Fwd: Lyme Disease Creates Psychiatric Disorders

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Lyme Disease Creates Psychiatric Disorders

Lynn Michaels

SSRI-Research

 

Controversies in Neuroborreliosis

http://www.ilads.org/goldings.htm

by Audrey Stein Goldings, M.D.

 

Updated October, 2002

 

 

 

The objectives of this article are to cover issues related to Lyme disease that

are not even-handedly addressed in the current literature. It will:

 

1. Present a practical approach for making the diagnosis of neuroborreliosis,

2. Explore the other side of the post-Lyme syndrome (i.e. the likelihood of

chronic ongoing infection),

3. Discuss the relationship between MS and Lyme,

4. Critique the current regimens published for treating neuroborreliosis, and

5. Present my own approach which may differ from some leading authorities.

 

 

³Anyone who, in discussion, relies upon authority uses not his understanding but

rather his memory.²

 

‹Leonardo da Vinci, Notebooks (c. 1500)

 

It is hoped this data will provide the reader with a broader understanding of

neuroborreliosis so that he or she may better use current and evolving knowledge

for clinical decision making.

 

I. NEUROBORRELIOSIS: MAKING THE DIAGNOSIS

 

 

Because of difficulties in making the diagnosis of neuroborreliosis, the

physician will need a familiarity with the most common forms of presentations,

which will be emphasized. The following points will help evaluate the patient

for neuroborreliosis:

 

1. For most patients, systemic features of disease coexist with, or predate,

neurologic manifestations.

2. Both central nervous and peripheral nervous system involvement is frequent

with Lyme disease and typically occur together.

3. Laboratory data may or may not confirm the diagnosis, and other disease in

the differential diagnosis must be evaluated thoroughly in cases where

diagnostic ncertainty exists.

4. Although history of exposure to B. burgdorferi should be sought, for

various reasons, patients may not remember a history of a tick bite, or the

pathognomonic rash particularly if the disease is presenting years after the

exposure.

5. Early on, personality changes, psychiatric symptoms, or cognitive

manifestations may be the first, and occasionally the only, symptoms that the

patient or family is aware of.

 

 

 

CLINICAL DESCRIPTIONS OF NEUROBORRELIOSIS

 

 

CENTRAL NERVOUS SYSTEM INVOLVEMENT

 

* Meningismus with normal CSF

* Lymphocytic Meningitis

* Meningoencephalomyelitis

* Subacute Encephalopathy (SAE)

 

 

PERIPHERAL NERVOUS SYSTEM INVOLVEMENT

 

* Cranial Neuropathy

* Painful Radiculitis

* Distal Neuropathy

* Plexopathy

* Myositis

* Polymyalgia Rheumatica

 

 

CENTRAL NERVOUS SYSTEM

 

MENINGISMUS

 

Patients may present with headache and stiff neck without evidence of CSF

inflammation. Since early CNS seeding has been described, as well as culture

positivity during latent disease without concurrent CNS inflammatory changes,

these symptoms probably indicate active infection. Stiff neck might

alternatively be due to axonal degenerative changes of the cervical paraspinal

musculature, but there should be other evidence of a more widespread neuropathy

when this is the case.

 

LYMPHOCYTIC MENINGITIS

 

Lymphocytic Meningitis may appear to be indistinguishable from aseptic

meningitis during early-disseminated disease (weeks to months after inoculation

with B. burgdorferi). Most patients will have headaches that will fluctuate in

intensity. Associated features may include a cranial neuropathy in about

one-third. Low-grade encephalopathy is present in up to one-half, with mild

memory concentration deficits, mood changes, and sleep disturbance.

 

MENINGOENCEPHALOMYELITIS

 

Rarely, focal parenchymal CNS lesions occur. The MRI may show punctate white

matter lesions best seen on T2-weighted images; larger lesions occur

infrequently. One brain biopsy showed increased numbers of microglia cells, rare

spirochetes, and minimal inflammation. Transverse myelitis, movement disorders

(extrapyramidal cerebellar, chorea and myoclonus), and hemiparesis can occur.

 

PSYCHIATRIC DISORDERS

 

Psychosis, mood swings (mild or bipolar), profound personality changes,

depression, anorexia nervosa, obsessive-compulsive disorder, and panic attacks

may occur. CSF may be normal.

 

SUBACUTE ENCEPHALOPATHY (SAE)

 

The most common chronic CNS manifestation is a SAE, characterized by memory

problems and depression. Many patients (or their families) will complain of

their excessive daytime sleepiness and extreme irritability. These patients

generally come to the office disorganized (despite a supreme effort to be

organized), unable to give a coherent history. They will bring copious notes,

which are invariably in the wrong order. Most patients will complain of fatigue,

and about one-half have headaches. Coincident polyneuropathy is very common with

spinal or radicular pain, or distal paresthesias. Quantifiable deficits in

memory, learning and retrieval, attention and concentration, perceptual-motor

skills, and problem solving are common. MMPI testing generally shows a stable

psychological pattern without significant psychopathology, similar to other

medically ill patients.

 

ADDITIONAL CNS TESTING:

NEGATIVE TEST RESULTS DO NOT RULE OUT THE DIAGNOSIS OF NEUROBORRELIOSIS

 

Confirmation by CSF CULTURE is seldom practical because the organism is very

fastidious, present in small numbers, takes a long time to grow out, and may

undergo changes to forms which cannot be cultured easily.

 

CSF ANTIBODY TITERS may be present but are inconsistent and therefore their

absence does not rule out CNS infection. The MRI is seldom abnormal and the

findings, when present, are not specific for Lyme.

 

CSF PCR (test for spirochetal DNA) is a useful tool, but at present, because the

capture of DNA is inconsistent, a few questions still need to be addressed.

 

OLIGLOCLONAL BANDS AND IGG INDEX ‹ Looking for evidence of an intrathecal immune

response may be helpful, but it is not specific. As a rule, oligoclonal bands

and an elevated IgG index are not present in North American Lyme disease and

their presence should suggest other diseases.

 

THE PERIPHERAL NERVOUS SYSTEM

 

Cranial neuropathy, painful radiculitis, distal neuropathy, and plexopathy are

seen and generally reflect different clinical presentations of mononeuritis

multiplex (polyneuropathy). Bell¹s Palsy occurs in almost 11% of all Lyme

patients and is bilateral in up to 1/3. Therefore, a bilateral Bell¹s Palsy is

very suspicious for Lyme in an endemic area. Painful radiculitis or cranial

neuropathy can be seen with meningitis but also with normal CSF due to axonal

neuropathy. Myositis may occur with Lyme as well as polymyalgia rheumatica.

Symptoms of chronic involvement of the peripheral nervous system in a series of

patients with chronic neurologic manifestations of Lyme disease developed a

median of 16 months after the onset of infection, while CNS involvement began a

median of 26 months after the onset of disease.

 

PERIPHERAL NERVOUS SYSTEM TESTING

 

Electrophysiological testing may show evidence of a mild peripheral neuropathy.

Axonal degeneration and perivascular inflammatory infiltrates are noted on

pathological specimens.

 

CHRONIC NEUROBORRELIOSIS

 

THE MOST COMMON PRESENTATION IS SAE, POLYNEUROPATHY, AND ARTHRITIS

 

Most typically, patients present with SAE, most often combined with

polyneuropathy. Brief episodes of arthritis, primarily involving the knees,

generally predate the symptoms and may persist after onset of neurological

abnormalities. The TRIAD OF SAE, POLYNEUROPATHY, AND ARTHRITIS IS HIGHLY

SUSPICIOUS FOR NEUROBORRELIOSIS.

 

Since serologies may be contradictory or negative, the physician will have to

settle for treating if clinical suspicion is strong enough and assess whether

the patient has ³possible² or ³probable² neuroborreliosis. Vigilant attempts to

rule out other disorders should be undertaken. Screening should be done for

collagen vascular disease, other infections, cancer, metabolic or

endocrinological disturbances, etc. when a definite diagnosis cannot be made.

 

 

II. CURRENT MEDICAL MYTHOLOGY

 

 

³YOU HAVE FIBROMYALGIA. YOU MIGHT HAVE HAD LYME DISEASE IN THE FIRST PLACE, AND

EVEN IF YOU DID, YOU WERE GIVEN ENOUGH ANTIBIOTICS. RETREATMENT WILL NOT HELP.²

 

PERSISTENT INFECTION VERSUS POST-LYME SYNDROME

 

Many patients are sent home with antidepressants, muscle relaxers, but no

antibiotics from doctors¹ offices because they have symptoms of fibromyalgia.

Pictures similar, or identical, to fibromyalgia may be part of the constellation

of symptoms of Lyme; it may occur more rarely as an isolated symptom, or surface

after what would otherwise be considered successful treatment.

 

Symptoms of fibromyalgia due to Lyme disease have not been cured with short-term

oral or intravenous antibiotics, so some argue fibromyalgia is not due to active

infection. I would question whether those particular antibiotic regimens were

adequate to eliminate the infection, rather than assume the patient has

developed ³Post-Lyme Syndrome² (some yet to be defined immunologically triggered

disorder).

 

THE SCOPE OF THE PROBLEM

 

Bujak et al. evaluated patients a mean of almost five years after treatment. 15%

of these patients had symptoms of fatigue and arthralgia. Almost one-half met

criteria for fibromyalgia or chronic fatigue syndrome. Fibromyalgia is thought

to be a variant of the chronic fatigue syndrome. Of note, nearly all patients

continued to complain of memory loss or concentration difficulties. One quarter

had objective evidence of cognitive impairment, and 15% manifested depression.

 

SYMPTOMS OF FIBROMYALGIA AND CHRONIC FATIGUE SYNDROME IN LYME DISEASE MAY BE

ATTENUATED FORMS OR CHRONIC MANIFESTATIONS OF THE FLU-LIKE SYMPTOMS ASSOCIATED

WITH EARLY DISSEMINATION

 

All physicians experienced with treating Lyme disease have had patients who

present with a recurrence of flu-like symptoms, months to years after they have

completed the usual antibiotic course of therapy, oral or intravenous, and

re-exposure had not occurred. These patients describe their flu-like symptoms as

identical to their early-disseminated stage of Lyme disease. The flu-like

symptoms may reoccur following what appears to be a trivial stressor, such as an

uncomplicated viral URI. Patients may be able to ³contain² their symptoms

without specific antimicrobial therapy, but many will have to resume

antibiotics. These patients complain of having to go to bed due to excessive

fatigue or hypersomnolence. They cannot think straight, their muscles and joints

ache, and they may have a low-grade fever. Do these symptoms sound like a

³fibromyalgia-like syndrome² or ³acute fatigue syndrome?² Prior medical

experience suggests reactivation of infection. Despite what may appear to have

been

a previous ³cure,² relapse of symptoms in this context would appear to be due

to failure to eradicate the infection and with reactivation after a period of

dormancy. Reoccurrence of symptoms due to immunologically triggered disease,

INDEPENDENT of persistent infection seems unlikely. In reality, DISTINCTIONS

BETWEEN FLU-LIKE SYNDROME, FIBROMYALGIA, AND CHRONIC FATIGUE BLUR. It seems more

logical to postulate that fibromyalgia and chronic fatigue syndrome, when seen

with Lyme disease, may be attenuated forms of chronic manifestations of earlier

flu-like symptoms associated with early dissemination.

 

 

III. THE ASSOCIATION BETWEEN MULTIPLE SCLEROSIS AND LYME DISEASE: THREE

DIFFERENT SCENARIOS

 

 

1) LYME CAN LOOK LIKE MS BUT SYMPTOMS AND PATHOLOGY RESIDE OUTSIDE THE CENTRAL

NERVOUS SYSTEM

 

Lyme may present as a MS-like illness, but on many occasions the pathology is

not actually in the CNS. Since chronic Lyme symptoms often are predominantly

shifting, vague, behavioral-psychological, psychiatric, and, as mentioned,

neurological, they are likely to conjure up the diagnosis of MS in patients and

physician alike. However, the existence of pathology outside the CNS should rule

out the diagnosis of MS. Some of the vague symptoms that can be mistaken for MS

include those that are better attributed to peripheral nervous system damage, as

part of the mononeuritis multiplex that may occur. This might cause numbness,

tingling, facial weakness, diplopia, etc. The diagnosis of MS cannot be made in

the absence of CNS symptoms and signs. MRI and CSF findings would also help

support the diagnosis of MS. In addition, a significant CSF pleocytosis may

occur with Lyme disease, which should not be present with MS.

 

2) OTHER LYME PATIENTS DO HAVE CNS LESIONS, BUT THESE ARE GENERALLY DISTINCTLY

DIFFERENT, CLINICALLY, AND PATHOLOGICALLY FROM MS

 

Patients can have CNS lesions in the brain or spinal cord with Lyme disease. The

European literature includes many more cases than the American for

encephalomyelitis, strokes, etc. In those cases where there is focal involvement

of the brain or spinal cord, it may be more difficult to distinguish

neuroborreliosis from MS. Again, a brisk CSF pleocytosis would help diagnose

Lyme and the specific aforementioned test for CNS Lyme antibodies. Simultaneous

appearance of peripheral nervous system abnormalities or arthritis should

suggest the diagnosis of Lyme.

 

3) ANOTHER GROUP OF PATIENTS HAS MULTIPLE SCLEROSIS AND LYME

 

There are some patients who have a clear-cut preexisting history of MS before

the onset of Lyme disease. The Lyme appears to accelerate their clinical course.

For others, it appears to be the initiating infection that triggers the MS.

These patients are most likely genetically predisposed to MS and the Lyme

bacteria exerts its major effect by ³turning on² immunologically directed CNS

injury. It is not uncommon to get a history of the onset of an exacerbation of

MS related to infections, so Lyme exacerbating MS would be expected. HLA Class

II molecules determine the intensity of the immune response to pathogenic

foreign or self-antigens. With MS, the HLA-DR4 DQw8 haplotype has been

associated with chronic progressive MS and the HLA-DR2 DQw6 haplotype has been

associated with susceptibility to both chronic progressive and relapsing or

remitting MS. It is possible that in genetically predisposed patients of certain

HLA types that infection by Lyme bacteria would cause a high production

of cytokines that would mediate the demyelination and destruction of

oligodendrocytes.

 

Most recently, researchers are studying positive outcomes when antibiotics that

are most useful in treating Lyme disease are used to treat ³MS.²

 

 

IV. WHAT'S WRONG WITH ³CURRENT GUIDELINES FOR TREATMENT² OF NEUROBORRELIOSIS?

First, read the fine print.

 

 

It is interesting to note that recommendations for treatment in the medical

literature may carry provisos in small print that can easily be overlooked but

are instrumental to understanding how important individualization of therapy is

at the current time. For instance, in the past and in small print Dr. Alan

Steere has written, ³treatment failures have occurred in all these regimens, and

retreatment may be necessary; the duration of therapy is based on clinical

response, and the appropriate duration of therapy with late neurological

abnormalities may be longer than two weeks.² A more recent article written by

Rahn and Malawista states ³these guidelines are to be modified by new findings.

It should always be applied with close attention to the clinical course of

individual patients.² Dr. Katzel surveyed several Lyme Borreliosis conferences,

including international ones. He finds a trend towards the use of antibiotics

for longer periods than previously described and lack of

standardization of care worldwide. 50% of physicians responding considered

using antibiotics for time periods greater than one year in symptomatic

seropositive patients, with almost as many extending therapy up to one and a

half years when necessary.

 

THE CASE FOR PERSISTENT INFECTION

 

Studies have shown that Lyme bacteria can be an intracellular pathogen and may

evade the normal host immune response. The causative spirochete, B. burgdorferi,

for instance, may persist within fibroblasts and survive at least 14 days of

exposure to ceftriaxone. In addition, B. burgdorferi has been cultured from CSF

more than a half year after a standard regimen of IV antibiotics, according to

Preac-Mursic. Logigian and Steere looked at patients with chronic

neuroborreliosis, evaluating them six months after two weeks of IV ceftriaxone.

Over one-half of the patients had already been treated with therapy that was

thought appropriate for their stage of illness, yet the illness progressed. The

majority of patients studied had subacute encephalopathy and polyneuropathy.

Most had persistent fatigue, and almost one-half had headaches. One-third of

these patients had to stop working or had to go part-time, underscoring the

disability that may be seen with Lyme disease on an individual and

societal level. After therapy, two-thirds of patients improved markedly, but

seldom completely. Twenty-two percent improved but then relapsed, and fifteen

percent had no change in their condition.

 

This study suggests that additional antibiotics greatly helped the majority with

neuroborreliosis but they were insufficient to cause long lasting remission in

those patients who subsequently relapsed. Persistent residual or irreversible

disease may explain the fifteen percent who had no change in their condition.

 

 

For those clinicians who have had extensive experience with chronic

neuroborreliosis, more recent recommendations suggesting that a regime of only

20 to 28 days or even 6 weeks of intravenous antibiotics is sufficient for cure

proved contrary to clinical experience. That brief dosing does not appear to

prevent relapse or improve long-term outcome dramatically in many cases.

Perhaps, as recent information has instructed, that is because the immune system

does not begin to repair itself until the beginning of the fourth month of

antibiotic treatment. A trial of prolonged use of oral antibiotics seems more

reasonable in many cases, given these circumstances.

 

Antibiotics used for chronic neuroborreliosis should be able to penetrate the

blood-brain barrier, express activity against intracellular organisms, and

assure good intraphagocytic penetration. It is anticipated that the microbe

during late disease has achieved maximal adaptation to its host environment.

Also, because of the long generation time of the organism, lengthier therapy is

warranted.

 

 

 

V. WE DON'T HAVE ALL THE ANSWERS BUT HERE¹S WHAT IS RECOMMENDED

 

 

If a patient has meningitis or appears acutely ill, particularly with possible

arrhythmia, admit him or her to the hospital for intravenous antibiotics and

observation. Generally, however, in patients with stable late disease, oral

antibiotics can be tried first. The majority of patients will have some

improvement or gradual resolution of encephalopathic symptoms with a better

energy level. After a six-week trial of appropriate antibiotics, the patient is

re-evaluated. If there is no Herxheimer response or some clinical improvement

during this interval, it is worrisome, and the physician needs to be concerned

about: 1) misdiagnosis, 2) noncompliance, and/or 3) permanent end organ damage.

These possibilities should be addressed with the patient before proceeding with

intravenous antibiotics since they may not be maximally beneficial either

 

Over the long haul, whether intravenous antibiotics are used for two weeks or

longer, with chronic refractory disease, ultimately other methods are necessary.

A lengthier use of oral antibiotics seems more logical than intravenous

antibiotics for some patients. Unfortunately, there are no current tests that

adequately measure disease activity with neuroborreliosis in all patients.

 

We are sorely in need of a test similar to the CSF VDRL for syphilis that would

give us a measure of disease activity. Culture negativity or disappearance of a

specific immune response in the serum or CSF has not been useful at this time to

establish cure. CSF antibodies may persist for years after otherwise successful

treatment. Particularly in the CNS, judging response of therapy is problematic

because pathological changes may incompletely or, at least, very slowly reverse.

Any clinical improvement would be expected to occur in a delayed fashion after

therapy is given. Likewise, one would expect neuropathy related to axonal

degeneration to remit slowly and/or incompletely. Formal neuropsychiatric

testing is of value in documenting pathology and following the patient. It also

helps delineate what the patient can and cannot do. It also can help to define

the disease for the patient, family, insurer, and the employer. The patient

needs to be told that his or her symptoms should remit

slowly and incompletely, when on antibiotic treatment. This is particularly

important when the symptoms have been chronic.

 

 

VI. IN SUMMARY

 

 

The premise of this approach to diagnosing and treating neuroborreliosis needs

to be reinforced.

 

1. There is no current laboratory test that makes or breaks the diagnosis of

neuroborreliosis. It is a clinical diagnosis substantiated by laboratory data

when possible. Fortunately, the majority of cases are fairly uniform in their

lack of uniformity, and other diagnoses are easily ruled out. In situations

where the physician simply cannot achieve diagnostic certainty, he or she should

notify the patient that the diagnosis is ³possible² or ³probable²

neuroborreliosis. This has been done previously with MS (i.e., possible,

probable, and definite MS), another disease where laboratory testing does not

make the diagnosis in and of itself.

2. There is no perfect current laboratory test to monitor success of therapy,

and this is critically needed. Until better testing is available, assessing

progress, or lack thereof, will largely be determined with clinical acumen.

3. The infection is difficult to eradicate and may require long-term

treatment. The spirochete, particularly in later stages, becomes well adapted to

survival within its host environment. There are some patients that we may not be

able to cure, but will be able to palliate with currently available antibiotics.

4. Although immunopathogenic factors may play a crucial role in disease

presentation, the presence of chronic infection appears necessary to perpetuate

the process and play a causative role in persistence of immunologically

triggered symptoms.

5. There is no Diagnostic and Statistic Psychiatry Manual (DSM IV) category

for ³antibiotic seeking behavior.² It is common for physicians who are unable to

explain patients¹ symptoms or effect their cure to ascribe a psychiatric cause

to their malady. This is easily done with Lyme since objective findings may be

subtle or non-existent. Because neuropsychiatric symptoms may pre-dominate, it

is easy in some patients to attribute their symptoms to depression or secondary

gain. These patients do not in any other way seek other medication that would be

associated with habituation or addiction (i.e., pain medicine).

 

 

Many patients suffer unfairly at the hands of physicians who refuse to make the

diagnosis because blood tests are either contradictory or negative. ³Lyme

bashing,² for instance, referring to Lyme disease as ³yuppie flu,² is demeaning.

The ³just say no² attitude of certain physicians towards Lyme patients who

request retreatment with antibiotics should not be condoned in the face of

continuing experience with this potentially chronically disabling infectious

disease.

 

 

Audrey Stein Goldings, MD is a private practice neurologist in Dallas. She is

member of ILADS and a founding member of the Board of Directors.

 

 

 

 

 

 

 

 

 

 

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