Archive for the ‘research’ Category

EBV Protein Can Turn-on Genes for Autoimmune Diseases

https://www.nih.gov/news-events/news-releases/epstein-barr-virus-protein-can-switch-risk-genes-autoimmune-diseases

Monday, April 16, 2018

Epstein-Barr virus protein can “switch on” risk genes for autoimmune diseases

EBV may trigger some cases of lupus, say NIH-supported researchers.

Infection with Epstein-Barr virus (EBV), the cause of infectious mononucleosis, has been associated with subsequent development of systemic lupus erythematosus and other chronic autoimmune illnesses, but the mechanisms behind this association have been unclear. Now, a novel computational method shows that a viral protein found in EBV-infected human cells may activate genes associated with increased risk for autoimmunity. Scientists supported by the National Institute of Allergy and Infectious Diseases report their findings today in Nature Genetics.

“Many cases of autoimmune illness are difficult to treat and can result in debilitating symptoms. Studies like this are allowing us to untangle environmental and genetic factors that may cause the body’s immune system to attack its own tissues,” said NIAID Director Anthony S. Fauci, M.D.  “A better understanding of the complex causes of autoimmunity promises to lead to better treatment and prevention options.”

EBV infection is nearly ubiquitous in the human population worldwide. Most people acquire EBV in early childhood, experience no symptoms or only a brief, mild cold-like illness, and remain infected throughout their lives while remaining asymptomatic. When infection first occurs in adolescence or young adulthood, EBV can lead to a syndrome of infectious mononucleosis characterized by prolonged fever, sore throat, swollen lymph nodes and fatigue.  This syndrome, also known as “mono” or the “kissing disease,” generally resolves with rest and only rarely causes serious complications.

When EBV infects human immune cells, a protein produced by the virus — EBNA2 — recruits human proteins called transcription factors to bind to regions of both the EBV genome and the cell’s own genome. Together, EBNA2 and the human transcription factors change the expression of neighboring viral genes.

In the current study, the researchers found that EBNA2 and its related transcription factors activate some of the human genes associated with the risk for lupus and several other autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis and celiac disease.

Previous studies suggested that EBV infection may result in autoimmune diseases, particularly lupus.  In the current work, researchers led by John B. Harley, M.D., Ph.D., director of the Center for Autoimmune Genomics and Etiology (CAGE) at Cincinnati Children’s Hospital Medical Center, with his colleagues Matthew T. Weirauch, Ph.D., and Leah C. Kottyan, Ph.D., also of CAGE, wondered whether genetic analysis could further explain the relationship between EBV infection and lupus. Their team developed a new computational and biochemical technique known as the Regulatory Element Locus Intersection algorithm, or RELI. Sifting through and comparing a large collection of genetic and protein data from healthy individuals and those with autoimmune diseases, the team used RELI to identify regulatory regions in genes associated with the risk of developing lupus that also bound EBNA2 and its related transcription factors.

“We were surprised to see that nearly half of the locations on the human genome known to contribute to lupus risk were also binding sites for EBNA2,” said Dr. Harley. “These findings suggest that EBV infection in cells can actually drive the activation of these genes and contribute to an individual’s risk of developing the disease.”

In follow-up analyses, the investigators used RELI to probe regulatory genes associated with other autoimmune diseases and found that EBNA2 bound to genes associated with the risk for multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis and celiac disease.

“Because EBV is most often encountered in early childhood, avoiding infection is practically impossible,” said Daniel Rotrosen, M.D., director of the Division of Allergy, Immunology and Transplantation at NIAID. “However, now that we understand how EBV infection may contribute to autoimmune diseases in some people, researchers may be able to develop therapies that interrupt or reverse this process.”

Researchers note that EBV infection is not the only factor that contributes to the development of the seven autoimmune conditions discussed in the paper. Many of the regulatory genes that contribute to lupus and other autoimmune disorders did not interact with EBNA2, and some individuals with activated regulatory genes associated with disease risk do not develop disease.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®

Reference

J Harley, et al. Transcription factors operate across disease loci, with EBNA2 implicated in immunity. Nature Genetics DOI: 10.1038/s41588-018-0102-3 (2018).

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**Comment**

Folks with Lyme/MSIDS have been misdiagnosed with EBV:  https://madisonarealymesupportgroup.com/2017/04/11/diagnosed-with-ebv-had-lyme/ and others have it as well as tick-borne infections.  The involvement with numerous viruses is quite common in patients as well.  https://madisonarealymesupportgroup.com/2016/03/28/combating-viruses/

https://madisonarealymesupportgroup.com/2017/07/14/another-dies-from-powassan/

https://madisonarealymesupportgroup.com/2018/04/08/novel-viruses-found-in-lone-star-american-dog-black-legged-ticks/

https://madisonarealymesupportgroup.com/2018/04/21/neurological-lyme-disease-what-you-need-to-know/  “Once microbes start becoming active, inflammation increases and immune functions are further compromised, establishing what I call Chronic Immune Dysfunction (CID). In its weakened state, the immune system allows reactivation of viruses such as Epstein Barr virus (EBV), Cytomegalovirus (CMV), and other similar viruses — all of which most people harbor in their tissues. These viruses are commonly associated with neuroinflammation, and they tend to complicate the picture of LNB.”

https://madisonarealymesupportgroup.com/2017/11/04/24514/  EBV a Key Player in Chronic Illness & Tips to Treat Reactivated EBV.

 

 

 

 

Can Infectious Disease Physicians Help Prevent Violence?

http://www.contagionlive.com/news/can-infectious-disease-physicians-help-prevent-violence

Can Infectious Disease Physicians Help Prevent Violence?

APR 17, 2018 | ROBERT C BRANSFIELD, MD, DLFAPA
Robert Bransfield, MD, DLFAPA
About 1.6 million individuals die from violence each year on a global scale; in fact, more Americans have died from gunshot wounds in the past 50 years than have died from all wars combined since the American Revolution.

Where peace has been shown to correlate strongly with education, health, economic opportunity and a lower prevalence of infectious disease, the world is currently struggling with a long-term epidemic of violence. As new high-velocity bullets increase the severity of trauma seen with gunshot wounds, there is a growing concern that weapon technology may be more advanced than the scientific capacity to understand and prevent the violence they contribute to.

Although violence occurs on a daily basis, it periodically makes media headlines, especially when it comes to mass shootings, which often lead to a worldwide debate focused on 2 major elements: gun control and mental illness. Gun owners strongly defend their right to own guns, while mental health organizations state that the vast majority with mental illnesses are not violent and should not be unfairly stigmatized. However, the formula to explain violence is much more complex than guns and mental illness.

We need to methodically understand all contributors, deterrents, and acute triggers to violence in the same way in which we study airplane crashes and perform hospital quality assurance. Some of the contributors to violence that are well-recognized include the following: homelessness, social isolation, being single, living alone, gang membership, low education, unemployment, incarceration, a history of violent behavior or a fascination with weapons, having had been a victim of violence and/or exposure to violence. Others can include having opposed religious, political, ethnic or lifestyle beliefs; gender or genes (monoamine oxidase A, catechol-O-methyltransferase, serotonin transporter gene, FK506 binding protein s, XYY); and/or grudge holding.

There are also several psychiatric disorders and diagnoses that can make individuals more prone to violence, these can include: child conduct disorder, intermittent explosive disorder, narcissistic personality disorder, antisocial personality disorder, psychopathy, bipolar illness, depression, social communication disorder, among other conditions. Treatment nonadherence, substance abuse, intoxication, toxicity, among others also make the list.

On the other hand, just as there are contributors to violence, there are also deterrents, which are just as important to understand. These deterrents can include empathy, frustration tolerance, restraint capabilities, a higher education, strong coping skills, supportive relationships, social connections, ethical and/or religious beliefs, access to psychiatric and medical care, as well as social structure.

Triggering events can include acute stress, apperception of threat, jealousy, obsession, psychotic delusions, post-traumatic flashbacks, hopelessness, competition, exposure to violence, traumatic brain injury, unintentional injury, being suicidal, self-harm, impairment from substance use, intoxication, and losing a parent.

Notable among these contributors to violence are impairments caused by a number of past and present infections resulting in immune processes associated with certain types of brain dysfunction. There is a long history of infectious diseases associated with and following warfare. Many infections during and after WWI may have resulted in residual neuropsychiatric impairments in those who had been infected; these impairments associated with violence in the general population and leaders could have been one of the many contributors to WWII. It is also possible that current war zones endemic to violence may follow a similar pattern in which there is a repetitive cycle of infection, brain impairments contributory to violence, and resulting violence.

My most recent article; Aggression, Violence, Homicidality, Homicide and Lyme Disease is a follow-up to a prior article on suicide and Lyme and associated diseases in which I found 68% of late-stage Lyme disease patients had some form of aggressiveness and 11% of these patients, as well as 26% of the suicidal Lyme patients, were also homicidal.

In the current article, I first provide a basic background and formula to analyze violence and then apply this formula to a statistical analysis of patients with Lyme disease. When applying this formula to Lyme disease, the impairments caused by Lyme disease contributing to homicidal risk within the 95% confidence interval included suicidality, sudden abrupt mood swings, explosive anger, paranoia, anhedonia, hypervigilance, exaggerated startle, disinhibition, nightmares, depersonalization, intrusive aggressive images, dissociative episodes, de-realization, intrusive sexual images, marital/family problems, legal problems, substance abuse, depression, panic disorder, memory impairments, neuropathy, cranial nerve symptoms, and decreased libido. Most aggression in these patients was associated with poor impulse control, sometimes triggered by intrusive images, thoughts, and emotions; sound or other stimulation and frustration, and the resulting aggression was invariably bizarre and senseless. In a past interview, I spoke with Contagion® about this topic.

Cross-disciplinary bridges need to be built and maintained between psychiatrists, infectious disease physicians, psychoimmunologists, and neuroscientists to better understand and prevent tragedies in order to save lives. We need to keep current with fields outside of our specialty and avoid silo mentality. If physicians do not keep up with advances in psychiatry and are inattentive to cognitive and psychiatric symptoms in their patients with infectious diseases, they are in danger of misclassifying these symptoms as being “subjective, non-specific, medically unexplained symptoms or bodily distress symptoms.” It is also important for infectious disease physicians to recognize the significant limitations of 2 tier testing for Lyme disease, to perform psychiatric screening examinations on their patients with Lyme and other infectious diseases associated with causing psychiatric symptoms, to recognize that the progression of these symptoms may be a clinical indication of persistent infection.

If we are successful at improving research, prevention, diagnosis, and treatment; I hope someday to reach a point where I stop receiving calls from defense attorneys after someone with Lyme or some other infectious disease committed homicide or some other crime. With better communication and collaborations across disciplines, we could work to prevent these things from happening, and ultimately, save lives.

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**Comment**
Unfortunately, many Lyme/MSIDS patients are misdiagnosed with mental illness and are prescribed psychiatric drugs that are causing problems:

Bb SpoVG DNA & RNA-binding Protein Modulates Physiology of the LD Spirochete

https://www.ncbi.nlm.nih.gov/m/pubmed/29632088/

Borrelia burgdorferi SpoVG DNA- and RNA-binding protein modulates physiology of the Lyme disease spirochete.

Savage CR, et al. J Bacteriol. 2018.

Abstract

The SpoVG protein of Borrelia burgdorferi, the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of spoVG during the natural tick-mammal infectious cycle, and in response to some changes in culture conditions. Bacterial levels of spoVG mRNA and SpoVG protein did not necessarily correlate, suggesting that post-transcriptional mechanism(s) also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the glpFKD operon and to two RNA sites in glpFKD mRNA. That operon encodes genes necessary for glycerol catabolism, and is important for colonization in ticks. In addition, spirochetes engineered to dysregulate spoVG exhibited physiological alterations.  IMPORTANCE  B. burgdorferi persists in nature by cycling between ticks and vertebrates. Little is known about how the bacterium senses and adapts to each niche of the cycle. The present studies indicate that B. burgdorferi controls production of SpoVG, and that this protein binds to specific sites of DNA and RNA in the genome and transcriptome, respectively. Altered expression spoVG exerts effects on bacterial replication and other aspects of the spirochete’s physiology.

PMID

29632088 [ – as supplied by publisher]

Persistent Borrelia Infection in Patients With Ongoing Symptoms of Lyme Disease

http://www.mdpi.com/2227-9032/6/2/33

Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease

Marianne J. Middelveen 1, Eva Sapi 2OrcID, Jennie Burke 3, Katherine R. Filush 2, Agustin Franco 4, Melissa C. Fesler 5 and Raphael B. Stricker 5,* OrcID

Published: 14 April 2018
(This article belongs to the Special Issue Lyme Disease: The Role of Big Data, Companion Diagnostics and Precision Medicine)

Abstract
Introduction: Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi, in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. Methods: In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of ten control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Results: Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR)-based approaches. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Conclusions: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

healthcare-06-00033-g001

Figure 1  (A) Top left:  Darkfield microscopy of blood culture showing live spirochete and spherules.  Magnification 400x.  (B) Botom left:  Fieterle silver stain culture fluid from Case 10 showing live spirochetes  Magnification 1000x.  (D) Bottom right:  Typical dermal filaments from patient with Morgellons disease.  Magnification 100x

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For more:  https://madisonarealymesupportgroup.com/2017/08/25/sleeper-cells-the-stringent-response-and-persistence-in-the-borreliella-burgdorferi-enzootic-cycle/

https://madisonarealymesupportgroup.com/2017/08/18/drexel-prof-lyme-persists/

https://madisonarealymesupportgroup.com/2016/12/21/dr-zhang-on-persisters/

https://madisonarealymesupportgroup.com/2017/05/10/chronic-lyme-disease-a-case-definition-at-last/

https://madisonarealymesupportgroup.com/2018/04/13/chronic-lyme-post-mortem-study-needed-to-end-the-lyme-wars/

LD & The Brain – Podcast With Dr. Bransfield

Episode 23: Lyme Disease and the Brain

Cindy Kennedy, FNP, is joined by Dr. Robert C. Bransfield, M.D., F.A.P.A., who discusses Lyme disease and the brain, including the connection between Lyme disease and mental health and how Lyme disease and co-infections can cause cognitive impairments, sleep disorders and various psychiatric issues.

Dr. Bransfield is a graduate of Rutgers College and the George Washington University School of Medicine. He completed his psychiatric residency training at Sheppard and Enoch Pratt Hospital. He is board certified by the American Board of Psychiatry and Neurology in Psychiatry. 

Dr. Bransfield’s primary activity is office-based private practice of psychiatry with an emphasis upon treatment resistant cases. In addition, Dr. Bransfield is the Associate Director of Psychiatry and the Chairman of Quality Assurance at Riverview Medical Center in Red Bank, N.J.

He has held teaching appointments at Hahnemann Medical College and Eastern Virginia Medical School. He has taught in many settings to physicians, mental health professionals and the public. He has performed research, and has a particular interest in psychopharmacology, a unified theory of mental health and illness, the link between microbes and mental illness, Lyme and other tick-borne disease, violence, and the link between microbes and violence.

Dr Bransfield has authored and co-authored a number of publications in peer-reviewed literature, other medical publications and books. He has held a number of administrative positions for various organizations involved with a number of health, mental health and community related activities.

Dr Bransfield has been active in political advocacy on a national, state and local level. He has appeared on network and regional television, radio and various publications.

Transcript of Episode 23: Lyme Disease and the Brain

https://madisonarealymesupportgroup.com/wp-content/uploads/2018/04/lwle23.mp3

Cindy K.: This is Cindy Kennedy your host and we are on the Living with Lyme today. We have the great honor of having Dr. Robert Bransfield with us. He is well versed and considered an expert in the area of Lyme and other tickborne diseases and the treatment of neuropsychiatric symptoms. He’s active in political advocacy on national state and local levels. He’s also been an author and a speaker. He has notable publications in peer-reviewed literature. We’ve had a lot of technical issues today but we finally have him and I’d like to welcome Dr. Bransfield. How are you today?

Robert B.: Good Cindy. It’s good to be here.

Cindy K.: Oh it is. It is. I’m so thankful because your expertise goes beyond the scope of anything I can imagine. I’m sure the information that you and I are going to talk about are going to be very, very helpful to a lot of people. So, my question to you is, we know that Lyme is certainly underdiagnosed and undertreated. I think for most healthcare professionals that a psychiatric presentation is highly unlikely and they wouldn’t consider Lyme and all the symptoms that go along with it. Can you give your experience on that?

Robert B.: Yes. What happens is many of the doctors who have capability, experience, credentials for treating early infectious disease invariably have very little training in psychiatry. So, you may find that patients go to infectious disease doctors, rheumatologists and they haven’t had much current experience with psychiatry. When I ask them, “What’s your training in psychiatry?” They may say that 40 years ago they did a one-month rotation in a state psychiatric hospital and that might be the extent of their psychiatric training. So, they have difficulty seeing the connection between the physiological process that occurs that impacts the brain that then results in psychiatric symptoms.

Cindy K.: You know Dr.-

Robert B.: You can tell their training may go back to the old Freudian theories and it’s hard for them to understand the physical basis to the mental symptoms that we see.

Cindy K.: Dr. Bransfield, hold on one second. Don’t speak so close to the phone because it’s hissing a little bit. So, I’m sorry. I’m going to go back to the point where I asked you, what is your experience with these doctors not understanding that there can be psychiatric presentations?

Robert B.: I think many doctors just lack the training in understanding the physiology as how mental illnesses are caused by brain inflammation. Many doctors who treat earlier cases of Lyme disease have knowledge in infectious disease but they don’t have knowledge or extensive knowledge in psychiatry. Some have only had maybe one-month rotation decades ago when they were in medical school and have not kept current with current physiology, understanding as how brain processes can cause mental symptoms. So, I think that’s a big problem is the disparity, the gap between infectious disease in psychiatry.

Cindy K.: Is there any certain type of patient that comes to you with particular psych issues that would prompt you to immediately think “Geez, could this be Lyme?”?

Robert B.: Yes. The more common cases often it’s progressive. So, the mental symptoms keep getting worse and a particularly common case would be someone who is partially treated for Lyme disease. The partial treatment may be enough to help some of the … or major part of musculoskeletal symptoms, but not enough to help the cognitive and the neuropsychiatric and some of the neurological symptoms. So, that’s the case. It can go under the radar for diagnosis since it’s not your migratory arthralgia, your type of presentation that most people would recognize Lyme disease.
So, this typical case is someone who’s symptoms keep getting worse with time and you give a treatment that works for a while and then they keep getting worse. It’s a combination. It’s a multisystem illness and you have to look at all the different ways it presents and every patient is all but different but you see invariably fatigue, multiple cognitive impairments, multiple psychiatric symptoms, anxiety, depression, irritability and sleep disorders and then neurological symptoms, neuropathy. So, it spans almost every system in the body.

Cindy K.: Do certain co-infections exaggerate psychiatric symptoms or would you see a particular psychiatric symptoms more often with say babesia?

Robert B.: So, invariably when we look at the more severe psychiatric cases we find co-infections. It may be that when someone has Lyme alone maybe that’s not as bad. When co-infections are present, it’s not an additive effect. It’s an interactive effect. So, when you add to infections, they interact in a way that can magnify the degree of severity. So, we babesia, bartonella, mycoplasma and these are opportunistic viruses. Probably other things that we aren’t really testing for chlamydia, rickettsia, ehrlichia, the more severe cases often have multiple co-infections.

Cindy K.: Now you said I’m thinking to myself and we had a discussion a little earlier about someone that I know having an onset which looks to be Parkinsonian and of course that goes along with when your body is not really … it’s breaking down in some sorts that you get depression. So, when you’re talking out psychiatric issues, is it something that’s kind of insidious that leads you? Is there a rapid onset of say dementia that would trigger some sort of a concern because maybe it’s not in the family, maybe again it wasn’t something that … it just came up very quickly. Is that something you’d see?

Robert B.: Sometimes. I think the more common case seems to be someone who has infection more in the body there’s an immune reaction. Rather than adaptive immunity and the infection’s gone, you see with these infections persistent inflammation and autoimmunity and disease progression. Now there are some cases where … these are the cases I think where there’s infection in the brain rather than infection in the body provoking the immune system which causes mental symptoms. The cases where there’s clear infection in the brain, those can appear as a more rapidly progressive dementia case. We used to call these pre-senile dementia but this can be a relatively young person and it’s a very rapid downhill course even with a fair amount of antibiotics that may just slow it down. These are very difficult cases.
Fortunately, they’re the minority but they’re very tragic when we see them and invariably on an autopsy then you can find borrelia in the central nervous system, but your average run-of-the-mill cases more rather than neuroborreliosis more Lyme encephalopathy where we have it in the body and it can affect the brain. So, you don’t have to have spirochetes inside the brain to get mental symptoms from Lyme disease. You can have it in the body and has that immune effects and that orders neural functioning because the cytokines and certain antigens from the infection can cause the blood brain barrier and cause mental symptoms. That’s why it can be episodic. Someone can be good in the morning and then several hours later be very impaired.

Cindy K.: I understand that oral antibiotics is not a great way to treat complications that are arising in the brain. It typically doesn’t cross the blood brain barrier. That you need to use more IV or possibly intramuscular injections. Is that true?

Robert B.: Right. If it’s actually in the brain, that might be true although it’s more an issue of how high a blood level you can get with antibiotics. If someone’s GI tract tolerates it, then you may be able to do it with orals and it might be effective. I think you do see more use of orals proportionally now than used to be the case whereas before in the earlier era of the Lyme epidemic, people would start out more with IV. One hesitation about that is if you start with a very aggressive antibiotic treatment, you might get a neuropsychiatric Herxheimer reaction where someone could have an exacerbation of their neuropsychiatric including suicidality. That could provoke a suicide attempt. So, I find it’s often better to gradually ramp up the treatment so that there isn’t too much of a Herxheimer reaction that could be destructive to the patient.

Cindy K.: This is an interesting question and I don’t have an answer. If you’re bitten by a tick that’s infected and it’s on the upper portion of your body, say you found it in your scalp versus something on a lower limb behind your knee. Does that trigger more neurologic per se?

Robert B.: Yes.

Cindy K.: It does.

Robert B.: Yes. There was one study done where they looked at the different quadrants of the body, because some of it’s dissemination through the blood but some of it’s local spread. In part this is why children may have more severe … one of the reasons why children may have more severe symptoms is because their … what happen is a tick would first get on the lower part of the body, work their way up until there’s some constriction. Then they would attach there. So, children are closer to the ground or their brains are closer to the ground than adult. There may be a three-foot trip instead of a six-foot trip to get up the length of an adult. So, when the ticks are attached, more in the head and neck region and that’s a common place where they are attached. You see that in deer also. They could be in the hairline, above the hairline. It does seem they do have more of the CNS symptoms when the attachment is closer to the brain.

Cindy K.: What type of neuro symptoms do children have versus adults? Is there any difference?

Robert B.: Yes. Well, one difference can be they invariably don’t have a reference point of what it’s like to not have symptoms. They don’t know what healthy is. So, if you’re an adult and at the age of 30 you get an infection, you know what you were like before the date of that infection then you may struggle to try to function at the level that you used to be at. So, you know what should be but a child who is developing doesn’t have that reference point. So, that’s a major problem. You invariably see a lot of tantrums, irritability, low frustration tolerance. It can be like behavior problems, obsessiveness, aggressive outbursts, difficulty with school. Some of it, it can look somewhat like attention deficit disorder but it qualitatively is different. There is a difference between Lyme and attention deficit disorder although some of the symptoms overlap.

Cindy K.: I did read an interesting story about a young boy who was very obsessive about being on his bicycle. It just came on very quickly. If he wasn’t eating in school or sleeping, he had to be on his bicycle. They were saying this child is obsessive compulsive. That’s all it is and the mom wouldn’t settle for that. It went on and went on. One doctor finally laid out all the paperwork, went through with a fine tooth comb and did find that he had a tick bite sometime prior and wasn’t treated. When they tested him, he was Lyme positive. They treated him and that compulsion to be on the bike just went away. I find that-

Robert B.: That was the famous case of bicycle boy with Andy Pachner. That goes back 30 years ago.

Cindy K.: Oh it does.

Robert B.: So, that case as a 30-year-old case and that was one of the earlier recognitions of the psychiatric manifestations of Lyme disease. Then that was also published in the magazine in Washington DC and that was included in the case histories. It was around ’87 or ’88 that that was published. So, that’s a 30-year-old case. So, this isn’t anything new to connect the psychiatric symptoms with Lyme disease. This has been around for a while and there’s been expanding recognition with many journal articles. Yet even with that, it’s … so for the rank-and-file doctor to catch on and see that connection.

Cindy K.: That might be a very hard one. Let’s talk about the nitty-gritty, because the vast majority of the people that are suffering are suffering with certain types of problems. I think we need to hear about why these problems are occurring. I’m going to start first with brain fog, that horrible inability to process things, to feel like you’re on your game. It commonly goes with that horrific fatigue. Where is that coming from?

Robert B.: Well bran fog is supported what we call sickness syndrome. Sickness syndrome, you could replicate it and it’s replicated when people have interferon treatment or when they get the cold or the flu and their inflammatory … part of their immune system is activated. So, lupus patients call it lupus fog. Fibro patients call it fibro fog. That fog, the best way to compare it is go take 100 mg of Benadryl in the morning and then go back your daily activities and see how you feel. So, it’s that fog that’s a thought like your brain is sluggish. Now you can see why it’s called the terrible triad. Terrible triad can be nonrestorative sleep, cognitive impairment and fatigue. So, the three can go together.
Now brain fog can be akin to like mental fatigue. Mental fatigue and physical fatigue have some similarities where there’s a sluggishness, the slowness and fatigue in the body is a lack of physical energy unrestored by rest. Compared to exhaustion, exhaustion you ran a marathon and now you’re exhausted because you expanded some energy whereas fatigue you wake up after 12 hours of sleep and you feel like you ran a marathon even though you did not. So, it’s that both cases that lack of physical energy. It’s a very frustrating symptom.
I think overall it’s very hard. People get the symptoms and they wish they didn’t have them. They can’t explain them. They can’t understand them. Their family can’t understand it. Just stop it and everybody wishes it would work that way. Then their doctors don’t understand it. Your insurance company doesn’t want to understand it. It’s baffling but there is a very clear explanation for it. It takes more complicated model and then we can understand it very clearly.

Cindy K.: You can’t just draw blood. See, that’s the thing. You can’t just draw blood that shows this particular issue, can you?

Robert B.: Well, this is a complex disease. You can’t use a simple diagnostic model to explain a complex disease. You have to use a complex model to explain a complex disease. Now it’s not that simple that you could just do one simple test. The reality if you look at the history of medicine, diseases that are simple have all been discovered, well understood well explained. What is left that is still at the leading edge of discovery in medicine are the more complex diseases that require more complex formula. If people keep using the simple “Let’s just do a blood test. If it’s positive, you have it. If it’s negative, you don’t.”
As long as you approach a complex disease in that way, you’ll be going around in circles never understand it, never solve it. You have to shift to a different model and recognizing the full complexity, there may be multiple interactive co-infections, multiple immune reactions and multiple manifestations. Now probably looking forward, there’s more in the way of gene testing and particularly these more sophisticated DNA testing for microbes. As that gradually gets online, I think that we can understand this much better. How you have a mix of infectious agents and then once this disease takes hold, orders what genes are turned on and turn off in our body. Often you’re looking at immune system genes. Then that correlates with the symptoms. That’s the model you need. Anything short of that is futility.

Cindy K.: Right. The other things that people experience are confusion or memory or word find issues. That lack of ability to concentrate or you’re reading something and you’re reading it five times and you still can’t remember. Is that also a process of that inflammation that happens as your body is trying to recover itself from an infection?

Robert B.: Yes. I think you can break it down in a couple areas. One is executive functioning and another is slow processing. Maybe slow processing … I’ll talk about that first. It’s easier to understand. Now think of a computer that has a slow processor. Invariably that’s a white line is more of a white matter dysfunction in the brain. When you do a MRI you see white matter hyperintensities. You see changes with the SPECT scan.

Cindy K.: What does that mean?

Robert B.: So, white matter is more the inside of the brain that has to do with processing. It is making the connections whereas something like Alzheimer’s is more of a gray matter disease where memory content is lost. So, if someone doesn’t remember the thing grandchildren that’s more a gray matter disease, but slowness of processing is white matter. So, invariably one way to compare it is in a Peanuts cartoon where when the adults are talking it’s wah, wah, wah, wah and the person is sitting there and they hear the words but they’re not digesting the content. So, it’s slow processing going in and going out, both. So, if it’s slow that helps.
Often a person can keep up with the conversation. So, like in a lecture hall in school, they’re not able to keep pace and digest the content. They can’t process it fast enough. Think of it like an assembly line. So, that’s going in but also going out. On going out, you can see that because a person’s struggling with word finding problems. You can see how they’re groping to correct, that they’re trying to solve. That type of thing. That’s what you’re seeing.

Cindy K.: [inaudible 00:22:37] I got nervous there. I see that you were trying to replicate what [crosstalk 00:22:42].

Robert B.: That’s why it works. So, it’s obvious and also if you explain something and you talk too fast, a person will just sit there with a blank expression on their face. You can see that they’re not really grasping what they’re saying. They need that slowness and-

Cindy K.: Is that because of inflammation though or do we not know?

Robert B.: [crosstalk 00:23:11] exactly but somehow it’s the connections are slow. Probably invariably inflammation is contributing to that. I first ran into that. I worked in a mental health clinic in North Carolina and there were these loggers that were there. I think looking back a lot of them had Lyme disease. It was a low-budget clinic and the consultation rooms are very small. You’d be in a tiny consultation room looking at someone maybe a foot or two in front of you and you’d say to them, “How are you doing today?” Then they’d look with a blank expression and say, “Who? Me?” A lot of them did this. It was very puzzling why they did that.
We tried to explain it and at the time we never could, but looking back I think the lot had Lyme disease. By saying, “Who? Me?” they were buying time to collect their thoughts. They couldn’t just answer because they weren’t processing fast enough. So, that’s the processing speed part of it. Then the other part is executive functioning. Executive functioning is the capacity to create sustained, monitor, regulate, goal-directed behavior. So, it’s when looking at the cognitive side of Lyme disease, it can be confused with Alzheimer’s. It can be confused with attention deficit disorder. It has unique qualities different from other cognitive impairments. In some ways it has more similarities to postconcussion syndrome.
With executive functioning, it’s hard to plan, prioritize, multitask. It’s hard to work and chew gum at the same time so to speak. Time management becomes poor. It’s hard to keep organized. People make careless mistakes. They [crosstalk 00:25:17] in the refrigerator and the milk in the cabinet. That goes with difficulty multitasking, getting sidetracked.
Then another part too can be the sensory hyperacuity, the excessive sensitivity to sound, light touch, smell, sometimes vibration. So, that there can be the sensory overload and the person deem it very flooded and emotionally react to the dog barking, noise and then they can’t hear themselves think. They get overwhelmed and then they become night owls, because only then can they hear themselves think. Then they stay up at night and they get sleep deprived. The sleep deprivation doesn’t help. So, all those things are a common vicious cycle of the disease progression that’s driven by these conditions.

Cindy K.: Now you just mentioned something that’s real important and we see a lot. My particular first symptom was a sleep disorder. I was waking 17 times that I could count at night but yet on a sleep study the sleep neurologist said to me, “You know what? You’re waking up like 30 times in an hour and I’ve never seen this before.” So, I was never getting restorative sleep. What cause that?

Robert B.: There’s a lot of different issues. Sometimes trouble falling asleep can increase the symptoms. There can be nightmares. There can also be … normally with healthy sleep, you get cycles of deep sleep in the beginning of the night which helps with your immune functioning. Then you get REM sleep towards early morning hours and then you’re recovered. One study looked at sleep patterns of Lyme patients and 100% of Lyme patients had sleep disorders. So, a lot of times one of the first things they attack is the sleep disorders.
Now I’ve also seen sleep apnea. It can be common. You can see narcolepsy with some patients. Cataplexy besides the nightmares. The anxiety and the depression that can be a part of Lyme disease can contribute to the sleep disorders. There’s multiple facets to it. So, it’s often can be … and the pain can be contributory. A person will lie in one position and we’re in pain. The pain interferes with their ability to sleep. So, the nonrestorative sleep when that perpetuates because sickness syndrome is often state where you curl up in a ball and you sleep and your body diverts it’s energy inside.
When that is effective, then it helps you recover, but if you’re never really sleeping, you’re never recovering. Sometimes getting the sleep better is more critical I think sometimes than antibiotics, because you play such in two ways. One is with narrowed immune system and the other is with whatever antibiotic a doctor thinks might work. Who’s smarter, your immune system or us as doctors trying to pick which antibiotic? An immune system is smarter. So, doing everything you can to help the body heal is a first step.

Cindy K.: What type of medicines are best for these people with sleep disorders since they’re so many of them and they affect the brain in a variety of different ways? What have you found to be the best to aid in sleep?

Robert B.: Well, all of your FDA approved sleep meds invariably help someone fall asleep and stay asleep longer, but none of the FDA except for one and that’s [inaudible 00:29:18]. None of the FDA approved sleep meds actually improve quality of sleep. So, by sleeping longer then there’s some improvement. So, there are certain meds particularly a couple of the antidepressants that we know improve deep sleep, sleep architecture. Those are sometimes one of the first things we try to distract them. Remeron, a couple of doxepin so those can promote more that deep sleep that is more critical, but of course you can’t have quality of sleep unless you also fall asleep. So, you want to look at can the person fall asleep, can they stay asleep, do they have an early-morning awakening and do they have good quality of sleep and then you break it down.
For instance, falling asleep is there trouble to turn of your head, is there trouble to calm down your emotions, is there difficulty relaxing your body, is there difficulty actually feeling sleepy and that would determine which approach we would take in treatment.

Cindy K.: We’re also battling adrenal issues and sometimes your time becomes your … you have such a hard time getting up in the morning and getting going and then you’re struggling. Then supper time happens and then all of a sudden you’re revving up.

Robert B.: That goes with the circadian rhythm. The theory there is you get the deep sleep and the deep sleep not only helps with immune functioning, but it also promotes the secretion of growth hormone which is the master hormone and help set circadian rhythm.

Cindy K.: Do you feel the severity of symptoms relate to the length of the time that they’ve been infected?

Robert B.: Yes. One of every occurs although you do see some people who have a very rapid progression of the symptoms. More commonly, when I see the psych symptoms, that’s usually a few years after infection. That doesn’t happen early. You can get brain fog. You can get some of the cognitive impairments earlier but the depression, the panic attacks, the various anxiety symptoms, aggressiveness, those things it usually several years later. A lot of times when people don’t make the connection, neuropathy, that’s often a later symptom. So, even though some people progresses quicker than others, my average patient that I see has been infected 5, 10, 15, 20 years sometimes longer.

Cindy K.: Yes. See, there’s just so much. A lot of people are unhealthy to begin with, because they’ve got other co-infections. I’m sorry no comorbidities such as diabetes or hypertension or cardiac especially as they get older. So, it can get most confusing. So, I do have one other question that I want to ask you. Then, I have a couple of other quick questions. In terms of the vascularity changes that happen, are people with Lyme more prone to have TIA which is a transient ischemic attack?

Robert B.: I haven’t seen that much although that may be more in Europe where there’s some .. one way to think of how Lyme affects the brain is where it’s neuroborreliosis in the brain, Lyme encephalopathy in the body affecting the brain and then the third way can be vascular. It does affect the vascular system. People can [inaudible 00:33:26] a part of that but when people have that vascular form, there’s vasculitis or it’s impacting the vasculature that some people for instance they get aneurysms. So, when they have that vascular form, I think it can but that does seem more common with European strains than what we see here. For some reason, in fact Carolina there’s what’s called the stroke belt. What is it in South Carolina where there’s more that there? You’d wonder is there a local pathogen that may be contributes to some vascular anomaly. Also with vascular disease, you can’t just think of Lyme. You could also think of dental spirochetes. That’s playing a role there chlamydia. So, it’s a number of other infections not just Lyme and looking vascular issues.

Cindy K.: Yeah. No wonder why this is so complicated. Well, I’ll tell you this has been a wonderful learning lesson from you. It’s very complex and we run the gamut of people having the sleep issues, the anxiety, the depression, the anger, the rage that can occur with this. So, again it’s very complicated and thank God for people like you that can invariably look at this at a whole different way. I know that you’re helping other people to understand this and teaching people to be open to this type of psychiatric neuro changes that can happen. So, now we’ve got a couple of fun things. Okay?

Robert B.: Okay.

Cindy K.: All right. So, what ticks you off?

Robert B.: What ticks me off? Okay.

Cindy K.: Got to be something.

Robert B.: I guess when someone has an answer before they even think about your question.

Cindy K.: Okay. I hope I didn’t do that.

Robert B.: [inaudible 00:35:39].

Cindy K.: I hope I didn’t do that.

Robert B.: No. I found that you can … I see relevant to Lyme disease where you think something and someone has like they don’t even think. They don’t process it. They have already made knee jerk answers without really thinking or the context. That’s part of why they end up in the controversy.

Cindy K.: Okay. That’s absolutely true. The second thing. So, I look at it. I had Lyme disease. Now I’m able to be a facilitator for education and that’s basically having lemons and turning it to lemonade. So, what has been your lemonade?

Robert B.: I wasn’t really looking for Lyme. Lyme kept finding me whether I wanted to deal with it or not. Being a doctor, I think it’s been very gratifying to help people and particularly helping people in ways where they otherwise would not have had help before. That’s a lot more gratifying than doing something that’s a rubber stamp assembly line part of medicine that anybody could do. So, I think it’s good to feel that I’ve had some impact on helping advance understanding in a piece of medicine that previously wasn’t well understood.

Cindy K.: I’ll tell you I hope that more people are going to think about this. I think that it’s unfortunate that the Lyme community is small. It’s not as broad. Medical schools aren’t really putting this as part of their education or it is but very limited. So, thank you so much for this talk, this interview. It’s been most enlightening. I hope that everyone out there listening has enjoyed Dr. Bransfield. He’s just super, super knowledgeable. I thank you and I want to say I hope that I meet you sometime soon. Again, thank you. You al-

Robert B.: Okay, thank you.

Cindy K.: Yes. You all have been listening to Living with Lyme another episode. This is Cindy Kennedy, nurse practitioner and I want to encourage you to reach out and subscribe to the website so you can stay connected http://www.livingwithlyme.us. Everybody have a great day. Come back and listen real soon.