Abstract

We present a rare and complex case of a 30-year-old Central American immigrant woman with progressive neurological decline due to Haemophilus influenzae encephalitis, complicated by meningitis and features suggestive of superimposed encephalitis lethargica. Despite initial diagnostic uncertainty and minimal past medical history, the patient exhibited notable clinical improvement with appropriate antimicrobial therapy. This report highlights the importance of early neuroimaging, thorough infectious workup, and high clinical suspicion in managing such challenging presentations.Hemophilus influenzae, while primarily associated with respiratory infections and paediatric meningitis, can rarely present as encephalitis in adults. The emergence of additional encephalitic syndromes, such as encephalitis lethargica, may obscure diagnosis and delay treatment. Encephalitis lethargica (EL), also known as von Economo's disease, was a neurological illness that emerged in epidemic form between 1917 and the late 1920s. It is characterized by sleep disturbances, ocular motility problems, and movement disorders, and can lead to post-encephalitic parkinsonism. The exact cause of EL remains unknown. Theories include a post-viral response possibly linked to the 1918 influenza pandemic, streptococcaltriggered autoimmunity, and overlap with autoimmune encephalitis (e.g., anti-NMDA receptor encephalitis). This report captures the diagnostic journey, imaging findings, and recovery of a patient with this rare constellation of neuroinfectious disorders. Case Presentation Patient Background A 30-year-old female immigrant from Central America with no significant past medical history presented to the emergency room (ER) with one month of progressively worsening generalized weakness. Her condition deteriorated to the point of being unable to ambulate, with severe fatigue, right shoulder pain, and lethargy. She denied chest pain, dyspnea, palpitations, or gastrointestinal symptoms. No recent travel, animal bites, or exposure to sick contacts were reported. She had previously visited an outside facility where B-vitamin supplementation was prescribed but reported no benefit. Initial Evaluation In the ER, she appeared severely lethargic but oriented to name, location, and place. Cranial nerves II–XII were intact. She had no facial asymmetry, responded to stimulation, and maintained 5/5 strength throughout but exhibited no ambulation, drift, or ataxia. Reflexes were intact.This case underscores several key considerations: Haemophilus influenzae is a rare but possible cause of adult encephalitis, particularly in patients without up-to-date vaccination or from endemic areas. While meningitis is more common, parenchymal involvement suggests either hematogenous spread or direct extension. MRI findings, particularly bilateral thalamic involvement, raise suspicion for viral or autoimmune encephalitis. In this case, microhemorrhage further supported an infectious/viral etiology. Profound lethargy and cognitive slowing, without frank coma or seizures, may represent postinfectious neuroinflammation or encephalitis lethargica. Though rare today, clinicians must remain alert to this presentation, especially when it overlaps with infectious or autoimmune causes. Prompt initiation of medication likely contributed to the patient’s improvement. Administration of IV immunoglobulin (IVIG) for 5 days targets potential immune-mediated mechanisms. The therapeutic rationale for IVIG included: 1. Modulation of inflammatory cytokines in suspected post-infectious neuroinflammation 2. Potential neutralization of autoantibodies in EL-like syndromes 3. Immunomodulatory effects on microglial activation long-term monitoring was advised for potential residual neurological sequelae. This case highlights the diagnostic challenge of distinguishing acute infectious encephalitis from its postinfectious complications and underscores the importance of early immunomodulatory therapy in suspected autoimmune-mediated encephalitis. Being an immigrant from Central America, with potential gaps in vaccination or exposure to vector-borne illnesses, expanded the differential and justified a broader infectious workup. Conclusion This unique case of Haemophilus influenzae encephalitis, complicated by meningitis and a rare encephalitis lethargica-like syndrome, highlights the diagnostic and therapeutic challenges in neuroinfectious disease. Early imaging, comprehensive neurological assessment, and empirical antimicrobial therapy are essential to guide management. This report emphasizes the interplay between infection and neuroinflammation, advocating for a multidisciplinary approach in managing encephalitis with atypical postinfectious features. Early IVIG may be pivotal in mitigating long-term disability in such cases. The patient's significant clinical improvement underscores the potential for recovery when appropriately treated—even in complex, overlapping CNS pathologies.