Distinct pattern of cognitive impairment noted in study of Lyme
patients
by Marian Rissenberg, Ph.D. & Susan Chambers, M.D.
the Lyme Times, Vol.
20, January-March 1998, pp. 29 -32
1) Cognitive
Characteristics of Chronic Lyme Encephalopathy
On the basis of both a formal neuropsychological study of 49 patients (APA
5/96) and on clinical observation and comprehensive neuropsychological
examination of well over 100 patients, a distinct pattern of cognitive
impairment occurring chronic Lyme disease can be described. These patients
consistently demonstrate deficits in directed, sustained and divided attention,
planning and organization of responses, temporal ordering, verbal fluency,
abstract reasoning, speed of processing, and motor programming. The overall pattern
of intellectual impairment is not unlike that seen with diffuse brain injury,
and it most often results in some degree of work-related disability.
Although performance is impaired on measures of cognitive functions associated
with specific brain regions — receptive and expressive language, visuospatial
problem solving and memory — the quality of performance is not suggestive of
focal lesions in these areas. Rather, deficits are secondary to impairment of
higher level integrative functions, likely mediated by complex neuronal
systems. Specifically, the receptive language deficit is secondary to impaired
auditory tracking and slowing of mental processing. The expressive language
deficit is secondary to impaired word retrieval and response planning, The
visuospatial problem solving deficit is secondary to impairment of mental
flexibility, conceptualization and the ability to compare and contrast
necessary in decision making. Finally, deficits on test of memory function are
most often secondary to impairment of the encoding or initial processing of
information, which depends on attention, and the retrieval of stored
information. The storage of new information, or memory per se, is rarely
impaired.
This pattern suggests that cognitive dysfunction in chronic Lyme, while
expressed variably across individual patients, results from a common factor —
the breakdown of diffusely represented processes involving both integration and
activation, and impacting primarily on attention and reasoning. The fluctuation
of impairment over short periods of time suggest that a physiologic rather than
a structural mechanism is responsible.
2) Neuropsychological deficits in chronic Lyme disease (A study presented at
the annual meeting of The American Psychiatric Association
, May
1996)
The neuro-psychological characteristics of 49 patients with Lyme disease were
examined. The study set out to answer three questions:
1) Do all patients
with subjectively perceived cognitive dysfunction have measurable intellectual
impairment on objective testing?
2) In those without measurable impairment, does depression account for the
perception of cognitive dysfunction?
3) What is the nature of the cognitive impairment in Lyme disease when it does
occur?
Subjects were patients seen consecutively between 1990 and 1994 in a private
neuropsycological practice with complaints of cognitive dysfunction and a
symptom complex consistent with Lyme disease. Diagnosis was based on former CDC
criteria. Mean duration of illness, defined as the time from the onset of
general symptoms to the neuro-psychological exam, was 4.7 years (range: 3.3 to
14 years). Mean age was 39.9 years (range: 21 to 58 years) from 18 to 60 years.
Mean level of education was 15.3 years (range 12 to 20 years).
Subjects were interviewed and administered a comprehensive battery of tests,
including the complete WAIS-R and WMS-R, and additional test of language,
attention, reasoning, visuospatial processing and complex motor function. They
also completed the Beck Depression Inventory and a symptom checklist. Tests
were divided into seven groups based on the cognitive functions they are
presumed to measure: Attention, Memory, Language, Visuospatial Processing,
Reasoning, Verbal Fluency and Motor programming.
Subjects were grouped into three levels of impairment based on their
neuropsychological performance: Intact (N=11; 22%), with no functions impaired,
Moderate (N=31; 63%) with two functions impaired, and Severe (N=7; 14%) with
three or more functions impaired. Subjects in the Severe group met diagnostic
criteria for dementia. The correlation between depression and cognitive
impairment was nonsignificant, but the trend was positive, rather that
negative. Anxiety by self report was significantly greater in the impaired
groups that the Intact group. Duration of illness was greater in the Severe
group (nonsignificant).
Of the 38 subjects with cognitive impairment, deficits of attention were most
common, occurring in 26 subjects (68%) Deficits of memory storage were least
common, occurring in 8 subjects (21%), Motor, Verbal Fluency, Visuospatial,
Language and Reasoning deficits occurred in 24, 26, 29, 36 and 36% of the
subjects respectively.
3) Possible Pathophysiologic Mechanisms of Cognitive Impairment in Lyme
Disease
Based on these findings and on patients’ reports, two characteristics of Lyme
Encephalopathy arise which provide insight as to possible neurophysiologic
mechanisms:
One, the nonfocal
nature of the cognitive functions affected, and
Two, the subtle fluctuations and reportedly abrupt and global shifts in
cognitive function from one day to another in a given patient.
Four broad categories of possible neurophysiologic mechanisms might be
compatible with this pattern:
1) Diffuse cerebral
diffusion abnormalities — Single photon emission computerized tomography
(SPECT) scans of the brain in Lyme disease often display a diffuse pattern
consistent with heterogeneous areas of hyperfusion and/or diminished neuronal
metabolism. While vasodilators are often capable of reversing these abnormal
patterns on SPECT scan, this reversal does not consistently correlate with a
symptomatic improvement in cognitive function.
2) Alterations in cellular metabolism at the cortical level — Evidence of
alterations in neurotransmitter function is suggested by clinical evidence of
cognitive improvement following treatment with selective serotonin reuptake
inhibitors (SSRI’s) which appears to be independent of their antidepressant
effect. Systematic studies of the impact of SSRI’s on cognitive function, as
well as the role of other transmitters, are required.
3) Neuro transmitter abnormalities (imbalances of synthesis and/or receptor
activity) — Neurotoxic substances may well play a role in Lyme Encephalopathy.
given the neurotropic nature to Treponema pallidim , and the
close parallel between syphilis and Lyme disease, it is possible that
Borrelia
burgdorferi could produce intracellular or extracellular neurotoxins
which we have yet to identify.
4) Neurotoxic substances produced endogenously or possibly exogenously —
Endogenous neurotoxins have been identified as by-products of the humoral
immune response. Among these is quinolinic acid, a product of the interleukin
cascade system, which accumulates as a result of the humoral response to acute
infectious agents and functions as a neuronal excitotoxin. As there are many
similarities between Lyme Encephalopathy and the nonspecific mental dysfunction
of acute systemic infections, such as influenza, it is quite possible that
continue stimulation of production of quinolinic acid and other cytokines plays
a role in the pathophysiology of Lyme encephalopathy.
4) Clinical Impressions and Implications for Diagnosis and Treatment in
Chronic Lyme Disease
This study demonstrates that for the majority of chronic Lyme patients with
cognitive complaints, there is in fact a measurable and significant decline in
intellectual acuity. The nature and severity of the cognitive impairment is
such that it interferes with all aspects of normal functioning: employment, home,
marriage, social interactions, and general emotional well-being. Rather than
the cognitive complaints being secondary to anxiety or depression, as is
sometimes suspected, depression and anxiety increase with, and are apparently
secondary to, cognitive impairment and the emotional and practical impact of a
loss of competence. Thus, while patients with chronic Lyme disease can present
a confusing and “psychiatric” picture to the clinician, it is
important that their concerns be properly investigated and addressed.
Patients with Lyme encephalopathy complain of problems with memory and
concentration, word retrieval, confusion, problems with thinking, “mental
fogginess”, a decline in job performance, difficulty with calculations,
directions, and judgment. Decreased initiative, manifest as difficulty getting
started with or following through with projects is often noted. Mood
disturbance is common with complaints of irritability, explosiveness or “a
short fuse,” sadness, hopelessness or guilt, increased anxiety or mood
swings. Sleep disturbance is also common, and can present as initial, middle or
terminal insomnia or some combination of these. Fatigue is universal. Headache
is common, and of course joint and muscle pain. Increased sensitivity to light
and noise, visual disturbance, and tingling in the extremities are also common.
On interview patients with Lyme encephalopathy tend to be vague and
disorganized in the presentation of the history of their illness. This is
despite their close attention to their symptoms and having recounted them many
times before. Although in most cases memory of discreet events – tests, dates,
diagnoses, responses to medications — is intact, the patient is unable to
recall them spontaneously or organize them in temporal order. They may be
unclear as to their chief complaint. They may completely lose track of what
they were saying, sometimes repeatedly, or of what the question was. They may
get off on a tangent and have trouble re-orienting themselves. Frequent
prompting and refocusing will be necessary. beginning the interview with an
open-ended question like “Tell me what the problem is” will allow
these qualities to become clear.
Often patients with chronic Lyme disease will seem overly focused on their
illness, or overly concerned with convincing the clinician that they are ill.
The clinician may be tempted to interpret this as evidence of a primary
psychiatric disorder. It is important to understand that the frustration many
of these patients experience is real, and results from the general attitude of
doubt toward Lyme disease as a serious and chronic illness, the invisibility of
their symptoms, the difficulty in getting a definitive diagnosis and getting
approval for extended treatment from insurance carries. Many have been accused
of hypochondriasis or malingering. As with head injury, the patient may
“look fine” though they are having difficulty with very basic work,
social and day to day functioning.
The cognitive deficits in chronic Lyme disease involve primarily attention and
arousal mechanisms. Patients have difficulty keeping track of external and
internal events, retrieval of information from memory and with planning and
sequencing, as occurs in attention deficit disorder. However their experience
is different from that of ADD, in that rather than having the experience that
there are many thoughts competing for attention, the Lyme patient has
difficulty bringing any thought into clear focus. They experience difficulty
thinking. One patient described it as the universe ending six inches from his
face. He can’t process information that is not immediately apparent,
immediately experienced. Another said that when he tries to think about
something, or figure something out, all he can do is repeat the question — he
can’t get to the meaning. This is like the idea of “surface” versus
“deep” processing in cognitive psychology. Reading a passage for
typing errors would be surface processing, while reading for meaning is deep
processing. One patient, a physician, described it as a “mental intention
tremor” — the more she tries to focus on something the more out of focus
it becomes.
The clinician should proceed with empathy and reason. Specific cognitive
complaints in previously high functioning individuals are unusual and indicative
of serious illness, either psychiatric or neurologic. Comprehensive
neuropsychological evaluation will most often differentiate the two.
Where the neuropsychological exam is normal or there is a significant
psychiatric component, a psychiatric evaluation is advised. Psychiatric
symptomatology is not uncommon in Lyme and the presence of depression, anxiety,
obsessive compulsive symptoms, flat affect and so on may cloud the issue of
significant cognitive decline. Both the cognitive and psychiatric symptoms
would be expected to improve with antibiotic treatment in Lyme encephalopathy.
However sometimes concurrent treatment with psychotropic medication is
necessary.
Unfortunately for some patients significant cognitive impairment persists even
after years of antibiotic treatment. These patients may never be able to return
to their premorbid level of employment, or be gainfully employed at all.
Cognitive remediation can help them learn strategies for improving memory and
concentration and relieving stress. Support and advice in regard to living with
a chronic condition is equally important. Strategies include reducing work
hours when possible, taking regular rest periods during the day, limiting the
number of outings in a week, and using a calendar to stay organized and
structure their time.
5) Cognitive impairment in Lyme disease: specific functions and the impact
or deficits
1. Attention and
mental tracking: includes directed and sustained attention: the ability to direct
and maintain one’s focus on a particular event or idea, whether in the
environment or internally; and divided attention: the ability to simultaneously
attend to two events, or dot two or more things at a time, or to retain
awareness of one thing while doing another.
Impact: difficulty functioning
effectively in many situations, remembering what one was doing before a
distraction, keeping track of conversation, taking notes while someone is
speaking, remembering that someone is on hold or what you were about to say.
2. Memory: Retaining new information.
Impact: secondary to
impaired attention, slowing of processing and the retrieval of stored
information, but not storage per se, a tendency to lose or forget things, miss
appointments, repeat oneself.
3. Receptive language: understanding spoken or written language
Impact: secondary to
impaired attention and speed of processing, difficulty participating in
meetings or social conversation, difficulty with reading comprehension.
4. Expressive language: Using spoken or written language to express
ideas
Impact: difficulty finding
the right word, using the wrong word and not noticing, not being able to
express oneself or communicate
5. Visuospatial Processing: Efficient scanning of the visual field,
making sense of how things are related in space, visuospatial conceptualization
and problem solving.
Impact: a tendency to get
lost, difficulty with reading comprehension.
6. Abstract reasoning: The ability to generalize from the particular, to
identify the common factor between related concepts, to compare and contrast
two things or ideas, to see the “big picture”, to identify the
critical factor in a situation, to anticipate consequences and make inferences
regarding cause and effect.
Impact: difficulty with
decision making, planning, and problem solving.
7. Speed of mental and motor processing: the ability to think and
respond quickly, critical to understanding speech which occurs at a fairly
constant rate.
Impact: difficulty
understanding or keeping up a conversation, functioning in a timely manner in
day to day situations, meeting deadlines.
