Archive for the ‘research’ Category

Post-Treatment Lyme Disease as a Model for Persistent Symptoms in Lyme Disease

https://www.frontiersin.org/articles/10.3389/fmed.2020.00057/full

REVIEW ARTICLE
Front. Med., 25 February 2020 | https://doi.org/10.3389/fmed.2020.00057

Post-treatment Lyme Disease as a Model for Persistent Symptoms in Lyme Disease

Alison W. Rebman and John N. Aucott*
  • Lyme Disease Research Center, Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States

It has long been observed in clinical practice that a subset of patients with Lyme disease report a constellation of symptoms such as fatigue, cognitive difficulties, and musculoskeletal pain, which may last for a significant period of time. These symptoms, which can range from mild to severe, have been reported throughout the literature in both prospective and population-based studies in Lyme disease endemic regions. The etiology of these symptoms is unknown, however several illness-causing mechanisms have been hypothesized, including microbial persistence, host immune dysregulation through inflammatory or secondary autoimmune pathways, or altered neural networks, as in central sensitization. Evaluation and characterization of persistent symptoms in Lyme disease is complicated by potential independent, repeat exposures to B. burgdorferi, as well as the potential for co-morbid diseases with overlapping symptom profiles. Antibody testing for B. burgdorferi is an insensitive measure after treatment, and no other FDA-approved tests currently exist. As such, diagnosis presents a complex challenge for physicians, while the lived experience for patients is one marked by uncertainty and often illness invalidation. Currently, there are no FDA-approved pharmaceutical therapies, and the safety and efficacy of off-label and/or complementary therapies have not been well studied and are not agreed-upon within the medical community. Post-treatment Lyme disease represents a narrow, defined, mechanistically-neutral subset of this larger, more heterogeneous group of patients, and is a useful definition in research settings as an initial subgroup of study. The aim of this paper is to review the current literature on the diagnosis, etiology, risk factors, and treatment of patients with persistent symptoms in the context of Lyme disease. The meaning and relevance of existing patient subgroups will be discussed, as will future research priorities, including the need to develop illness biomarkers, elucidate the biologic mechanisms of disease, and drive improvements in therapeutic options.  (See link for article)

__________________

**Comment**

When you read the entire thing you realize Aucott and Rebman elucidate the many groups of patients that have Lyme disease. While I appreciate the separation of groups for research purposes, it is this very slicing, dicing, and narrowly categorizing that has kept the sickest patients from ever being researched, diagnosed, and treated.  If you don’t test positive on a serology test that is inaccurate 70% of the time, or are in the highly variable group of 25-80% who have the EM rash, you simply don’t make the cut.  Sorry – “go home and be well.”  

And while these study authors clearly understand the complexity of PTLD (some might be chronically infected while others are dealing with an immune response, or both at once) trust me when I say other researchers don’t.  

In this day and age where it’s become abundantly clear the importance of touting the accepted narrative or else, hopefully we can all see that “chronic Lyme” is the ugly duckling nobody wants to touch with a 10-foot pole (unless you are an independent researcher with no purse-strings attached to the NIH).  

For more:

Category:

Lyme, research

Could Cytokine Storms Lead to Brain Fog in Lyme Disease Patients?

https://danielcameronmd.com/cytokine-brain-fog-lyme-disease/

COULD CYTOKINE STORMS LEAD TO BRAIN FOG IN LYME DISEASE PATIENTS?

brain-fog-lyme-disease

Lyme disease and COVID-19 patients often complain of having ‘brain fog.’ In a recent study, Remsik and colleagues suggest that brain fog reported by COVID-19 patients may be due to cytokines rather than an infection with the coronavirus SARS-CoV-2.

By

In their article, published in the journal Cancer Cell,¹ the authors explain, “One of the dozens of unusual symptoms that have emerged in COVID-19 patients is a condition that’s informally called ‘COVID brain’ or ‘brain fog.’ It’s characterized by confusion, headaches, and loss of short-term memory. In severe cases, it can lead to psychosis and even seizures.”

The authors expected to find evidence of COVID-19 infection in the cerebral spinal fluid (CSF) of 13 patients hospitalized with COVID-19. They did not.

Instead, Remsik and colleagues found an elevation of cytokines in the spinal fluid of their COVID-19 patients with brain fog. According to the authors, “These patients had persistent inflammation and high levels of cytokines in their cerebrospinal fluid, which explained the symptoms they were having.”

“These increased CSF cytokines are likely the result of both increased blood barrier permeability and local production by cells in the CNS,” the authors write.

Investigators have previously raised concerns that Lyme disease spirochetes could cross the blood-brain barrier leading to brain fog. In his article, Dr. Robert Bransfield raised concerns that persisting immune activation causes a cytokine storm in patients with chronic Lyme disease.²

Remsik et al. add support to the role of cytokines in patients with brain fog, leading to the question: Are cytokine storms associated with brain fog in Lyme disease patients?

Related Articles:

Disseminated Lyme disease more likely in those with weakened immune system

Persistent Lyme infection or inflammatory immune response?

Brain fog in COVID-19 and Lyme disease patients

References:
  1. Remsik J, Wilcox JA, Babady NE, et al. Inflammatory Leptomeningeal Cytokines Mediate COVID-19 Neurologic Symptoms in Cancer Patients. Cancer Cell. Feb 8 2021;39(2):276-283 e3. doi:10.1016/j.ccell.2021.01.007
  2. Bransfield RC. The psychoimmunology of lyme/tick-borne diseases and its association with neuropsychiatric symptoms. Open Neurol J. 2012;6:88-93. doi:10.2174/1874205X01206010088

Category:

Lyme, Psychological Aspects, research

16-Year-Old Boy With Lyme Disease Presenting as Depression

https://danielcameronmd.com/16-year-old-boy-lyme-disease-presenting-depression/

16-YEAR-OLD BOY WITH LYME DISEASE PRESENTING AS DEPRESSION

Adolescent with Lyme disease and depression holding his head

There has been increasing research linking COVID-19 with the development of neuropsychiatric symptoms, including depression and anxiety. But multiple studies have already found an association between other infections, such as Lyme disease, and the onset of depression.

By
 

One study found a high prevalence of depression in Lyme disease patients. Between January 2008 and December 2014, 1 in 5 patients treated at the Lyme Center Apeldoorn in the Netherlands was diagnosed with depression and Lyme disease. ¹

Meanwhile, Dr. Robert Bransfield, a psychiatrist specializing in the diagnosis and treatment of tick-borne illnesses, reports “In my database, depression is the most common psychiatric syndrome associated with late-stage Lyme dis­ease.”

“I estimate that there are at least 1,200 people per year who commit suicide as the result of Lyme disease,”  Bransfield writes in his article “Suicide, Lyme and Associated Diseases.” ²

Borrelia burgdorferi, the causative agent of Lyme disease, “may be diagnosed as a persistent infection with immune suppressant and evasive capabilities or there may be a postinfectious process,” Bransfield writes. “In either case, the psychiatric symptoms are associated with an immune-mediated process.”

Brian Fallon, MD, director of the Lyme and Tick-Borne Diseases Research Center at Columbia University, describes the case of a 16-year-old adolescent who presented with long-standing depression, which suddenly worsened.³

Neuropsychiatric symptoms

He reported anger, frustration, insomnia, poor appetite, mild weight loss, and passive suicidal ideation. He would say, “I wish I could just die in my sleep.”

The boy complained of brain fog and had a steep decline in cognitive abilities. His symptoms were initially presumed to be caused by “either laziness or mild depression.” He suffered from ongoing knee pain and was forced to quit sports.

His grades dropped from “A’s” in 7th grade to nearly failing by 10th grade. He suffered from fatigue and forgetfulness. “He appeared lazy because he found it hard to get out of bed in the morning,” Fallon writes.

The boy’s symptoms were extensive and included:

• severe headaches
• facial fasciculations, myalgias
• stiff neck
• hyperacusis
• episodic paresthesias of his face and hands
• sudden sweating
• painful joints
• sore throats
• palpitations
• electric shock-like pains
• word-finding problems, such that it was hard to finish sentences
• semantic paraphasias
• short-term memory problems, such that he could not recall conversations
• testicular pain

Since he reported having embedded ticks in the past, Lyme disease was clinically diagnosed “given the suspicious clinical history.”

His Lyme ELISA results were negative twice in the prior 3 months, but his IgG Western blot revealed 4 of the 5 requisite CDC specific bands. A brain SPECT revealed findings consistent with encephalitis, vasculitis, and Lyme disease.

Treatment response

The boy was diagnosed with probable Lyme encephalopathy and treated with 12 weeks of intravenous ceftriaxone.

He improved on sleep, appetite, headaches, joint pains, numbness, distractibility, short-term memory, and emotional behavior. His depression cleared without the need for antidepressant medications. His IQ improved by 22 points, and his school performance markedly improved.

Related Articles:

Don’t confuse somatic symptoms with depression in early Lyme disease

Chronic neurological Lyme disease or co-morbid conditions?

Oppositional behavior in children with Lyme disease

References:
  1. Zomer, T.P., et al., Depressive Symptoms in Patients Referred to a Tertiary Lyme Center: High Prevalence in Those Without Evidence of Lyme Borreliosis. Clin Infect Dis, 2017. 65(10): p. 1689-1694.
  2. Bransfield RC. Suicide and Lyme and associated diseases. Neuropsychiatr Dis Treat. 2017;13:1575-1587. Published 2017 Jun 16. doi:10.2147/NDT.S136137.
  3. Fallon BA, Kochevar JM, Gaito A, Nields JA. The underdiagnosis of neuropsychiatric Lyme disease in children and adults. Psychiatr Clin North Am. 1998;21(3):693-703, viii.

____________________

**Comment**

If there was ever a great example of the importance of Lyme/MSIDS being clinically diagnosed, this is it!

This poor teenager would have continued spiraling down until he might just have achieved his wish of dying.  

This study points out a number of things parents and doctors should be considering:

  1. The plethora of symptoms that suggest a systemic infection(s)
  2. The drop in grades
  3. The stiff neck (few things cause this – but it’s hallmark for Lyme)
  4. The fact antibiotics helped so many of the symptoms – including the depression – without any antidepressants
  5. He was seronegative – and so many are.  Doctors have to stop relying upon testing to diagnose this and must become more educated on tick-borne illness.
The CDC just upped numbers again from 300,000 to 476,000 new cases of Lyme diseases per year – highlighting the fact this plague is serious, isn’t going away, and something needs to be done about it.

For more:

We can be thankful he fell into the hands of Dr. Fallon or this young man would most probably not had a favorable outcome.

Category:

Lyme, Psychological Aspects, research, Ticks

Sequelae in Adults at 6 Months After COVID-19 Infection

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776560

Research Letter
Infectious Diseases
February 19, 2021

Sequelae in Adults at 6 Months After COVID-19 Infection

Jennifer K. Logue, BS1; Nicholas M. Franko, BS1; Denise J. McCulloch, MD, MPH1; et alDylan McDonald, BA1; Ariana Magedson, BS1; Caitlin R. Wolf, BS1; Helen Y. Chu, MD, MPH1
Author Affiliations Article Information
JAMA Netw Open. 2021;4(2):e210830. doi:10.1001/jamanetworkopen.2021.0830
COVID-19 Resource Center
Introduction

Many individuals experience persistent symptoms and a decline in health-related quality of life (HRQoL) after coronavirus disease 2019 (COVID-19) illness.1 Existing studies have focused on hospitalized individuals 30 to 90 days after illness onset2–4and have reported symptoms up to 110 days after illness.3 Longer-term sequelae in outpatients have not been well characterized.

Methods

A longitudinal prospective cohort of adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was enrolled at the University of Washington with a concurrent cohort of healthy patients in a control group (eAppendix in the Supplement). Electronic informed consent was obtained, and the study was approved by the University of Washington human participants institutional review board. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. COVID-19 symptom data were obtained at the time of acute illness or retrospectively recounted at a 30-day enrollment visit. A total of 234 participants with COVID-19 were contacted between August and November 2020 to complete a single follow-up questionnaire between 3 and 9 months after illness onset. We did not perform statistical tests for this descriptive analysis because of the small numbers in each subgroup. Data analysis was conducted in R version 4.0.2 (R Project for Statistical Computing).

Results

A total of 177 of 234 participants (75.6%; mean [range] age, 48.0 [18-94] years; 101 [57.1%] women) with COVID-19 completed the survey. Overall:

  • 11 (6.2%) were asymptomatic
  • 150 (84.7%) were outpatients with mild illness
  • 16 (9.0%) had moderate or severe disease requiring hospitalization (Table).
  • Hypertension was the most common comorbidity (23 [13.0%]).

The follow-up survey was completed a median (range) of 169 (31-300) days after illness onset among participants with COVID-19 (Figure, A) and 87 (71-144) days after enrollment among 21 patients in the control group.

Among participants with COVID-19, persistent symptoms were reported by:

  • 17 of 64 patients (26.6%) aged 18 to 39 years
  • 25 of 83 patients (30.1%) aged 40 to 64 years
  • 13 of 30 patients (43.3%) aged 65 years and older
  • 49 of 150 outpatients (32.7%), 5 of 16 hospitalized patients (31.3%), and 1 of 21 healthy participants (4.8%) in the control group reported at least 1 persistent symptom.
  • Of 31 patients with hypertension or diabetes, 11 (35.5%) experienced ongoing symptoms.

The most common persistent symptoms were:

  • fatigue (24 of 177 patients [13.6%])
  • loss of sense of smell or taste (24 patients [13.6%]) (Figure, B)
  • 23 patients (13.0%) reported other symptoms, including brain fog (4 [2.3%])
  • A total of 51 outpatients and hospitalized patients (30.7%) reported worse HRQoL compared with baseline vs 4 healthy participants and asymptomatic patients (12.5%); 14 patients (7.9%) reported negative impacts on at least 1 activity of daily living (ADL), the most common being household chores.
Discussion

In this cohort of individuals with COVID-19 who were followed up for as long as 9 months after illness, approximately 30% reported persistent symptoms. A unique aspect of our cohort is the high proportion of outpatients with mild disease. Persistent symptoms were reported by one-third of outpatients in our study, consistent with a previously reported study,4 in which 36% of outpatients had not returned to baseline health by 14 to 21 days following infection. However, this has not been previously described 9 months after infection.

Consistent with existing literature, fatigue was the most commonly reported symptom.2–4 This occurred in 14% of individuals in this study, lower than the 53% to 71%2–4 reported in cohorts of hospitalized patients, likely reflecting the lower acuity of illness in our cohort. Furthermore, impairment in HRQoL has previously been reported among hospitalized patients who have recovered from COVID-19; we found 29% of outpatients reported worsened HRQoL.5

Notably, 14 participants, including 9 nonhospitalized individuals, reported negative impacts on ADLs after infection. With 57.8 million cases worldwide, even a small incidence of long-term debility could have enormous health and economic consequences.6

Study limitations include a small sample size, single study location, potential bias from self-reported symptoms during illness episode, and loss to follow-up of 57 participants. To our knowledge, this study presents the longest follow-up symptom assessment after COVID-19 infection. Our research indicates that the health consequences of COVID-19 extend far beyond acute infection, even among those who experience mild illness. Comprehensive long-term investigation will be necessary to fully understand the impact of this evolving viral pathogen.

Article Information

Accepted for Publication: January 16, 2021.

Published: February 19, 2021. doi:10.1001/jamanetworkopen.2021.0830

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Logue JK et al. JAMA Network Open.

Corresponding Author: Helen Y. Chu, MD, MPH, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, 750 Republican St, Room E691, Seattle, WA 98109 (helenchu@uw.edu).

Author Contributions: Ms Logue and Dr Chu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Mr Franko and Ms Logue contributed equally to this study and are joint first authors.

___________________

**Comment**

Please keep in mind that nearly 91% were asymptomatic or outpatients with mild illness!

I wish the same effort was being put into the 60% of Lyme/MSIDS patients that suffer with persistent symptoms which are far more severe than fatigue and loss of taste and smell.

Category:

research, Viruses

43-Year-Old Man With Meningitis & Radiculitis Due to Lyme Disease

https://danielcameronmd.com/meningitis-and-radiculitis-lyme-disease/  Podcast Here

43-YEAR-OLD MAN WITH MENINGITIS AND RADICULITIS DUE TO LYME DISEASE

meningitis-lyme-disease

Hello, and welcome to another Inside Lyme Podcast. I am your host Dr. Daniel Cameron. In this episode, I will be discussing a unique case involving a 43-year-old man with neurological manifestations of Lyme disease including both meningitis and radiculitis.

By

The case was published in the journal Neurology International. [1] According to Dabiri and colleagues, the patient had a history of “scaly erythematous macular rash on his proximal medial upper and lower extremities.”

Within two weeks he presented with a broad range of symptoms “including cough, fever, anorexia, malaise, fatigue, myalgias, cervicalgia/neck stiffness with flexion and extension, mild photophobia, headache,”  the authors wrote.

The patient had extensive lab testing which revealed a mild abnormal liver function but no evidence of Lyme disease.  At the onset of symptoms, the patient refused to have a spinal tap.

Doctors presumed the man suffered from viral meningitis.

One month later, the patient developed progressive weakness, severe radicular lancinating pain, emotional lability along with depression and anxiety, an occasional action tremor in hands interfering with fine motor tasks, and tremor in his legs causing imbalance and instability.

Manifestations of the central nervous system (i.e, meningitis), as well as peripheral nervous system presentations (i.e., radiculitis) can occur in isolation or together.

Radiculitis or inflammation of the nerve root involving the peripheral nervous system (PNS) can lead to intractable pain, muscle denervation, and areflexia over one or a few adjacent dermatomes, wrote the authors.

At this point, results from a spinal tap were consistent with Lyme disease.  “A lumbar puncture was performed, and the patient’s cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis with white blood cell count of 225 and elevated protein of 77 and decreased glucose 38,” the authors wrote.

The patient was treated with a 5-day course of doxycycline, followed by a month of intravenous ceftriaxone.

Approximately two weeks after starting treatment, the patient “noted his symptoms were significantly improved including resolution of the pain, weakness, constitutional and affective symptoms, while he still had some ambulatory difficulties.”

This podcast addresses the following questions:

  1. What is Lyme meningitis?
  2. What is Lyme radiculitis?
  3. Why is this case considered “unique”?
  4. CNS and PNS manifestations can occur in isolation or together?
  5. Can you discuss the patient’s symptoms of emotional lability, depression and anxiety?
  6. What is the significance of the rash?
  7. Initial testing for Lyme disease was inconclusive but follow-up tests were positive?
  8. Any significance to MRI and spinal tap results?
  9. What if the significance of a diagnosis of viral meningitis?
  10. What were the other symptoms that might have helped the diagnosis?
  11. Would clinical judgment to treat with antibiotics have been helpful?
  12. What are your thoughts regarding the course of treatment?
  13. Would it have been helpful to consider additional treatment for the remaining ambulatory difficulties?
    • Thanks for listening to another Inside Lyme Podcast. You can read more about these cases in my show notes and on my website @DanielCameronMD.com. As always, it is your likes, comments, reviews, and shares that help spread the word about Lyme disease. Until next time on Inside Lyme.

Please remember that the advice given is general and not intended as specific advice as to any particular patient. If you require specific advice, then please seek that advice from an experienced professional.

Inside Lyme Podcast Series

This Inside Lyme case series will be discussed on my Facebook and made available on podcast and YouTube.  As always, it is your likes, comments, and shares that help spread the word about this series and our work. If you can, please leave a review on iTunes or wherever else you get your podcasts.

References:
  1. Dabiri I, Calvo N, Nauman F, Pahlavanzadeh M, Burakgazi AZ. Atypical presentation of Lyme neuroborreliosis related meningitis and radiculitis. Neurol Int. 2019 Dec 2;11(4):8318.
_____________________
https://madisonarealymesupportgroup.com/2019/03/17/first-case-of-b-corocidurae-in-native-european-presenting-as-meningitis-with-cranial-polyneuritis-cavernous-sinus-thrombosis/  European cases of B. crocidurae infection have been reported in travelers returning from endemic areas. We report the first autochthonous case in Europe of B. crocidurae infection, presenting as meningitis…..

Category:

Lyme, research