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From the Townsend Letter
October 2015

'Lyme Brain': Causes and Solutions
by Nicola McFadzean Ducharme, ND
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Having worked with Lyme disease patients for the past 10 years, I am painfully aware of the far-reaching and growing problem that it is. Lyme disease involves a myriad of symptoms and manifestations, but one of the most prevalent ones is what we call "Lyme brain." This term encompasses broad-based cognitive decline – memory loss, memory retrieval issues, difficulty with focus and concentration, word retrieval issues, slower processing speeds, and so on.
Lyme brain is not just about cognitive deficits, either. It often involves psychoemotional elements such as anxiety and depression. The majority of my patients experience anxiety and/or depression (usually both). Some people experience panic attacks, obsessive-compulsive tendencies or suicidal thoughts, nightmares and night terrors, rage, and impulsiveness. These too, are tremendously hard to deal with.
To some extent the anxiety and depression are a natural response to a chronic illness such as Lyme. But I also remind my patients that anxiety and depression are also symptoms of Lyme, just as real as joint pain and headaches.
In an article published in Lyme Times, 70% of Lyme disease patients report some degree of cognitive dysfunction.1 In my opinion that is a conservative estimate – amongst my own patients, I see numbers closer to 90%.

What Causes Lyme Brain?
Lyme brain has a number of causes. Firstly, there is the presence of microbes themselves in the brain. Bacteria in the brain are invasive and can invade neurons (nerve cells that conduct electrical impulses) and glial cells (supporting cells of the nervous system that do not conduct impulses).2,3 That invasion can lead to death of the nerve cells.
may also cause demyelination of the white matter in the brain. The myelin sheath is a protective sheath that surrounds the axon of the nerve cell and potentiates nerve impulses. This can also contribute to the early demise of nerve cells.
The second major mechanism of Lyme brain is the inflammatory response. In fact, this may be the most significant mechanism.
When there is a pathogen such as Borrelia, the immune system will become active to try and counter the threat and kill the pathogen. This process, while protective, results in inflammation, with chemical mediators such as cytokines and chemokines. These mediators can create an environment of reduced oxygenation, blood stasis and increased coagulation, and a disruption in the normal working of the cells. It is important to note that the infection does not have to be in the brain itself for this to occur – the cytokines from infection in the body tissues can travel to the brain and cross the blood–brain barrier, affecting the brain and causing brain-related symptoms.
The third mechanism is by production of neurotoxins. Borrelia and related infections trigger neurotoxin release, particularly when they are killed off by antimicrobials, and this can worsen Lyme brain symptoms. Other neurotoxins can worsen the situation, such as heavy metals, molds, and toxins from Candida.
may release its own neurotoxin known as BbTox1.4 It can also trigger increased levels of ammonia, which can act as a neurotoxin (this can be worsened by candidiasis, as well as a metabolic condition called kryptopyrroluria).5,6
Another contributing factor to Lyme brain is neurotransmitter imbalance. This may be more of an effect than a cause; however, it is something that I frequently see in my patients.
Neurotransmitters are brain chemicals that transmit impulses from one nerve cell to another. Some neurotransmitters are stimulatory and "awakening," such as norepinephrine and epinephrine, while some are inhibitory and "calming," such as serotonin and GABA. Others such as acetylcholine relate to motor system function, and play a role in emotion, learning and short-term memory. Neurotransmitters influence cognition, as well as emotional states.

Some Treatment Options for Lyme Brain
Now that we have a brief overview of some of the key causes of Lyme brain – the infections themselves, the inflammatory cascade created, toxins, and neurotransmitter imbalances being the main ones – I am going to outline some of my favorite ways to help Lyme brain. Of course, this is just a sampling, as there are many options; but these are the ones I have seen work the best in my patients.

Bicillin L-A
You might be surprised to see an antibiotic at the top of my list; however, Bicillin is the primary therapy I have used and seen tremendous benefit in the Lyme brain symptoms. (Note: intravenous antibiotics can have the same benefit, but they are outside the scope of my practice in California, so I use the injectable instead).
Bicillin L-A is a long-acting penicillin given by intramuscular injection 2 to 3 times weekly. The key here is that it crosses the blood–brain barrier very effectively, far more than oral antibiotics, so it affects the neurological system more than oral antibiotics do. It attacks the spirochete forms of Borrelia, so other medications still need to be given for the cell-wall deficient and cyst forms.
Bicillin itself has been around for a long time and is quite well tolerated. An obvious contraindication to its use is penicillin allergy. It can cause powerful Herxheimer reactions, which is a reflection of how well it works. I see more of that than I do actual side effects. Some people Herx after a few days on Bicillin; some people experience a delayed Herx around day 25.
Bicillin injections are not everyone's favorite activity. Some people find it quite tolerable, no problem at all, while others find it uncomfortable. However, it is the medication that my patients tell me "gives them their brain back," so many are willing to go through it to get the benefit.

Smilax Glabrae
Smilax glabrae is one of my favorite herbs in Lyme treatment, especially for helping with Lyme brain. This is due to its ability to cross the blood–brain barrier. The glabrae form of Smilax is the form with best blood–brain barrier penetration, so that is the form that must be used.

Smilax glabrae
helps to offset Herxheimer reactions in 90% of my patients, helping to neutralize neurotoxins. Very rarely, in highly sensitive patients, I have seen it cause a detox reaction, so dosing very much depends on sensitivity levels.
Along with working directly in the brain, Smilax can also neutralize endotoxins in the intestines. Many endotoxins are cleansed from the gut by the lymphatic system and liver. Binding the toxins in the gut before they reach the bloodstream helps to minimize the inflammatory response that they can cause.
Another potential role of Smilax glabrae is protecting against the harmful effects of toxic metals. One study evaluated the effects of lead acetate on oxidative stress in the brain, and found that Smilax glabrae showed significant efficiency in reducing blood and tissue levels of lead. It also increased protective antioxidants such as superoxide dismutase and the ever-important glutathione.7 Given that many Lyme patients struggle with heavy metals, and given that toxic metals can contribute to Lyme brain, this added benefit makes Smilax a great option.
I find that Smilax combined with glutathione is my winning combination for supporting Lyme brain. Together they typically have a huge impact, more than any other herbs or supplements that I have found.

Anyone who knows me knows that I'm huge fan of glutathione. Among many other benefits, I have seen it help with Lyme brain in so many of my patients.
Two of glutathione's primary roles are acting as an oxidant and neuroprotective, and as a facilitator of detoxification. Third and less well known is glutathione's ability to support neurotransmitter levels and hence mood. Glutathione is one of the most important substances that I know of in keeping the brain healthy and functioning well.
Glutathione is one of the brain's most significant protectors, functioning as its master antioxidant. While the brain only accounts for 2% of body weight, it consumes 20% of the body's oxygen. Therefore, the brain produces a high proportion of reactive oxygen species. Glutathione is one of the key defenses to counter these reactive oxygen species, which can otherwise be quite harmful, producing oxidative stress and neuronal cell damage.
Along with being the crucial antioxidant for the brain, glutathione plays a significant role in detoxification, combining with toxic elements and allowing their excretion from the body. There are many toxic insults to the brain – including toxic metals, mycotoxins, and pesticides – and all can, and do, deplete glutathione. Poor diet, stress, trauma, chronic infections, aging, medications, and radiation can further deplete glutathione. Yet glutathione is critical in detoxing these toxic agents and countering these biological stressors.
There are also genetic factors that can lead to reduced production of glutathione. This is certainly one of the reasons why some people have such high toxic load and impaired ability to clear toxins from the body.
I do have some patients who do not tolerate glutathione well. Those with extreme sulfur sensitivity may not do well with it, as it is a sulfur-based compound. Certain methylation defects will also make one less tolerant of glutathione. But in my clinical experience, this is the minority. Many patients have told me that their cognitive function has improved immediately upon starting glutathione.
A less well-recognized benefit of glutathione is in balancing brain chemistry. Glutathione makes receptors in the brain more sensitive to dopamine and serotonin – two crucial neurotransmitters for healthy brain function. Further, antidepressants have been found to deplete glutathione, again setting up yet another double-edged sword – the medications taken to try to help depression may worsen one of the contributing factors to the depression itself.
In our population of Lyme patients, with high levels of inflammation in the brain, often coupled with infection in the brain, and a myriad of other exogenous toxins, there are frequently depleted glutathione levels. And yet these are exactly the circumstances that create a high requirement for glutathione. I utilize liposomal glutathione in my practice for optimal absorption, along with glutathione given intravenously where possible.

Vitamin B12
When we think of B12, we often think of its energy-boosting properties, and it certainly does have those. But what is less known about B12 is its profound impact on, and benefit for, the brain. This is a double bonus for Lyme patients who have chronic fatigue and Lyme brain.
B12 deficiency is widespread but unrecognized. Some people will exhibit neurological limitations at low-normal levels, not just "deficient" levels, so optimizing B12 is key. Testing methylmalonic acid may be a better indicator than serum B12 levels.
One of the important factors is the role of B12 in methylation, a series of biochemical and metabolic pathways that can influence emotional regulation, learning, cognition, and memory. Many Lyme patients are undermethylators and do well with methyl-B12.
Other than its role in methylation, B12 also has several benefits for the brain in and of itself. It has been found to improve blood–brain barrier function in people with cognitive impairment. By measuring proteins in the central nervous system, one study determined that B12 (along with folate and B6) tightened the junctions of the blood–brain barrier. Cognitive function was also stabilized in these patients. This demonstrates that good cognitive function is compromised when blood–brain barrier strength is compromised (which occurs when there is chronic inflammation in the body and brain).8
Other research indicates that a B12 deficiency can lead to brain shrinkage. Lower B12 status markers correlated with not only total brain volume but also global cognitive function. This is why B12 deficiency in the aging population is associated with high rates of dementia and cognitive decline, and possibly also Alzheimer's disease.9
Vitamin B12 is also needed to produce the protective lining around nerves known as the myelin sheath. Demyelination of that sheath occurs in diseases such as multiple sclerosis and other degenerative neurological conditions. Given that the myelin sheath is involved in nerve impulse signals traveling from one nerve to another, it follows that if that structure is weak, nerve signaling will be compromised. This can manifest as memory loss, difficulty with focus/concentration, word-finding difficulties, and slurred speech.

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