The LivLyme conference in 2023 had an excellent presentation from Dr Brian Fallon, who is well-known for his publications in lyme disease. These are not comprehensive notes of the presentation, but points that I thought were useful to write down and reference back to.
Many of my own patients have not had sustained responses to antimicrobial therapy alone, and the immunological and neurological approaches have been very helpful.
Dr Fallon reminded us all that lyme disease is characterized by excessive inflammation, including cytokine elevations as well as activation of microglial immune cells in post-treatment lyme disease syndrome.
Dr Fallon describes how various studies have shown that brain metabolism and blood flow are decreased in lyme encephelopathy. Immune antibodies against our own neurological tissues, including anticardiolipin and antiganglioside antibodies have been demonstrated. The levels of antineuronal antibodies are similar to that seen in systemic lupus (an autoimmune disease) and levels in lyme patients are higher than those seen in patients who have recovered from lyme.
Of note, antibodies may cross react between the flagellum protein of lyme and peripheral nerves, as well as lyme's outer surface protein A cross reacting with the brain.
In neuropsychiatric symptoms, we have to consider autoimmune possibilities, generalized inflammation, and alterned neural pathways / circuitry. Dr Fallon notes that his studies have found that 90% of lyme patients will have complaints of cognitive problems, but on standardized testing somewhere between 7-30% of patients have measurable changes.
Dr Fallon also brings up an important study in Denmark, that showed that hospital-based diagnosis of lyme disease (conventional two step testing) found an increased risk of any psychiatric diagnosis by ~30%, affective disorders by 40%, and had a 2-fold risk of suicide attempt.
Because of this, there should be an emphasis on monitoring for mental health complications especially during the first year of diagnosis and treatment. He recommends incorporating the PHQ-9 for depression or the C-SSRS for monitoring risk of suicidal ideation. And of course, suicide prevention lifelines.
In discussing guidance for treatment, there needs to be consideration of mechanism of symptoms. He describes:
- immune dysregulation
- central or peripheral nerve dysregulation
- persistent lyme infection
- unrecognized but persistent other infection or other infection
Dr Fallon describes correlations with Long COVID, and quotes a study by Davis et al, published recently in January 2023 which describes how multiple mechanisms may affect multiple systems causing a variety of symptoms.
For example, if inflammation is affecting the heart, there may be symptoms of chest pain, palpitations, or there may be myocardial inflammation. If the immune system regulation is affected there may be autoimmunity or MCAS (mast cell activation syndrome).
The multiple mechanisms affecting multiple systems in long COVID similarly apply to long lyme.
Therapeutic approaches might include:
- targeting persistent infection (repeated antibiotic or antiviral therapy)
- targeting immune activation
- targeting altered neurotransmitter systems (GABA, noradrenaline, serotonin)
- targeting an altered microbiome
- neuromodulation (transauricular Vagus Nerve Stimulation, transcranial direct current stimulation)
- stress reduction and psychotherapy
- cognitive and physical rehabilitation
Dr Fallon also described a study by Murray et al on Kundalini yoga in post treatment lyme. There was improvement in multisystem symptom burden as well as cognition. There was not any statistical improvement in pain and fatigue, though Dr Fallon felt this might be due to the small sample size.
Dr Fallon described some studies on transauricular vagal nerve stimulation. The vagus nerve innervates multiple organ systems but also can modulate inflammation and excessive neural activation. It can thus act as a cognitive enhancer, neuroprotectivor, antidepressant, and immunoregulator. In lupus, despite being a small study there were improvements in pain, fatigue, and less joint tenderness and swelling. This was apparent within 5-12 days.
He also mentions a study using vagal nerve stimulation in long COVID, with a reduction in symptoms by 57% (study by Natelson - no control group, but at least a third of the group had improved.)
In treating brain fog, Dr Fallon described his own study of repeated IV ceftriaxone (IV antibiotics) showing a benefit, but one that was not sustained. In looking for alternatives, guanfacine and NAC supplement were discussed as possible treatments based on a long-covid study by Fesharaki-Zadeh et al. 8/12 patients improved and could resume normal workloads.
Dr Fallon's key messages included recommendations to identify the mechanim behind the symptoms, which may involve one system, but often more. Focus should be put on the most burdensome symptom, and to not avoid standard mental health treatment as lyme affects the brain, and we should be doing all we can to improve brain functioning.
He also describes that if someone has had a prior episode of lyme, and they receive another exposure, there can be an immune priming effect and thus there may be a greater burden on an autoimmune process. Repeated infections are thus problematic - for example having lyme and then covid, or even repeated covid.
Finally, he did respond to a question as to when his study on the off-label use of disulfiram in lyme disease would be published, which is estimated to be in the summer of 2023.