{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:19:56Z","timestamp":1788347996706,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T00:00:00Z","timestamp":1500940800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007100","name":"Sandler Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007100","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010246","name":"William K. Bowes, Jr. Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["KL2TR000143"],"award-info":[{"award-number":["KL2TR000143"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Immunodeficient patients are particularly vulnerable to neuroinvasive infections that can be challenging to diagnose. Metagenomic next generation sequencing can identify unusual or novel microbes and is therefore well suited for investigating the etiology of chronic meningoencephalitis in immunodeficient patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We present the case of a 34\u2010year\u2010old man with X\u2010linked agammaglobulinemia from Australia suffering from 3 years of meningoencephalitis that defied an etiologic diagnosis despite extensive conventional testing, including a brain biopsy. Metagenomic next generation sequencing of his cerebrospinal fluid and brain biopsy tissue was performed to identify a causative pathogen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sequences aligning to multiple Cache Valley virus genes were identified via metagenomic next generation sequencing. Reverse transcription polymerase chain reaction and immunohistochemistry subsequently confirmed the presence of Cache Valley virus in the brain biopsy tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Cache Valley virus, a mosquito\u2010borne orthobunyavirus, has only been identified in 3 immunocompetent North American patients with acute neuroinvasive disease. The reported severity ranges from a self\u2010limiting meningitis to a rapidly fatal meningoencephalitis with multiorgan failure. The virus has never been known to cause a chronic systemic or neurologic infection in humans. Cache Valley virus has also never previously been detected on the Australian continent. Our research subject traveled to North and South Carolina and Michigan in the weeks prior to the onset of his illness. This report demonstrates that metagenomic next generation sequencing allows for unbiased pathogen identification, the early detection of emerging viruses as they spread to new locales, and the discovery of novel disease phenotypes. Ann Neurol 2017;82:105\u2013114<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.24982","type":"journal-article","created":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T23:24:44Z","timestamp":1497914684000},"page":"105-114","source":"Crossref","is-referenced-by-count":126,"title":["A novel cause of chronic viral meningoencephalitis: <scp>C<\/scp>ache Valley virus"],"prefix":"10.1002","volume":"82","author":[{"given":"Michael R.","family":"Wilson","sequence":"first","affiliation":[{"name":"Weill Institute for Neurosciences University of California San Francisco, San Francisco CA"},{"name":"Department of Neurology University of California San Francisco, San Francisco CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Suan","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Allergy Westmead Hospital Westmead New South Wales 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