Category: Treatment

An Interview with the Neurosurgeon – Anand Rughani, M.D.

Rughani_AnandAs part of a pair of articles on the topic of deep brain stimulation (DBS) in this issue, I met with Dr. Anand Rughani recently to ask a few questions.  I hope these articles will give readers a little insight into what it might be like going through the procedure.  I also wanted people to know a little about Dr. Rughani, and why we are so lucky to have him here in Maine, not just for the high level of skill he brings with his subspecialty training in functional neurosurgery, but also a bit about the man and his motivations.  This interview is not intended to be exhaustive, but focused on a few relevant points.  What follows is a transcript of our meeting.

BS:  I think a good place to start would be in explaining why you are interested in deep brain stimulation.  What drew you to this specific area of medicine?

AR: My pathway to neurosurgery started off with an interest in neuroscience and in understanding the mind-brain interaction.  The connection between mind and brain is most visible to me on a daily basis in neurosurgery, and specifically in the area of functional neurosurgery, which deals with mapping the functional areas of the brain to understand how different brain structures lead to different experiences and behaviors.  We see that through disease, and in treating some of those diseases, we get insight into how the brain works.   That’s what lead me to neurosurgery to begin with and then specifically, functional neurosurgery and deep brain stimulation.   Deep brain stimulation itself is a good example of how you see those interactions in a very real way, through implanting electrodes in an awake patient to treat symptoms from various diseases.  So, I gain insight on a daily basis as to how the brain leads us to be who we are, and how we work.

BS: Your training started out with undergraduate college, then medical school, then neurosurgery residency. After this, you had a fellowship in functional neurosurgery.  Can you tell us about the fellowship?

AR: My fellowship at the University of Toronto offered exposure to a deep enthusiasm for not just doing surgery or DBS for some of the more conventional indications, but really exploring new indications for surgery.  Whereas the FDA currently has indications for Parkinson’s disease, tremor, and dystonia, I was also able to be involved in cases for anorexia, for OCD, depression, and for Alzheimer’s disease.

BS: What brought you to Maine?

AR: I grew up in Eugene, Oregon, but then spent ten years in Montreal for my Bachelor’s degree and medical school, and each year that I spent there I grew more nostalgic for the idea of ending up in a small coastal town.  However, the more time I spent in Montreal and in my subsequent training, the more I found myself doing increasingly subspecialized training.  First, it was neuroscience, then it became medicine, then it became neurosurgery – and there are only so many places you can do that.  Then, even more subspecialized was functional neurosurgery.  In the process of that training I got to spend a year at Maine Medical Center, and it turned into the ideal opportunity because I could offer surgeries that weren’t previously available in Maine.

BS: Can you walk through what it is like to have the DBS procedure in the operating room?

AR: Deep brain stimulation is a significant undertaking.  We do it in a couple different steps, but the most important is the step where we implant the electrodes in the brain.  There are a couple of different ways of doing that now.  The traditional way of doing that is recording from the neurons in the brain and then stimulating through those electrodes.  The way we do that is with the patient awake, and most patients do fantastically well.  People are comfortable because we use a local anesthetic, but the surgery itself takes a couple hours. The hardest parts of the operation are probably a couple of things: one is for patients with Parkinson’s disease being off of their medication.   That can be quite challenging. Another part is being stuck in one position for two, or three or four, hours.  The local anesthetic can burn quite a bit when it goes in. I think the actual operation where we do the work isn’t the biggest source of discomfort, it’s more from being stuck in one position for a couple hours and being off of regular medications for those with Parkinson’s disease.

BS: People complain about the sound of the drill a lot too.

AR:   I think the drill is probably like being at the dentist, or an aggressive version of being at the dentist.  The drilling takes about 30 seconds. After, some patients may have a mild headache, but there are no pain receptors in the brain, so no discomfort from the next steps.

BS: Tell me a little about the risk of the procedure.

AR:  I categorize the risk of surgery into four areas.  First, there is the risk of the operation itself.  This includes things like bleeding into the brain, which can happen in about 2% of patients, and can lead to new symptoms in about 1% of patients.  The second category of risks are related to having implanted hardware, for example a delayed infection could occur, or a disconnection or other device complication can occur.  These types of events probably occur in up to 10-15% of patients over the years.  The third category of complications that I think of are the stimulation-related complications.  We try to minimize these by doing testing in the operating room with patients awake.  These depend on the location where the electrode is implanted, but could consist of changes in speech, or mild tingling sensations.  The last category of complications are the medical complications, for example things like developing a pneumonia, or blood clot in the leg, or a heart attack.

BS: Who is in the room while the surgery is taking place?

AR:  The operating room is busy for this surgery.  In addition to the patient and surgeon, there is also the anesthesiologist, or nurse anesthetist, there is an operating room nurse, and there is a scrub tech that passes the sterile instruments.  There is also a neurologist, and usually one or two additional people involved in the surgery.

BS:  What else would you want people to know about DBS?

AR:  It is really important to have a good understanding of the goals of surgery, and the surgery process.  Specifically, it’s important to know which symptoms are most likely to respond to surgery, and which aren’t.  With that in mind, and a good understanding of the involvement and risks of surgery, patients and their families can make the best decision about whether or not it is right for them.  I am always happy to discuss the surgery in detail with patients who think they might want to consider it.

NEW DRUG: Pimavanserin Approved by the FDA

Pimavanserin, trade name Nuplazid, was approved by the FDA for the treatment of hallucinations and delusions in PD, per press release April 29.  Pimavanserin was granted an FDA breakthrough therapy designation, which is a program “designed to expedite the development and review of drugs intended to treat a serious condition and where preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint.” The drug was also granted a priority review, which provides for an expedited review of drugs that offer a significant improvement in the safety or effectiveness for the treatment, prevention, or diagnosis of a serious condition.  
 

Pimavanserin is an atypical antipsychotic, which is meant to bind to the serotonin receptor 5-HT2A in the brain and thus avoid exacerbation of motor symptoms seen with older typical antipsychotics (1).  Older antipsychotics are generally avoided and relatively contraindicated in PD due to blockade of dopamine receptors (the target of multiple drugs meant to improve motor symptoms). Pimavanserin exploits data that 5-HT2A serotonin receptors are specifically associated with visual hallucinations (2).

 

Phase II trial participants progressed to an average daily dose of 44.5 mg, and by day 28 revealed no impairment of motor function compared to placebo, nor did the drug cause sedation or hypotension (3). There were significant reductions in both hallucinations and delusions.

Phase III trial data showed an improvement in the quality of sleep and daytime wakefulness during a six-week period with 199 participants.  The drug was shown to be superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions without worsening the primary motor symptoms of Parkinson’s disease.  An open-label extension study presented at the 17th International Congress of Parkinson’s Disease and Movement Disorders reportedly showed that pimavanserin is safe and well-tolerated with long-term use.

Per the FDA press release (4), the most common side effects reported by participants taking Nuplazid were swelling, usually of the ankles, legs, and feet, nausea, and confusion. The FDA points out that “as with other atypical antipsychotic drugs, Nuplazid has a Boxed Warning alerting health care professionals about an increased risk of death associated with the use of these drugs to treat older people with dementia-related psychosis. No drug in this class is approved to treat patients with dementia-related psychosis.”

-Bill Stamey, M.D.

 
1. Neurochem Res. 2014 Oct;39(10):2008-17
2. Arch Neurol 2010;67:416–421
3. Neuropsychopharmacology 2010;35:881–892

Should you adjust your own Parkinson’s meds?

The short answer is “No.”
The medications used to treat Parkinson’s disease are primarily meant to deal with the issue of low dopamine in the brain. This seems like a fairly straightforward proposition and over time many people seem to get the hang of what I am doing when I adjust meds. They note that I may have started them on a very low dose and slowly increased the strength and/or the frequency. Major advances or changes in medication dosing should always be directed by a physician trained in movement disorders. There are some exceptions. Sometimes my colleagues will make adjustments if covering on call. It is possible that an emergency room physician might change the dose. If this happens, please let me or your normal PD doc know as soon as possible. Otherwise, these are the only times in which your medications should be changed. However, some patients take it upon themselves to change dose strength or timing. This is generally not a good idea. Advancing doses on your own can lead to unwanted side effects. In the case of carbidopa/levodopa (Sinemet), lightheadedness, nausea, confusion, worsening constipation, impulsivity, and hallucinations are only some of the potential problems.

There is also a less obvious issue of taking too much too soon early in disease, which can result in several issues, including the early appearance of unwanted involuntary movements such as dyskinesia. Patients who take too much medication early in disease may be causing irreversible damage and advance of disease. This is only one example.

In the case of dopamine agonists such as the drugs pramipexole (Mirapex), ropinirole (Requip), and rotigotine (Neupro patch), excess dosing can result in problems such as confusion, hallucinations, impulse control disorder, foot swelling, excessive daytime sleepiness, and sleep attacks. With each of the drugs used to treat Parkinson’s disease excess dosing can be quite serious.

Under dosing is also an issue. Some patients decide they don’t like the way they feel taking the medications, or perhaps they are just “not a pill person.”  They will sometimes decide to take lower doses or with less frequency than prescribed, which can result in the reemergence of symptoms over time. Sometimes this is obvious within a day or two. What many patients do not realize is that there is a longer term effect that may take weeks to show itself. This is a so-called steady-state effect of drugs. Any change in dosing may take up to 28 days to show full effect.

Some patients will abruptly stop drugs. This can actually be dangerous and in some rare cases life-threatening, especially when taking relatively high doses of PD medications.  Don’t do it.

What if my pharmacist doesn’t think I should take it?
Always call your PD doc to discuss before changing any medication, even if the pharmacist has raised concerns. Please understand that pharmacists are very well educated and intent upon helping you. Still, they are not physicians. Pharmacists dispense thousands of different medications written by every type of prescriber, and cannot possibly know the intimate details of each drug. They often raise concern about a so-called class effect, related to the family of a medication and not a specific warning related to a specific drug. For example, Azilect (rasagiline) is in the class of monoamine oxidase inhibitors. There are warnings for the class of drug which were specifically removed by the FDA for the drug Azilect after extensive demonstration of safety with this particular drug. Some of the warnings pharmacists have provided patients have wound up in my office, and appear to be generated by third-party software vendors.  These sheets may not be up-to-date and may occasionally be inaccurate. Conversely, most doctors tend to be very familiar with the 50 or so drugs they commonly prescribe.   I don’t mean to claim we never make mistakes, or that we don’t need the very valuable help of pharmacists, just that it is a complex situation. We all need to work together, so don’t put aside that prescription, call and let your doc know what’s going on.

-Bill Stamey, M.D.