Case Presentation: A 75 year old male with atrial fibrillation, osteomyelitis of the right first digit of the lower extremity on IV Vancomycin presented as a transfer from an outside hospital with 3 weeks of worsening pressured speech, delusions, insomnia, and a seizure like event. The patient was admitted for further work up and management of his symptoms, and his symptoms evolved during the course of hospital stay to include bulbar weakness with signs of slurred speech, dysphagia, and right sided tongue deviation. Work up for acute mania included extensive infectious, neurologic, metabolic, autoimmune and psychiatric evaluations. Figure 1 shows key pharmacotherapeutic agents used. On presentation he was afebrile, had a mildly elevated white blood cell count with increased neutrophils, and mild hyponatremia. Extensive serum evaluation was negative. Neurologic imaging ruled out structural abnormality and vascular event including cerebrovascular accident. Further neurologic work up with EEG was consistent with encephalopathy, but not seizure activity. Infectious work up for bacterial, fungal, parasitic and viral pathogens was unremarkable in the serum and in the CSF, except for serum EBV IgM which was positive. Endocrine and autoimmune work up in the serum and CSF was also negative, except for elevated Thyroperoxidase antibody without clinical significance. Additional work up for neuromuscular receptor antibodies and acute polyneuropathies were negative. With supportive and symptomatic management, the patient had spontaneous resolution of symptoms. This case presentation explores a rigorous and algorithmic process of diagnostic evaluation and highlights the reality of diagnostic ambiguity that sometimes occurs in medicine. It also explores a new and novel hypothesis connecting EBV infection to bipolar disorder.
Discussion: Work up for cerebrovascular, neurologic, autoimmune, metabolic, and infectious etiologies ruled out the most common causes of encephalopathy. Hematogenous spread of osteomyelitis was a possible cause of encephalopathy, yet this was not supported by cerebrospinal fluid or blood analysis. Viral encephalitis is a common cause of encephalopathy, however Epstein-Barr virus would be an uncommon causative pathogen in adults. Less likely infections like West Nile virus and Rickettsia rickettsii were included in the work up because these are endemic to his region, he is active outdoors, and he presented during early Autumn. Other animal borne diseases are believed to be lower yield due to currently known geographic boundaries, but these may be shifting due to climate change. A new onset psychiatric disorder was not conclusively ruled out; while uncommon, older individuals can have new onset bipolar disorder, but this would not explain his bulbar symptoms which may have been due to a secondary process. However, there is a new and novel hypothesis that aims to propose EBV infection as a cause of bipolar disease. Although not evidence based, perhaps this case adds to the discussion of this hypothesis.
Conclusions: This case highlights the importance of keeping a wide differential diagnosis in complex situations and diligent surveillance of hospitalized patients. Additional points of emphasis are atypical pathogenic etiologies of encephalopathy, climate change’s effect on the geographic ranges of animal borne pathogens, atypical cerebrovascular accident mechanisms, and the incidence of new psychiatric illness in the geriatric population.