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  • Writer's pictureP.K. Peterson

Neurological Manifestations of Lyme Disease

“I believe that illness has led me to a life of gratitude, so I consider Lyme disease at this point in my life to be a blessing in disguise.”

Rebecca Wells, American author, actor, and playwright

“In a study using specialized imaging techniques, Johns Hopkins Medicine researchers report distinctive changes in the ‘white matter’ and other brain tissue physiology of those with post-treatment Lyme disease, a condition affecting 10% to 20% of the nearly half a million Americans who contract Lyme disease annually.”

Haley Wasserman, MA, communications specialist, science writer


In August 2023, the Centers for Disease Control and Prevention announced that tickborne diseases were on the rise in the U.S. It’s too early to tell if this trend will extend into the 2024 tick season but given the extreme heat we experienced in 2023—a condition that favors tick breeding—it seems highly likely.

Of the 20 or more tickborne infections, Lyme disease is by far the most common. (I reviewed broadly the topic of tickborne infections in the April 12, 2023, Germ Gems post “Tick Encounters 2023.”) In today’s post, I focus on Lyme disease, and more specifically on the associated neurologic disorder called “post-treatment Lyme disease syndrome (PTLDS).”

Brief history of Lyme disease. Beginning in the last quarter of the 20th century, epidemiologists witnessed 140 or so “emerging infections” worldwide. In the 1970s, Lyme disease, a multisystem infection, was one of the first to emerge in the U.S. It was observed initially in Lyme, Connecticut, in children with unexplained arthritis. Since its inception, Lyme disease spread throughout the U.S. causing an estimated 300,000-500,000 new cases annually. (95% of cases occur in 14 states concentrated in New England and the Upper Midwest.)

In 1981, the scientist Willy Burgdorfer discovered that the bacterium Borrelia burgdorferi caused Lyme disease. (He was honored in the naming of the bacterium.) He also discovered that the deer tick (Ixodes scapularis) was the vector for transmitting the pathogen.

Lyme disease symptoms. Lyme disease occurs in three stages: early localized, early disseminated, and late disseminated. The first stage of Lyme disease develops seven to 30 days following the bite of an infected tick. This stage is characterized by a flu-like illness with fever, headache, and fatigue, and in about 75% of the cases, the development of a characteristic skin rash called erythema migrans. The diagnosis is determined by clinical examination and serological tests, e.g., Western blot, ELISA, and PCR.

Neurological complications of Lyme disease. Neurological manifestations of Lyme disease, often referred to as neuroborreliosis, occur most often in the second stage of the disease. These manifestations include numbness, pain, weakness, Bell’s palsy (temporary paralysis or weakness on one side of the face), visual disturbances, or meningitis-like symptoms (stiff neck and severe headache). In the U.S, neuroborreliosis is most commonly treated with intravenous antibiotics, such as ceftriaxone for 14 to 28 days. (Several European studies suggest that the oral antibiotic doxycycline is equally effective.)

Treatment. Lyme disease is usually effectively treated with antibiotics. If left untreated, it can spread to joints, heart, and the nervous system. Deaths from Lyme disease are extremely rare, however, and usually are related to Lyme carditis with interruption of the usual electrical functioning of the heart.

What is PTLDS? One of the biggest conundrums in the treatment of Lyme disease is the management of patients who remain ill after a course(s) of antibiotic treatment. Approximately 5-20% of patients report chronic, often disabling symptoms after getting Lyme disease and being treated. “Post-treatment Lyme disease syndrome (PTLDS),” “long-haul Lyme disease,” and “chronic Lyme disease” are terms that are used to describe this condition. This disorder is characterized by marked fatigue, muscular pain, insomnia, depression, and cognitive difficulties, such as trouble with concentration and memory. (“Brain fog” is the term commonly used to describe the patient’s cognitive impairment.)

Notable similarities between patients suffering with PTLDS and the diseases Long COVID and chronic fatigue syndrome (aka myalgic encephalomyelitis [ME/CFS]) suggest all three entities share a similar pathophysiology or underlying mechanism. While the pathogenesis of Long COVID is incompletely understood, the most convincing theory to me is the so-called “persistent antigen hypothesis,” first described by University of Minnesota neuroscientist Apostolos Georgopoulos.

In the case of Long COVID, persistence of the etiologic agent, SARS-CoV-2, or its components can cause brain disease.  Hypothetically, in PTLDS, persistent B. burgdorferi or its antigens stirs up damage within the central nervous system.

Researchers at Johns Hopkins provide support for the hypothesis regarding the pathogenesis of post-infection fatigue in Lyme disease. (See Haley Wasserman’s article “Neuroimaging study reveals brain abnormalities in people with post-treatment Lyme disease” in October 2022 PLOS ONE.) Using a specialized neuroimaging technology, they found unusual activity in the frontal lobe, an area of the brain responsible for cognitive tasks such as memory recall and concentration. These scientists say that their research “may help illuminate underlying mechanisms and potential therapeutic targets for neurologic Lyme disease.”

In addition, researchers at Tulane University reported recently on a promising new approach to treating PTLDS. (See “Potential new treatment path for long lasting Lyme disease symptoms,” Science News April 18, 2024.) These scientists found that fibroblast growth factor receptor inhibitors, previously studied in cancer, significantly reduced inflammation and cell death in infected brain and nerve tissue samples infected with B. burgdorferi. According to Science News, even though additional research is needed “to translate these findings into clinical treatments, the study represents an important step forward in understanding and potentially managing the complex aftermath of Lyme disease.”

Future directions. For dogs, there are several oral and topical tick-prevention medications as well as several Lyme vaccines. As New York Times science writer Dana G. Smith reported, dogs have more options that humans when it comes to preventing Lyme disease. (See April 23, 2024 New York Times article “Lyme Disease Is Spreading. Why Don’t We have Drugs to Stop It?”)  

In 1998, the Food and Drug Administration approved a human vaccine for Lyme disease after clinical trials showed the vaccine to be safe and effective.  But, shortly after people started receiving the vaccine, reports of side effects emerged. And even though federal health officials found no evidence that the vaccine was unsafe, sales of the vaccine fell and the manufacturer GlaxoSmithKline took the vaccine off the market. (The vaccine was on the market from 1999-2002.)

There is an urgent need for a vaccine to prevent Lyme disease in humans and some headway is being made. Two new vaccines for humans that target the same protein as in the dog vaccines are currently being tested in clinical trials. Many fingers should be crossed, especially in people living in New England and the Upper Midwest, that one of these vaccines allows us to join “man’s best friend” by getting a jab that prevents Lyme disease.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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