Viral Encephalitis of Unknown Cause: Current Perspective and Recent Advances

Kennedy, Peter G. E.; Quan, Phenix‐Lan; Lipkin, W. Ian

doi:10.3390/v9060138

Cited by 66 publications

(68 citation statements)

References 38 publications

(55 reference statements)

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“…Unfortunately, the diagnostic performance of NGS in the pilot study was not as high as expected. There are a series of challenges in the implementation of NGS tests, including sample collection, transporting, handling, storage conditions, differentiation of colonization from infection, extraneous sources of nucleic acid, method standardization, data storage, protection, analysis, and interpretation [25,26]. All of these factors can profoundly affect the quality of the sequencing results.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Next-Generation Sequencing for the Diagnosis of Infections of the Central Nervous System Caused by the Neurotropic Herpes Viruses: A Pilot Study

Xing

Zhang

et al. 2018

Eur Neurol

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Background: There are sparse and limited studies on small sample size reporting the application of next-generation sequencing (NGS) in the detection of central nervous system (CNS) viral infections. We assessed the diagnostic performance of NGS of cerebrospinal fluid (CSF) for predicting viral infections of the CNS caused by the neurotropic herpes viruses in a pilot population. Materials and Methods: We prospectively collected CSF samples from 24 patients with CNS viral infection from April 2017 to October 2018. Of the 24 patients, 19 patients were infected with herpes simplex virus 1 (HSV-1), 1 patient with HSV-2, and 4 patients with varicella-zoster virus (VZV). All CSF samples were screened for viral DNA using NGS technologies to detect viral CNS infections. Results: Of the 24 patients with confirmed viral CNS infection caused by the neurotropic herpes viruses, 10 (10/24, 41.67%) patients exhibited positive NGS results. With the help of NGS, HSV-1 DNA was detected in the CSF of 6 patients (6/19; 31.58%). HSV-2 DNA was detected in 1 patient (1/1; 100%) and VZV DNA was detected in 3 patients (3/4; 75%). The positive rate of virus detected by NGS decreased with time. The positive rates of NGS of CSF in the first, second, and third weeks were 54.5% (6/11), 44.4% (4/9), and 0% (0/4), respectively. Conclusions: NGS method is a promising pathogen detection tool for identifying viral CNS infections. It should be recommended to sequence viral DNA of CSF in the early stage of CNS viral infections.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Next-Generation Sequencing for the Diagnosis of Infections of the Central Nervous System Caused by the Neurotropic Herpes Viruses: A Pilot Study

Xing

Zhang

et al. 2018

Eur Neurol

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“…A specific viral pathogen was not identified, but up to 60% of encephalitis cases remain undiagnosed. 4 On hospital day 3, the patient developed weakness and myoclonic jerks of his right arm. Repeat EEG showed multiple focal seizures localized to his left centroparietal region.…”

Section: Sectionmentioning

confidence: 99%

Clinical Reasoning: A 22-year-old man presenting with headache and right leg jerks

et al. 2018

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A 22-year-old man with no pertinent medical history presented to our emergency department with headaches, nausea, vomiting, and right leg jerks. Two days prior, he developed a suddenonset, throbbing headache that was 6/10 in severity involving his entire head. He denied photophobia/phonophobia or visual changes. He felt dizzy and lightheaded without room spinning. The next day, he noticed his right leg felt "heavy." That evening, he had nausea and 2 episodes of emesis. The next morning, he awoke with insuppressible "twitches" in his entire right leg. These were not painful and occurred every few seconds at rest and with activity. No history of similar headaches, abnormal movements, trauma, seizures, sick contacts, or recent travel was noted. Family history was unremarkable. He had normal development, completed high school, and worked full-time installing solar panels. Upon examination, the patient was afebrile, alert, in no acute distress, and without nuchal rigidity. Funduscopic examination revealed no papilledema. Mental status and cranial nerve examinations were normal. Motor examination revealed normal bulk and tone, with 4/5 strength throughout his right leg. Right leg jerks were seen every 1-4 seconds at rest and during spontaneous movements (video 1). These were insuppressible, voluntarily or with tactile stimulation, and did not worsen with startle. He had decreased sensation to light touch in his right leg up to his proximal thigh circumferentially; vibratory, temperature, and pinprick sensation was preserved. Bilateral deep tendon reflexes were normal with downgoing toes. He was ataxic on right finger-to-nose and heel-to-shin testing. Gait was not assessed due to his frequent right leg jerks. Questions for consideration: 1. Where do you localize the patient's symptoms and clinical signs? 2. What do you include in your differential diagnosis? GO TO SECTION 2

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“…Despite advances, a significant proportion of the pediatric ARIs remain without a causative agent every epidemic season [16]. This fact is not exclusive of ARIs, more than 60% of the cases of viral encephalitis, and near 65% of all deaths from gastroenteritis and from foodborne disease, remain unassigned to a specific pathogen even after syndromic laboratory testing [17][18][19]. Although there are multiple reasons that explain these results that are not related with diagnostic technology failure (e.g.…”

Section: Introductionmentioning

confidence: 99%

Target-independent high-throughput sequencing methods provide evidence that already known human viral pathogens play a main role in respiratory infections with unexplained etiology

Pérez-Sautu

Wiley

Iglesias-Caballero

et al. 2019

Emerging Microbes & Infections

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Despite the advanced PCR-based assays available, a fraction of the pediatric respiratory infections remain unexplained every epidemic season, and there is a perception that novel viruses might be present in these specimens. We systematically collected samples from a prospective cohort of pediatric patients with respiratory infections, that returned negative results by validated molecular RT–PCR assays, and studied them with a target-independent, high-throughput sequencing-based approach. We also included a matched cohort of children with no symptoms of respiratory infection, as a contrast study population. More than fifty percent of the specimens from the group of patients with unexplained respiratory infections were resolved. However, the higher rate of detection was not due to the presence of novel viruses, but to the identification of well-known viral respiratory pathogens. Our results show that already known viral pathogens are responsible for the majority of cases that remain unexplained after the epidemic season. High-throughput sequencing approaches that use pathogen-specific probes are easier to standardize because they ensure reproducible library enrichment and sequencing. In consequence, these techniques might be desirable from a regulatory standpoint for diagnostic laboratories seeking to benefit from the many advantages of these sequencing technologies.

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Viral Encephalitis of Unknown Cause: Current Perspective and Recent Advances

Cited by 66 publications

References 38 publications

Evaluation of Next-Generation Sequencing for the Diagnosis of Infections of the Central Nervous System Caused by the Neurotropic Herpes Viruses: A Pilot Study

Evaluation of Next-Generation Sequencing for the Diagnosis of Infections of the Central Nervous System Caused by the Neurotropic Herpes Viruses: A Pilot Study

Clinical Reasoning: A 22-year-old man presenting with headache and right leg jerks

Target-independent high-throughput sequencing methods provide evidence that already known human viral pathogens play a main role in respiratory infections with unexplained etiology

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