Chronic “Toxic” Encephalopathy: The Other CTE
By Marcia H. Ratner PhD, DABT
CTE: Chronic Traumatic Encephalopathy
Many people are familiar with the medical diagnosis of chronic traumatic encephalopathy or “CTE” which has been associated with repetitive subtle brain injuries such as those which occur among professional football players. But far fewer people know that there is another common use for the CTE acronym based on the medical diagnosis of chronic “toxic” encephalopathy which is associated with repeated exposures to low levels of neurotoxic chemicals found in the workplace and environment. This less well-known cause of chronic “encephalopathy” and its related counterpart “acute” toxic encephalopathy are the topics I will be discussing in this blog post.
I want to begin this discussion by first clarifying what is meant by the term “encephalopathy”. According to Taber’s Cyclopedic Medical Dictionary, encephalopathy is “any dysfunction of the brain”. Needless to say, based on this overly broad definition it is very easy to see why the term encephalopathy needs to be further qualified. That said, in addition to being associated with traumatic brain injuries, encephalopathy is also seen in patients presenting with failure of the kidneys (uremic encephalopathy) and liver (hepatic encephalopathy) and, as previously mentioned, in persons exposed to toxic chemicals (toxic encephalopathy). In each of the examples cited above, the symptoms of encephalopathy will typically include changes in mood and affect, problems with attention and executive function, memory deficits, and disturbance of psychomotor function.
Next, I will take moment to unpack and provide qualifiers for the term toxic encephalopathy, which as the name implies, is a constellation of persistent neurobehavioral changes that can be associated chronologically with a history of exposure to neurotoxic chemicals. When symptoms of toxic encephalopathy emerge immediately following a single acute exposure to high levels of toxic chemicals the diagnosis is referred to as an Acute Toxic Encephalopathy. This type of toxic encephalopathy is relatively easy to diagnosis based on the exposure history and clinical manifestations alone. By contrast, the symptoms of Chronic Toxic Encephalopathy emerge insidiously over time in association with repeated or chronic exposures to low levels of neurotoxicants. Because chronic low-level exposure to toxic chemicals often does not cause any acute observable changes in behavior attributable to the exposure per se, this type of toxic encephalopathy is much more difficult to recognize and diagnose (see Feldman, Ratner and Ptak, 1999; Ratner and Jabre, 2017).
Toxic vs. Traumatic Encephalopathy
Now that we have defined the basic terminology, let’s take a moment to compare traumatic encephalopathy and toxic encephalopathy. The first important distinction worthy of further discussion is that both types of encephalopathy can be further qualified based on the duration and intensity of the events that gave rise to the encephalopathy. Severe blunt force trauma and exposure to high concentrations of toxic chemicals can both produce overt transient changes in behavior and/or a loss of conscious. In addition, both causes of acute brain injury can also leave the victim with permanent neurobehavioral dysfunction after they regain consciousness. From here on, I will be referring to these as acute traumatic encephalopathy and acute toxic encephalopathy.
The second important distinction is that both types of encephalopathy can occur following a series of relatively minor events that produce no overt changes in behavior or consciousness. Both the mild repetitive blunt force trauma that occurs among professional football players as well as the daily repetitive exposures to low concentrations of toxic chemicals as is typically encountered in occupational settings can, with time, lead to the insidious development of neurobehavioral changes without ever producing any immediate observable acute changes in the level of consciousness or behavior. Unlike the changes in behavior that follow a severe head injury or a high-level toxic exposure, the neurobehavioral changes associated with repetitive trauma and low-level toxic exposures are often subtle at first, emerge slowly over time and most importantly these occur in association with aging. As a result, the neurobehavioral changes associated with repetitive blunt force trauma and chronic exposure to toxic chemicals are not as readily attributable to their respective etiologies. From here on, I will be referring to these as chronic traumatic encephalopathy and chronic toxic encephalopathy respectively.
Making the Diagnosis
In each type of encephalopathy described thus far, the single most salient biological marker of effect is the change in behavior, which must be related to the putative cause of the brain injury before the qualifying term for the specific type of encephalopathy is defined and the diagnosed arrived at. This is achieved based in part on a very careful review of the occupational, para-occupational, and medical histories of the individual patient. For example, if the patient’s history includes playing professional football for 10 years with no history of occupational or para-occupational exposure to neurotoxic chemicals then a diagnosis of chronic traumatic encephalopathy should be considered. By contrast, if the patient has never played amateur or professional contact sports, reports no history of any acute head injuries resulting in a loss of consciousness but does have a history of chronic occupational exposure to neurotoxic solvents while working as a machinist for 10 years a diagnosis of chronic toxic encephalopathy should be considered. In both cases the symptoms of encephalopathy must also be differentiated from those associated liver or kidney failure as well as those associated with progressive neurodegenerative diseases such as Alzheimer’s disease.
In addition to taking a good history, there are also unique constellations of symptoms which aid a physician in the process of distinguishing one type of encephalopathy from another. For example, hepatic encephalopathy is typically associated with abnormal liver function tests while uremic encephalopathy is associated with biological markers of kidney dysfunction. In both cases, the symptoms of encephalopathy will often improve with treatment of the underlying medical condition (e.g. liver or kidney transplant). Alzheimer’s disease by contrast can be differentiated from these other causes of encephalopathy based on there being no abnormal biological markers of renal or hepatic function plus a relentless progression of the behavioral deficits over time. The same logic holds true for frontal temporal dementia.
Toxic encephalopathy must also be differentiated from each of the disorders described above. In some cases, the diagnosis of toxic encephalopathy is further complicated by the fact that toxic chemicals can also damage the liver and kidneys. In this case, the hepatic and/or renal dysfunction must be successfully treated before a diagnosis of toxic encephalopathy can be considered.
Because some patients will inevitably have a subclinical or latent neurodegenerative disease at the time of their exposure, the brain damage due to toxic chemical exposures may therefore unmask or worsen the symptoms of their idiopathic disease. In the case of an acute exposure unmasking a latent neurodegenerative disease this is a relatively simple diagnosis which can be made based on the chronology of events and the severity of the acute symptoms. By contrast, the interactions between chronic occupational and environmental exposures to toxic chemicals and the onset and progression of neurodegenerative disease is more complex. Nevertheless, in both cases a physician will need to order additional tests to elucidate the extent to which as well as how the toxic exposure exacerbated or modified the neurodegenerative disease process. These tests may include neuroimaging studies, serial neuropsychological assessments, and drug challenge tests designed to ascertain if a comorbid neurodegenerative process such as Alzheimer’s disease needs to be considered in the differential diagnosis.
The Differences Between Alzheimer’s and Toxic Encephalopathy
Because chronic toxic encephalopathy shares clinical manifestations in common with Alzheimer’s disease, no discussion of this topic would be complete without a brief review of how these two neurobehavioral disorders differ from one another both clinically and neuropathologically. The first and most important take home point to consider is that Alzheimer’s disease is a progressive neurodegenerative disorder. Therefore, serial neuropsychological assessments can be used to effectively document the progression of this disease over time. By contrast, serial neuropsychological assessments of patients diagnosed with chronic toxic encephalopathy will often reveal some improvement in function with cessation of exposure. In addition, any residual neurobehavioral signs and symptoms which do not resolve with cessation of exposure will often be stable showing little or no further progression with time. Second, the neuroimaging findings in Alzheimer’s disease are also relatively unique to this neurodegenerative disorder showing disproportionate bilateral atrophy of the medial temporal lobes. This neuroimaging finding is not typically seen in chronic toxic encephalopathy. Finally, patients with Alzheimer’s disease often have word finding problems known as “anomia” which are not typically seen in chronic toxic encephalopathy. A diagnostic trifecta on these three inclusion/exclusion criteria is a strong indication that the diagnosis is Alzheimer’s disease as opposed to chronic toxic encephalopathy.
In conclusion, chronic toxic encephalopathy is a clinical diagnosis that is made based on the occupational and environmental exposure histories and careful exclusion of all other possible causes of the observed clinical manifestations.
What To Do If You Have Been Exposed To Neurotoxic Chemicals
If you experience any behavioral symptoms that emerge abruptly either during or immediately following an acute exposure to potentially neurotoxic chemicals you should seek immediate medical attention. Likewise, you should seek immediate medical attention for any symptoms of acute distress or an acute medical emergency that emerge in association with repeated or chronic exposures to chemicals. On the contrary, if you are experiencing subtle neurobehavioral symptoms which have emerged insidiously over the course of months or years of working with chemicals and, you are also not experiencing any symptoms of acute distress or an acute medical emergency, you should consult with your primary care physician. While most physicians specializing in emergency medicine have experience managing and treating the acute neurobehavioral effects of exposure to toxic chemicals, it is uncommon for these specialists as well as general practitioners to have the expertise necessary to recognize, diagnose and/or treat the residual neurobehavioral sequelae associated with acute or chronic toxic encephalopathy. The good news is that there are physicians who specialize in occupational and environmental medicine. If your primary care physician is not familiar with diagnosing and treating he neurobehavioral effects of acute or chronic chemical exposures you should ask them for a referral to an occupational medicine specialist in your area. The occupational medicine specialist will have the necessary training and expertise to effectively work with a team of neurologists, neuropsychologists and toxicologists to make the correct diagnosis and develop an appropriate treatment plan.
- Feldman R.G., Ratner M.H., and Ptak T.: Chronic toxic encephalopathy in a painter exposed to mixed solvents. Harvard School of Public Health, Grand Rounds in Environmental Medicine. Environ Health Perspect, 107(5): 417-422, 1999.
- Ratner, M.H., Jabre, J.F. (2017) Neurobehavioral Toxicology. In: Reference Module in Neuroscience and Biobehavioral Psychology, Elsevier.
About Marcia H. Ratner PhD, DABT: “I earned my doctoral degree in Behavioral Neuroscience from Boston University School of Medicine where I trained in the Department of Neurology with the late Dr. Robert Feldman. I subsequently completed an NIH/NIA post-doctoral fellowship in the Biochemistry of Aging. I am a board certified toxicologist and a member of the Society of Toxicology and the American Academy of Clinical Toxicology. I currently use in vivo electrophysiological techniques to investigate the effects of chemicals on learning and memory function in healthy subjects and those with age-related neurodegenerative diseases. I have provided expert consultations to law firms, government agencies and industry.”
I earned my doctoral degree in Behavioral Neuroscience from Boston University School of Medicine where I trained in the Department of Neurology with the late Dr. Robert Feldman. I subsequently completed an NIH/NIA post-doctoral fellowship in the Biochemistry of Aging. I am a board certified toxicologist and a member of the Society of Toxicology and the American Academy of Clinical Toxicology. I currently use in vivo electrophysiological techniques to investigate the effects of chemicals on learning and memory function in healthy subjects and those with age-related neurodegenerative diseases. I have provided expert consultations to law firms, government agencies and industry.