Anaplasma encephalitis can present as acute confusion and fever with normal brain imaging, making diagnosis challenging without high clinical suspicion. A 62-year-old avid gardener developed sudden confusion, mild headache, and fever four weeks after a tick bite — unable to maintain meaningful conversation, he was treated empirically for viral encephalitis but worsened over 24 hours until PCR testing confirmed Anaplasma phagocytophilum infection. His complete recovery within 24 hours of IV doxycycline demonstrates the importance of considering tick-borne infections in patients with unexplained encephalitis, particularly in endemic areas where neurologic manifestations of anaplasmosis are becoming increasingly recognized.

Anaplasmosis: A Potentially Life-Threatening Tick-Borne Disease

Anaplasmosis is a tick-borne disease caused by the bacterium Anaplasma phagocytophilum. Symptoms typically start 1 to 2 weeks after a tick bite. And while some patients may be asymptomatic, others can experience life-threatening complications, including encephalitis.

In fact, the mortality rate is higher in patients who do not immediately receive doxycycline treatment, who are immunocompromised or have become infected through a blood transfusion.

Anaplasmosis is transmitted by the same blacklegged ticks (Ixodes scapularis) that transmit Lyme disease. The bacteria invade white blood cells, causing systemic infection that can affect multiple organ systems including the brain. Unlike Lyme disease which typically requires 24-48 hours of tick attachment, anaplasmosis transmission timing is less well-defined but can occur relatively quickly.

Case Report: Acute Confusion in a Gardener

In their article, “Anaplasma phagocytophilum Encephalitis: A Case Report and Literature Review of Neurologic Manifestations of Anaplasmosis,” Cosiquien and colleagues describe a 62-year-old patient who was admitted to the emergency department due to an acute onset of confusion.

The man was “confused and unable to maintain meaningful conversation,” the authors state. He had a mild headache and a slight fever but no other symptoms.

The patient had acute onset of confusion, a mild headache and a slight fever but no other symptoms.

He was an avid gardener and reportedly had a tick bite four weeks before his symptoms began.

The four-week interval between tick bite and encephalitis presentation is notable. While anaplasmosis symptoms typically begin 1-2 weeks after tick bite, neurologic complications can develop later in the disease course, particularly if initial systemic symptoms were mild or missed entirely.

Initial Treatment and Deterioration

“Given the symptoms of headache, confusion, and fever, encephalitis was suspected, and a lumbar puncture (LP) was performed,” the authors state.

The man was treated empirically with acyclovir, ceftriaxone, and vancomycin. But despite treatment, his fever and confusion worsened over the next 24 hours.

The empiric treatment covered common causes of encephalitis: acyclovir for herpes simplex virus (HSV), ceftriaxone for bacterial meningitis, and vancomycin for resistant organisms. This is standard practice when encephalitis is suspected. However, the worsening despite broad-spectrum coverage indicated the cause wasn’t HSV or bacterial infection.

Diagnosis and Rapid Recovery

Subsequent PCR testing was positive for anaplasmosis and the patient began treatment with IV doxycycline. He made a full recovery.

“Within 24 hours of doxycycline initiation, his symptoms improved.”

The dramatic improvement within 24 hours of starting doxycycline validates the diagnosis and demonstrates the reversibility of anaplasma encephalitis when treated appropriately. This rapid response is characteristic of anaplasmosis — unlike viral encephalitis which may take weeks to resolve, bacterial infections causing encephalitis typically improve quickly once appropriate antibiotics are started.

Neurologic Manifestations of Anaplasmosis

Neurologic manifestations of anaplasmosis are less common than in other tick-borne diseases, such as ehrlichiosis, Lyme disease, and Powassan virus infection, according to the authors.

“… our patient responded promptly to intravenous doxycycline which further confirms that this indeed was encephalitis due to Anaplasma phagocytophilum,” the authors state.

“As cases of anaplasmosis are becoming more frequent, it has become apparent that some patients, such as the one we report, present with predominantly neurological manifestations.”

This observation is critical for clinicians. Historically, anaplasmosis was considered primarily a systemic febrile illness with less neurologic involvement than ehrlichiosis or Lyme disease. But as case reports accumulate, neurologic presentations including encephalitis, meningitis, and cranial neuropathies are increasingly recognized.

Normal MRI Despite Clinical Encephalitis

The authors point out that although there was clinical and laboratory evidence of encephalitis, the patient’s MRI was normal.

They suggest, “In tick-endemic areas, clinicians should keep [an infection with anaplasma phagocytophilum] in mind in patients who present with encephalitis.”

The normal MRI is an important teaching point. Encephalitis is a clinical and laboratory diagnosis — brain inflammation confirmed by altered mental status, fever, CSF abnormalities. Brain imaging may show edema, enhancement, or focal changes, but can also be completely normal early in the disease course or with certain pathogens.

Normal MRI does not exclude encephalitis. Clinical symptoms (confusion, headache, fever) plus CSF findings (if lumbar puncture showed pleocytosis or elevated protein, though not mentioned in this case report) establish the diagnosis. Waiting for MRI abnormalities before treating suspected tick-borne encephalitis would delay critical therapy.

Why Anaplasma Causes Encephalitis

Anaplasma encephalitis occurs when A. phagocytophilum bacteria invade the central nervous system, though the exact mechanisms remain incompletely understood. Possible pathways include:

• Direct CNS invasion: Bacteria crossing the blood-brain barrier and infecting brain tissue
• Infected white blood cells: Anaplasma infects neutrophils and monocytes, which can carry bacteria into the CNS
• Vasculitis: Inflammation of brain blood vessels causing ischemia and edema
• Immune-mediated inflammation: Cytokine release and inflammatory response causing brain dysfunction
• Endothelial damage: Bacteria damaging blood-brain barrier allowing inflammatory cells to enter CNS

The rapid response to doxycycline suggests active bacterial infection rather than post-infectious autoimmune process. Doxycycline kills Anaplasma organisms, resolving the inflammation and restoring normal brain function.

Clinical Perspective

This case demonstrates several critical teaching points about anaplasma encephalitis. First, the acute onset of confusion should immediately raise suspicion for encephalitis in any patient with fever and headache. “Confused and unable to maintain meaningful conversation” indicates severe cognitive impairment requiring urgent evaluation.

Second, the tick bite four weeks prior is easily missed in the history. Patients may not remember tick bites, particularly if they occurred weeks before symptom onset. This patient was an avid gardener — regular outdoor exposure to tick habitat — which should elevate suspicion for tick-borne infections even without specific tick bite recall.

Third, the empiric treatment with acyclovir, ceftriaxone, and vancomycin was appropriate given the presentation. When encephalitis is suspected, treatment must begin immediately before confirmatory testing returns. Delaying antibiotics or antivirals while awaiting PCR results can result in preventable deterioration or death.

However, the worsening despite empiric treatment should have immediately prompted consideration of alternative diagnoses. When standard encephalitis treatment fails, atypical organisms including tick-borne pathogens, fungi, or parasites must be investigated.

Fourth, the normal MRI despite clinical encephalitis reinforces that imaging is supportive but not diagnostic. MRI can be normal in early encephalitis, with certain pathogens (Anaplasma, some viruses), or when inflammation is diffuse rather than focal. Clinical judgment and laboratory findings take precedence over imaging.

Fifth, the complete recovery within 24 hours of doxycycline is remarkable and diagnostic. This rapid response pattern — acute deterioration followed by dramatic improvement with appropriate antibiotics — is characteristic of treatable bacterial infections. It validates both the diagnosis and the critical importance of considering anaplasmosis in the differential.

Finally, the increasing recognition of neurologic manifestations in anaplasmosis has clinical implications. Historically considered primarily a systemic febrile illness, anaplasmosis is now known to cause encephalitis, meningitis, cranial neuropathies, and other CNS complications. As case numbers increase across North America, clinicians must maintain high suspicion for anaplasmosis in patients with unexplained neurologic symptoms and tick exposure.

The mortality risk in untreated or delayed treatment emphasizes urgency. Unlike viral encephalitis where supportive care may be the only option, anaplasma encephalitis is fully treatable with doxycycline. Every hour of delay increases risk of irreversible brain damage or death. In endemic areas during tick season, empiric doxycycline should be considered for encephalitis cases pending PCR results.

Frequently Asked Questions

Can anaplasmosis cause encephalitis?

Yes. Anaplasma encephalitis occurs when A. phagocytophilum bacteria invade the central nervous system, causing brain inflammation. Symptoms include confusion, fever, headache, and altered mental status. Neurologic manifestations are increasingly recognized as case numbers rise.

How is anaplasma encephalitis diagnosed?

Diagnosis requires clinical suspicion (confusion, fever, tick exposure), lumbar puncture showing CSF abnormalities, and PCR testing confirming Anaplasma phagocytophilum. MRI may be normal despite clinical encephalitis, as in this case.

What is the treatment for anaplasma encephalitis?

IV doxycycline is the treatment of choice. This patient showed dramatic improvement within 24 hours of starting doxycycline, with complete recovery. Delays in treatment increase mortality risk.

How long after a tick bite does anaplasma encephalitis develop?

Symptoms typically begin 1-2 weeks after tick bite, but this patient developed encephalitis four weeks post-exposure. Neurologic complications can develop later in the disease course, particularly if initial systemic symptoms were mild or unrecognized.

Can anaplasmosis be fatal?

Yes. Mortality is higher in patients who don’t receive immediate doxycycline, who are immunocompromised, or who acquired infection through blood transfusion. Early recognition and treatment are critical for survival.

Is anaplasmosis common?

Cases are increasing across North America. Anaplasmosis is transmitted by the same blacklegged ticks that transmit Lyme disease, and often occurs as a coinfection with Lyme or other tick-borne pathogens.

Can you have anaplasmosis with normal brain imaging?

Yes. This patient had clinical and laboratory evidence of encephalitis but normal MRI. Brain imaging can be normal early in encephalitis or with certain pathogens. Normal MRI does not exclude anaplasma encephalitis.