CSF Profiles in Anaplasmosis Rarely Track With Neurologic Severity
Anaplasmosis reached the central nervous system in this series less often than the bedside presentation suggested. In a multisite retrospective study from Minnesota and Wisconsin, clinicians identified 10 hospitalized adults with PCR-confirmed Anaplasma phagocytophilum infection who had neurologic symptoms severe enough to prompt lumbar puncture, yet half of the cerebrospinal fluid samples remained within reference ranges.
The clinical picture still looked dramatic. Six patients presented with meningitis, three with meningoencephalitis, and one with encephalitis. Four required intensive care. Two were immunocompromised, a relevant detail in a tickborne illness that can become more severe when host defenses are blunted. Despite that severity, the CSF pattern stayed surprisingly bland in most patients: 5 of 10 had normal cell counts, and 4 others showed only mild lymphocytic pleocytosis. Protein and glucose stayed within reference ranges in every patient except one traumatic lumbar puncture specimen.
The disconnect between neurologic symptoms and CSF inflammation matters at the bedside. In this cohort, the spinal fluid did not behave like a classic bacterial meningitis profile, and it did not mirror the intensity of neurologic dysfunction. That pattern supports a cytokine-mediated process rather than direct invasion of the central nervous system, which is biologically plausible for an intracellular pathogen that drives systemic inflammation out of proportion to overt CSF abnormalities.
Tick Exposure, Fever, and Focal Neurologic Complaints Drove the Workup
The study drew from 101 hospitalized patients with anaplasmosis diagnoses treated at Mayo Clinic Rochester or Mayo Clinic Health System sites over a 10-year period from November 1, 2014 through November 29, 2024. Investigators manually reviewed the charts and required three elements for inclusion: positive blood PCR for Anaplasma phagocytophilum, predominantly central nervous system symptoms at presentation, and lumbar puncture with CSF analysis. Ten patients met those criteria.
All 10 underwent an extensive infectious evaluation for alternative bacterial, viral, endemic fungal, and other tickborne causes. Those studies were negative, excluding coinfection in the cases reviewed. Every lumbar puncture occurred before doxycycline was started, so the CSF findings were not confounded by early antimicrobial therapy.
The symptom patterns were varied but recognizable. Severe headache, photophobia, neck stiffness, confusion, altered mental status, and focal neurologic deficits all appeared in the cohort. The most vivid cases resembled meningitis, but a few crossed into encephalitis or focal neurologic territory. In one patient, left-sided hemiparesis and urinary retention raised immediate concern for a stroke mimic, yet brain MRI showed no acute infarction. Another patient had abnormal involuntary movements, including akathisia and choreiform activity, alongside headache and photophobia. Those presentations reflect how tickborne infection can enter the differential long before the laboratory picture becomes definitive.
Doxycycline Brought Rapid Defervescence and Neurologic Recovery
The most striking feature in the series was the pace of clinical response after doxycycline.
In patient after patient, fever and neurologic symptoms eased within 48 to 72 hours once treatment began.
That rapid turn is clinically important because it reduces the temptation to attribute the syndrome to a progressive primary neurologic disorder, autoimmune encephalitis, or occult bacterial meningitis when a treatable tickborne infection is already present in the differential. In patient 1, an immunocompetent 75-year-old man with fever, headache, photophobia, chills, hemiparesis, and urinary retention, complete neurologic and systemic improvement occurred within 72 hours of intravenous doxycycline. He was discharged after 3 days to complete a 4-week course.
Patient 2, a 65-year-old immunocompetent woman, developed severe frontal and maxillary facial pain with headache, photophobia, blurred vision, fever to 103°F, nausea, and vomiting roughly 2 weeks after a tick bite. She had already failed amoxicillin/clavulanate for presumed sinusitis. At admission she met sepsis criteria, required intensive care, and improved within 48 hours after empiric broad-spectrum therapy including doxycycline. She completed 2 weeks of treatment and recovered fully.
Patient 3, a 74-year-old immunocompetent woman, came in with intermittent headaches, photophobia, and involuntary movements before fever and chills emerged on the day of admission. She improved markedly after the second doxycycline dose and was discharged on a 10-day course, though fatigue and cognitive slowing lingered for about 3 months before full recovery.
Patient 4, a 57-year-old man receiving prednisone for ulcerative colitis, presented with myalgias, arthralgias, chills, sweats, fever, and then left parietal headache. Laboratory results showed neutropenia, thrombocytopenia, transaminitis, and elevated C-reactive protein. His symptoms resolved completely within 2 days of intravenous doxycycline.
Patient 5, a 57-year-old man with primary sclerosing cholangitis and gallbladder carcinoma receiving chemotherapy, developed a 9-day headache worsened by light along with nausea, vomiting, photophobia, fever, chills, and neck stiffness. He met sepsis criteria and required ICU care. After doxycycline was initiated, he defervesced within 48 hours and completed 2 weeks of therapy with full recovery.
Patient 6, a 67-year-old woman with headache, fever, photophobia, neck stiffness, pancytopenia, hyponatremia, elevated aminotransferases, and heavy outdoor exposure with multiple tick bites, improved rapidly after doxycycline and ceftriaxone were started.
Why Normal CSF Does Not Exclude Central Nervous System Anaplasmosis
The practical lesson here is not that CSF can be ignored. It is that normal cerebrospinal fluid does not rule out neurologic anaplasmosis when the clinical context fits. Lymphocytic pleocytosis, when present, stayed mild. Glucose and protein were usually preserved. Even patients with striking neurologic symptoms could have CSF values that looked nearly unremarkable.
For clinicians in hyperendemic regions, that creates a diagnostic trap. A patient with fever, headache, confusion, meningismus, or focal deficits may trigger an expansive search for viral encephalitis, bacterial meningitis, fungal disease, stroke, or autoimmune neurologic syndromes. Those alternatives still require evaluation, but this series argues that empiric doxycycline should move early in the treatment sequence when tick exposure and systemic features point toward anaplasmosis.
The biology fits the pattern. Anaplasma phagocytophilum infects leukocytes and drives systemic inflammatory signaling rather than producing a robust purulent meningeal response. A cytokine-mediated neurologic syndrome can therefore generate substantial symptoms with limited CSF derangement. In that setting, lumbar puncture becomes a tool for exclusion and characterization, not a gatekeeper for therapy.
This study is still small, retrospective, and concentrated in a hyperendemic region, so the findings should not be stretched beyond the observed cohort. The series also leaves open how often similar CSF patterns occur outside Minnesota and Wisconsin, and whether certain host factors predict neurologic involvement better than spinal fluid metrics do. Even so, the message from these 10 patients is direct: when anaplasmosis reaches the nervous system, the CSF may stay deceptively quiet, and doxycycline can reverse the syndrome quickly if clinicians act early.