Chronic neurological Lyme disease patients remained severely symptomatic an average of 5 years after initial treatment — yet their ongoing fatigue, pain, cognitive problems, and neurologic symptoms were attributed to “comorbid conditions” like fibromyalgia, chronic fatigue syndrome, depression, and autoimmune diseases rather than persistent Lyme infection. This study of 258 patients with definite neuroborreliosis exposes a troubling pattern: when Lyme disease treatment fails to resolve symptoms long-term, doctors retrospectively assign alternative diagnoses without investigating whether the symptoms represent treatment failure, persistent infection, or post-infectious sequelae.

Five Years Later, Still Symptomatic

The study, “Patient-reported outcome after treatment for definite Lyme neuroborreliosis” by Eikeland and colleagues, describes 258 patients treated for definite Neurologic Lyme disease. Many of them with chronic neurological Lyme disease remained symptomatic an average of 5 years after their initial treatment.

These weren’t patients with questionable Lyme diagnoses. They had definite neuroborreliosis — confirmed by CSF findings, clinical presentation, and laboratory testing. They were treated according to standard protocols. Yet years later, many remained severely ill.

Severe Fatigue and Poor Quality of Life

According to the authors, a higher proportion of their chronic neurological Lyme disease patients reported severe fatigue. Furthermore, “Mental health-related quality of life was poorer among [neuroborreliosis] NB-treated patients than in normative data.”

The fatigue wasn’t mild. It was severe enough to significantly impact quality of life years after treatment. Mental health-related quality of life was measurably worse than population norms — indicating ongoing disability and suffering.

The Comorbidity Attribution Problem

Although many of the patients’ symptoms are consistent with those found in chronic neurological Lyme disease, the authors attributed the symptoms to co-morbid illnesses, based on a retrospective review of the medical records.

This is the critical issue. Instead of investigating whether symptoms represented treatment failure, persistent infection, or post-infectious complications of neurologic Lyme disease, the authors accepted comorbidity diagnoses from medical records at face value.

The Symptom List: Lyme or Comorbidities?

The symptoms included: radiating pain, general pain, fatigue, facial palsy, malaise, dizziness and/or unsteadiness, headache, numbness in arm and/or leg, memory and/or concentration problems, paresis in arm and/or leg, and diplopia.

Every single one of these symptoms is a known manifestation of neurologic Lyme disease:

• Radiating pain: Radiculopathy from Lyme
• General pain: Chronic pain in Lyme disease
• Fatigue: Classic Lyme symptom
• Facial palsy: Cranial neuropathy from Lyme
• Malaise: Systemic infection/inflammation
• Dizziness/unsteadiness: Autonomic dysfunction or central nervous system involvement
• Headache: Neuroinflammation
• Numbness: Peripheral neuropathy
• Memory/concentration problems: Lyme-related cognitive dysfunction
• Paresis: Neurologic weakness
• Diplopia: Cranial nerve involvement

These aren’t vague, non-specific complaints. They’re the classic neurologic manifestations of Lyme disease.

The Alternative Diagnoses

Co-morbid conditions listed for these patients included: fibromyalgia, allergies, depression or anxiety, multiple sclerosis, systemic disease sarcoidosis, systemic lupus erythematosus, Sjögren’s syndrome, rheumatoid arthritis, chronic fatigue syndrome, Parkinson’s disease, thyroid dysfunctions, and cancer.

This is an extraordinary list of comorbidities. It suggests one of two possibilities:

Possibility 1: These patients coincidentally developed multiple severe autoimmune and neurologic diseases after their Lyme diagnosis.

Possibility 2: These “comorbidities” are actually manifestations or sequelae of persistent or inadequately treated Lyme disease, and the alternative diagnoses represent medical dismissal of ongoing Lyme-related pathology.

Several of these diagnoses — fibromyalgia, chronic fatigue syndrome, depression, anxiety — are frequently given to persistent Lyme disease patients whose symptoms don’t resolve with standard treatment.

The Study’s Critical Limitation

Note: The study was not designed to assess whether the patient, in fact, had the co-morbidity listed in their records or instead had complications of chronic neurological Lyme disease.

This is the authors’ own acknowledgment of a fundamental limitation. They accepted comorbidity diagnoses from medical records without validating them. They didn’t investigate whether these diagnoses were:

• Based on objective diagnostic criteria
• Confirmed by specialists
• Distinguished from Lyme disease manifestations
• Actually present vs. diagnostic labels applied when Lyme symptoms persisted

This transforms the findings from “patients had comorbidities” to “patients had labels in their charts that doctors used to explain ongoing symptoms.”

The Pattern of Medical Dismissal

I see this pattern constantly in my practice:

1. Patient diagnosed with Lyme disease (often delayed)
2. Patient treated with standard antibiotics
3. Patient doesn’t fully recover
4. Ongoing symptoms are attributed to:
• Fibromyalgia
• Chronic fatigue syndrome
• Depression/anxiety
• Autoimmune disease
• “Post-treatment Lyme disease syndrome” (PTLDS)
5. Patient is told Lyme infection is “cured” and symptoms are from something else
6. No further investigation of persistent infection or extended treatment

This represents medical abandonment disguised as comprehensive differential diagnosis.

Lyme Can Trigger Autoimmune Disease

It’s also possible that some of these “comorbidities” are genuine autoimmune or inflammatory conditions — but triggered by Lyme disease.

There’s evidence that Lyme disease can trigger or unmask:

• Autoimmune conditions
• Thyroid dysfunction
• Inflammatory arthritis
• Neuroinflammatory diseases

In these cases, treating the underlying Lyme infection may help resolve or improve the secondary condition. But if we accept the comorbidity label and stop treating Lyme, the trigger remains active.

Clinical Perspective

This study’s findings are sobering but not surprising. A significant proportion of patients with definite neuroborreliosis remained symptomatic 5 years post-treatment, with severe fatigue and poor quality of life. Rather than investigating treatment failure or persistent infection, the authors attributed symptoms to comorbid conditions based on chart review.

The symptom list is particularly revealing. Every symptom — radiating pain, fatigue, facial palsy, dizziness, headache, numbness, memory problems, paresis, diplopia — is a known manifestation of neurologic Lyme disease. Yet when these symptoms persisted after treatment, they were attributed to fibromyalgia, chronic fatigue syndrome, depression, multiple sclerosis, and other diagnoses.

This raises fundamental questions about how we define treatment success and failure in Lyme disease. If a patient with confirmed neuroborreliosis is treated and continues to have the same neurologic symptoms years later, is that treatment success because we administered antibiotics? Or is it treatment failure because the patient remains disabled?

The comorbidity list itself suggests diagnostic confusion. Fibromyalgia and chronic fatigue syndrome are clinical diagnoses of exclusion — symptom patterns without identified underlying pathology. When applied to patients with documented infectious disease, they function as labels for “persistent symptoms we can’t explain” rather than independent conditions.

Depression and anxiety, similarly, may be consequences of chronic illness and ongoing disability rather than primary psychiatric conditions. Patients who remain severely fatigued and cognitively impaired 5 years after Lyme treatment have good reason to be depressed and anxious.

The autoimmune diagnoses — multiple sclerosis, lupus, Sjögren’s syndrome, rheumatoid arthritis — are concerning. While some may be independent conditions, Lyme disease can trigger autoimmune responses and cause neuroinflammation that mimics these conditions. Without investigating whether treating persistent Lyme might resolve the autoimmune symptoms, we risk leaving the underlying infection untreated.

The authors acknowledged the study wasn’t designed to validate whether patients actually had the listed comorbidities. This is critical. A diagnosis appearing in a medical record doesn’t mean it was rigorously confirmed — it may represent a doctor’s attempt to explain ongoing symptoms when standard Lyme treatment failed.

In my practice, I’ve seen countless patients with these exact comorbidity labels whose symptoms improved significantly with extended antibiotic treatment for Lyme disease. This suggests at least some of these diagnoses represent persistent infection rather than independent conditions.

The study also highlights the limitations of standard neuroborreliosis treatment. If significant numbers of patients with definite Lyme remain symptomatic years later, our treatment protocols may be inadequate for some cases. Rather than attributing ongoing symptoms to comorbidities, we should investigate whether longer treatment courses, combination therapies, or adjunctive treatments might improve outcomes.

Finally, the poor quality of life findings deserve emphasis. These patients aren’t mildly symptomatic — their mental health-related quality of life is measurably worse than population norms years after treatment. This represents ongoing disability and suffering that demands investigation and treatment, not dismissal as comorbidity.

Frequently Asked Questions

Can chronic neurological Lyme disease cause symptoms years after treatment?

Yes. This study found many patients with definite neuroborreliosis remained symptomatic an average of 5 years post-treatment, with severe fatigue, pain, cognitive problems, and neurologic symptoms. Whether this represents persistent infection, treatment failure, or post-infectious sequelae remains debated.

Are fibromyalgia and chronic fatigue syndrome comorbidities of Lyme disease?

These diagnoses are frequently applied to patients with persistent symptoms after Lyme treatment. However, they’re diagnoses of exclusion based on symptoms, not objective findings. Many patients labeled with fibromyalgia or chronic fatigue syndrome may actually have inadequately treated Lyme disease.

Can Lyme disease trigger autoimmune conditions?

Yes. Lyme disease can trigger or unmask autoimmune conditions including thyroid dysfunction, inflammatory arthritis, and other autoimmune diseases. Some “comorbidities” may be Lyme-triggered conditions that could improve with treating the underlying infection.

Why do some Lyme patients remain symptomatic after treatment?

Possible explanations include: persistent infection not eradicated by standard treatment, post-infectious immune dysfunction, inadequate treatment duration, undiagnosed coinfections, or Lyme-triggered secondary conditions. The study didn’t investigate which mechanism explained ongoing symptoms.

Is depression after Lyme treatment a comorbidity or consequence?

Depression and anxiety in patients who remain severely ill years after treatment are often consequences of ongoing disability, not independent psychiatric conditions. Chronic fatigue, pain, and cognitive impairment understandably cause depression and anxiety.

Should ongoing symptoms after Lyme treatment be investigated?

Yes. When patients with confirmed Lyme disease remain symptomatic after standard treatment, investigation should include: evaluating for persistent infection, testing for coinfections, assessing for Lyme-triggered conditions, and considering extended or combination treatment rather than simply attributing symptoms to comorbidities.

What does “definite neuroborreliosis” mean?

Definite neuroborreliosis means Lyme disease affecting the nervous system confirmed by CSF findings (pleocytosis, intrathecal antibody production), clinical neurologic symptoms, and laboratory evidence of Lyme infection. These weren’t questionable cases — they had documented neurologic Lyme disease.