Lyme disease, TBI, & Neuropsychiatric disorders

[philamom]

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

By Robert C. Bransfield, MD | December 1, 2007

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.

 

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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(Drug information on 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?

[ptcgirl]

Thanks for posting! Very interesting.

[philamom]

(Table 1) didn't open with post - so here it is.

 

Several factors are associated with the risk of infection as well as the different manifestations of Lyme borreliosis:

 

PREDISPOSING FACTORS

HLA DR2, HLA DR4 genotype

Compromised immune system

Coinfections that cause immunosuppression

Ecosystem that fosters tick-borne disease (infection)

Outdoor activities (infection)

 

 

PRECIPITATING FACTORS

Tick bite (initial infection)

Episode of acute stress (relapse)

Immunosuppression (relapse)

Vaccination (relapse)

Childbirth (relapse)

Auto accident (relapse)

Coinfection (relapse)

 

 

PERPETUATING FACTORS

High bacterial load

Reinfections

Coinfections

Chronic unremitting stress

Sleep deprivation

Corticosteroid exposure

Misdiagnosis

Undertreatment

[sf_mom]

Wow good one!!!! THANKS.

 

Important to note for our family and applies specifically to DH 'I think':

 

"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"

 

-Wendy

[RNmom]

Thank you for this post. This psychiatrist is a real hero to many who suffer from TBI.

[pathfinder]

Thank you SFmom for posting this.

It could have been a story of my son past 9years.

I feel so lucky that we know what it is that we have to do but at the same time I am saddened that it wasn't sooner.

I feel sooooo guilty that I did not believe my son when he complained about his toe hurting, sole hurting, headaches, shin/leg hurting, fatigue and so on. My son's psychiatric told me that it was all in my son's head. ( of course, all specialty doctors told me nothing was physically wrong with my son as well) Many ADHD books I had read listed unknown somatic complain as one of ADHD symptoms. If I did not find my way into this forum, I don't know where my son would be today. Thank you again for all your support and help.

Sometimes I still cannot believe all this is happening to us. When my son was dxed with pandas and mycoplasmas P last year, I thought they were bad enough but lyme/bartonella is something so scary and sinister, it is just so unbelievable that he has all of these in him and I did not know of this for last 9years.

pathfinder

[Iowadawn]

There has been some posts re Namenda. You'll note that Bransfield mentions the increase in NMDA receptors. Namenda works on this. Just a note. DAwn

[pathfinder]

Thank you SFmom for posting this.

It could have been a story of my son past 9years.

I feel so lucky that we know what it is that we have to do but at the same time I am saddened that it wasn't sooner.

I feel sooooo guilty that I did not believe my son when he complained about his toe hurting, sole hurting, headaches, shin/leg hurting, fatigue and so on. My son's psychiatric told me that it was all in my son's head. ( of course, all specialty doctors told me nothing was physically wrong with my son as well) Many ADHD books I had read listed unknown somatic complain as one of ADHD symptoms. If I did not find my way into this forum, I don't know where my son would be today. Thank you again for all your support and help.

Sometimes I still cannot believe all this is happening to us. When my son was dxed with pandas and mycoplasmas P last year, I thought they were bad enough but lyme/bartonella is something so scary and sinister, it is just so unbelievable that he has all of these in him and I did not know of this for last 9years.

pathfinder

 

 

Hi Pathfinder, I thought that your son was using helminthic therapy with TSO? Do you no longer believe in the hygiene hypothesis in that you are treating intracellular bacteria? It seems like your treating it aggressively, are you having more success with that?

 

Hello pandas 16

It is so funny you asked that question today as I decided to suspend TSO treatment for now. ( My ds drank a 2500 bottle just a week ago which makes it his 8th bottle) My ds has been on Levaquin for about 5weeks and we learned that Levaquin is working against TSO hence returning of allergy, gut issues so I am going to stop TSO altogether for now until we have some answers with Bartonella. We will continue with TSO once we know what is happening with his gut. We might have to choose one treatment out of TSO or Bartonella. Everything is up in the air right now.

I have been following your posts and am very grateful as they are very helpful for us.

thanks

Pathfinder

[pathfinder]

Levaquin interferes with TSO??? Can you elaborate a little on that please?? ( Because I had to take it for a week) It does not say anything about that on Biomonde and the president of Biomonde said it "should't be a problem" according to Stewart. I'm surprised I thought you said your son was doing great on TSO. In the end I was sort of under the impression that you chose one or the other, either you tackle all the bacteria or balance all the bacteria...(not both) Did you understand differently. The whole idea with the hygiene hypothesis is that we naturally co-exist with organisms...

 

Are you using anything like tindamax?

 

Hi pandas 16

I felt that my ds's bartonella has to go either with TSO or without. We were approaching my ds's OCD( mostly someone touching his things, someone's saliva getting to him while talking kind of OCD)and rage over a little thing ( if I misunderstood him he would have a fit)with bartonella medication and his gut issues ( gas, frequent bowel movement, skin rash in short food allergy to almost everything)with TSO. I think it was working very well as his gut issues were all gone and his OCD was at minimum until we introduced Levaquin to his system. We are on 5th week of levaquin and last 2 TSO were not effective at all. His gut issues were back in full force with OCD/rage so I was thinking levaquin was preventing TSO hosing in my ds's system. ( what other answer would there be since they were working really well before?)

But situation changed since yesterday. We went to see our Dr and he changed levaquin to bactrim so we will stay on with TSO.

I was told by an email friend that one gets worse before getting better ( by 7th or 8th bottle?) and since we never had a getting worse stage before maybe this was what it was?( always hoping!) My ds is to start a college in less than 2months and we need something very quick hence my aggressive approach to treatment. I really want Bartonella gone already!!!!!!!!!!!

We never did tindamax yet. SO far ignex test did not prove my ds has lyme so ds has only mycoplasma P, bartonella, and high strep titer via special lab.

pathfinder

[pathfinder]

Of all that happened to my ds, I am sure of one thing that is all his problem started with strep and augmentin/IVIG really helped us to see what was going on with my ds. I also believe that if we did not treat that chronic strep with those treatments, TSO would not have been any help to my ds at all.

I happened to believe bartonella is another one that has to be treated ( rooted out ) before any things else could work and TSO is no different.

I know I am sort of gambling at this point doing TSO with bartonella treatment but I feel like I don't have much to lose except $$$ with TSO.

We attained 90-95% with pandas treatment but still moved on to treat bartonella ( maybe lyme) regardless of herx symptoms and set backs because I believe treating Bart will get us that magical 99% we are dreaming of.

 

pathfinder