Case Presentation: A 33-year-old previously healthy woman presented with progressive facial paralysis, limb weakness, and dysesthesias. One month earlier, she was diagnosed with bilateral Bell’s palsy and treated with corticosteroids, which was later attributed to Lyme disease after a positive serum Lyme IgG. She was started on doxycycline but later required hospitalization for worsening symptoms and was discharged on IV ceftriaxone via a PICC line. Despite therapy, her weakness and neuropathic pain intensified, prompting readmission. Neurologic exam revealed decreased grip strength, mild bilateral lower extremity weakness with preserved sensation and reflexes, and a slow, unsteady gait requiring a walker. She also demonstrated decreased left arm biceps and brachioradialis reflexes, consistent with C6 root involvement, along with significant neuropathic pain in the feet and hands. CSF studies showed elevated protein with a normal cell count. Spinal MRI demonstrated enhancement of the proximal cauda equina and right T8 nerve roots, consistent with inflammatory radiculoneuritis. The constellation of bilateral facial weakness, painful radiculopathy, and enhancing nerve roots supported a diagnosis of Lyme neuroborreliosis. After multidisciplinary collaboration, the patient’s progressive pain and weakness were attributed to an inflammatory response in the setting of effective antibiotic therapy. Her facial palsy had markedly improved, supporting treatment response. She was transitioned to a 28-day course of doxycycline with adjunctive anti-inflammatory therapy, and the PICC line was removed.
Discussion: Lyme neuroborreliosis results from central or peripheral nervous system invasion by Borrelia burgdorferi, leading to a spectrum of neurologic manifestations including meningitis, radiculitis, and cranial neuropathies1. Diagnosis typically relies on compatible clinical features supported by positive Lyme serology and characteristic CSF findings, such as pleocytosis, normal or elevated protein, and intrathecal immunoglobulin synthesis2. In this patient, however, pleocytosis was notably absent, likely reflecting a partially treated or later-stage infection, as her prior steroid therapy may have suppressed inflammatory cell response in the CSF while protein levels remained elevated. This case highlights an unusual presentation of progressive neuropathic pain and weakness in neuroinvasive Lyme disease. The Jarisch-Herxheimer-like reaction, an acute inflammatory response triggered by bacterial lysis following antimicrobial treatment, is well documented in early Lyme disease, whereas delayed inflammatory responses occurring later in the disease course are less studied but may similarly reflect immune activation caused by residual bacterial antigens3. In this context, worsening pain and weakness may mimic true disease progression or treatment failure.
Conclusions: Persistent or worsening symptoms in Lyme neuroborreliosis should not be immediately attributed to treatment failure, as they may represent an inflammatory immune response to bacterial lysis rather than ongoing infection. Misclassification of this phenomenon can lead to unnecessary hospitalization or readmission for additional antibiotic therapy. Recognizing this distinction is critical to avoid unwarranted escalation of antibiotic therapy. Oral doxycycline remains as effective as IV ceftriaxone for most cases, offering comparable outcomes with less invasiveness and fewer complications4,5.