Center
Volume 2 Number 1
January 23, 2016
Neurologist 1: “We generally do not use microelectrode recordings for target location in the subthalamic nucleus.  We use the patient’s clinical response to DBS test stimulation and adjust the location of the lead if we need to.  However, our last patient had a remarkable microsubthalamotomy effect so we could only test whether the patient would have adverse effects.  The patient should do OK, right?”
Neurologist 2: “Maybe.”
Neurologist 1: “Gosh, I hope we do not have to surgically revise the DBS lead.”
Neurologist 2: “Maybe you should have asked your question before doing the surgery?”
                No one wants to have to revise a DBS lead placement because of a poor placement that fails to deliver efficacy.  The efforts to be extended in preventing the necessity of DBS lead revision surgery are proportional to the risks of the revision surgery.   Certainly, there is the 2% risk of significant perioperative morbidity and the approximate 0.1% risk of perioperative mortality with the  initial surgery.  However, this analysis underestimates the real risks.  For example, even if prior to the original surgery there is a 10% risk of needing a second surgery to revise the DBS lead placement, the risk going into the first DBS lead placement surgery is 2% for the first surgery, plus a 0.2% risk related to the probability of needing a second surgery.  The significance of the increased prior risk is proportional to the risk of requiring a second surgery.  The risks described here are rough estimates because of the lack of publically available data.  Also, the 10% risk for DBS lead revision surgery is probably an over estimation; however, this author is aware of an institution that had an approximate 9% revision rate.
                Whether the rough risk analysis described above is sufficient to warrant a re-evaluation of DBS lead implantation methodology, is a question that should be addressed.  Further, patients and their family members, caregivers, and friends expect that their physicians and surgeons will consider the question.
                In the hypothetical case described above, at least, there was the absence of adverse effects with DBS lead test stimulation that should provide reasonable reassurance that adverse effects will not limit the post-operative treatment.  Based on what is known about how the brain responds to DBS, there is no reason to believe that a microsubthalamotomy would disguise the risk for acute post-operative adverse effects, such as paresthesias, tonic muscle contraction, diplopia, and speech and language effects.  The other half of the equation is the estimation of efficacy.
                While there is little published  on a systematic prospective study of the question whether a microsubthalamotomy is predictive of efficacy, Maltête et al. (Maltête D, Derrey S, Chastan N, Debono B, Gérardin E, Fréger P, Mihout B, Menard JF, Hannequin D. Microsubthalamotomy: an immediate predictor of long-term subthalamic stimulation efficacy in Parkinson disease. Mov Disord. 2008 May 15;23(7):1047-50. doi: 10.1002/mds.22054. PubMed PMID: 18412281) did a great service by publishing their retrospective analysis of 30 patients.  The study was well done with the exception of the statistical analyses and the conclusions drawn.  Thirty consecutive patients were studied as a way of avoiding sampling bias.  The microsubthalamotomy and post-operative evaluations off drug and on stimulation were done carefully.  In particular, the post-operative assessments were performed after 6 months, which is a reasonably sufficient amount of time to optimize the DBS electrode configurations and stimulation parameters.
                Unfortunately, the main conclusion relative to the predictive value of a microsubthalamotomy for post-operative outcome was based on a regression analysis.  This is not optimal for assessing the diagnostic utility of a test.  In this case, the degree of a microsubthalamotomy effect should be considered as a diagnostic test for optimal post-operative response.  The problem is that a correlation may be statistically significant but of little diagnostic value.  In the correlation published between the microsubthalamotomy score and the 6-month off meds - on DBS score, the correlation was significant at p = 0.005, leaving little doubt about a relationship (see figure).  However, the correlation coefficient was 0.4, which roughly translates to an adjusted R2 of 0.13.  Thus while there is a statistical correlation between the microsubthalamotomy and the 6-month off meds – on stimulation scores, the microsubthalamotomy score can only account for 13% of the variability in the post-operative score.  Hardly a strong predictor.
                The more appropriate analysis would be to examine the Receiver-Operator Characteristics Curve that relates true and false positives.  Reanalysis of the data provided by Maltête et al. is shown below.  For the purposes of the reanalysis a positive result is a post-operative improvement of at least 50%.  This is consistent with large scale prospective clinical trials.  The finding of a positive result for any specific range of microsubthalamotomy scores is taken as a true positive, while the failure to achieve at least 50% improvement in the post-operative scores is taken as a false positive.  Visual inspection of figure 1 in the study by Maltête et al. allowed determination of the true positive and false positive ratio for each 20% range in the microsubthalamotomy score.  For example, of the 9 patients who had a microsubthalamotomy score between 0% - 20%, 7 had at least 50% improvement in post-operative score (taken as true positive score) while 2 had less than a 50% improvement (taken as a false positive).  The Receiver-Operator Curve was plotted (see figure).  As can be seen, the Receiver-Operator Curve is a flat line with a regression equation of y = -x +1.  The area under a curve with this repression equation would be 0.5.  This means, as a diagnostic test, the using the microsubthalamotomy score as a predictor of post-operative improvement would be operating at chance.  In other words, one might just as well roll the dice.  This is not unexpected, as the estimated adjusted R2 was so low.  Also, the majority of patients who acutely worsened with the microsubthalamotomy had better than a 50% improvement post-operatively.
                A caution needs to be taken about the analyses as the number of subjects was relatively small given the variability in the data.  This was particularly important in determining the true and false positive rates for patients with a microsubthalamotomy score between -20% to 0%, where there was only a single subject.
                Maltête et al. offered another important observation.  Based on visual inspection of figure 1 in their paper (see figure below), 19 of the 30 patients (63%) had a microsubthalamotomy effect greater than 20% (positive or negative) relative to the pre-operative assessment.  This means that without some other intraoperative method to validate the optimal location for the DBS lead, such as microelectrode recordings, the surgeon will only have neuroimaging studies, either pre- or intra-operatively.  The majority of the time DBS lead testing for efficacy will likely be invalidated by the microsubthalamotomy effect.

                The risk of a microsubthalamotomy effect compromising intra-operative DBS lead testing is directly proportional to the frequency of a microsubthalamotomy effect.  The question is why there is such a high rate of microsubthalamotomy effects in the study by Maltête et al.   This incidence seems higher than what this author would expect, based on the author’s anecdotal experience, but Maltête et al. did a careful study and their observations likely are valid, notwithstanding this author’s experience.  The only possible explanation available to this author, and note it is a possibility not a probability, is the use of the five microelectrode array.  In this author’s experience and reasoning, the use of five electrodes inserted simultaneously is more likely to traumatize local neural tissue and thereby increase the incidence of microsubthalamotomy effects (see GNC Professional Newsletter Microelectrode Arrays versus Single Electrodes).

Figure. A shows the correlational analysis between the microsubthalamotomy effect and the 5 –month post-operative off medications – on stimulation percent improvement (from Maltête D, Derrey S, Chastan N, Debono B, Gérardin E, Fréger P, Mihout B, Menard JF, Hannequin D. Microsubthalamotomy: an immediate predictor of long-term subthalamic stimulation efficacy in Parkinson disease. Mov Disord. 2008 May 15;23(7):1047-50. doi: 10.1002/mds.22054. PubMed PMID: 18412281).  B shows the reanalysis to determine the Receiver-Operator Characteristics Curve based on visual inspection of the data presented in A (see text).  There are two caveats.  The data point shown for 60 -100% improvement in the microsubthalamotomy score includes three different microsubthalamotomy ranges, 80% to100% and 60% to 80%, where the True Positive ratio was 1 and the False Positive ratio was 0.  The third data point at these True and False Positive ratio was for the microsubthalamotomy range -20% to 0%; however, there was only single patient in this range.