The bacteria that cause Lyme disease and its associated infections can affect the central, peripheral and autonomic nervous systems. Lyme neuroborreliosis refers to central nervous system dysfunction caused by Lyme disease. In an early infection with Lyme disease, the bacteria can penetrate the central nervous system leading to symptoms such as facial palsy, headaches, nausea/vomiting, vertigo, meningitis, and neck stiffness. Later in the disease progression, bacteria and subsequent immune response to the bacteria can lead to damage in the peripheral and autonomic nervous systems causing symptoms such as numbness/tingling or burning sensation in the extremities, lightheadedness with standing, muscle weakness, cognitive impairment and more.
Do you recall having a tick bite?
Neurological Lyme disease has been studied extensively in the United States and Europe. Researchers have analyzed clinical presentation, diagnostic testing, and treatment response. One of the most significant challenges is recognition of neuroborreliosis in both an acute setting such as an emergency room department and in an outpatient clinic such as a primary care or neurology office. Acutely, someone may recall a tick bite or a rash prior to the onset of symptoms which would direct the diagnosing physician. However, many people with late-stage Lyme do not recall finding an attached tick or a specific rash if their symptoms begin years after the exposure. In addition, the neurological symptoms caused by Lyme disease are not unique to neuroborreliosis so may not be considered as a diagnosis in a non-endemic area.
Neurological Symptoms of Early Lyme Disease
The onset of neurological symptoms can occur between one week and two months following a tick bite. In this early stage of neurological involvement, common symptoms have emerged. Meningitis from the Borrelia bacteria will present with nausea/vomiting, mild to severe headaches and a stiff neck. Light sensitivity and fever may also occur. However, meningitis caused by Lyme disease may be less severe than other bacterial infections so may be misdiagnosed as viral meningitis.
Encephalitis, or inflammation of the brain, can cause confusion, sleepiness, mood swings, personality changes or hallucinations. When the cranial nerves are affected in early Lyme disease, facial nerve palsy (sometimes referred to as Bell’s palsy) can cause muscle weakness or paralysis on one or both sides of the face leading to facial drooping. Additional cranial nerve symptoms include difficulty with eye closure, moving lips and smiling, and wrinkling of the forehead. Vision and smell can also be affected by cranial nerve inflammation.
Radiculoneuritis is the third common nervous system dysfunction seen in acute neuroborreliosis. “Radicular” pain follows nerves and can be sharp, shooting, stabbing or burning. The other sensory manifestation of radiculoneuritis is numbness and tingling along a nerve. Nerve involvement is typically near the site of a tick bite. When nerve inflammation from Lyme disease causes motor dysfunction, it presents as muscle weakness. When this occurs in the lower extremities and progresses to the upper body in acute neuroborreliosis, it can be incorrectly diagnosed as Guillain-barre syndrome.
Neurological Symptoms From Late-Stage Lyme Disease
If Lyme disease or associated infections are not adequately treated or go untreated, the persistence of the bacteria, and the inflammation from the immune response, can affect nerve function leading to a myriad of neurological symptoms. One study indicated it took an average of a year and a half following a tick bite for symptoms to manifest in the peripheral nervous system (PNS) and two years to the onset of symptoms in the central nervous system (CNS). The significant length of time from bacterial exposure to onset of symptoms creates a challenge in associating Lyme disease as the cause of chronic neurological symptoms.
Neuropathy is a general term for disease of the nerves.
Polyneuropathy refers to multiple nerves involved in the pathology. In late-stage Lyme disease, polyneuropathy typically manifests as numbness, tingling or burning and can include any nerve but most commonly begins in the hands/arms and feet/legs. Less frequently, chronic neuropathy can lead to radicular pain.
Michelle was diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) by her neurologist. She suffered from debilitating pain, tingling and burning in her lower legs, feet, and hands. Michelle’s pain was so severe she could not type for her sales job so had to use dictation software. She also experienced difficulty with swallowing which was previously misdiagnosed as eosinophilic esophagitis. Occasionally she got headaches, and she took daily naps because she was so fatigued in the afternoon. Michelle had been an avid hiker 15 years before the onset of her symptoms. She had been tested for Lyme disease by her previous integrative doctor however, the results were not discussed with her. When we tracked down those results, we were both surprised to see they were positive for Lyme disease. I ordered an updated complete tick-borne disease panel from a Lyme-specific laboratory, and those results confirmed Lyme was still positive. Michelle also tested positive for bartonellosis.
Throughout the next year, I treated Michelle with specific herbal formulas directed at both infections. She also took vitamin, mineral, and herbal supplements to help modulate her immune system and support detoxification. Michelle also received a series of an intravenous phosphatidylcholine protocol to repair myelin and cell membrane damage caused by the infections and the subsequent inflammation. Soon Michelle stopped complaining about her inability to swallow, and her neuropathy began to improve. This allowed her to type for the first time in years. We have continued to successfully use low-dose immunotherapy (LDI) to downregulate the persistent immune response that can occur after infections have resolved.
Encephalopathy refers to generalized brain dysfunction
Encephalopathy can cause symptoms such as headaches, fatigue, depression, irritability, speech, and memory impairment. When caused by Lyme disease, these symptoms are sometimes incorrectly referred to as neurological Lyme disease. However, inflammation from Lyme disease – or another infection – can cause encephalitis and does not necessarily indicate the infection is in the central nervous system. Brain imaging of patients with encephalopathy demonstrates areas of decreased blood flow and metabolism suggesting physiological changes cause the symptoms.
POTS, Constipation and Lyme Disease
POTS stands for postural orthostatic tachycardia syndrome which means the heart rate will increase when someone changes position, from laying or sitting to standing. POTS is very common in late-stage Lyme disease since the autonomic nervous system does not maintain tone in blood vessels causing a drop in blood pressure. When the blood pressure drops, the heart rate has to increase to stabilize blood pressure. Mast cell activation syndrome (MCAS) is another common cause of POTS and MCAS is frequently seen as a consequence of Lyme disease.
Another common symptom associated with autonomic nervous system dysfunction is constipation. Termed gastroparesis, constipation can happen when the nerve that signals intestinal muscular contraction become damaged by the bacteria and the resulting immune response.
PANS/PANDAS and Lyme Disease
PANDAS an acronym for pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections. It was first recognized in 1998 and characterized by a group of neurological symptoms following a strep infection. In PANDAS, the antibodies formed against strep also attack neuronal receptors in the brain leading to repetitive behavior, decreased concentration, decreased social engagement, aggression/rage, anxiety, insomnia, and phobias.
In the past 20 years since PANDAS was first recognized, other infections were identified as causing anti-neuronal antibodies that produce similar symptoms. In one study, 60% of patients with late-stage Lyme disease tested positive for anti-neuronal antibodies. Other published research has identified a protein on Borrelia that has a similar structure as strep, suggesting antibodies similar to strep can be triggered by Lyme disease and manifest similarly to PANDAS.
Neurologist Amir Katz, MD has proposed the term ANDAL – autoimmune neuropsychiatric disorder associated with Lyme – when anti-neuronal antibodies are formed in response to the bacteria that causes Lyme disease. The symptoms of ANDAL are the same as PANDAS. The diagnosis of ANDAL can be made by using specific Lyme disease tests and the Cunningham panel that was developed to diagnose PANDAS. Dr. Katz performed a study using the Cunningham panel to diagnose ANDAL in children with Lyme disease, and 91% were positive. Since many children and adults test positive from past exposure to strep infections, it is essential to consider other infectious causes of autoimmune neuropsychiatric symptoms.
Diagnosing Neurological Lyme Disease
The first step in the diagnosis of Lyme disease and associated infections is to order blood tests through a Lyme specific laboratory. It is well-established the traditional two-tiered test (ELISA that reflexes to a western blot if positive) has low sensitivity for diagnosing Lyme disease.
The diagnosis of acute central nervous system involvement of Lyme disease requires a lumbar puncture to analyze cerebral spinal fluid (CSF). The analysis of the CSF should include IgM and IgG antibodies to Borrelia bacteria and a test looking for the bacteria DNA (called PCR). If either of these markers is elevated, it is diagnostic of Lyme neuroborreliosis.
An increased level of white blood cells in the CSF – known as pleocytosis – also aids in the diagnosis. However, some people with neuroborreliosis do not have elevated antibodies in the CSF, and since pleocytosis can be present in other central nervous system infections, Lyme disease may not be considered.
The chemical attractant – something known to call the immune system to fight an infection – CXCL13 in the CSF has become an important marker to help diagnose Lyme neuroborreliosis. In a 2018 study of Lyme neuroborreliosis patients with elevated white blood cells but no detectable Lyme antibodies in their CSF, 73% had raised levels of CXCL13. The authors of the study have proposed a CXCL13 result greater than 160 pg/mL is consistent with Lyme neuroborreliosis.
The presence of oligoclonal bands in the CSF is part of the diagnostic workup for multiple sclerosis (MS). Studies have also demonstrated the presence of oligoclonal bands in the CSF of people with neurological Lyme disease, so this finding is not diagnostic of MS alone.
Electrophysiological testing aids in the diagnosis of neuropathy and would demonstrate decreased nerve conduction. However, in one study of chronic neurological Lyme disease not all patients with neuropathy tested positive on nerve conduction studies (EMG), so a negative test does not rule out neuropathy. Biopsies on the upper and lower leg can also be performed to diagnose small fiber neuropathy.
Treatment of Acute Neuroborreliosis
In acute Lyme neuroborreliosis, treatment needs to be directed at the bacterial infection. Administering the antibiotic ceftriaxone (Rocephin) intravenously for 14 days has proven to be effective at treating the bacteria in the central nervous system. Blood levels of oral antibiotics or herbal formulas may not reach high enough concentrations to treat central nervous system infections effectively.
Treatment of Chronic Lyme Disease
Damage to the peripheral and autonomic nervous system is common in late-stage Lyme disease. Numbness, tingling, burning and nerve pain experienced in peripheral neuropathy and radiculitis require effective treatment of the involved infections. Therapies directed at decreasing the inflammatory response by the immune system and repair of the damaged nerves is also part of the strategy when treating symptoms associated with chronic neurological Lyme disease.
Neuropathy is one of the most debilitating – and challenging to treat – symptoms of chronic neurological Lyme disease. Intravenous immunoglobulin (IVIG) therapy can be useful at reversing any form of neuropathy including CIDP caused by Lyme disease. The biggest hurdle in using IVIG as a therapy is the expense (which can be as much as $5000 per treatment), so insurance coverage of this therapy is typically necessary. Often, criteria for health insurance approval is a positive nerve conduction study and a biopsy demonstrating small fiber neuropathy. Treatments are usually once per month, and it can take 6-18 months to see results.
Another therapy that has shown promising results in treating neuropathy is phosphatidylcholine. Phosphatidylcholine is a fatty acid that is a component of cell membranes. Due to immune-mediated and direct damage from Lyme disease, cell membranes throughout the body – including nerves – become damaged. The use of phosphatidylcholine repairs the damaged cell (and mitochondrial) membranes of nerves restoring their ability to function properly. Phosphatidylcholine can be taken orally, however, intravenous administration is more effective in treating neuropathy and other cell damage. An intravenous protocol combines butyrate, glutathione, folate, and vitamin B12 with phosphatidylcholine, and may be more effective than IV phosphatidylcholine alone.
High doses of biotin have been shown to be effective at repairing myelin in neuropathy from multiple sclerosis. I have found this helpful in some of my patients with Lyme-induced neuropathy, but not everyone. “High” dose refers to 300mg per day – which is significantly higher than typical dose – so should only be taken under a physician’s care. Note, high doses of biotin will affect thyroid lab results so should be stopped a week before thyroid testing.
Excellent article! We have been fighting lyme/co-infections now for almost three years, and my eight year old is still symptomatic with PANS symptoms, despite the aggressive treatment with a lyme-literate neurologist and another LLMD to help support with herbals. I have never heard of ANDAL, but the description is exactly what what my son is dealing with. The neurologist is recommending IVIG as the next step, but it makes me nervous for many reasons.
Dr. Todd Maderis says
I am glad you enjoyed the article. I am sorry to hear your child is still experiencing symptoms after three years of treatment. I have seen PANS symptoms and positive Cunningham panel caused by mold (mycotoxin) illness. Mold illness treatment improved symptoms and the anti-neuronal antibodies normalized.
Thank you for such a great article! I was diagnosed with Lyme disease a year ago when I started feeling POTS like symptoms. I was given multiple antibiotics and herbals, but still have POTS symptoms, which greatly diminishes my ability for everyday activities. Have you seen anyone heal from POTS caused by Lyme?
Dr. Todd Maderis says
POTS symptoms can improve with effective treatment of tickborne infections. You may need to be on treatment for POTS while treating the infection(s) and the autonomic nervous system function normalizes.
Marissa Del Rio says
I wish when I had Neurological Lyme Disease in 2013 more was known about it. Drs thought I had a stroke or a schwannoma. I never saw a bulls eye or tick. I lost my hearing, developed a stutter, bells palsey, couldn’t figure out where I was and more. I’m way better now, just left with some damage that people can’t see.
Why is there no research on post patients with Neurological Lyme?
Dr. Todd Maderis says
Thank you for sharing your experience with Lyme. There is some research on active neuroborreliosis, but patients are rarely tracked long-term to follow their outcome.