Neuropsychological aspects 
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 Neuropsychological aspects

<Appl Neuropsychol 1999;6(1):39-45

Long-term cognitive effects of Lyme disease in children.

Adams WV, Rose CD, Eppes SC, Klein JD
Department of Pediatrics, duPont Hospital for Children, Jefferson
College, Wilmington, Delaware 19899, USA.
 "...studies of {*filter*}s with LD, the results of long-term follow-up of the
pediatric population continue to strongly support the finding that
treated appropriately for LD have an excellent prognosis for normal
cognitive functioning...."  >>

I heard Eppes lecture on Lyme and he said--more or less--"the neurological
features, well, I am not even going to get into that...". This was to a room
full of physicians--he dismissed the neurological aspect of the disease and
concentrated on  the rheumatological.
This study will come in handy when appropriate treatment is defined
   In the meantime this is what will happen to the untreated and inadequately
children when they become {*filter*}s.


Brian A. Fallon, M.D. (1)
Jennifer A. Nields, M.D.
Joseph J. Burrascano, M.D.(2)
Kenneth Liegner, M.D. (3)
Donato DelBene, B.A. (1)
Michaell R. Liebowitz, M.D. (1)

PSYCHIATRIC QUARTERLY, Vol 63, No. 1 Spring 1992



The purpose of this section is to better acquaint the clinician with
some of the typical, often bizarre, neuropsychiatric symptoms seen
in late-stage Lyme disease as well as with some of the psychological
stresses that specific aspects of this illness and its treatment
place on patients and their families.  Psychiatrists should be alert
to these clinical aspects of the disease in order not to miss the
diagnosis of Lyme disease in patients who present with primarily
psychiatric complaints and in order to render more effective care to
patients with known disease.  Accordingly, this section is
descriptive; it is based on clinical interviews with {*filter*} and
pediatric patients and their families as well as written
descriptions from among 200 seropositive patients who responded to a
questionnaire regarding neuropsychiatric symptoms.  Symptom
frequencies drawn from an initial sample of 85 seropositive patients
with clinical symptoms of late stage Lyme disease will be presented.
A full description of this questionnaire and detailed results will
be published elsewhere.  The frequencies should not be considered
representative Lyme disease patients in general but rather of a
subgroup with severe, longstanding and/or chronic disease.


Among the respondents to the questionnaire, some described syndromes
indistinguishable from major depression, generalized anxiety diorder
or panic attacks.  Patients also described a variety of other
neuropsychiatric symptoms, and the most prevalent and distinctive
among such symptoms will be detailed here. (The arthritic,
dermatologic, and cardiac symptoms will not be discussed.)  Not all
of the neuropsychiatric symptoms that follow are specific to Lyme
borreliosis nor is the list comprehensive, but taken together they
provide a clincial pattern typical of the cases in our study.


Some of the most commonly reported symptoms in our sample were
fatigue (94%) and memory problems (83%).  Sometimes the fatigue is
relatively mild, allowing the patient to continue working, perhaps
in a diminished capacity.  Sometimes, however, the symptoms may be
quite severe, such that the patient may be bedridden due to
intractable fatigue.  Memory problems, too, can be mild or quite
severe.  One woman in our sample who had been a telephone
switchboard operator for 20 years reported suddenly being unable to
remember how to transfer calls.  In this woman's case, the memory
problems resolved completely following antibiotic treatment.
    The differential diagnosis between fatigue and memory problems
due to active Borrelial infection versus as part of another
disorder, such as fuctional depression or chronic fatigue syndrome,
is an important one.  Patients with active borrelial infection who
have prominent fatigue and memory problems may respond well to
antibiotic treatment whereas for patients with a non-Lyme related
syndrome such treatment would be of no benefit.  A history of tick
exposure, positive serologies, erthema migrans, and other associated
neurologic or arthritic symptoms may alert the clinician to the
diagnosis of Lyme disease.  If Lyme disease has been diagnosed and
the patient has persistent symptoms despite having receivec a prior
"adequate" course of antibiotics, some clinicians will recommend no
further antibiotic treatment (based on the post infectious
autoimmune hypothesis) while others may recommend continued
treatment until all symptoms remit (based on the persistent
sequestered infection hypothesis).  Treatment responses may be
difficult to gauge both because fluctuations in symptomatology occur
even in untreated Lyme disease, and because the clinical response to
effective antibiotic treatment may be delayed in some cases.


As in various other infections and or CNS disturbances (e.g.
menigitis, migraine, psittacosis, typhus, Rocky Mountain Spotted
Fever), photophobia may be a prominent feature.  In our sample, 70%
of respondents reported photophobia.  The severity of this symptom
can be quite striking, and there may be variants, including
idiosyncratic reponses to particular kinds of light.  Patients may
need to wear sunglasses or glacier glasses, even indoors, even at
night.  Several patients reported feeling "faint" or "dizzy" in
particular when exposed to fluorescent lights, making it difficult
to go to supermarkets or other public places.  Of note: such a
patient might be referred to a psychiatrist because of what seemed
like agoraphobia.  Some patients have developed panic-attacks that
seemed to be triggered by sound or light stimulation-especially
bright lights that flicker, such as fluorescent lights - and which
resolved following atnibiotic treatment.  Others have developed
nausea in response, again, to lights that flicker:fluorescent
lights, TV or computer screens, strobe lights during EEG testing or
headlights of cars moving in the opposite line of traffic.  The
hypersensitivity to light can be incapacitating or merely
uncomfortable.  It may preclude driving at night or going outdoors
during the day or it may make what are normally routine or even
pleasurable activities seem noxious.


A more distinctive, somewhat less common but often very intense
symptom, reported in 48% of our sample , is hypersensitivity to
and/or idiosyncratic responses to sound stimulation.  One boy
developed sound sensitivity so severe that ordinary conversation was
deafening to him; he wore head phones and put pillows over his head
to block out the sound.  To one woman even the sound of another
person's breathing seemed unbearably loud.  In her case, the sound
sensitivity also included vertigo, nausea and nystagmus in response
to sounds.  Any sudden sound, like the phone ringing, and certain
household sounds, like the running of tap water, could cause her to
fall or retch.  This peculiar short-circuiting of the inner ear's
auditory and vestibular functions is known as the Tullio phenomenon.
This phenomenon has been deemed pathognomonic for syphilis (43) but,
as it appears, can occur in Lyme disease as well(41), and thus
provides one more example of the "new great imitator," Lyme disease,
imitating the old "great imiatator," syphilis(1).


As previously reported in illnesses caused by other species of
borrelia (44), hypersensitivity can occur in other sensory
modalities as well: touch, taste and smell.  Abnormalities of taste
and smell occured in 30% and 25% of our sample, respectively.  Foods
may taste abnormally sour or bitter; smells may seem overly intense
and noxious.  Alterations in the perception or processing of other
kinds of sensory stimulation occur also.  One patient, before she
realized she was ill with Lyme disease, noticed one day that her car
was vibrating with unusual {*filter*}.  She took the car emergently in
to a mechanic, thinking that the shock absorbers were shot or the
ball bearings loose and that it would be dangerous to continue to
drive the car in that condition.  As it turned out, there was
nothing wrong with the car.  The problem was in the patient who had
suddenly and unwittingly developed a heightened sensitivity to
vibrations.  She subsequently became alert to this heightened
vibration sense in other contexts as well.  When the diagnosis of
Lyme disease was finally made, this symptom, along withother, more
common symptoms of Lyme disease, resolved with antibiotic treatment.


Many patients reported mood and behavi{*filter*}changes during the course
of their illness.  In our sample, 84% of patients reported increased
irritability and/or emotional lability in association with symptoms
suggestive of meningeal irritation: neck stiffness and headache.
The mood and behavior changes are often so severe and pervasive as
to constitute a personality change.  Sudden, intense irritability is
most often triggered by sensory stimulation in patients who are
acutely sensitive to sound, touch or light but may also occur
unprovoked and seemingly inexplicably.  One man, acutely senstive to
sound, was so intensely bothered by the noise his three year old son
was making that he picked him up and shook him in a sudden and
unprecedented fit of {*filter*}.  His wife was shocked and alarmed by
this behavior, as was the patient himself.  A woman, typically
reserved and eager to please, became
uncontrollably irritable one day at work and found herself yelling
at her boss in a most uncharacteristic fashion.  Others have found
themselves bursting into tears, sometimes several times a day, on
what seems like very little provocation.


These odd, idiosyncratic but quite common symptoms were reported in
69% of our sample.  Patients with no prior history of dyslexia have
found themselves writing letters backwards, reversing numbers or
routinely reversing the first and second letters of a word. One
patient recalls also switching her shoes: putting the left shoe on
the right foot and the right shoe on the left foot before she
realized her mistake.  This patient also experienced what might be
understood as reversals in temp{*filter*}sequencing: for instance, saying
the work "tomorrow" when she meant "yesterday" and vice versa.


Reported in 57% of our sample.  A not uncommon scenario is of a
patient who, recalling no rash or flu-like symptoms, had experienced
some aches and pains and/or memory problems but had not paid much
attention to these symptoms until he found himself, on two
consecutives days, lost in his own neighborhood, on his way home
from work.  Such a scenario suggests a disorder of topographic
orientation and geographic memory such as may be seen among patients
with parietal lobe dysfunction (45). Patients have reported other
behaviors as well which seem to relate to disturbances of the
body-environmental schemata.  A young woman described repeatedly
bumping into things on the left side of her body, dropping things
from her left hand despite having no weakness in that hand and
occasionally placing objects, such as a milk carton, several inches
short of a table edge with the result that they would fall to the
floor.  These difficulties remitted completely following adequate
antibiotic treatment.


This can be one of the most frustrating and perplexing aspects of
the illness.  A patient with late-stage Lyme disease might feel
totally drained one day, the next day be able to function almost
normally and and day after experience such mental confusion as to be
unable to focua on even the simplest of tasks.  Sometimes the
fluctuations may be brought on by exertion or stress or exposure to
sensory stimuli or by the initation of antibiotic treatment, but
sometimes no explanation can be found.  The fluctuations make it
impossible for patients to make plans, and may make it seem to
friends, teachers, family members or even the patients themselves as
if the symptoms were somehow under voluntary control or as if they
were hysterical in origin.  Of course psychological factors, too,
can influence symptomatology, but fluctuations are typical
regardless of mental state.
    Such vicissitudes raise a particular problem in children who may
experience fluctuating cognitive impairments: short-term memory
problems, word finding difficulties, dyslexia, problems with
calculations or inability to concentrate.  School systems are by and
large unaware of the cognitive aspects of late-stage Lyme
disease and, in particular, of the ways in which cognitive
impairments may fluctuate from day to day in a given child.
Teachers may assume the child is just moody or uncooperative.
Family dynamics, too, may be complicated by confused expectations of
the sick member, and resentments may build when a person's
functional status, mood and ability to participate in family life
seem inexplicably erratic.  Patients and family members alike find
it difficult to have their hopes raised repeatedly by a transient
clinical improvement, only to be slapped down again by a
recrudescence of debilitating symptoms.  Even with treatment,
recovery from late-stage Lyme disease is most often a lengthy
process involving significant fluctuations in symptoms even in the
context of overall improvement.


Nearly half of the patients in our sample reported a transient
worsening of neuropsychiatric symptoms during the first few days of
antibiotic treatment.  The worsening of syymptoms during initiation
of antibiotic treatment is thought to be a variant of Herxheimer
reaction as seen in the treatment of syphilis (33).  In Lyme
disease, however, this Herxheimer-like reaction can be quite
prolonged - lasting a few days or longer - and can be frightening to
patients who are expecting a resolution, not worsening, of their
symptoms.  The reaction can sometimes be difficult to distinguish
from an allergic reaction to the medicine, a distinction with
obvious and crucial treatment implications.
    This Herxheimer-like reaction may be experienced as a worsening
of psychiatric symptoms:some patients in our sample experienced
panic attacks for the first and only time when starting on
antibiotics.  Others have reported an intensification of depressive
symptoms, suicidality or anxiety.  Many reported an increased
startle response and photophobia during the first few days of
antibiotic treatment.


A great deal is unknown about Lyme disease at this point in time,
and experts disagree regarding its diagnosis and management.  Some
patients remain seronegative, for a variety of reasons (some known,
some unknown) (30) and therefore remain undiagnosed and untreated
for long periods of time.  The medical literature now documents that
some patients, even following what has been presumed to adequate
treatmen, go on to develop late-stage symptoms, sometimes months or
years later (2).  Even now, some doctors think that so-called
seronegative Lyme disease is fairly common and others that it is
virtually nonexistent.  Some doctors believe that prolonged
antibiotic treatment may be necessary in late Lyme disease (33,46),
and others, emphasizing the less specific symptoms of late Lyme
disease (similar to fibromyalgia or chromic fatigue syndrom),
consider such treatment in many cases to be excessive and
unreasonable (47).  Patients may be told that Lyme disease is easily
curable with antibiotics and that further concern about it is a
matter "Lyme anxiety"(48); from other sources, they may learn that
Lyme infection in some cases may lead to a chronic, severly
debilitating, perhaps irreversible disease (2).
    Such manifold uncertainties as to diagnosis, treatment and
prognosis at this state in the history of Lyme disease put the
patient in a difficult position.  The patient may get conflicting
advice from reputable sources and not know what to do.  He may be
told that his symptoms are not related to Lyme disease.  He may be
told there is no medical cause for his complaints and be referred to
a psychiatris.  And, especially since Lyme disease may in fact
involve the brain and manifest as depression  or confusion or
irritability, it may be hard not only for the clinician, but also
for the patient himself to recognize the effects of the disease as
against his emotional reactions to it.  Some patients, who have
subsequently been effectively treated, have said that, prior to
being diagnosed, they had feared they were just going crazy.


It is important to make a clear diagnostic assessment of the range
of problems a patient brings.  In cases where the diagnosis is
unknown or uncertain or where the psychiatric picture is atypical,
aspects of the medical history, such as living in an endemic area,
hiking, tick exposure, neck pain or past history of a swollen knee
might alert the clinician to the possibility of Lyme disease.  If
Lyme disease is suspected, a thorough medical evaluation is
    Among patients presenting to a psychiatrist with a known
diagnosis of Lyme disease, some complaints, such as irritability or
depression with sleep disturbances or hypersensitivity to sensory
stimuli, may be directly related to the disease process.  Other
problems, such as depressed mood, feelings of inadequacy, bitterness
or guilt may be secondary effects of having a severe chronic
illness.  Such problems may result from alterations in functional
status, loss of social relationships  or problematic family dynamics
precipitated by the illness.  The psychiatrist may help patients to
address these problems, for instance, by a process of mourning and
acceptance, by cognitive reframing responsibilities.  Psychotropic
medications may be helpful as an adjunct to medical treatments for
Lyme disease.  Most commonly used are anxiolytics, low-dose
antidepressants for pain and sleep and higher dose antidepressants
for major depression.  Given that Lyme disease can cause conduction
abnormalities, it is of particular importance to obtain an EKG
before starting treatment with tricyclic antidepressants.
    When patients suffer from irritability related to sensory
hyperacusis, as described earlier, it may be useful to help such
patients identify the triggers and avoid them if possible.  It may
also be quite helpful just to explain to patients and/or to family
members that such irritability and the resultant behavior changes
can indeed be a function of the disease.  One man developed extreme
irritability related to audirory hyperacusis.  His wife recalls
thinking: "This is not the man I married."  She doubted that she
could continue to live with  him if this personality change were to
persist.  Even after he had been treated and returned to normal,
both husband and wife remained uneasy until they found an
explanation for the change: that it had to do with the illness, and
was not some inexplicable, inextricable newly emergent part of the
man himself.
    Family therapy may be indicated especially where a sick child is
concerned.  Siblings may feel short-changed because of a relative
lack of attention while the sick child may envy - and
resent - his or her siblings for their capabilities and lack of
physical suffering.
    Couples therapy may be indicated is some cases.  Most patients
report a significant loss of libido.  This can lead to frustration,
alienatiion and anger in the spouse, and may in any case make it
difficult for some couples to maintain intimacy.  There may be a
diffuse sense of loss on both sides which is then displaced and
experienced as anger or resentment against the spouse.  Defenses
that have served the partners well throughout most of their marriage
may be overwhelmed by the manifold adjustments the illness demands;
couples may need help in finding alternative ways of coping and
    Many patients have felt abandoned by their medical doctors when
the diagnosis was uncertain or the treatment not fully curative.
Others have had to see many different doctors before one was able to
put together the diversity of their symptoms and come up with a
diagnosis.  Several patients have said tha the hardest thing to bear
- even more than the pain and disability - had been the feeling that
they were somehow inexplicably altered, in their emotional and
personality and ability to function, without hope of finding a cause
or cure, and without a doctor who could honor their difficulty,
whether or not he or she could solve it.  For some patients, then,
the ambiguities surrounding diagnosis and treatment and the
consequent sense of abandonment by medical professionals were among
the most distressing aspects of the illness experience.  The
psychiatrist can be of help by lending respectful support to such
patients: by listening and by helping them to clarify their options.


In most cases, Lyme disease, when treated early, is a mild illness
with no long-term sequelae.  When first identified in its late
stages, however, some of the symptoms of the illness may be less
responsive to antibiotic treatment, resulting in a disabling,
chronic disorder.  From the foregoing clinical vignettes, it should
be clear that Lyme disease, particularly when it involves the
central nervous system, can is some patients be an extremely
debilitating, bizarre, terrifying and perplexing disease.  It can
present in a great variety of ways, and the symptoms can fluctuate
dramatically and unpredictably.  At the same time, there are
patterns to its emergence that can suggest the diagnosis in cases
where laboratory indices are inconclusive.  Much uncertainty
surrounds the diagnosis and treatment of Lyme disease at this stage
in its history, and such uncertainty adds to the distress that the
illness causes fo patients.  Lyme disease is aptly called the "new
great imitator," and it can imitate psychiatric disorders no less
that medical ones.  Psychiatrists working in endemic areas are well
advised, then, to keep Lyme disease in mind as part of their
differential diagnosis for a broad range of disorders including, for
instance, panic attacks, somatization disorder, depression, and
dementia, especially in cases that are atypical or otherwise
suggestive of systemic disease.  It should be borne in mind also
that new clincial manifestations of Lyme disease are sill being
discovered and described.  In cases of known Lyme disease, it is
important for psychiatrists to take a comprehensive approach to
treatment as so many aspects of the patient's life - physical,
emotional, cognitive, familia, {*filter*}, social and occupational - may
be significantly affected by the illness.


Supported in part by NIMH Research Fellowship to Dr. Fallon


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