Neuropsychiatric Assessment of Lyme Disease
Robert Bransfield, M.D.
Objective: A structured clinical
interview is proposed to assist in the overall clinical assessment when late state Lyme
disease is suspected.
Method: From a combination of clinical experience, journal review, and
discussion with colleagues, a structured interview was developed. Information from
patients with late stage neuropsychiatric Lyme disease (NPLD) was entered into a database
to serve as a reference point for diagnosis and tracking the patients status after
Results: An analysis of symptoms acquired from a thorough history and
mental status exam can be quite helpful towards the total clinical assessment when
suspecting late stage Lyme disease. Details are provided in the text of this article.
Conclusion: When NPLD is a diagnostic possibility, a detailed, well-focused
interview and mental status exam is proposed, and a database of symptoms seen in NPLD is
established. It is recommended to continue perfecting the assessment as well as expanding
the database. If diagnostic accuracy is improved, there would be better consensus
regarding treatment strategies.
There are many unanswered questions regarding
chronic Lyme disease. They remain unanswered as a result of our inability to accurately
diagnose the presence or absence of the causative agent B. burgdorferi. The usual
laboratory tests alone are not totally reliable to confirm or refute the diagnosis of Lyme
disease (1). When we combine the current laboratory tests with a very thorough history,
physical, and mental status exam, the accuracy of diagnosis is greatly increased. If we
can improve the accuracy of diagnosing the presence of Lyme disease, there would then be
more agreement regarding treatment guidelines. In an effort to improve diagnostic
accuracy, I have developed a psychiatric diagnostic and tracking system.
There are an increasing number of patients with
chronic Lyme disease (neuroboreliosis) presenting in psychiatric offices. Lyme disease
does not begin as a psychiatric illness. Other symptoms occur in early stage disease. Late
in the progression of this disease neurological, cognitive, and psychiatric symptoms
predominate. If not well understood, these symptoms are sometimes viewed as non-specific
and bizarre. Actually the symptoms can be quite specific with a clear physiological basis,
but far too often a routine evaluation is insufficient to adequately evaluate these
patients. When the evaluation is not property targeted, key symptoms can be overlooked and
these patients may be mistakenly diagnosed with chronic fatigue syndrome, fibromyalgia,
M.S., lupus, Epstein barr, as well as many other medical and psychiatric symptoms. (2)
They are considered by some to be "hypochondriacal" or "crazy." As a
result, many of these patients feel alienated from the mainstream of the health care
system. (3,4,5). The recent work of Drs. Fallon and Nields drew attention to the
significance of the psychiatric component of chronic Lyme disease. (2,6,7,8,9,10).
As a psychiatrist practicing in a Lyme endemic
area, I have evaluated and treated many of these patients from a psychiatric perspective
over a period of years. Most of these patients were previously diagnosed with Lyme disease
and many were considered to have been cured by prior adequate antibiotic treatment. I
would like to share some of my observations, experience, and impressions from working with
this population. Clinical experience is critical to add towards our total understanding of
chronic Lyme disease (11).
We can view Lyme disease as a stealth Phoenix - it
is difficult to find, and even more difficult to eradicate after it has penetrated deep
into body tissue. (1,11) Once late stage disease exists, it is impossible, with current
technology, to prove that B. burgdorferi has been eradicated. Constant vigilance is,
therefore, required. Years of failure to recognize, diagnose, and adequately treat these
patients has led to an ever expanding epidemic of chronic Lyme disease. (12,13,14,15,16).
All involved with late state Lyme disease agree
there is a large amount of inaccurate information on this subject. This disagreement
exists at every level - journals, scientific meetings, clinical practice, media outlets,
etc. (17,18,19) Some of this disagreement can best be viewed as the normal difference of
opinion seen when scientists approach a very complex problem from a very different
perspective. To fuel the intensity of these disputes, some approach these issues with a
significant bias. The full recognition of this illness has implications, which could
effect tourism, real estate values, disability, insurance company/managed care liability,
workmans compensation cases, motor vehicle issues, some criminal cases, and
political issues. Bias issues can adversely effect patient care, research funding, and
medical regulatory issues. Some of those previously impacted by bias now have difficulty
approaching this disease with full-unhampered objectivity.
As physicians, it is our responsibility to protect
life and quality of life. A tenacious pro-active stand prevents bias from obstructing
access and quality of care.
Lyme disease is clearly a very complex disease.
When considering a similar spirochete disease, syphilis, it has been said, "To know
syphilis is to know medicine." However, to know Lyme disease is not only to know
medicine but also neurology, psychiatry, politics, economics, and law. The complexity of
this disease and all that surrounds it challenges our scientific as well as our ethical
capabilities. I shall not address every aspect of this disease but I shall focus on
diagnosis, in particular from a psychiatric perspective.
The diagnosis of Lyme disease and in particular
late stage Lyme disease is a total clinical diagnosis (20). We need to return to basics.
In my opinion, a very thorough history, mental status exam, neurological, and physical are
the most significant components of the examination. We, in psychiatry, are uniquely
trained to perform the type of exam that is needed for these patients. Laboratory tests,
which are highly controversial, are also helpful, but the interpretation of the findings
is complex and requires clinical correlation.
The commonly used blood, urine, and spinal fluid
tests have a significant rate of false negatives in the chronic neuropsychiatric Lyme
disease population. (See
addendum - Seronegative Lyme)
Other tests that may be useful include P.E.T. and
SPECT. Brain SPECT scans in Lyme patients sometimes show a swiss cheese pattern of
In my experience, the location of the
hypoperfusion may correlate with brain areas noted to be dysfunctional on the clinical
exam. Although often reliable, not every neuropsychiatric Lyme disease patient
demonstrated SPECT findings.
Some patients show findings on MRIs, but
more commonly after illness has persisted for a few years. HTL tissue typing may be useful
in showing who is more vulnerable to a more severe form of the illness. (21,22,23) Spinal
taps (24) and nerve conduction studies can provide additional information. Psychological
testing by an examiner who is experienced with evaluating Lyme disease may also be
helpful.(2) Lyme urine antigen tests and PCR are being used with more frequency in the
assessment of chronic Lyme disease. In addition to B. burgdorferi infections, coinfections
with other agents leading to interactive infections are a significant issue. Some of these
coinfections are other tick borne diseases, such as babesiosis, human granulocytic
ehrlichiosis, human monocytic ehrlichiosis, etc. Other non-tick borne coinfections may
also be significant, such as CMV, strep, etc. None of these tests can, however, exclude
the diagnosis of Lyme disease. Many of our colleagues in internal medicine find the
evaluation of this disease to be highly frustrating since compared to other illnesses
there are less so called "objective" findings which are present. In both
psychiatry and primary care, we are trained to contend with this gray zone of diagnostic
criteria in which a skillful interviewer can recognize that subjective symptoms are valid.
We are more accepting of Sir William Oslers quote - "If you listen long enough,
the patient will give you the answer." Effective communication with the patient is
critical in considering the diagnosis. For us, Lyme disease presents with more objective
symptoms than we commonly see with other mental disorders. There has been a recent trend
to incorrectly view so called "objective" signs and symptoms as more valid than
those which are "subjective." Often a machine or lab test is perceived as giving
validity to these "objective" signs. Many of these "objective" tests
are far less valid and are based on questionable techniques, faulty assumptions, and
flawed logic. On the other hand, "subjective" complains are sometimes viewed
with excessive suspicion. When a credible patient describes a symptom that challenges our
medical capability, it is an error to assume without the proper supporting evidence that
they are lying, delusional, or hypochondriacal. In an effort to create predictability,
reliance upon cookbook medicine has given us a recipe for disaster. Algorithms should be
viewed as teaching tools and very rough guidelines, but should never be given more
significance than a detailed thorough exam and sound clinical judgment. We, as physicians,
owe it to our patients to always retain our courage and never defer our sound clinical
judgment to dictatorial guidelines. When considering a diagnosis of Lyme disease, a
distinction is made between the following groups:
1. Never infected by B. burgdorferi.
2. Infected by a Lyme like bacteria. (i.e., some other spirochete)
3. Infected by a B. burgdorferi and manifesting.
- Subclinical illness
- Minimal self-limiting illness
- Early stage disease
- Disseminated disease
4. Infected, never manifesting late stage disease, and currently either cured or
5. Infected, having manifested late stage disease and:
- Not previously diagnosed with Lyme disease.
- Previously diagnosed and treated with:
a. Possible cure
c. Subsequent progression of Lyme disease symptoms.
d. Current illness unrelated to Lyme disease.
e.Progression of Lyme disease symptoms and comorbid illness (es)
Late stage neuropsychiatric Lyme disease can best
be conceptualized as a disseminated and progressive, (predominately sub-cortical),
encephalopathy. Animal studies and autopsies have contributed to our understanding of the
disease process. (25,26,27,28). As symptoms progress, additional symptoms occur and
increase in severity.
These symptoms may be categorized in the following
1. Brain Stem
- Cranial Nerve symptoms
- Autonomic symptoms. Dysautonomia may be the result of involvement of brain stem,
involvement of other parts of the autonomic nervous system, or end organ pathology - i.e.:
migraine, temperature dysregulation, sexual dysfunction, bright light sensitivity, mitral
valve prolapse, irregular pulse, neutrally mediated hypotension, asthma, non-ulcerative
dyspepsia, irritable bowel, and irritable bladder
- Hormonal symptoms: From the result of either hypothalamus or end organ
involvement, i.e., thyroid disease, HPA axis dysregulation, decline of sex hormone
- Long track disconnection syndromes (very late in the progression of the disease)
- Cerebellar symptoms
2. Limbic system, greater limbic system, extended amygdala
- Altered attention, emotional, and behavioral modulation
- Pathological psychiatric syndromes
3. Cortical (May be from either cortical or sub-cortical nuclei involvement)
- Signature syndromes
- Processing difficulties
4. Peripheral Neuropathy
The Structured Interview
When evaluating a patient, I recommend completing
the following structured interview. I have found it to be quite helpful and cost effective
in evaluating the possibility of neuropsychiatric Lyme disease. I have gradually developed
this examination after interviewing many patients with neuropsychiatric Lyme disease.
Since these patients have multiple deficits, which impair effective communication, we
cannot expect the patient to volunteer the relevant information. Therefore, we must
methodically ask the appropriate questions in order to acquire an accurate history. The
thoroughness of this exam combined with sound clinical judgment helps us to differentiate
between who may have had Lyme disease, who may be in remission, who is showing active
disease, and who may have some closely related condition. When the diagnosis is unclear, I
suggest repeating the exam at a later date to consider whether the symptoms are
increasing, stable or improving. The exam should also be repeated during and after
treatment to further track the patients status.
On the structured interview, at the left is a
database for each item. The first data base column shows the incidence of a given symptom
based on history prior to infection to serve as a control. The second column shows the
incidence of these symptoms in the same population after infection in cases with
significant clinical and laboratory findings. I am still in the process of completing this
database. Many of the patients I have seen with LD are children, teenagers, and young
adults. As a group, it has been my experience to find their pre-morbid status to be
healthier than the average, both mentally and physically. This is a disease that more
commonly attacks "lovers of life." (29) - young, healthy active individuals who
engage in more outdoor activities, particularly those living in suburban and rural areas.
Many report they have never had any significant illness prior to the onset of Lyme
disease. After becoming ill, most of the patients report they had previously been
diagnosed with Lyme disease and were given, what was considered by some standards, to be
an adequate treatment. Subsequently, their symptoms progressed with increasing cognitive,
psychiatric, and neurological components. Most of the patients tested positive at some
point in the course of their illness. Some were not seropositive until after treatment had
progressed. Some were seronegative which resulted in a significant delay in treatment and
a progression to a greater number and more severe symptoms. When comparing the symptoms,
there appeared to be no significant difference between the strongly seropositive (some of
whom sell their blood to be used as a reference for labs), and the patients with more
moderate laboratory findings and the seronegative group. The longer the interval between
initial infection and effective treatment, the worse the prognosis.
Some symptoms are more specific than others. The
control database is useful as a reference point. By looking at the patients profile
and comparing it to the database, we can see that some symptoms are more prevalent than
others. Symptoms with an asterisk correlate with high diagnostic significance. Any single
symptom may be seen in other illnesses, but the cluster of symptoms combined with our
total knowledge of psychiatry, neurology, and medicine helps us to make the appropriate
diagnosis. Patients with NPLD show significant number of positive responses. Patients with
a different diagnosis do not demonstrate a large number of positive responses.