This patient is E.R., a 52-year-old male from the Philippines, with a significant medical history of newly-diagnosed diabetes mellitus (glycohemoglobin level = 13.2%). He presented with a chief complaint of decrease in sensorium. He works as a dentist and is independent on all activities of daily living. He is not on any maintenance medications and he has no other known comorbid illnesses. He has poor health-seeking behavior and he completed his primary doses of AstraZeneca COVID-19 vaccination 1.5 months prior to hospital admission at St. Luke’s Medical Center. He had no other known vices such as smoking and alcoholism.

On August 13, 2021, he started experiencing high-grade fever, nonproductive cough, generalized body weakness and decrease in appetite, for which febrile episodes would resolve with as needed antipyretics. Interim history showed persistence of symptoms. On August 26, 2021, because of persistence of symptoms, he self-medicated with 108 mg of Ivermectin (12mg per tablet, total of 9 doses given) with no noted improvement of symptoms. On August 27, 2021, his symptoms had further worsened, he again self-medicated with 216 mg of Ivermectin (12mg per tablet, total of 18 doses given, cumulative dose of 4mg/kg taken in a 24-hour time period), and approximately 5 hours after intake, he then became drowsy, restless, agitated, confused and had experienced complex visual hallucinations, tremulousness and gait instability. These symptoms eventually prompted hospital admission. On assessment, his systemic physical examination was significant for high oxygen requirement (on high flow nasal cannula with flow rate 30 liters per minute, FiO2 requirement of 100%), stable other vital signs, no signs of cardiorespiratory distress, a clinically hypovolemic state, and coarse bilateral crackles. The rest of his systemic physical examination was unremarkable. There were no noted skin or oral lesions, rashes, pallor, jaundice or organomegaly. Neurological examination showed nonsustained eye opening to vigorous stimulation, inconsistent regard, unable to follow commands, with psychomotor agitation, pupils 3mm isocoric and briskly reactive to light, midline gaze, roving eye movements, no facial asymmetry, limited verbal output with no noted involuntary movements, with spontaneous and symmetric movement of all extremities. He was able to localize to pain on the bilateral upper extremities and withdraw to pain on the bilateral lower extremities, with supple neck, no pathologic reflexes while full cerebellar and gait examination were difficult to assess given the level of consciousness. The differential diagnosis on admission included toxic-metabolic encephalopathy versus COVID-related septic and hypoxic encephalopathy, to rule out a CNS infection (viral encephalitis) and nonconvulsive seizures.

Laboratory examinations (Table 1) showed hyperglycemia, mild hyponatremia, hyperkalemia, elevated inflammatory markers, mildly elevated creatinine kinase, normal hemoglobin and hematocrit, normal white blood cell count and platelet count, normal kidney and thyroid function, normal bilirubin and liver enzymes, normal bleeding parameters, ketonuria, normal sinus rhythm on electrocardiogram, trace serum ketones, normal acid base status on arterial blood gas, positive SARS-CoV2 reverse transcriptase polymerase chain reaction test, and bilateral middle to lower lung pneumonia on chest radiograph. No available serum nor urine assay to measure Ivermectin was available. Cranial magnetic resonance imaging with contrast showed unremarkable findings (Figure 1). A 2-hour video electroencephalogram (Table 2) showed mild to moderate diffuse cerebral dysfunction and absence of seizure activity. Patient was admitted to the progressive care unit, maintained on high flow nasal cannula and nasogastric tube, administered with Ceftriaxone 2 grams and Azithromycin 500mg intravenously. He was then given two doses of activated charcoal (total of 100mg) and laxatives. A CSF analysis was no longer done since his neurologic status had significantly improved within 24 hours after initiation of treatment, where he was now noted to be awake, alert, oriented, able to follow commands, with no other focal neurologic deficits. He was then subsequently managed as a case of multifactorial encephalopathy secondary to COVID-19 infection and Ivermectin toxicity. By the second hospital day, patient’s neurological symptoms had completely resolved, antibiotics were continued and he was gradually weaned off oxygen support. He was then discharged stable after eight hospital days. Clinical outcome on follow-up of the patient shows no residual symptoms and neurologic deficits, and he was able to resume his normal daily activities thereafter.

Table 1: Serum tests performed during the course of the hospital admission.