THE NEUROPSYCHIATRIC MANIFESTATION

OF LYME BORRELIOSIS

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

--------------------------------------------------------------------

(1)Department of Psychiatry, College of Physicians and Surgeons of

Columbia University, and Division of Therapeutics, New York State

Psychiatric Institute, New York, N.Y.

(2)Southampton Hospital, Southampton, New York

(3)Northern Westchester Hospital Center, Mt. Kisco, New York

Address correspondence to Brian A. Fallon, M.D. New York Psychiatric

Institute, 722 West 168th Street, Box 13, New York, New York 10032

-------------------------------------------------------------

Since the identification of the cause of syphilis in the early

1900s, psychiatrists have been aware that: (1) severe psychiatric

disorders may be caused by a central nervous system infection; and

(2) early antibiotic treatment may prevent permanent neurological

damage. Syphilis was known as the "great imitator" because its

multiple manifestations mimicked other known diseases. Today a new

epidemic has emerged that has multiple manifestations and has been

dubbed "the new great imitator" - Lyme borreliosis (Lyme

disease)(1). Because Lyme borreliosis, like syphilis, has

neuropsychiatric manifestations, psychiatrists are being asked to

see these patients-often before they are diagnosed. Incorrectly

labeling these patients as having a functional psychiatric disorder

may result in a delay in initiating antibiotic treatment. Such

delay can lead to severe disability and, possibly, irreversible

neurologic damage(2). Because of the epidemic of Lyme borreliosis

in areas of New York State and its rapid spread nationwide (3), it

behooves mental health professionals to be aware of its multiple

typical and atypical presentations.

Part 1 of this paper consists of a general overview of Lyme

disease and a review of its neuropsychiatric manifestations. Part 2

provides more detailed clinical descriptions of the neuropsychiatric

aspects of Lyme borreliosis and suggests ways in which psychiatrists

can be of help. The clinical vignettes will be based on data

collected from approximately 200 patients with sero-negative Lyme

disease.

PART 1.OVERVIEW (BRIAN A. FALLON)

Diagnosis

Lyme borreliosis, caused by the spirochette Borrelia burgdorferi,

is an infection commonly transmitted by the bite of an infected

arthropod - primarily ticks. A tick feeding may take up to 3 days

and disease transmission appears to take 12-24 hours. The clinical

spectrum of the disease includes dermatologic, neurologic,

opthalmologic, cardiac, rheumatologic, and psychiatriac

manifestations (4).

The criteria for diagnosising Lyme disease vary depending upon

the purpose. For surveillance studies (3), the diagnosis requires a

history of exposure in an endemic area and either : (1) a

physician-diagnose erythema chromicum migrans rash, or, (2) se

rologic evidence of exposure to Borrelia burgdorferi and one of the

following: (a) arthritic symptoms-recurrent brief attacks of joint

swelling or joint pain; (b) neurologic symptoms - such as

lymphocytic meningitis, cranial neuritis, radiculoneuropathy, and/or

encephalomyelitis; or (c) cardiac conduction defects-second or third

degree -----.

This definition, while for research purposes, is unduly

restrictive because about one-third of patients do not recall a rash

and because current serologic testing is generally considered

inadequate, producing false negatives and false positives (5).

Thus, the diagnosis of Lyme disease at this point remains clinical

not serologic.

Because Lyme borreliosis is multisystemic, the differential

diagnosis had to be broad, including viral infections, aseptic

meningitis, disseminated gonococcal infection, rheumatoid arthritis,

late stage syphilis, mutlipule sclerosis, Guillian-Barre, AIDS,

systemic lupus, subacute bacterial endocarditis, thyroiditis,

Reiter's syndrome, fibromyaligia, chronic fatigue symdrome, and

psychiatric disorders. If treated early, the disease may be limited

to an asymptomatic rash or only a few days to a week of flu-like

symptoms. In its later stages, patients may have multisystemic

disease, leading to an inability to work for months or years. The

simplest tasks may become insurmountable.

Distribution

Ticks infected with borrelia burgdorferi have been found across the

United States and around the world (6). The number of United States

cases has increased dramatically since record keeping started in

1980. Between 1985 and 1988, the number of states with reported

cases of Lyme borreliosis rose from 8 to 46 (3). Although

distributed nationwide, certain states carry the heaviest burden of

illness. In 1988, for example, New York State accounted for more

reports than any other state, contributing 56% of the national Lyme

case reports (3). Between 1986 and 1989, the annual incidence of

Lyme disease in NYS (based on reported cases which met the

surveillance definition) increased 7-fold. Many additional cases

were reported which did not meet the surveillance case definition.

These data indicate that Lyme disease is a steadily increasing

national public health problem.

History

Although many people believe that Lyme disease was discovered in

Lyme Connecticut in 1975, an illness very much like Lyme disease has

been recognized in Europe for over 100 years. In 1883, a German

physician described the rash common in the later forms of

Lyme disease-acrodermatitis atrophicans(7). In 1909 a Swedish

physician described the classic Lyme rash, known as erythema

chronicum migrans (ECM), and linked it to a tick-borne infection

(8). In 1922, Dr. Garin-Bujadoux described what is now recognized

as a disseminated form of Lyme disease. His patient developed ECM

after a tick bite, followed by radiculopathy, peripheral paralysis

of one arm, and meninigitis (9). In 1941, Dr. Bannwarth described a

similar neurologic syndrome and callled it "chronic lymphocytic

meningitis" (10). Principal signs were radicular pains, lymphocytic

meningitis without meningeal signs, and involvement of the

peripheral nervous system, particularly facial palsy. In Europe,

Lyme disease with neurological manifestations has been described

under many labels, including neuroborreliosis, the Garin-Bujadoux

syndrome, and Bannwarth's syndrome. Lab studies often demonstrate

an elevated ESR, an elevated spinal fluid IgM level, and pleocytosis

in the spinal fluid, often with lymphocytic predominance. As will

be discussed later, these abnormal lab findings are not always

present in the American form of neuroborreliosos.

Although the first report of a tick-induced ECM rash was from

Wisconsin in 1970 (11), Lyme disease first came to critical

attention in the United States in 1975 when Dr. Alan Steere

described what seemed to be a illness after investigating an

unusually high prevelance of presumed juvenile rheumatoid arthritis

in Old Lyme Connecticut. Naming this outbreak after the town in

which it occurred, he called this illness Lyme Arthritis (12). By

the late 1970's it was recognized tha the illness had systemic

manifestations including neurologic, rheumatologic, dermatologic,

cardiac components and so the name of the illness was changed from

Lyme arthritis to Lyme disease. In 1982, the infectious agent

Borrelia burgdorferi was identified (4). Soon thereafter, reports

indicated that the European neuroborreliosis was caused by a similar

if not identical organism (13). In acknowledgement of this

infectious agent, Lyme diseas is now referred to as Lyme

borreliosis.

Clinical Profile

There are a wide variety of symptoms associated with Lyme

borreliosis. Symptoms vary greatly, one or more systems may be

involved, and new manifestations continue to be described. The

progression of illness has generally been separated into early and

late borreliosis.

The most identifiable early symptom of Lyme disease is the rash,

erthema chronicum migrans, which may appear days to weeks after the

bite. The rash typically is a bull's eye rash that may enlarge from

its site of origin to 10cm or greater. Commonly the patient may

experience flu like symptoms-fatigue and malaise, arthralgias,

myalgias (backaches, stiff neck), fever, headaches. These symptoms

however may be mild and therefore unremarkable.

The patient may not notice any symptoms until weeks or months

after the original tick bite when late stage infection has already

set in. Such late stage symptoms include neurologic, arthritic,

opthalmologic, psychiatric, dermatologic and/or cardiac symptoms.

If untreated, the symptoms may last for months and years, sometimes

punctuated by spontaneous remissions and recurrences. About 15

percent of infected patients develop objective neurologic

abnormalities, most commonly displaying part of the triad of

aseptic meningitis, cranial neuritis, and motoror sensory

radiculitis. ASEPTIC MENINGITIS may begin with recurrent attacks of

headaches, stiff neck, photophobia, nausea, and vomiting. The

headaches may fluctuate from mild to severe. Spinal fluid abnorma

lities may include a pleocytosis or lymphocytosis, and increase in

the IgG synthesis rate, an elevated CSF protein, and oligoclonal

immuoglobulins. The opening pressure may not be elevated (15).

CRANIAL NEURITIS, such as Bell's palsy, may be unilateral or

bilateral and may be seen in 5-10% of patients with neuroborreliosis

(16). Other cranial nerves may be involved as well, especially the

3rd, 4th, and 6th. The RADICULOPATHIC SYNDROMES may also be

unilateral or bilateral, with a predominance of motor over sensory

symptoms. The most common dermatomes involved are the fifth

cervical dermatome and T8 through T12 (14). Formal pain testing may

show diminished or absent pain sensation in affected dermatome. In

Europe, the syndrome of meningitis and radiculitis was known as

Bannwarth's syndrome.

The most common CARDIAC PROBLEM is an atrioventricular block

(second or third degree) (17). Other cardiac problems may include

acute myopericarditis, left ventricular dysfunction, and

cardiomegaly. Although most cardiac symptoms tend to be brief,

lasting from 3 days to 6 weeks, and rarely lead to residual

dysfunction, increasing evidence suggests that Lyme disease carditis

may be of long duration and lead to permanent heart damage(18).

Later into the disseminated phase of the illness, patients may

develop arthritic, other neurologic, opthalmolgic, and other

dermatologic symptoms. The timing may be variable, occurring within

weeks of the early symptoms or after a gap of several years. The

ARTHRITIC SYMPTOMS may begin as a migratory musculoskeletal

discomfort (similar to fibromyalgia). In 60% of untreated patients,

an inflammatory arthritis develops, typically affecting large

joints, such as the knee. Subsequently a small portion of patients

with arthritis develop chronic synovitis. Arthritis attacks,

lasting days to weeks, amy recur for several years. OPTHALMOLOGIC

manifestations in the early stage may include conjunctivitis,

iritis, and uveitis while in late stage illness optic neuritis and

optic atrophy may occur (4). The late DERMATOLOGIC entity, known as

acrodermatitis chronica atrophicans, is more common in Europe than

in the United States (13).

The LATE NEUROLOGIC SYMPTOMS consist primarily of mild to severe

ENCEPHALOPATHY, A POLYNEUROPATHY, AND PROFOUND FATIGUE. This

encephalopathy which is thought to occur in 9 of 10 patients with

chronic neuroborreliosis is often characterized by subtle

disturbances in mood, memory and sleep (2). It is in ruling out

subacute encephalopathy that psychiatrists will have their greatest

diagnostic challenge, for these patients may be irritable, tearful,

depressed, and have poor concentration and sleep. A diagnostic tip

in favor of Lyme disease as the cause of the depression and

irritability might be concomitant memory loss, word finding

problems, or a concomitant polyneuropathy. The POLYNEUROPATHIES,

often demonstrable on electrophysiologic testing, include spinal or

radicular pain, paresthesias, sensory loss, and/or lower motor

neuron weakness.

A recent study (2) indicated that chronic neurologic

abnormalities may emerge anywhere from 1 month to 14 years after

infection. Like syphilis, therefore, Lyme borreliosis may remain

latent and asymptomatic for a long period of time. Patients may

have chronic neurologic symptoms for more than one year, with some

patients suffering for 10 years or more despite having received

antibiotic therapy.

Cognitive impairmants among patients with late Lyme disease may

be subtle. Some patients may demonstrate initial abnormalities on

neuropsychological testing, while others may not (2,19). Serial

neuropsychological testing before and after antibiotic treatment may

reveal significant improvement after treatment. In on study (19),

improvement was noted on tests of memory (California Verbal Learning

Test, Wechsler Memory Scale), attention and concentration (Symbol

Digit Modalities), conceptual ability (Booklet Categories Test), and

psychomotor and perceptual motor function (Block Design Subtest of

the WAIS and Purdue Pegboard). Initial scores fell within normal

range on some of these tests (eg. Wechsler Memory Scale) but

nevertheless improved after treatment; this demonstrated that some

patients with subjective memory loss that is not apparent on initial

neuropsychological testing may nevertheless benefit from antibiotic

treatment. Noteworthy is that many patients with cognitive deficits

did not have clinical evidence of focal CNS disease. EEG's CSF

studies, and most other laboratory investigations were often normal.

MRI scans were abnormal in many of the patients with moderate to

severe memory impairment. The MRI abnormalities, which may be

indistinguishable from those seen among patients with multiple

sclerosis, indicated edema or inflammation suggesting the the Lyme

disease patients may be suffering from a mild inflammatory

encephalomyelitis. Finally, it should be noted that some patients

even after a course of intravenous antibiotic treatment continue to

have memory impairments demonstrable on neuropsychological testing

(Selective Reminding Test) (20).

The course and severity of illness can vary. In most cases,

Lyme disease if treated early is a transient illness with mild

symptoms and no long term sequelae. In a smaller portion of

patients, the course may be chronic and severe. Case reports have

linked a variety of neurologic syndromes to late Lyme disease,

including blindness (21), progressive demyelinating-like syndromes

(mimicking Multiple sclerosis) (2) or Amyotrophic lateral sclerosis

(22), Guillain-barre (23), progressive dementias (24), seizure

disorders (25), strokes (26), and extrapyramidal disorders (27).

Encephalomyelitis can be caused by borrelia burgdorferi and is

characterized by spastic paraparesis, ataxia, cognitive impairment,

bladder dysfunction, and cranial neuropathy (28). Finally, although

transplacental transmission of borrelia burgdorferi does occur and

only rarely leads to fetal injury, neonatal death has been linked

with Lyme borreliosis based on culture positive frontal cortex

specimens (29).

Laboratory Tests

Because borrelia burgdorferi is difficult to culture, physicians are

using indirect methods to detect the spirochetes. Antibody tests,

such as indirect immunofluorescence and the enzyme-linked

immunosorbent assay (ELISA), were initally thought to be dependable

lab tests for the diagnosis of Lyme borreliosis. Now it is

recognized that these tests give both false negative and false

positive results (5). In addition, results from different

laboratories on the same specimen may be highly variable, with one

indicating no reactivity and another reporting significant antibody

titers. Seronegative Lyme borreliosis, once a source of

controversy, is now recognized as a diagnostic problem (30).

Patients may have no detectable antibodies to Borreia burgdorferi in

either their serum or their CSF, but still have clinical disease. A

recent report described 6 patients who were seronegative and

CSF-antibody negative who were subsequently shown to have evidence

of the spirochetes in the CSF based on a positive polymerase chain

reaction assay (31).

The Western blot is often used to confirm positive results from

an ELISA or IFA, although it too may be falsely negative or falsely

positive. When meningopolyneuritis or encephalomyelitis is

suspected, intrathecal antibody determinations should be attempted.

The spinal fluid may reveal a mononuclear pleocytosis and/or an

elevated CSF IgG or IgM for borrelia burgdorferi. CT and MRI

findings may occur in the encephalitis cases, as well as EEG slowing

and epileptic discharges. However, as previously noted, serologic

and other objective abnormalities are not always found. Silver

staining has been used for detecting spirochetes in tissues, but the

yield is low. The polymerase chain reaction (31), which amplifies a

target DNA sequence specific for Lyme disease, has promise as a

sensitive and potentially specific means for identifying Borrelia

burgdorferi. This test's commercial usefulness, given marked

difficulties in avoiding contamination which cause false positives,

remains to be determined.

Treatment

Lyme disease is treatable with antibiotics, however treatment may be

less effective in the late stage of illness (32). Oral antibiotics,

such as amoxacillin and doxycline, are considered effective for the

early stage of the illness. When the central nervous system is

involved, intravenous antibiotic treatment with third generation

cephalosporins, such as ceftriaxone sodium and cefotaxime, is

indicated for at least 10 days to 3 weeks. Recent reports now

suggest that longer courses of treatment may be needed, as well as

repeated courses if symptoms recur (2,33,42). Early during the

antibiotic tratment patients may experience a sudden worsening of

symptoms. This Jarisch-Herxheimer-like reaction is thought to be an

inflammatory response to spirochetal lysis (33).

Patients given antibiotics early in illness tend not to have

major late complications, although an unknown percentage of patients

treated early still develop late complications. It is now thought

that relapse is due to continued presence of spirochetes (2,42).

Although most patients do improve with treatment, a subgroup of

patients with late Lyme disease may not improve after a course of

intravenous antibiotics (2).

Psychiatric Manifestations

A review of the world literature on the psychiatric manifestations

of Lyme borreliosis suggests that psychiatric problems may be a

prominent feature of Lyme borreliosis. The literature consists

largely of case reports and small series and thus must be regarded

as suggestive rather that definitive.

In 1930 a patient was described who three months after an ECM

rash developed an encephalitis with psychotic symptoms and marked

CSF abnormalities (34). More recently, a patient with Lyme

borreliosis was described whose clinical picture was indistingui

shable from an endogenous schizophrenia (35). The

patient's paranoia and hallucianations remitted after one week of

antibiotic treatment with ceftriazone, but aftrwards the patient

showed a mild organic brain syndrome.

In Europe, two recent review articles have stated that

psychiatric symptoms can be a prominent feature of Lyme borreliosis,

including agitated depression and psychosis (36,37). Kohler

described a staging of psychiatric symptoms which parallel the

neurologic ones. In stage I, fibromyalgia, painful muscular

fasciculations, and mild depression may dominate the clinical

picture. In stage II, a lymphocytic meningopolyneuritis may occur

along with an organic psychiatric disorder, such as organic

affective syndrome or an organic personality syndrome. In stage

III, chromic encephalitides and myelitides may be accompanied by

severe psychiatric syndromes, such as organic psychoses, dementia,

and anorexia nervosa. This staging was based on clinical

observation not systematic studies.

In the United States, Pachner (38) presented two patients whose

symptoms were largely psychiatic. A 12 year old boy with confirmed

Lyme arthritis treated with oral antibiotics subsequently became

depressed an anorectic. After being admitted to a psychiatric

hospital with the diagnosis of anorexia nervosa, he was noted to

have positive serologic tests for Borrelia burgdorferi. Treatment

with a 14 day course if intravenous antibiotics led to a resolution

of his depression and anorexia; this improvement was sustained on 3

year follow-up. A 21 year old man seropositive for Borrelia

burgdorferi developed progressive confusion, agitation,

disorientation, inapproppriate laughter, and violent outbursts; a

temporal lobe biopsy revealed spirochetes. Treatment with IV

penicillin resulted in a return to normality within 3 months.

In one U.S. study of 27 patients with late neuroborreliosis, 33%

were depressed based on their scores on the Minnesota Multiphasic

Personality Inventory (2). 89% of these 27 patients also had

evidence of mild encephalopathy, characterized by memory loss (81%),

excessive daytime sleepiness (30%), extreme irritability (26%), and

word finding difficulties (19%). Controlled studies indicate

significantly more depression among patients with late Lyme

borreliosis than among normal controls (20) and other chronically

ill patients (39).

Confounding accurate diagnosis is the fact that many of the

prominent symptoms of Lyme disease share features with depressive

illness, including irritability, fatigue, emotional lability, poor

concentration, memory problems, and impaired sleep (2). Ruling out

Lyme disease as a cause of these depressive symptoms can be

difficult because currently available serological tests are

inadequate, a third of all patients do not recall a rash or tick

bite, and a long quiescent period may precede the late symptoms.

Even when the diagnosis of Lyme disease is clear, optimal treatment

of these depressive symptoms is uncertain because in many patients

the symptoms persist even after the standard 3 week course of

antibiotics. While some doctors feel that depressive syptoms in the

context of Lyme disease are evidence of continued disseminated

infection, others believe that these represent a secondary emotional

response to having a serious illness. Appropriate treatment if the

former is true would consist of further antibiotics, which if the

latter is true psychotherapy and/or anti depressant therapy would be

the treatment of choice. Delayed additional antibiotic treatment

due to an incorrect assessment of the disease process may enable an

acute illness to develop into a chronic one (2).

In conclusion, further systematic study is clearly needed to

better understand the prevalence and pathophysiology of psychiatric

problems among patients with Lyme borreliosis and to identify

optimal treatment. A critical review of the literature indicates

that disturbances of mood, memory, and sleep are prominent features

of this illness. Whether borrelia burgdorferi also causes psychotic

disorders and eating disorders remains an open question.

Neurosyphilis, also caused by a spirochete, is known to be

associated with memory problems, depression, mania, psychosis, and

personality changes, such as irritability, emotional lability, and

apathy (40). Given the remarkable similarities between syphilis and

Lyme borreliosis, it is possible that the full range of psychiatric

symptoms seen in neurosyphilis may also soon be recogmized as

features of Lyme borreliosis.

THE NEUROPSYCHIATRIC MANIFESTATIONS

OF LYME BORRELIOSIS

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

PART II. THE CLINICAL EXPERIENCE OF LYME

DISEASE: PATIENTS' PERSPECTIVES AND THE

PSYCHIATRIST'S ROLE (JENNIFER A. NIELDS)

-------------------------------------------------------------------

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 adult 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.

PHENOMENOLOGY

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.

FATIGUE AND MEMORY LOSS

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.

PHOTOPHOBIA

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.

SOUND SENSITIVITY

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).

SENSORY HYPERACUSIS

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 violence. 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.

EXTREME IRRITABILITY AND/OR EMOTIONAL LABILITY

Many patients reported mood and behavioral 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 violence. 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.

WORD REVERSALS WHEN SPEAKING AND/OR LETTER REVERSALS WHEN WRITING

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 temporal sequencing: for instance, saying

the work "tomorrow" when she meant "yesterday" and vice versa.

SPATIAL DISORIENTATION

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.

FLUCTUATIONS IN SYMPTOMS

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.

WORSENING OF SYMPTOMS DURING ANTIBIOTIC TREATMENT

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.

UNCERTAINTY AS TO DIAGNOSIS AND 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.

HOW CAN THE PSYCHIATRIST BE OF HELP?

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

essential.

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

interacting.

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.

CONCLUSION

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, sexual, social and occupational - may

be significantly affected by the illness.

ACKNOWLEDGEMENT

Supported in part by NIMH Research Fellowship to Dr. Fallon

REFERENCES

1. Pachner AR. Borrelia burgdorferi in the Nervous System the New

"Great Imitator" In Lyme Disease and Related Disorders,. Annals New

York Academy of Sciences 539. 56-64, 1988.

2. Logigian EL, Kaplan RF, Steere AC. Chronic neurologic

manifestations of Lyme disease. NEJM 323: 1438-1444, 1990.

3. White DJ, Chang HG, Nenach JL, et al The geographic spread and

temporal increase of the Lyme disease epedemic. JAMA 266: 1230-1236,

1991.

4. Burgdorfer W. Lyme borreliosis:ten years after discovery of the

etiologic agent, Borrelia burgdorferi. Infection 19: 257-262, 1991

5. Magnarelli LA Laboratory Diagnosis of Lyme disease Rheumatic

Disease Clinics of North America. 15:735-745, 1989

6. Schmid GP. The global distribution of Lyme disease Rev Infect

Dis 7:41-50, 1985

7. Weber K, et al. Erthema Migrans Disease and related disorders

Yale J Biol Med 57 13-21, 1984.

8. Alzehus A. Erthema Chronicum Migrans Acta Derm Vernereol 2

120-125, 1921

9. Garun, Bujadoux:Paralysie par les tiques. J Med Lyon 71 765-767,

1922

10. Bannwarth A Chronisch lymphocytare meningitis, entzundliche

polyneuritis and "rheumtisums:, Arch Psychiatr Nervenkr 113 284-376,

1941

11. Scriment RJ Erthema chronicum migrans Arch Dermatol 102

104-105, 1970.

12. Steere AC, Malawista SE, Hardin JA, et al Erythema chromicum

migrans and Lyme arthritis Ann Int Med 86 685-689, 1977

13. Asbrink FE Hovmark A. Hederstedt B The spirochetal etiology of

acodermatitis ------- atrophians Herxheimer Acta Derm Vernereol 64

506-512, 1984

14. Pachner AR, Steere AC. The triad of neurological manifestations

of Lyme disease meningitis, cranial neuritis, and radiculoneuritis.

Neurology 35 47-53, 1985.

15. Finkel MF. Lyme disease and its neurologic complications. Arch

Neurol 45 99-104, 1988.

16. Halperin JJ. Nervous System Manifestation of Lyme Disease,

Rheumatic Disease Clinics of North America. 15 635-647, 1989.

17. Reznick JW Braunstein DB, Walsh RI, Smith Cr, Wolfson PM,

Gierke IW, Gorelkin I, Chandler RW. Lyme carditis.

Electrophysiologic and histopathologic study. Am J Med 5:923-927,

1986.

18. Stanek G, Klein J, Bittner R, Glogar D. Isolation of Borrelia

burgdorferi from the myocardium of a patient with longstanding

cardiomyopathy. NEJM 322:249-252, 1990.

19. Halperin JJ, Pass HL, Anand AK, Luft BJ, Volkman DJ, Dattwyler

RJ. Nervous system abnormalities in Lyme disease. Annals NY Acad

Sciences 539:25-34, 1988.

20. Krupp LB, Masur D, Schwartz J, Coyle PK, Langenbach LJ,

Gernquist SK, Jandorf L, Halperin JJ. Cognitive functioning in late

Lyme borreliosis. Arch Neurol 48: 1125-1129, 1991

21. Steere AC, Duray PH, Danny JH, et al: Unilateral blindness

caused by infection with Lyme disease spirochete, Boreelia

burgdorferi. Ann Int Med 103: 382-384, 1985.

22. Halperin JJ, Kaplan GP, Brazinsky S et al: Immunologic

reactivity against Borrelia burgdorferi in patients with motor

neuron disease. Arch Neurol 47: 586-594, 1990

23. Clavelou P, Beytout J, VernayD, et al:Neurologic manifestations

of Lyme disease in the northern part of the Auvergne. Neurol 39

(suppl 1): 350, 1989.

24. MacDonald AB, Miranda JM. Concurrent neocortical borreliosis

and Alzheimer's disease. Human Pathology 18: 750-761, 1987.

25. Reik L, Smith L, Khan A, et al. Demyelinating encephalopathy in

Lyme disease Neurology 35: 267-269, 1985.

26. Kohler J, Kern U, Kaper J, Rhese-Kupper B, Thoden U. Chronic

central nervous system involvement in Lyme borreliosis. Neurology

863-867, 1988.

27. Kohlhepp W, Kuhn W, Kruger H. Extrapyramidal features in

central Lyme borreliosis. Eur Neurol 29: 150-155, 1989.

28. Ackerman R, Rehse-Kupper B, Gollmer E, Schmidt R. Chronic

neurologic manifestations of Erthema migrans borreliosis. In Lyme

Disease and Related Disorders Annal NY Acad Science. 539: 16-23,

1988.

29. Lavoie PE, Lattner BP, Duray PH, Malawista SE, Barbour AG,

Johnson RC. Culture positive, seronegative, transplancental Lyme

borrelosis infant mortality. Int. Conf. Lyme borreliosis 1990

(abstract).

30. Dattwyler, RJ Volkman DJ, Luft BJ et al. Seronegative Lyme

disease. NEJM 319: 1441-1446, 1988.

31. Keller TL, Halperin JJ, Whitman M. PCR detection of Borrelia

burgdorferi DNA in cerebrospinal fluid of Lyme neuroborreliosis

patients. Neurology 42: 32-42, 1992.

32. Rahn DW, Malawista SE, Lyme disease:recommendations for

diagnosis and treatment Ann Intern Med 114: 472-481, 1991.

33. Burrascano J. Late-stage Lyme disease: treatment options and

guidelines. Int. Med 10:102-107, 1989.

34. Hellerstron M. Erythema chronicum migrans Afzelii. Acta Derm

Venereol (Stockh) 11:305-321, 1930. (referenced in Kohler et al:

Neurology 38: 863-867, 1988)

35. Barnett W, Sigmund D, RoelckeU, Mundt C. Endogenous

paranoid-hallucinatory syndrome caused by Borrelia encephalitis.

Nervenarzt 62: 445-7, 1991.

36. Omasits M, Seiser A, Brainin M. Recurrent and relapsing

borreliosis of the nervous system. Weiner klinische wochenschrift

102: 4-12, 1990.

37. Kohler VJ. Lyme disease in neurology and psychiatry. Forschr

108:191-194, 1990.

Pachner AR. Central Nervous System Manifestations of Lyme disease

Arch Neurol 46: 790-795, 1989.

39. Fallon BA, Nields JA, DelBene D, Saoud J, Wilson K, Liebowitz

MR. Depression and Lyme disease a controlled survey American

Psychiatric Association, 145 Meeting. 1992 (abstract).

40. Rondell JR, Wise MG. Neurosyphilis a psychiatric perspective

-------- 26:287-295, 1985

41. Nields JA. Kveton JF. Tullio phenomenon and seronegative Lyme

borreliosis Lancet 338:128-129, 1991

42. Preac-Mrusic V, Weber K, Pfister W, et al Survivial of Borrelia

burgdorferi in antibiotically treated persons with Lyme borrelisos

Infection 17:355 1989.

43. Schuknecht HF. Pathology of the Ear Harvard University Press.

Cambridge p 144. 1974.

44. Felsenfeld O. Borrelia Warren Green Press. St Louis p. 105,

1971.

45. Adams RD, Victor M Principles of Neurology 4th Edition McGraw

Hill, NY p. 362-366, 1989

46. Lavoie PE, Lyme Disease (Lyme Borreliosis) In Conn's Current

Therapy 1991 Rukel RE, ed. WB Saunders, 1991.

47. Sigal LH. Summary of the first 100 patients seen at a Lyme

disease referral center Amer J Med 88: 577-581, 1990.

48. Lettau L. Lime vs. Lyme disease. Ann Int Med 115: 157, 1991.