Week 3 - Joseph

This past week saw a change of pace for my clinical experience following the neurological surgery department. My clinician, Dr. Stieg, was out of town this week, so aside from simply jumping in on a couple of assorted surgeries (such as an interesting pituitary tumor case) I had to find a different clinician to follow around. As a result, the majority of my time this week was spent shadowing Dr. Kaplitt, an associate professor in the department who I will be doing my research project with and an expert on several neurological surgeries which diverged quite a bit from my experience with Dr. Stieg. In several sessions of clinics I saw a variety of pain and Parkinson’s patients that represented a very different side of neurological surgery. The key difference was one of acute versus chronic patients. My previous experiences with patients of Dr. Stieg were often revolving around problems of an acute nature: a tumor or aneurysm had just been discovered, and action was required immediately. These patients of Dr. Kaplitt's were very different – many had struggled with phantom nervous pain (such as trigeminal neuralgia) or Parkinson’s for around a decade before seeking a surgical option. Indeed, their faces and their emotions were a world apart from people just told that they happened to have a life-threatening complication in their brain – these people knew their condition, had studied it, had suffered from it, had slowly watched their lives be irrecoverably transformed by it. The average person had tried an odd assortment of drugs and alternative therapies mixed in with simply trying to ignore it for years, and they all were looking for the promise of a true cure from surgery. Another interesting point to watch, of course, was how Dr. Kaplitt handled each patient. For example, he would calmly explain to one patient how surgery probably wasn’t the best option for a variety of reasons, and then turn around and make a vigorous case for that very surgery to a patient in the next room. Everyone’s story, symptoms, and disease itself were different, and Dr. Kaplitt had the difficult job of not only deciding what was the best option on a patient-by-patient basis, but of explaining just why that decision was the right one to a group of patients with highly variable age, medical knowledge, and personal health convictions. The most interesting explanation had to be concerning deep brain stimulation for treatment of Parkinson’s (described in my last blog entry). From the distance of a shadowing student, it was easy to balance the advantages and disadvantages of the surgery like any other surgery and come to my own conclusions concerning the importance of a surgery for a man that could barely move without heavy medication that made him suffer from almost equivalently debilitating dystaxia. But that’s from a student’s perspective that had spent the last several weeks observing a dozen people getting their skull cut open. This was a man who had never had any treatment other than that of a pill to swallow, and here he was being told the next step was to have electrodes plunged deep into his brain while he was still awake. Needless to say, the explanation took a good deal of time and finesse, and it was impressive to see how important the ability to communicate information from doctor to patient was for a surgeon that specialized in such dramatic surgical treatments.

My clinician returned for the final bit of the week, which saw me continuing my rounding with him. Though many of the patients were the same (patients on their 18-month recheck to ensure the MRI confirmed continued successful aneurysm resolution, patients back to have their ventriculoperitoneal shunt flow rate turned down from 110 to 100), this lull in having to learn a field of medicine basically in medias res gave me the opportunity to develop some (finally) intelligent questions for a leader in the field. It struck me, for instance, that the hydrodynamics of hydrocephalus (the buildup of cerebrospinal fluid in the ventricles of the brain) following a ruptured aneurysm don’t truly make a lot of sense. It turns out, according to my mentor, that the field agrees with me: it doesn’t make a lot of sense, and no one really understands how the hydrodynamic portion of the phenomenon works. It’s very well characterized in terms of pathologoy and symptomatic classification (i.e. the medical side of the equation), but the physics is pretty much an uncharacterized (i.e. the engineering side of the equation). I found myself reflecting on my own experiences with the divide between medical classification and engineering understanding, how a pathologist might look at a tumor and know right away the level of tumor progression the patient was experiencing, an oncologist would know what drug to prescribe, yet the biomedical engineer is still trying to figure out the complex weave of genetics, mechanics, and chemistry that answers the crucial question “why?”. And just like with cancer, who knows what a true physical understanding of hydrocephalus might mean for better treatment, and even prevention? Perhaps such questions are indeed the value of our time here.

As a final note of interest, I finally have a concrete project to work on for my time here (indeed, there were more “grad student days” to be had this week). I met with Dr. Kaplitt and discussed the ways I might be able to make the most meaningful contribution to his research in the area of viral vector gene therapy, and we decided I should work on a design project. You see, Dr. Kaplitt’s group is currently using an unmodified adeno-associated virus (AAV) as a gene delivery vector for treatment of Parkinson’s disease. This method actually has made it through Phase 2 clinical trials, which is a big deal for gene therapy in general, but it has the drawback of requiring the same subthalamic deep brain direct insertion of the vector as the current treatment, the electrode placement. In other words, you still need very invasive surgery. Dr. Kaplitt has funding for a project to figure out how to mutagenically and/or chemically modify the AAV vector to be systemically administered and cross the blood-brain barrier independently of surgery, but he and his collaborator have run into some problems getting their current ideas to work. My project, therefore, is to come up with fresh ideas to solve this problem and demonstrate that they may be feasible solutions for implementation. This will be done using protein mutagenesis modeling as well as genetic design software, all of which I am familiar with from my time doing undergraduate work in viral engineering. This will be a different experience though, to be sure. Previously, I engineered viruses as biologically-derived nanoparticles, using them as convenient platforms for biosensor and drug delivery applications. Now I have to do similar mutagenic work but with substantially more elegant design, as the natural DNA-delivery function of the virus needs to be preserved throughout all mutagenic manipulation to ensure retention of gene therapy capability. Thus the project is a very nice fit: it makes use of a current specific skill set, but with a new twist of difficulty and a brand-new medical application to learn about. Needless to say, I am very excited to see what we manage to come up with by the end of July!