Thursday, March 25, 2021

Brain Fog

 


“Brain fog” or “brain-fog” is a popular term that has penetrated the medical literature fairly recently.  In talking with hundreds of patients who have used the term in my evaluations most of them mean an actual fogginess to their mentation.  That typically occurs in two ways. The first is an underwater feeling and noticing that both the speed and content of thought is not quite up to par.  The second is more of a problem in concentration and focus where it takes a noticeable effort to sustain both.  I have personally had these experiences during illness and probably on a developmental basis.  In the case of the illness, I was running my usual team meeting at about 8AM, and suddenly realized my thoughts were clouded. I developed chills and knew that there was a mini-epidemic of influenza in my staff. I told my team members that I had to stop due to illness and went home.  It took about 48 hours for that to clear.  Since that time, I have been very interested in how infectious diseases and diseases in general have that effect on the brain.

The closest term that I could think of that might approximate brain fog is “clouding of consciousness”.  This term from descriptive psychiatry and psychopathology is commonly associated with neurocognitive disorders. It is typically a criterion for delirium but in most texts, it is also associated with other anatomical and functional brain disorders.  The best review of the psychopathology and phenomenology of clouding of consciousness is from Lipowki’s text (1).  Lipowski reviews the 2500 year history of delirium and how confusion and clouding of consciousness became critical concepts in advancing research in this area.

A lot of the current psychopathology texts have very little to say about clouding of consciousness and symptoms of delirium.  There are a few exceptions.  Sims discusses it in a chapter “Consciousness and Disturbed Consciousness”.  He starts with defining consciousness by three components an inner awareness of experience, intentional reaction to objects, and knowledge of the conscious self.  He also has an excellent diagram (Fig 3.1 p. 40) that ties together the medical use of the term, clinical context, and changes that can occur in that context.  Since I cannot get permission to post the diagram I will describe it.  Normal consciousness is the central component and it is transitioned to reduced wakefulness, sleep, and stages of sleep and deep sleep.  There is another transition to the unconscious mind (via preconsciousness).  The final transition is to clouding of consciousness, drowsiness, stupor, and coma. The latter transition is obviously the only pathological one, but in terns of psychopathology there is obvious overlap between reduced wakefulness transitioning to normal sleep and drowsiness that may be a prelude to neurocognitive disorders.  That is also a critical decision point in thinking about brain fog.  Is the underlying mechanism one of reduced wakefulness or a focal or global decrease in brain metabolism seen in neurocognitive disorders?  Sims also defines clouding of consciousness as: “most intellectual functions are impaired including attention and concentration, comprehension and recognition, understanding, forming associations, logical judgement, communication by speech and purposeful action”. (p. 41).  Sims definition is most consistent with an early delirious state but not “brain fog” described by a person who is going to work every day and subjectively feels that their work performance could be better.

I have followed the evolution of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) across the last 3 versions of Lahita’s text on SLE.  There are generally 2 chapters dedicated to this topic in each text.   Over the years, there has been much more specificity in terms of the biological mechanisms involved in NPSLE.  There are 19 separate neuropsychiatric syndromes involving neurocognitive symptoms and constellations of more pure psychiatric symptoms like anxiety and depression.  From a purely cognitive standpoint, an interesting concept is that many of the mechanisms that are thought to moderate cognitive function like long term potentiation (LTP), synaptic plasticity, and neurogenesis are immune cells and inflammatory molecules.  The diagram below illustrates some upstream perturbations in the cytokine system that can result in impaired learning and memory.  There are additional immune systems affecting neurogenesis.


     

In the review that I constructed this diagram from, the author states: “‘‘Lupus brain fog’’ is an extremely common patient complaint that refers to periods of forgetfulness and confusion that are related to impaired cognition.”  She cites the range of 21-80% of SLE patients having some degree of cognitive impairment leading to some degree of disability or impaired quality of life.  NPSLE and the associated studies of how inflammation and immune function impair learning and memory is an excellent example of how various disease processes can have effects on cognition. It is also a good example of how the term “brain fog” has developed recently in this clinical population with clear CNS pathology.  It also suggests a lack of specificity for the term given the range of impairment.

At this point – a few clinical vignettes of “brain fog” can be considered as additional examples:

Vignette 1:  60-year-old man referred for assessment and treatment of mania and possible bipolar disorder.  He gives a history of drinking 750 ml/day of alcohol and appears intoxicated at the time of the evaluation.  As part of the initial evaluation, he is given a standard cognitive exam and scores a perfect 30/30 points indicating no deficits in orientation, attention span, short term memory or language skills (comprehension, repetition, or naming).  He has no subjective cognitive symptoms.  He returns a week later for reassessment and does not recall meeting the same physician or doing any cognitive testing. He does not believe he was ever at the clinic in the past.

This patient essentially blacked out or was amnestic for the initial interview with the psychiatrist.  Like many heavy drinkers he has a sustained mood disturbance at times that resembles manic episodes, but these symptoms resolve after detoxification and abstinence from alcohol. Patient with these problems are likely to described brain fog during episodes of intoxication, withdrawal, detoxification, sleep deprivation from the effects of alcohol, decreased attention span and concentration that is probably multifactorial and during mood changes that are alcohol induced.  Heavy alcohol consumption can lead to profound and persistent cognitive changes, most notable from untreated Wernicke encephalopathy the result of Vitamin B1 deficiency that can accompany persistent alcohol use.

Vignette 2: 40 yr old woman referred for assessment of severe anxiety and panic. She attributes both symptoms to “chronic Lyme disease” despite extended course of antibiotic treatment by experts and extended treatment by non-medical personnel using more atypical types of treatment.  She was previously very vigorous and physically active but that is no longer the case.  She describes fatigue, hypersomnia, and “brain fog” that puts her job at risk because of decreasing productivity and performance. She is being treated with benzodiazepines for anxiety and z-drugs for sleep.

This is a familiar scenario for psychiatrists. In this case the patient is diagnosed with a controversial illness and has not recovered despite very aggressive treatment.  She is anxious because of the decrease in her level of functioning and describes fatigue, hypersomnia, and brain fog.  It is often difficult to determine the progression of symptoms without detailed records – depending only on the patient’s recollection of what happened over a number of years.  In these cases I have found that it is best to track all of these symptoms and see how they fluctuate with logical changes based on the patients current clinical status. In these cases I would typically proceed with tapering and discontinuing the benzodiazepines and z-drugs and monitoring the fatigue, hypersomnia, and brain fog while simultaneously providing psychotherapy that I thought would be most effective for the target symptoms.

Vignette 3: 50 yr old man being seen for severe alcohol use disorder, persistent depression disorder, major depression, chronic insomnia, and possible attention- deficit/hyperactivity disorder. He has had lifelong insomnia, onset of chronic depression at age 18, and heavy daily drinking for the past 15 years. He describes inattentiveness, distractibility, procrastination, and “brain fog”.  He is requesting that treatment for the “brain fog” be prioritized since it is currently his most significant problem.

Very common scenario in treatment settings.  The ADHD diagnosis is more controversial lately based on the idea that some people may develop it as an adult.  I always ask adults about childhood sleep problems and it is a very common finding.  Childhood sleep disturbance also results in erroneous diagnoses of ADHD, but it is often difficult to establish that diagnosis in generations where it was not emphasized on school.  The diagnosis of alcohol use disorder is a complicating factor. In the case of heavy drinkers, they are often drinking all day long, in a state of intoxication or withdrawal, and typically wake up in the middle of the night and need to decide whether to drink in order to fall back asleep or tolerate withdrawal until the morning and then drink to reduce more severe withdrawal symptoms.  Clearly, every one of those transitional states is associated with some cognitive impairment and some have described it as “brain fog”.  An additional patient-based bias is wish that a medication can correct all of this cognitive impairment.  That wish is complicated by the fact that many heavy drinkers have used cocaine or amphetamines to drink more and improve their concentration and attention.  They have also used benzodiazepines as a way to treat insomnia and withdrawal symptoms, especially withdrawal symptoms in the morning that could otherwise lead driving to work with high blood alcohol levels and risking legal problems.  In all of these cases, the patient needs to be followed and serially reassessed up to the 60-day mark.  In my experience, the transient cognitive symptoms should be clear at that point and the baseline symptoms and their severity can be determined.

If brain fog exists can it be phenomenologically separated from other psychiatric diagnostic terms?  Sedation or excess somnolence is a common form of clouding of consciousness.  There is a temporal aspect to both related to a combination of both alerting mechanisms and circadian rhythms and the biological basis of both has been grossly determined (6).  I would anticipate that sedation or somnolence would fluctuate over the course of the day, with the exception excessive sleep deprivation or external sources of sedation like a sleeping agent.  Most people tend to describe brain fog as unrelenting.

In the final analysis, is brain fog a useful term?  Is it a colloquialism rather than a technical term that should be used in medicine? My argument suggests that it may be a useful descriptor of a sub delirious state or very early clouding of consciousness.  There are multiple associated etiologies and conditions including some that are just a temporary disruption in normal physiology.  Based on my clinical experience it is clearly a word that patients frequently use. From the PubMed search, it is also being used more frequently in the medical literature, just over the past 20 years. 

 


A word of caution is needed before it is adopted on any widespread basis. Lipowski points out how 19th century psychopathologists advanced the field by specifying a class of disorders based on clouding of consciousness and confusion arising in the context of acute brain dysfunction.  What followed was a proliferation of terms that set back further research for decades (p. 27).  Time will tell if the term becomes more widely adapted or it is fitted into existing nomenclature.  Based on the recent tightening of the nomenclature for delirium (7) it is not likely.  Since most people seem to be using it to cover both mild and moderate subjective cognitive impairment - it does not add much precision. On the other hand psychiatrists are focused on the patient’s subjective state and use of language so it is undoubtedly useful for beginning the early exploration of the problem that led to the consultation.

 

George Dawson, MD, DFAPA

 

References:

1:  Lipowski ZJ.  Delirium: Acute Confusional States.  New York: Oxford University Press, Inc; 1990.

2:  Sims A.  Symptoms in the Mind: An Introduction to Descriptive Psychopathology. 3rd ed. Amsterdam: Elsevier Limited; 2003.

3:  Mackay M, Ulug AM, Volpe BT.  Neuropsychiatric Systemic Lupus Erythematosus: Mechanisms of Injury.   In:  Lahita RG, Tsokos G, Buyon J, Kolke T.  Systemic Lupus Erythematosus. 5th ed. London: Academic Press; 2011. p. 491- 512.

4:  Hanley J.  The Nervous System and Lupus. In:  Lahita RG, Tsokos G, Buyon J, Kolke T.  Systemic Lupus Erythematosus. 5th ed. London: Academic Press; 2011. p. 727-746.

5:  Mackay M. Lupus brain fog: a biologic perspective on cognitive impairment, depression, and fatigue in systemic lupus erythematosus. Immunol Res. 2015 Dec;63(1-3):26-37. doi: 10.1007/s12026-015-8716-3. PMID: 26481913.

-Reference 5 is an excellent open access review of the relationship between inflammation, immune systems, and cognition (especially memory and learning).

6:  Valentino RJ, Volkow ND. Drugs, sleep, and the addicted brain. Neuropsychopharmacology. 2020 Jan;45(1):3-5. doi: 10.1038/s41386-019-0465-x. Epub 2019 Jul 16. PMID: 31311031; PMCID: PMC6879727.

7:  Slooter AJC, Otte WM, Devlin JW, Arora RC, Bleck TP, Claassen J, Duprey MS, Ely EW, Kaplan PW, Latronico N, Morandi A, Neufeld KJ, Sharshar T, MacLullich AMJ, Stevens RD. Updated nomenclature of delirium and acute encephalopathy: statement of ten Societies. Intensive Care Med. 2020 May;46(5):1020-1022. doi: 10.1007/s00134-019-05907-4. Epub 2020 Feb 13. PMID: 32055887; PMCID: PMC7210231.

 

 

 

Graphic Credit:

Graphic was downloaded from Shutterstock per their standard agreement.  The artist in this case had many similar brain fog graphics and these depictions are probably an indication of how common this term has become.

 


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