Lyme Disease: Stories From the Front Lines of an Epidemic – Nonfic Insert – Lyme Encephalopathy

Lyme Encephalopathy


By Angela Castle on Wednesday, September 14, 2011 at 1:47pm

(Used with permission. Unchanged from original.)


Distinct pattern of cognitive impairment noted in study of Lyme



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




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




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




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




Based on these findings and on patients’ reports, two characteristics of Lyme

Encephalopathy arise which provide insight as to possible neurophysiologic



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


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




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



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.


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