A novel cause of chronic viral meningoencephalitis: Cache Valley virus

Wilson, Michael R.; Suan, Dan; Duggins, Andrew; Schubert, Ryan D.; Khan, Lillian M.; Sample, Hannah A.; Zorn, Kelsey C.; Rodrigues Hoffman, Aline; Blick, Anna; Shingde, Meena; DeRisi, Joseph L.

In 2013, the patient traveled to the United States on 3 occasions. The first trip was to Raleigh, North Carolina in the spring. The second visit, in the summer 3 months later, started in Raleigh, but also included a trip to Charleston, South Carolina, where the patient participated in tubing along the local river. It was during this nearly month-long trip that the patient complained of a mosquito bite to his traveling companion. Two weeks later, he traveled to East Lansing, Michigan. Upon returning home to Australia 3 weeks later, the patient fell ill within 2 days, with his parents reporting fatigue, anorexia, and lethargy. Six days later, the patient suffered an acute encephalitic illness characterized by fevers to 39 8C, confusion, and postictal drowsiness following 2 generalized tonic-clonic seizures. The patient was intubated and transferred to the intensive care unit. Blood tests revealed lymphocytosis (23.3 3 10 9 /l, normal range [NR] 5 1.0-3.0 3 10 9 /l) and a C-reactive protein level of 17.9mg/l (NR 5mg/l). Cerebrospinal fluid (CSF) studies revealed normal concentrations of protein (32 mg/dl) and glucose (77 mg/dl), with 87 3 10 6 /l white blood cells (11% neutrophils, 38% lymphocytes, 51% monocytes) and 19 3 10 6 /l red blood cells. Magnetic resonance imaging (MRI) of the brain revealed increased T2 signal and restricted diffusion through the right fornix, extending into the right hippocampus and amygdala (Fig 1A, B) with interval development of contrast enhancement in the same brain structures 2 weeks later (Fig 1C, D) . Microbiological tests, including culture and polymerase chain reaction (PCR) for candidate pathogens, failed to identify an organism (Tables 1 and 2). The patient was treated empirically with acyclovir, ceftriaxone, benzylpenicillin, and vancomycin. Vancomycin and benzylpenicillin were discontinued due to the development of a rash on the patient's hip, and azithromycin was started due to left-sided consolidation observed on his chest x-ray. The patient completed 10 days of antimicrobial therapy with clinical improvement, and his seizure disorder was controlled with levetiracetam and sodium valproate. He was discharged from the hospital, but was readmitted 4 days later with hypersomnolence and a fluctuating level of consciousness. His antiepileptic medications were adjusted, and he was discharged home again. The patient made a partial recovery over the next 2 months but had new short-term memory loss. He was ultimately able to return to work in a reduced capacity. Over the next 2 years, the patient remained seizure free. He utilized compensatory coping strategies at work due to the significant short-term memory deficit, but he was otherwise independent with activities of daily living at home with his parents. There were reports of anxiety and fatigue, but no specific diagnoses were made.