Author: Josip A. Borovac

Josip is a medical student at the University of Split, School of Medicine in Croatia. He graduated from the State University of New York with B.Sc. degree (cum laude) in Molecular and Cellular Biology. During his undergraduate career, he conducted biomedical research focused on mechanisms of epilepsy at the Barrow Neurological Institute (St. Joseph's Hospital and Medical Center) in Phoenix, Arizona. He also spent a year at California State University - Bakersfield through a National Student Exchange (NSE) program where he studied at the Department of Biology. His medical interests include Neurology & Neurosurgery, Psychiatry and Clinical Pharmacology. In addition, he is interested in statistics, scientific writing and he co-authored some scholar peer-reviewed papers in this regard. He is an avid lover of books, music, movies, and good people.

Categories
Clinical Opinion

Mental Disorders: Are We Over Medicating?

In 1948, the World Health Organization (WHO) defined health as “a state of complete physical, mental and social well-being, and not merely the absence of disease or infirmity.” However, mental illnesses are not seen in the same light as physical illnesses. People who get labeled with psychiatric diagnoses often carry a heavy burden of social stigma regarding those diagnoses, and are generally uncomfortable disclosing and/or discussing them openly.

In ordinary conversation, it is not considered strange to mention that you had an appendectomy or discuss how you’ve been dealing with your diabetes for years. However, saying that you’ve been manic-depressive for years or that you’ve been desperately trying to overcome panic attacks is something that typically generates a negative response, and raises red flags for some people.

Why is mental health perceived so differently than somatic and physical health?

My inspiration for writing this piece was a debate about mental disorders held at the Emmanuel Centre in London, entitled: We’ve Overdosed. Psychiatrists and the Pharmaceutical Industry are to Blame for the Current Epidemic of Mental Disorders. Psychoanalyst Darian Leader, and accomplished author on the issue Will Self, argued for the “overdosed” side, while Dr. Declan Doogan and Professor Sir Simon Wessely, president of the Royal College of Psychiatrists, argued against it.

Is it true that mental disorders are made up by big pharma? Or is it just that we have a difficult time accepting that our psyche can, indeed, be a subject (or object, depending how you see it) of pathologic deviance and aberration? And that such aberration could and should be subjected to medical treatment?

Some critics view mental disorders as illnesses that have no definitive pathomorphological substrates. Are physicians overprescribing these agents to satisfy big pharma interests? Do they purposefully try to make the psychiatric bible (a.k.a. Diagnostic and Statistical Manual of Mental Disorders – DSM) thicker and thicker in each subsequent edition by bloating it with irrelevant and artificially fabricated diagnoses?

No one is claiming that every form of deviation from the “gold standard” of behavior (if such thing exists at all) is and should be proclaimed as a psychiatric disorder. No one is saying that every psychiatric disorder needs to be treated pharmacologically. No one is denying that many psychotropic drug treatments, unfortunately, fail among some patients. No one is saying that some classes of psychotropic drugs don’t induce debilitating side effects.

However, as future physicians we always have to remember that we will have a person with a problem sitting in front of us. This person will be seeking our help. We only have what is available to help them. We can only fight with the weapons that we have. Yes, sometimes treatment in psychiatry feels like we are trying to kill a mosquito with a rocket launcher. But it is the only thing we have got and for some it can be a salvation, regardless of the collateral damage.

My psychiatry professor once said, “if there is an equivalent of hell on Earth, it would be in a soul of a depressed person.”  I could not agree more.

Severe mental disease is not a joke. It is not something that can be solved with a thoughtful late afternoon conversation, by reading a line or two from Coehlo, or by reciting a poem by Neruda. Sure, activities like those are great adjuncts and can help ameliorate the situation to a degree, but people who are in trouble often need and demand much more from us.

Let’s not forget that when we’re talking about mental disease we are talking about the state of a diseased brain (physical) and mind (cognitive/psychiatric), which is most likely due to a neurochemical imbalance within the central nervous system circuits. This imbalance needs to be medically treated, especially in cases where it severely interferes with daily living. For some people, psychotropic medication is their only hope and the only chance they are going to get. For some people these medications perform miracles. We do not have a right to deny them such a possibility.

References

  1. Angermeyer MC, Matschinger H. The stigma of mental illness: effects of labelling on public attitudes towards people with mental disorder. Acta Psychiatrica Scandinavica. 2003;108(4):304-9. doi: 10.1034/j.1600-0447.2003.00150.x.
  2. Schomerus G, Schwahn C, Holzinger A, Corrigan PW, Grabe HJ, Carta MG, et al. Evolution of public attitudes about mental illness: a systematic review and meta-analysis. Acta Psychiatrica Scandinavica. 2012;125(6):440-52. doi: 10.1111/j.1600-0447.2012.01826.x.
  3. Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. Jama. 2010;303(1):47-53. Epub 2010/01/07. doi: 10.1001/jama.2009.1943.
  4. Arroll B, Elley CR, Fishman T, Goodyear-Smith FA, Kenealy T, Blashki G, et al. Antidepressants versus placebo for depression in primary care. Cochrane Database of Systematic Reviews. 2009(3). doi: 10.1002/14651858.CD007954.
  5. Leucht C, Huhn M, Leucht S. Amitriptyline versus placebo for major depressive disorder. The Cochrane database of systematic reviews. 2012;12:Cd009138. Epub 2012/12/14. doi: 10.1002/14651858.CD009138.pub2.

Featured image:
Reeve041788 by Otis Historical Archives National Museum of Health and Medicine

Categories
Clinical Innovation Opinion Technology

The 21st century Frankenstein Revival

Background

Human head transplantation (the head anastomosis venture project – HEAVEN) has been for a long time merely a neurosurgical and medical theoretical concept that did not enjoy much attention among the medical community. However, in recent times, there have been voices trying to revitalize this question. Italian neurosurgeon, Dr. Sergio Canavero, is one of the most prominent protagonists in this regard. The idea behind this concept is to help people who have severe physical disabilities (such as neuromuscular dystrophies or tetraplegia), but have an intact head and brain. There is a vast array of medical, ethical and physiological questions and obstacles that are ahead of this endeavor. Despite a lot of skepticism, Dr. Canavero has laid out a couple of transplantation protocols he believes can get the job done. In these protocols, he tried to answer and address every possible challenge that is expected to occur during this delicate and immensely complex procedure. The main purpose of this short article is to analyze the crucial components of his protocols and try to determine if they have any rational scientific relevance and ethical/medical justification.

Why do it?

Before you chop someone’s head off, you’d better have some good reasons, right? This is fundamental. In medicine, conditions are treated if the potential benefits of the treatment outweigh the potential risks. For each particular disease state, there has to be a justified medical indication and logical/rational foundation behind treatment. This is the sine qua non of every medical intervention. You have to bear in mind that anything you do has to lead, ultimatively, to a better quality of life. In that regard, I doubt that this procedure would accomplish that goal  at the present moment and it principally acts as an academic exercise, albeit lethal one. I generally do not support doing things just for the sake of doing them, especially in medicine where such behavior can be costly and unethical. Sure, you can become hero of the day and act in a „told you so“ manner if things go your way, but what if they don’t?

Even if you theoretically manage to overcome the technical and technological barriers that are inherent to this procedure, the question still remains: will this person experience improved quality of life? Dr. Canavero’s logic is that people who suffer from severe and/or progressive neurological conditions, e.g. muscular dystrophy or quadriplegia, could potentially benefit from this procedure. How? Well, if your peripheral nervous system does not work but you do have preserved cognitive functions (brain and brain stem), then you would be able to theoretically join healthy brain with healthy body of a deceased donor. The idea is that this body would be donated by those people who were clinically confirmed as brain-dead due to, for example, severe head trauma, but still had a fully functional body to offer. On the other hand, the „recipient“ of the body would give an informed consent that he/she is willing to undergo a body transplantation procedure, regardless of a high risk that this procedure could end in death. In  popular jargon – „people who have nothing to lose“ are the group of people that are targeted as candidates for this procedure in Dr. Canavero’s opinion.

Feasability

Dr. Canavero laid out 2 operative protocols that provide a theoretical framework for this type of experiment. One of them is called HEAVEN1 and addresses head-to-body anastomosis, while the other is named GEMINI2 and features a spine fusion protocol. The physiological obstacles that Dr. Canavero needs to overcome in order to succeed in this endeavour are tremendous, but I will try to briefly tackle the 4 major ones.

  1. Brain perfusion problems – in only a few minutes post-decapitation, it is expected that neurons will be exposed to a hypoperfusive state, ultimately resulting in brain tissue death.
  2. Fusion of two ends of the spinal tract – this has never been done before in humans.
  3. Reparation and regeneration of neuronal connections and spinal tracts/projections within the CNS and the restoration of the motor and sensory functionality.
  4. Post-transplantation complications – this includes potential tissue transplant rejection reactions that are immunologically mediated.

Should we do it?

At this point, we just do not know enough about the proposed procedures. Some of them have been performed on animal models and some were done only in a Petri dish. Results obtained through animal experiments and in-vitro molecular models might not correlate (and most commonly they don’t) with human physiology. In the early 1970s, American neurosurgeon Robert Joseph White performed the first monkey head transplantation onto a body of another monkey3. The recipient monkey lived for 8 days, and there were no surgical complications encountered. However, the monkey was quadriplegic since the surgical protocol did not address the problem of spinal fusion4. This resulted in a monkey who was completely paralyzed from the neck down, but who could still eat and follow objects with its eyes since the cranial nerves, brain stem and other brain structures were intact and perfused by the circulatory system of the donor’s body. Moreover, it was reported that the transplanted head could hear sounds and smell/taste food. However, immunologic reactions in the form of graft rejection ensued and the monkey died from them.

In this regard, Canavero’s protocol is essentially just a „compilation“ of biotech solutions for a wide spectrum of problems in medicine. Successful translation of any of these theoretical concepts into the clinical arena would be a giant leap in medicine. However, strictly lege artis, there is no strong evidence that these techniques will be successfull at all. Patients undergoing this procedure could be left in much more catastrophic and miserable conditions than those endured prior the procedure. Transplantation of a human head onto a new human body should not be perceived merely as transplanting a flower from one pot to another. We do not know how the brain would interact with the new neurochemical and biochemical milleu of the body that it just received. How would the brain integrate and process new signals arriving from the newly discovered periphery? How would the brain process perception and information coming from these new muscles and other body structures? These problems were emphasized in a recent letter written by Dr. Cartolovni and Dr. Spagnolo, published in the Surgical Neurology International journal. In this letter, the authors argue that Canavero’s perception of the human body functional framework is strictly mechanistic, and largely disregards the importance of body self-cognition, which plays a real part in the formation of human self.

Additionally, they state that head transplant procedures raise significant social and ethical problems in terms of organ donation. A leading medical ethicist, Dr. Arthur Caplan from NYU’s Langone Medical Center, states that the implications of this procedure are far-reaching and extremely dangerous from the ethical and medical standpoint. Similarly, Dr. Jerry Silver from Case Western University states that he perceives human transplants as a barbaric method at this point in time. Moreover, he said that he does not expect such procedures to be successfully performed for at least the next hundred years.

In my opinon, we are not ready for this type of procedure, at least in light of the most recent evidence-based medicine. Even if the tremendous technical difficulties could be surpassed, it still remains a question how the brain (center) would integrate with the periphery. At this point, I assume that the brain would be overwhelmed with the amount of input that it would receive from the periphery, ultimately leading the transplant recipient to derangement, pain and insanity. The prospects of this experiment are simply grim and unfavorable, with our present knowledge and, therefore, I would advocate for its halt.

References

  1. Canavero S. HEAVEN: The head anastomosis venture Project outline for the first human head transplantation with spinal linkage (GEMINI). Surg Neurol Int. 2013;4(2):S335-42.
  2. Canavero S. The „Gemini“ spinal cord fusion protocol: Reloaded. Surg Neurol Int. 2015;6:18.
  3. White RJ, Wolin LR, Massopust LC Jr, Taslitz N, Verdura J. Primate cephalic transplantation: Neurogenic separation, vascular association. Transplant Proc. 1971;3:602-4.
  4. White RJ. Hypothermia preservation and transplantation of brain. Resuscitation. 1975;4:197-210.
  5. Čartolovni A, Spagnolo AG. Ethical considerations regarding head transplantation. Surg Neurol Int. 2015;6:103.

Featured image:
Floating head, neck redone by TaylorHerring

Categories
General Literature

A farewell to Oliver Sacks

In my life, I haven’t had many heroes. Yes, I have been fascinated with some athletes, scientists, artists, and people around me, but I cannot say that I have had many true role models. In terms of science and medicine, one soul in particular stands out – Oliver Sacks.

In my introductory histology & embryology course, a professor mentioned a funny story during a rather uneventful lecture concerning ocular histology. The story told of an interesting “optical illusion”, and the lecture suddenly became much more engaging. He briefly mentioned that the clinical tale presented was described by Sacks in “The Man Who Mistook His Wife for a Hat”[1]. I often leave many off-side notes, and in this instance I scribbled: do check this guy out. While revising my histology notes for the exam, I spotted this side-note in my “trademark” hieroglyphic handwriting and decided to follow up on it. With that, a new influence in my life began.

Most articles will state that Sacks was a British neurologist, physician, scientist, and prolific author. Although he was born in London, he spent most of his life in New York City. Sacks was a meticulous examiner and analyst of neurological disorders, and he devoted his life to patients who suffered from these debilitating conditions. Many of his works became classics and best-sellers in the arena of popular medicine.

Sacks’ book “Awakenings” was used as a scenario for a major Hollywood motion picture [2] . In this true story, Sacks used a new experimental drug, L-DOPA, to treat patients in a state of total paralysis due to “encephalitis lethargica”. The treatment looked promising, as patients seemed to be resurrected and displayed dramatic improvements over their original condition. Unfortunately, the patients eventually regressed, once again falling into despair; once again drifting through the abyss of mere existence, which is what they had been enduring for years before the L-DOPA treatment briefly brought them out of it (the infamous “on-off” pharmacological feature of L-DOPA/Levodopa [3]). This was only one of many adventures that Oliver Sacks embarked upon and described in his novels. He was an intelligent, witty, compassionate, and truly unique writer and clinician who knew how to transpose the emotions, atmosphere, and feelings he encountered during his medical career.

In medical education, we explore different avenues – from basic to clinical sciences, bench to applied medicine, bedside to operating room, small rural ambulances to comprehensive medical centers. We try to reach a correct diagnosis. We try to adjust and find a sweet spot in our therapeutic modalities. We do our best to cut out what is sick and preserve what is still functional. Likewise, we are all attracted to different things. My “thing” is the nervous system and it has been for quite some time. If I was ever in doubt about such a choice, people like Sacks were there to remind me of my passion. Sacks’ stories of neurology and intricate brain puzzles consumed my attention on a daily basis. A few of his books, in particular, made a profound impression on me.

In “Musicophilia”, Sacks writes about the relationship of music and neurological disorders [4]. I was impressed when I learned how different clinical neurologic entities like stroke, cerebral hemorrhage, or head trauma can modify the processing of the sound and even alter someone’s musical inclinations. Likewise, in his book “Hallucinations” he talks extensively about how hallucinations can be generated as a consequence of trauma, drugs, or other physiological alterations [5]. Reading through Sacks’ books, I am continuously re-fascinated by his scholarly capacities alongside his humble and gentle nature. If the equation of human ego equals 1/knowledge, then Sacks had a miniscule, irrelevant amount of ego within himself. I rarely encounter such a trait these days, especially on the wards in daily clinical routines.

The last day of the August was humid and I had just returned home from a beautifully refreshing swim. I was soon struck with the news that Sacks had passed away. I was overwhelmed by the feeling of sadness. The world lost an outstanding individual, a soul that will be dearly missed by many. A few months earlier, in his New York Times column, Sacks wrote that he was diagnosed with metastases originating from his ocular melanoma. In this farewell piece, Sacks sensed his end was near and reflected on his life, which was well lived by any standard [6]. He announced that his final work, an autobiographical sketch of his life entitled “On the Move: A Life”, would soon become available [7]. His life was one of compassion and dedication; he was a source of warmth and kindness for those who were in need. He genuinely understood human suffering and worked to alleviate it to the best of his ability. Although I lived in New York City during my college days, I did not have the privilege of meeting Sacks. Regardless, I can find some consolation in the fact that he only departed physically – his writings, works, and grand opus will continue to inspire generations of minds to come. Goodbye, dear Dr. Oliver Sacks and thank you!

References

  1. Sacks O. The Man Who Mistook His Wife For A Hat: And Other Clinical Tales: Odyssey Editions; 2010.
  2. Sacks O. Awakenings: Knopf Doubleday Publishing Group; 2013.
  3. Lloyd K, Davidson L, Hornykiewicz O. The neurochemistry of Parkinson’s disease: effect of L-dopa therapy. Journal of Pharmacology and Experimental Therapeutics. 1975;195(3):453-64.
  4. Sacks O. Musicophilia: Knopf Doubleday Publishing Group; 2008.
  5. Sacks O. Hallucinations: Pan Macmillan; 2012.
  6. Sacks O. My Own Life New York, NY: The New York Times; 2015 [cited 2015 02/19/2015]. Available from: http://www.nytimes.com/2015/02/19/opinion/oliver-sacks-on-learning-he-has-terminal-cancer.html.
  7. Sacks O. On the Move: A Life: Knopf Doubleday Publishing Group; 2015.
Featured image:
oliver_sacks by Mars Hill Church Seattle