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Neuropsychiatryczna ocena boreliozy- R.C. Bransfield:

http://borelioza.gazetka.eu/artyk/neuro ... ryczna.pdf

(zgoorek- świetna robota!)

P&S Journal: Winter 1998, Vol.18, No.1

Research Reports

Lyme Disease and Psychiatric Disorders

Brain scans and neuropsychiatric tests can help doctors determine whether psychiatric problems are a result of Lyme disease or a primary psychiatric disorder, P&S research has demonstrated.
The findings are important because many people with Lyme disease do not exhibit the classic rash and flu-like symptoms but later experience secondary symptoms, such as depression, panic attacks, paranoia, personality changes, mood swings, attention problems, or short-term memory loss. These symptoms can be easily attributed to primary psychiatric disorders, especially when the patient's clinical presentation does not include joint swelling or Bell's palsy, two of the more commonly recognized signs of Lyme disease, and when standard laboratory tests for the disease prove inconclusive, which can be the case in chronic Lyme disease.


"Such mislabeling may have particularly detrimental effects on the Lyme disease patient, as a delay in diagnosis and treatment may result in a curable acute infection becoming a chronic, treatment-refractory illness, wrote study leader Dr. Brian Fallon, associate professor of clinical psychiatry at P&S, in an issue of Clinical Infectious Diseases.
In an earlier study, Dr. Fallon found that depression was three times more common in patients with Lyme disease than in patients with comparable diseases (lupus, rheumatoid arthritis, and osteoarthritis). "That was surprising to us, and it suggested that there is something going on in the brain of Lyme patients that is directly causing the depression.
Dr. Fallon, in collaboration with Dr. Ronald Van Heertum, Dr. Jeffrey J. Plutchok and their colleagues in radiology, subsequently found that at least half of patients with chronic Lyme disease have brain abnormalities, evident on SPECT (single photon emission computed tomography) scans. "The specific appearance is a heterogeneous pattern of decreased perfusion," says Dr. Fallon, who is also director of the Lyme disease research program at the New York State Psychiatric Institute.
In a follow-up study, the researchers found that blood flow to the affected areas of the brain improved in approximately half of the patients who were given intravenous antibiotic treatments.

Since this pattern of decreased brain perfusion is seen in patients with other diseases, including HIV encephalopathy, chronic cocaine abuse, chronic fatigue syndrome, and lupus, SPECT imaging alone cannot be used to confirm a diagnosis of chronic Lyme disease, says Dr. Fallon. A thorough evaluation should include a physical examination and standard laboratory tests plus formal neuropsychological testing, such as the Wechsler Memory Scale, and brain imaging, such as MRI, SPECT, or PET scanning.

When should a doctor suspect that a neuropsychiatric problem is the result of Lyme disease? If the only thing a patient has is depression or anxiety, Lyme disease would be low on the list of possibilities, Dr. Fallon says. "But if he or she has mood swings, attention problems, or memory problems, as well as some joint pains and some numbness and tingling, you have to consider Lyme disease, especially in the greater New York area, where it is endemic. And anytime you see a young patient with memory problems, then you have to start wondering: Could this be Lyme disease?
________________________________________
copyright ©, Columbia-Presbyterian Medical Center

Distinct Pattern of Cognitive Impairment Noted in Study of Lyme Patients

Marian Rissenberg PhD & Susan Chambers MD, The Lyme Times, Vol. 20, Jan-Mar 1998, pp. 29-32

I. Cognitive Characteristics of Chronic Lyme Encephalopathy

On the basis of both a formal neuropsychological study of 49 patients (APA 5/96) and on clinical observation and comprehensive neuropsychological examination of well over 100 patients, a distinct pattern of cognitive impairment occurring chronic Lyme disease can be described.

These patients consistently demonstrate deficits in directed, sustained and divided attention, planning and organization of responses, temporal ordering, verbal fluency, abstract reasoning, speed of processing, and motor programming.

The overall pattern of intellectual impairment is not unlike that seen with diffuse brain injury, and it most often results in some degree of work-related disability.

Although performance is impaired on measures of cognitive functions associated with specific brain regions -- receptive and expressive language, visuospatial problem solving and memory -- the quality of performance is not suggestive of focal lesions in these areas. Rather, deficits are secondary to impairment of higher level integrative functions, likely mediated by complex neuronal systems. Specifically, the receptive language deficit is secondary to impaired auditory tracking and slowing of mental processing. The expressive language deficit is secondary to impaired word retrieval and response planning, The visuospatial problem solving deficit is secondary to impairment of mental flexibility, conceptualization and the ability to compare and contrast necessary in decision making.

Finally, deficits on test of memory function are most often secondary to impairment of the encoding or initial processing of information, which depends on attention, and the retrieval of stored information. The storage of new information, or memory per se, is rarely impaired.

This pattern suggests that cognitive dysfunction in chronic Lyme, while expressed variably across individual patients, results from a common factor -- the breakdown of diffusely represented processes involving both integration and activation, and impacting primarily on attention and reasoning.

The fluctuation of impairment over short periods of time suggest that a physiologic rather than a structural mechanism is responsible.


II. Neuropsychological deficits in chronic Lyme disease
(A study presented at the annual meeting of The American Psychiatric Association , May 1996)

The neuro-psychological characteristics of 49 patients with Lyme disease were examined. The study set out to answer three questions:

1) Do all patients with subjectively perceived cognitive dysfunction have measurable intellectual impairment on objective testing?

2) In those without measurable impairment, does depression account for the perception of cognitive dysfunction?

3) What is the nature of the cognitive impairment in Lyme disease when it does occur?

Subjects were patients seen consecutively between 1990 and 1994 in a private neuropsycological practice with complaints of cognitive dysfunction and a symptom complex consistent with Lyme disease. Diagnosis was based on former CDC criteria. Mean duration of illness, defined as the time from the onset of general symptoms to the neuro-psychological exam, was 4.7 years (range: 3.3 to 14 years). Mean age was 39.9 years (range: 21 to 58 years) from 18 to 60 years. Mean level of education was 15.3 years (range 12 to 20 years).

Subjects were interviewed and administered a comprehensive battery of tests, including the complete WAIS-R and WMS-R, and additional test of language, attention, reasoning, visuospatial processing and complex motor function. They also completed the Beck Depression Inventory and a symptom checklist. Tests were divided into seven groups based on the cognitive functions they are presumed to measure: Attention, Memory, Language, Visuospatial Processing, Reasoning, Verbal Fluency and Motor programming.

Subjects were grouped into three levels of impairment based on their neuropsychological performance: Intact (N=11; 22%), with no functions impaired, Moderate (N=31; 63%) with two functions impaired, and Severe (N=7; 14%) with three or more functions impaired. Subjects in the Severe group met diagnostic criteria for dementia. The correlation between depression and cognitive impairment was nonsignificant, but the trend was positive, rather that negative. Anxiety by self report was significantly greater in the impaired groups that the Intact group. Duration of illness was greater in the Severe group (nonsignificant).

Of the 38 subjects with cognitive impairment, deficits of attention were most common, occurring in 26 subjects (68%) Deficits of memory storage were least common, occurring in 8 subjects (21%), Motor, Verbal Fluency, Visuospatial, Language and Reasoning deficits occurred in 24, 26, 29, 36 and 36% of the subjects respectively.



III. Possible Pathophysiologic Mechanisms of Cognitive Impairment in Lyme Disease

Based on these findings and on patients' reports, two characteristics of Lyme Encephalopathy arise which provide insight as to possible neurophysiologic mechanisms:

One, the nonfocal nature of the cognitive functions affected, and

Two, the subtle fluctuations and reportedly abrupt and global shifts in cognitive function from one day to another in a given patient.

Four broad categories of possible neurophysiologic mechanisms might be compatible with this pattern:

1) Diffuse cerebral diffusion abnormalities -- Single photon emission computerized tomography (SPECT) scans of the brain in Lyme disease often display a diffuse pattern consistent with heterogeneous areas of hyperfusion and/or diminished neuronal metabolism.

Note: I think this is a typo and should read hypOperfusion.

While vasodilators are often capable of reversing these abnormal patterns on SPECT scan, this reversal does not consistently correlate with a symptomatic improvement in cognitive function.

2) Alterations in cellular metabolism at the cortical level -- Evidence of alterations in neurotransmitter function is suggested by clinical evidence of cognitive improvement following treatment with selective serotonin reuptake inhibitors (SSRI's) which appears to be independent of their antidepressant effect. Systematic studies of the impact of SSRI's on cognitive function, as well as the role of other transmitters, are required.

3) Neuro transmitter abnormalities (imbalances of synthesis and/or receptor activity) -- Neurotoxic substances may well play a role in Lyme Encephalopathy, given the neurotropic nature to Treponema pallidim, and the close parallel between syphilis and Lyme disease, it is possible that Borrelia burgdorferi could produce intracellular or extracellular neurotoxins which we have yet to identify.

4) Neurotoxic substances produced endogenously or possibly exogenously -- Endogenous neurotoxins have been identified as by-products of the humoral immune response. Among these is quinolinic acid, a product of the interleukin cascade system, which accumulates as a result of the humoral response to acute infectious agents and functions as a neuronal excitotoxin. As there are many similarities between Lyme Encephalopathy and the nonspecific mental dysfunction of acute systemic infections, such as influenza, it is quite possible that continued stimulation of production of quinolinic acid and other cytokines plays a role in the pathophysiology of Lyme encephalopathy.



IV. Clinical Impressions and Implications for Diagnosis and Treatment in Chronic Lyme Disease

This study demonstrates that for the majority of chronic Lyme patients with cognitive complaints, there is in fact a measurable and significant decline in intellectual acuity. The nature and severity of the cognitive impairment is such that it interferes with all aspects of normal functioning: employment, home, marriage, social interactions, and general emotional well-being. Rather than the cognitive complaints being secondary to anxiety or depression, as is sometimes suspected, depression and anxiety increase with, and are apparently secondary to, cognitive impairment and the emotional and practical impact of a loss of competence. Thus, while patients with chronic Lyme disease can present a confusing and "psychiatric" picture to the clinician, it is important that their concerns be properly investigated and addressed.

Patients with Lyme encephalopathy complain of problems with memory and concentration, word retrieval, confusion, problems with thinking, "mental fogginess", a decline in job performance, difficulty with calculations, directions, and judgment. Decreased initiative, manifest as difficulty getting started with or following through with projects is often noted. Mood disturbance is common with complaints of irritability, explosiveness or "a short fuse," sadness, hopelessness or guilt, increased anxiety or mood swings. Sleep disturbance is also common, and can present as initial, middle or terminal insomnia or some combination of these. Fatigue is universal. Headache is common, and of course joint and muscle pain. Increased sensitivity to light and noise, visual disturbance, and tingling in the extremities are also common.

On interview, patients with Lyme encephalopathy tend to be vague and disorganized in the presentation of the history of their illness. This is despite their close attention to their symptoms and having recounted them many times before. Although in most cases memory of discreet events - tests, dates, diagnoses, responses to medications - is intact, the patient is unable to recall them spontaneously or organize them in temporal order. They may be unclear as to their chief complaint. They may completely lose track of what they were saying, sometimes repeatedly, or of what the question was. They may get off on a tangent and have trouble re-orienting themselves. Frequent prompting and refocusing will be necessary; beginning the interview with an open-ended question like "Tell me what the problem is" will allow these qualities to become clear.

Often patients with chronic Lyme disease will seem overly focused on their illness, or overly concerned with convincing the clinician that they are ill. The clinician may be tempted to interpret this as evidence of a primary psychiatric disorder. It is important to understand that the frustration many of these patients experience is real, and results from the general attitude of doubt toward Lyme disease as a serious and chronic illness, the invisibility of their symptoms, the difficulty in getting a definitive diagnosis and getting approval for extended treatment from insurance carriers. Many have been accused of hypochondriasis or malingering. As with head injury, the patient may "look fine" though they are having difficulty with very basic work, social and day to day functioning.

The cognitive deficits in chronic Lyme disease involve primarily attention and arousal mechanisms. Patients have difficulty keeping track of external and internal events, retrieval of information from memory and with planning and sequencing, as occurs in attention deficit disorder. However their experience is different from that of ADD, in that rather than having the experience that there are many thoughts competing for attention, the Lyme patient has difficulty bringing any thought into clear focus. They experience difficulty thinking. One patient described it as the universe ending six inches from his face. He can't process information that is not immediately apparent, immediately experienced. Another said that when he tries to think about something, or figure something out, all he can do is repeat the question -- he can't get to the meaning. This is like the idea of "surface" versus "deep" processing in cognitive psychology. Reading a passage for typing errors would be surface processing, while reading for meaning is deep processing. One patient, a physician, described it as a "mental intention tremor" -- the more she tries to focus on something the more out of focus it becomes.

The clinician should proceed with empathy and reason. Specific cognitive complaints in previously high functioning individuals are unusual and indicative of serious illness, either psychiatric or neurologic. Comprehensive neuropsychological evaluation will most often differentiate the two.

Where the neuropsychological exam is normal or there is a significant psychiatric component, a psychiatric evaluation is advised. Psychiatric symptomatology is not uncommon in Lyme and the presence of depression, anxiety, obsessive compulsive symptoms, flat affect and so on may cloud the issue of significant cognitive decline. Both the cognitive and psychiatric symptoms would be expected to improve with antibiotic treatment in Lyme encephalopathy. However sometimes concurrent treatment with psychotropic medication is necessary.

Unfortunately for some patients, significant cognitive impairment persists even after years of antibiotic treatment. These patients may never be able to return to their premorbid level of employment, or be gainfully employed at all. Cognitive remediation can help them learn strategies for improving memory and concentration and relieving stress. Support and advice in regard to living with a chronic condition is equally important. Strategies include reducing work hours when possible, taking regular rest periods during the day, limiting the number of outings in a week, and using a calendar to stay organized and structure their time.



V. Cognitive impairment in Lyme disease: specific functions and the impact of deficits

1. Attention and mental tracking. Includes directed and sustained attention: the ability to direct and maintain one's focus on a particular event or idea, whether in the environment or internally; and divided attention: the ability to simultaneously attend to two events, or do two or more things at a time, or to retain awareness of one thing while doing another.

Impact: difficulty functioning effectively in many situations, remembering what one was doing before a distraction, keeping track of conversation, taking notes while someone is speaking, remembering that someone is on hold, or what you were about to say.

2. Memory: Retaining new information.

Impact: secondary to impaired attention, slowing of processing and the retrieval of stored information, but not storage per se; a tendency to lose or forget things; miss appointments; repeat oneself.

3. Receptive language: understanding spoken or written language

Impact: secondary to impaired attention and speed of processing; difficulty participating in meetings or social conversation; difficulty with reading comprehension.

4. Expressive language: Using spoken or written language to express ideas

Impact: difficulty finding the right word; using the wrong word and not noticing; not being able to express oneself or communicate.

5. Visuospatial Processing: Efficient scanning of the visual field, making sense of how things are related in space; visuospatial conceptualization and problem solving.

Impact: a tendency to get lost; difficulty with reading comprehension.

6. Abstract reasoning: The ability to generalize from the particular; to identify the common factor between related concepts; to compare and contrast two things or ideas; to see the "big picture"; to identify the critical factor in a situation; to anticipate consequences and make inferences regarding cause and effect.

Impact: difficulty with decision making, planning, and problem solving.

7. Speed of mental and motor processing: The ability to think and respond quickly; critical to understanding speech which occurs at a fairly constant rate.

Impact: difficulty understanding or keeping up a conversation; functioning in a timely manner in day to day situations; meeting deadlines.

A PDF version of this article is available for easier printing.

The Lyme Times is published quarterly by the Lyme Disease Association.

Psychiatric Times grudzień 01, 2007 Vol. 24 No. 14

Lyme Disease, Comorbid Tick-Borne Diseases, and Neuropsychiatric Disorders

Robert C. Bransfield, MD


Dr Bransfield is associate director of psychiatry at Riverview Medical Center in Red Bank, NJ. Psychiatrists interested in joining the Microbes and Mental Illness Discussion Group may e-mail the author at bransfield@comcast.net. He is President Elect of the International Lyme and Associated Diseases Society. The author reports that he is on the Speakers' Bureau of Abbott, AstraZeneca, Cephalon, Forest, GlaxoSmithKline, Jazz, Lilly, Pfizer, Sanofi Aventis, Takeda, UCB, and Wyeth; and he is on the advisory board for the Lyme Disease Association, Turn the Corner Foundation, Morgellons Research Foundation, and Lyme Induced Foundation.
________________________________________




Many recall the phrase "To know syphilis is to know medicine." Now Lyme disease (Lyme borreliosis), the new "great imitator,"1 is the ultimate challenge to the breadth and depth of our knowledge. In psychiatry, we generally treat mental symptoms or syndromes rather than the underlying cause of a disorder. A greater awareness of immune reactions to infections and other contributors to mental illness enhances our psychiatric capabilities. Lyme disease, like syphilis, is caused by a spirochete with a multitude of pos-sible manifestations and 3 stages: early with dermatological symptoms, disseminated, and late stage.
Unlike Treponema pallidum, the cause of syphilis, the causative agent of Lyme disease, Borrelia burgdorferi, can be much more difficult to eliminate, diagnostic testing is less reliable, and interactive copathogens are major contributors in the pathophysiology.2,3 B burgdorferi is highly adaptable with 6 times as many genes as T pallidum and 3 times as many plasmids as any other bacteria that allow rapid genetic adaptations.4,5 It is a stealth pathogen that can evade the immune system and pathophysiological mechanisms.6,7 Knowingly or not, most psychiatrists have at some point been perplexed by patients with late-stage psychiatric manifestations of Lyme borreliosis. Several factors are associated with the risk of infection as well as the different manifestations of Lyme borreliosis (Table 1).


A problematic case


The following composite case illustrates a number of problems that may make diagnosis and treatment of Lyme borreliosis anything but straightforward. The patient is in good health and enjoys outdoor activities. Often this person has the HLA DR4 genotype. He or she may acquire a small tick bite that goes unnoticed because the subsequent rash may not be of the classic bull's-eye type, may be easily overlooked in dark-skinned individuals, may be misdiagnosed, or may occur only with a second or subsequent infection. There may be flu-like symptoms with migratory musculoskeletal aches and pains. If a diagnosis of Lyme disease is made, the initial course of antibiotic treatment may not have been sufficient to eliminate the infection. (Although standardized by 1 set of guidelines, psychiatrists often see the failures of some of the "standard" treatments.) Low-grade symptoms may remit and periodically relapse over time. An accident, emotional stress, vaccination, or childbirth can trigger an exacerbation of symptoms.

The patient, who did not have psychosomatic symptoms and was not hypochondriacal in the past, now complains of an increasing number of somatic, cognitive, neurological, and psychiatric symptoms. Although Lyme disease may be suspected, the laboratory tests available to most clinicians often lack sensitivity and thus are read as negative for Lyme disease. Fibromyalgia, chronic fatigue syndrome, or multiple sclerosis (MS) may be erroneously diagnosed.

Treatment of some symptoms with corticosteroids may initially provide relief, but a more rapid decline often follows. The patient sees multiple specialists, each of whom restricts the examination to his area of expertise. Nothing is resolved, and the patient is frustrated that his symptoms cannot be explained. In view of the growing list of unexplained symptoms, including psychiatric symptoms, the patient is treated with tranquilizers and antidepressants with some benefit, but gradual decline persists.

The major complaints include fatigue, multiple cognitive impairments, depression, anxiety, irritability, head-aches, and a multitude of other symptoms. When general medical treatment fails, the patient may be referred to a psychiatrist for 3 reasons: the unexplained medical symptoms give the appearance of a psychosomatic or somatoform condition; complex mental symptoms are thought to require psychiatric assessment; and a psychiatrist is thought to be needed to more effectively manage psychiatric treatments.

The Figure presents single photon emission CT (SPECT) images of the brain of a depressed 51-year-old woman with Lyme disease, before and after treatment with ceftriaxone. She walked on nature trails at home and on vacations, recalled frequent tick bites and an expanding bull's-eye rash on her abdomen with no other symptoms, but considered it of no special significance at the time. Over 8 years, there was a progressive development of unexplained symptoms that began with GI complaints, followed by cognitive impairment, fatigue, depression, arthritis, and shortness of breath. The primary diagnosis was atypical depression. Although the patient failed to respond to 51 different drug trials, the treating psychopharmacologist assured her the mental symptoms could not possibly be caused by an underlying physical condition.
The initial SPECT scan demonstrated "extensive hypoperfusion... predominantly in the frontal and temporal lobes and to a less degree in the parietal and occipital lobes," which is consistent with Lyme disease and neurodysfunction. Neurocognitive testing demonstrated significant abnormalities. An MRI scan ruled out frontal temporal dementia. The patient tested negative for Lyme disease by CDC epidemiological criteria, but the Lyme IgG Western blot test result was positive at one laboratory and equivocal at another. The CD57 lymphocyte count was low at 17/µL (60 to 360) and the patient tested positive for 4 other tick-borne infections (Mycoplasma fermentans, Babesia microti, Babesia WA-1, and Bartonella henselae). The patient was intolerant to oral antibiotics and was treated with 8 months of intravenous ceftriaxone. The second SPECT scan demonstrated "marked improvement of the hypoperfusion pattern in the temporal, frontal, and parietal lobes and small areas of hypoperfusion pattern remain." The depression never returned, but some mild residual symptoms persist, including fatigue, neuropathy, and arthritis; however, she has mostly returned to her active lifestyle. The failure to diagnose and treat these infections for several years resulted in an escalation of symptoms and a loss 8 years of her life that could have been prevented by earlier diagnosis and treatment.

General theoretical issues

The causes of most psychiatric illnesses are unknown. The catecholamine hypothesis does not adequately explain the cause of abnormal neurotransmitter functioning. Mendel stated that human traits are determined by individual genes that function independently of other genes and environmental influences. Koch believed that many human diseases are caused by microbes that exert their effect independently of other microbes, environmental factors, and genes. The cause of most mental illnesses cannot be explained by neurotransmitters, genes, or infections alone. Instead, as stated by Yolken,8
most common human diseases are caused by the interaction of environmental insults and susceptibility genes.Many of the susceptibility genes are diverse determinants of human response to environmental factors, including infections, and prevention or treatment of the infections may result in the effective treatment of complex disorders.

Neuropsychiatric disease is often associated with an interaction of environmental insults and susceptibility factors that frequently results in a pathological interaction including inflammation, oxidative stress, mitochondrial dysfunction, and excitotoxicity, which leads to neuronal dysfunction.3

Numerous studies document that infections, such as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, syphilis, hepatitis C, and zoonotic (animal) diseases, can cause mental illness.9-13 The same syndrome may be caused by different infections in different individuals, and the same infection can cause different syndromes in different individuals. For example, obsessive-compulsive disorder has been caused by infection with Streptococcus, B burgdorferi, Japanese B encephalitis virus, herpes simplex virus 1, Borna disease virus, Epstein-Barr virus, and Mycoplasma, as well as by thepandemic influenza of 191814-16; I have also observed cases caused by Hong Kong influenza and coxsackievirus infection. Of course, many of these infections have also been shown to cause other psychiatric and somatic symptoms. Some infections result in residual injury even after the infection itself no longer persists, while other infections may persist in a chronic relapsing and remitting state. Chronic infections are most commonly viral, venereal, and vector-borne zoonotic.8

Tick-borne diseases and chronic infectious diseases

B burgdorferi, the principal organism associated with Lyme borreliosis, is one of the most complex bacteria known to man. In addition, a tick bite can presumably transmit more than 1 disease-causing organism. Thus, 2 major clinical hurdles in diagnosis and management are the absence of a clear therapeutic end point in treating Lyme borreliosis and the potential presence of tick-borne coinfections that may complicate the course of the illness.3 The more common interactive coinfections may be caused by M fermentans, Mycoplasma pneumoniae, B microti, Ba- besia WA-1, Chlamydia pneumoniae, Ehrlichia, Anaplasma, and B henselae, and multiple viruses and fungi.2,3,17 When multiple microbes grow together, they can promote immunosuppressive effects and cause marked symbiotic changes that alter their functioning.18

Neuroborreliosis is an infection within the brain; however, infections in the body that do not pass through the blood-brain barrier may also impact the brain indirectly via immune effects. All the clinical manifestations, acute or chronic, of infection with B burgdorferi are characterized by strong inflammation with the production of several proinflammatory and anti-inflammatory cytokineswith an aberrant innate proinflammatory response19 and inflammatory brain changes.20 Most of the dysfunction caused by these infections is associated with immune reactions.
Lyme borreliosis and other tick-borne infections are associated with a combination of inflammatory reactions and autoimmune symptoms. The proinflammatory cytokines associated with these infections increase indoleamine 2,3-dioxygenase, which decreases serotonin and kynurenic acid, a neuroprotective glutamate antagonist. In addition, the cytokines increase the level ofquinolinic acid, an N-methyl d-aspartic acid (NMDA) agonist and neurotoxin, which contributes to the neurological and cognitive deficits seen in patients with tick-borne infections.21-23 This change may produce over-stimulation of hippocampal (NMDA) receptors leading to apoptosis and hippocampal atrophy. Hippocampal atrophy in the temporal lobes caused by NMDA overstimulation has been associated with depression and dementia.24

Lyme borreliosis and other tick-borne infections can exist as an asymptomatic chronic carrier state, they can present with occasional or chronic fluctuating low-level symptoms, or they can lead to severe multisystem dysfunction and a multitude of psychiatric presentations.2

Assessment

Some helpful screening questions for a person with suspected late or complicated B burgdorferi infection are listed in Table 2. Positive responses require a thorough history, review of systems, and assessment of cognitive, emotional, vegetative, behavioral, psychiatric, neurological, and somatic symptoms.

TABLE 2
Screening for suspected late or complicated Lyme disease


1. Do you live or have you vacationed in areas that may expose you to ticks?
2. Have you engaged in activities that may have exposed you to ticks? expectations
3. Have family members, neighbors, or the family dog been infected?
4. Is there a history of a tick bite, possibly with a flu-like illness and/or a bull's-eye or other rash?
5. Is there a point at which the patient s health declined, followed by a relapsing progression and development of multisystemic symptoms, including cognitive, psychiatric, neurological, and physical symptoms?
6. Have antibiotics ever caused a sudden worsening followed by an improvement of symptoms?*
*Refer to Jarisch-Herxheimer reaction in Discussion section.


Lyme borreliosis and other tick-borne infections are clinical diagnoses. Although no test can rule out the possibility of infection,2,25,26 common laboratory testing may include Lyme IgGWestern blot from a reliable laboratory, brain SPECT, and cognitive testing. Other diagnostic assessment may include polymerase chain reaction, C-6 enzyme-linked immunosorbent assays in spinal fluid, flow cytometry, and testing for coinfections. CD57 natural killer cell panel testing is useful for tracking clinical progress.27

Caution should be taken because some patients may have an exacerbation of symptoms caused by a Jarisch-Herxheimer reaction (a short-term immunological reaction to antibiotic treatment that may include fevers, chills, head-aches, and myalgias) and may become acutely suicidal, violent, psychotic, and/or confused in response to antibiotic treatment.9 A trial course of antibiotics that causes a worsening of psychiatric symptoms followed by improvement suggests a Jarisch-Herxheimer reaction and can help support the impression that a chronic infectious process is contributing to psychiatric symptoms.

The differential diagnosis may include any medical or psychiatric condition, but particularly other conditions with complex presentations and fatigue, such as MS, lupus, and posttraumatic stress disorder.
Although co-occurring symptoms may be caused by multiple diseases, more commonly a single disease process can have multiple manifestations. The greater the comorbidity, the greater the likelihood that it is a systemic disease process with multiple manifestations. Multiple psychiatric syndromes, especially those with neurological and cognitive symptoms, suggest a CNS pathological process, while significant psychiatric and somatic comorbidity suggest systemic disease. Significant comorbidity increases the suspicion of Lyme borreliosis and other tick-borne infections.

Comorbidity

Psychiatric and somatic comorbidity is the norm and Lyme borreliosis can often be associated with atypical presentations of psychiatric syndromes with relapsing and remitting progressive deterioration.12,13 For example, there may be an atypical presentation of attention-deficit/hyperactivity disorder (ADHD) with a predominance of executive dysfunction and sensory hyperacusis, panic disorder with attacks that last longer than 30 minutes, or presenile dementia.28 In addition, borreliosis can exacerbate preexisting psychiatric illness. It has been my clinical observation that this is particularly apparent with preexisting ADHD, depression, and psychotic disorders. Chronically mentally ill homeless persons frequently sleep in parks, increasing their risk for Lyme borreliosis and other tick-borne infections, which could exacerbate illness severity.

Treatment

Although there is no FDA-approved treatment for the psychiatric symptoms associated with Lyme borreliosis, it has been my experience, as well as that of my colleagues, that many of the common psychopharmacological strategies for symptom reduction are beneficial. Patients with neuropsychiatric manifestations of Lyme borreliosis and other tick-borne infections often respond favorably to treatments that combine psychotropics and antimicrobials.2,29,30 Patients with inadequately treated late-stage infection may experience significant impairment and disability. Based on the collective experience of colleagues, the leading cause of death in borreliosis and tick-borne infections is believed to be suicide.31 Inadequately treated borreliosis and other tick-borne infections have been associated with autism spectrum disorder.11,32

A mild case may improve following treatment with either psychotropics or antibiotics. Patients who have mostly been treated with antibiotics often need psychotropics, while patients who have mostly been treated with psychotropics often need antibiotics. The physician should prioritize which symptoms are most severe and contribute most toward perpetuating chronic illness and treat those first. If psychotropics are needed, the choice of drug type depends on the presenting symptoms.

Commonly, the most disabling neuropsychiatric symptoms include sleep disorders, fatigue, cognitive impairments, depression, anxiety, pain, and headaches. Becauseimpaired sleep andchronic stress cause compromised immune functioning and contribute to fatigue and cognitive impairment, normalizing the circadian rhythm is often a treatment priority. Delta-sleep-promoting agents, such as pregabalin, trazodone, quetiapine, and tiagabine, are treatment options. Modafinil is often effective for excessive sleepiness, fatigue, cognitive impairment, and apathy.29,30,33
Memantine can improve white matter dysfunction and processing speed, reduce word inventions (neologisms), improve word retrieval, and reduce "static and crackle in the head." In addition, better verbal comprehension, and better focus have been reported.30 Atypicals can treat acute suicide risk. Mood stabilizers (anticonvulsants, atypicals, and lithium) can reduce aggression, migraines, and/or neuropathy and control seizures.29,30,34 Serotonin norepinephrine reuptake inhibitors can treat pain, anxiety, and depression. Doxepin in low doses is helpful for irritable gut. Acetylcholinesterase inhibitors are helpful for long-term memory impairments in late-stage disease. Although none of these are approved for treatment of neuropsychiatric symptoms associated with Lyme disease or other tick-borne infections, neither are they contraindicated, and there are no currently approved treatments. (We must treat with the best that we have, however flawed the evidence may be.) Prolonged antibiotic therapy may be useful and justifiable in patients with persistent symptoms of Lyme disease and coinfection with other tick-borne agents.2,10,35

The controversy

Controversial issues surrounding Lyme disease include the reliability of laboratory tests, persistence of infections, clinical manifestations, pathophysiology, and treatment strategies. In 1975, a rheumatologist undertook an investigation using an acute infectious disease model that focused primarily on the objective early, musculoskeletal (arthritis) symptoms and CNS symptoms; mental health capabilities were not considered. Some clinicians still believe that there is no later-stage encephalopathy and maintain the original, highly restrictive definition of Lyme disease from 1975. However, many reports have discussed the expanded complexity of the clinical presentations and pathophysiology, and the role of tick-borne and non-tick-borne interactive coinfections.35-38
Recognition of the mental impairments associated with these infections has been incorporated into a broader set of evidence-based guidelines from the National Guideline Clearinghouse for the treatment of Lyme disease.39 Other evidence-based guidelines, endorsed by the Infectious Diseases Society of America (IDSA) and the American Academy of Neurology, are more restrictive and do not incorporate psychiatric morbidity associated with Lyme borreliosis and other tick-borne infections.40,41 Insurance companies were quick to adopt the more restrictive guidelines and the legal system responded by investigating the IDSA guidelines.42
Since there are complex interactions between the brain, microbes, and the immune system, better communication is needed between psychiatrists, infectious disease specialists, and immunologists to reconcile the controversy.

Conclusion

Multisystemic diseases are often poorly managed because of the fragmentation in our health care system. In addition, patients with Lyme disease, similar to patients with psychiatric disorders, may have invisible disabilities and may have great difficulty with accessing adequate health care and disability coverage. Psychiatrists need to understand health care delivery issues and may be asked for opinions and assistance in these cases.
Additional information on neuro-psychiatric Lyme borreliosis is available from many online sources. Several of these are listed in Table 3.

TABLE 3
Web sites with information on neuropsychiatric Lyme disease


• Lyme Info: www.lymeinfo.net/neuropsych.html


• Lyme Disease Research Studies: www.columbia-lyme.org/index.html


• CDC Lyme Disease: www.cdc.gov/ncidod/diseases/submenus/sub_lyme.htm


• Mental Health and Illness. Neuropsychiatric Assessment Database: www.mentalhealthandillness.com/lymeframes.html


• National Guideline Clearinghouse: www.guideline.gov/search/searchresults. ... ase&num=20


• Lyme Disease Association, Inc: www.lymediseaseassociation.org


• International Lyme and Associated Diseases Society (ILADS): www.ilads.org


Accessed October 17, 2007.

REFERENCE GUIDE
Therapeutic Agents Mentioned in This Article
Ceftriaxone (Rocephin)
Doxepin (Adapin, Sinequan)
Memantine (Namenda)
Modafinil (Provigil)
Pregabalin (Lyrica)
Quetiapine (Seroquel)
Tiagabine (Gabitril)
Trazodone (Desyrel)
Brand names are listed in parentheses only if a drug is not available generically and is marketed as no more than two trademarked or registered products. More familiar alternative generic designations may also be included parenthetically.


________________________________________
EVIDENCE-BASED MEDICINE:
• Cameron D, Gaito A, Harris N, et al; The International Lyme and Associated Disease Society. Evidence-based guidelines for the management of Lyme disease. Available at: www.ilads.org/files/ILADS_Guidelines.pdf. Accessed October 17, 2007.
• Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134.
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Dzięki za ten artykuł. Po przeczytaniu i analizie mam wrażenie, że w znacznej części zawarty jest tu opis przypadku mojego męża.