VIEWPOINT Matthew J. Burke, MD, FRCPC Division of Cognitive Neurology, Department of Neurology. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; and Department of Psychiatry, Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Corresponding Author: Matthew J. Burke, MD, FRCPC, Division of Cognitive Neurology, Department "It's All in Your Head"-Medicine's Silent Epidemic "It's all in your head" is a phrase sometimes said by phy- sicians to patients presenting with symptoms unex plained by medical disease. As a neurologist specializ- ing in neuropsychiatry, nothing bothers me more than overhearing medical colleagues proclaim this one-liner at the bedside or snicker about these patients during rounds. Unbeknownst to them, I also hear my patients' version of being on the other end of this phrase and find myself constantly trying to repair the damage that these words can cause. Whether physicians like to admit it or not, medically unexplained symptoms encompass a vast terrain of clinical practice. In neurology, these symp- toms fall under functional neurological disorder, but ev- ery specialty has their own variants and favored termi- nologies (eg, chronic fatigue syndrome, fibromyalgia). The inadequate management of this segment of medi- cine represents a silent epidemic that is slowly eroding patient-physician relationships, perpetuating unneces- sary disability, and straining health care resources. The irony of it's all in your head" is that although this phrase is often used inappropriately and dismissively, it is technically correct. The problem does indeed lie within the head. More specifically, it lies within the brain and its com- plex networks that we are just beginning to understand. Over the past 10 years, neuroimaging research studies have consistently identified brain abnormalities in patients with medically unexplained symptoms-yes, biologically based changes in the activity and connections of brain regions, such as the amygdala, prefrontal cortex, temporal-parietal junction, and other structures. These brain circuit abnor malities provide physiological explanations for once mys- terious links between regions implicated in emotional processing and the generation of "physical" symptoms (eg, pain, fatigue, weakness). Jean-Martin Charcot, MD, a famous 19th century French neurologist and early pioneer of this field, reportedly insisted that a "functional lesion would be found when microscopes were sufficiently powerful? Well, our microscopes are getting better, and we are now starting to see evidence of the predicted functional or software disruptions in the brain. We still do not fully un- derstand what causes these software problems; however, recent research suggests a multifactorial etiology, includ ing genetic predisposition, environmental risk factors (eg, childhood adverse events), and psychological stressors. Despite the growing scientific literature, there has been minimal shift in physician attitudes toward these pa- tients. Physicians seem quite comfortable with the idea of structural brain lesions causing psychological symptoms, such as a frontal lobe stroke causing depression or atem- poral lobe tumor causing delusions. However, the reverse causality of psychological factors (bome of the same substrates-neurotransmitters, neurons, and synaptic con- MA 02215 (mburke@nections) leading to neurological or systemic symptoms is often hastily dismissed and remains highly stigmatized. of Neurology Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, KS-274, Boston, bidmc.harvard.edu). jamaneurology.com Thus, many physicians either simply ignore these kinds of symptoms or wrongfully assume that patients are malin- gering. Based on such attitudes, a typical physician-patient interaction may proceed as follows: (1) the physician pro- vides a rundown of normal investigations, (2) the patient is told they have no known medical diagnoses, (3) abrief awkward exchange occurs, and (4) little further explana- tion, guidance, resources, or facilitation of an appropriate referral process is given. Even if the infamous phrase is not explicitly stated, this sequence leaves the patient to infer for themselves that it must be all in their head. Unfortu- nately, they do not perceive this as, "I have a real dysfunc- tion of networks in my brain," but instead understandably conclude that, "they think I'm crazy" or "faking it."* Some- times, patients may hear the distant utterance of, "Maybe you should see a psychiatrist," as they exit the office door, but in this context, such advice is rarely productive. Many of these patients can be so offended by this encounter that they quickly seek multiple second opin- ions and subsequent rounds of pricey and unnecessary investigations. Depending on the jurisdiction and medi- cal record system, the original physician may be com- pletely unaware of these additional rounds of care. Mounting negative and invalidating clinical interac- tions can become a source of distress and cause medi- cal trauma. At this point, patients often either fall through the cracks or stumble on a fringe medical specialist or al- ternative medicine practitioner who may offer the "physical" diagnosis they've been yearning for. This could include a growing list of unsubstantiated metabolic de- ficiencies, infectious disorders, or autoimmune hyper- sensitivities. Anecdotally, the most common current ex- ample seems to be the diagnosis of chronic Lyme disease by unvalidated assays. Let me be clear that many of these practitioners are well intentioned and can offer ho- listic approaches that medicine could learn a lot from. However, there appears to be a subset that take advan- tage of these patients' desire for a "physical" diagnosis and exploit their vulnerabilities. For the patient, receiving such a concrete, "organic" diagnosis often quells mounting anxiety, which in itself could be partially therapeutic. However, now wedded to their given diagnosis with no knowledge of their actual soft- ware problem, patients do not see a need to address un- derlying factors that may be contributing to their disorder nor do they receive the multidisciplinary care that they may so badly need. The saddest part of this epidemic is that if addressed early, these symptoms may be reversible, how- ever, with delays to proper diagnosis and management, prognosis worsens considerably. So how can we prevent or interrupt this concern- ing trend? Often, the first step to addressing a problem in medicine is providing data to prove that the problem exists. This is where the challenge begins and what JAMA Neurology Published online September 16, 2019 2019 American Medical Association. All rights reserved. Opinion Viewpoint makes this a silent epidemic. The magnitude of this crisis is difficult to demonstrate because these patients largely elude the billing codes used for case ascertainment in large population-based studies. This is because of a combination of gaps in current billing and diagnostic codes (country specific) and because of the fact that codes are not being used appropriately by many physicians. The latter may hap- pen for multiple reasons, including lack of comfort with these diag noses and concerns of medicolegal ramifications. Despite a few isolated efforts to estimate prevalence and health care costs, the evidence base needed to sway research granting or ganizations, government policy makers, and health care and insur- ance systems has been largely elusive. I am optimistic that it is only a matter of time until the scope of this crisis is fully appreciated. I see firsthand the high patient volumes and health care resource utilization that currently escape record keeping. I raise these con- cerns to my colleagues, who wholeheartedly agree, but the conver- sation ends there and the silence continues. I am hopeful that new research technologies, such as natural language processing, could identify these patients in medical records despite the lack of ad- equate billing code data and that improved records systems will bet- ter track these patients through different health care pathways. ARTICLE INFORMATION Published Online: September 16, 2019. doi:10.1001/jamaneurol.2019.3043 Conflict of Interest Disclosures: Dr Burke is supported by funding from the Sidney R. Baer Jr Foundation. Disclaimer: The content of this article is the opinion of the author and does not necessarily represent the official views of Harvard University or the University of Toronto (and their affiliated academic health care centers) nor the Sidney R. Baer Jr Foundation. Additional Contributions: I thank Saadia Sediqzadah, MD, SM (Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada), for her helpful comments and review of the manuscript. Dr Sediqzadah did not receive compensation for her contributions. REFERENCES To address the epidemic itself, we desperately need more cli- nicians and researchers dedicated to interrogating the complex interfaces of mind, brain, and health. Currently, there are small pockets in different specialties, but these are not nearly commen- surate with the volume and impact of these disorders. Second, and arguably more importantly, we need to fundamentally change the culture within the medical community to eliminate the nega- tive connotations associated with these disorders. This change requires buy-in from hospital and health care leadership and a sup- portive infrastructure. These patients have complex conditions and require additional upfront consultation time, resources, and collaborative care. To prevent the cycles described previously. physicians need to be incentivized to take the time necessary to optimize the initial patient encounter. This includes delivering and explaining the diagnosis in a transparent and supportive context, providing patient-friendly resources (eg, https://www. neurosymptoms.org/), and referring appropriately for interdisci- plinary management (eg, physical therapy, occupational therapy. psychotherapy). New educational and training initiatives across medical and allied health professions will be critical for enabling a successful transition. 1. Voon V, Cavanna AE, Coburn K, Sampson S, Reeve A, LaFrance WC Jr; American Neuropsychiatric Association Committee for Research. Functional neuroanatomy and neurophysiology of functional neurological disorders (conversion disorder). J Neuropsychiatry Clin Neurosci. 2016;28(3):168-190. doi:10.1176/appi. neuropsych.14090217 2. Kanaan R, Armstrong D, Barnes P, Wessely S. In the psychiatrist's chair: how neurologists understand conversion disorder. Brain. 2009;132 (pt 10):2889-2896. doi:10.1093/brain/awp060 3. Espay AJ, Aybek S, Carson A, et al. Current concepts in diagnosis and treatment of functional neurological disorders. JAMA Neurol. 2018;75(9): 1132-1141. doi:10.1001/jamaneurol.2018.1264 4. Robson C, Lian OS. "Blaming, shaming. humiliation": stigmatising medical interactions among people with non-epileptic seizures. Wellcome Open Res. 2017;2:55. doi:10.12688/ wellcomeopenres.12133.2 5. Lantos PM. Chronic Lyme disease. Infect Dis Clin North Am. 2015;29(2):325-340. doi:10.1016/j.idc. 2015.02.006 6. Gelauff J, Stone J, Edwards M, Carson A. The prognosis of functional (psychogenic) motor symptoms: a systematic review. J Neurol Neurosurg Psychiatry. 2014;85(2):220-226. doi:10.1136/jnnp- 2013-305321 7. Stone J, Carson A, Duncan R, et al. Symptoms 'unexplained by organic disease' in 1144 new neurology out-patients: how often does the diagnosis change at follow-up? Brain. 2009;132 (pt 10):2878-2888. doi:10.1093/brain/awp220 8. Barsky AJ, Orav EJ, Bates DW. Somatization increases medical utilization and costs independent of psychiatric and medical comorbidity. Arch Gen Psychiatry. 2005;62(8):903-910. doi:10.1001/ archpsyc.62.8.903 9. Stone J. Functional neurological disorders: the neurological assessment as treatment. Pract Neurol. 2016;16(1):7-17. doi:10.1136/practneurol-2015-001241