Central nervous system (CNS) enterovirus infections: A single center retrospective study on clinical features, diagnostic studies, and outcome

Torres, Sarah; Jia, Dan; Schorr, Emily; Park, Brian L.; Boubour, Alexandra; Boehme, Amelia K; Ankam, Jyoti; Gofshteyn, Jacqueline S.; Tyshkov, Charles; Green, Daniel A.; Vargas, Wendy; Zucker, Jason; Yeshokumar, Anusha K.; Thakur, Kiran T.

doi:10.1007/s13365-019-00784-5

Cited by 7 publications

(7 citation statements)

References 20 publications

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“…These patients had clinical and neuroradiographic findings suggestive of encephalitis or encephalomyelitis, including multifocal T2/FLAIR (T2-weighted fluid-attenuated inversion recovery) hyperintensities in the brain and spinal cord (M006), superrefractory epilepsy with T2/FLAIR hyperintensity in the right posterior subinsular/anterior temporal stem (M032), and longitudinally extensive transverse myelitis (M075). This finding supports interpretations that CNS complications of mycoplasma infections likely reflect a parainfectious antibody-mediated response rather than direct infection ( 45 ).…”

Section: Discussionsupporting

confidence: 85%

Enhanced Virus Detection and Metagenomic Sequencing in Patients with Meningitis and Encephalitis

Piantadosi

Mukerji

et al. 2021

mBio

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Section: Discussionsupporting

confidence: 85%

Enhanced Virus Detection and Metagenomic Sequencing in Patients with Meningitis and Encephalitis

Piantadosi

Mukerji

et al. 2021

mBio

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“…The clinical presentation (signs, symptoms, date of onset, neurological symptoms with details on central or peripheral nervous system involvement) was inferred from the medical chart. Independence of the patients prior to the infection was assessed by the modified Rankin Scale (mRS) (Torres et al., 2020 ). Patients were considered as immunosuppressed or at risk depending on their comorbidities: mild risk included diabetes, pregnancy, HIV infection with CD4+ lymphocyte count > 500/mm 3 , and/or chronic renal disease whereas severe risk included malignancy (solid tumor or hematologic), HIV infection with CD4+ lymphocyte count < 500/mm 3 , transplant, and ongoing immunosuppressive treatments.…”

Section: Methodsmentioning

confidence: 99%

Neurological complications of varicella zoster virus reactivation: Prognosis, diagnosis, and treatment of 72 patients with positive PCR in the cerebrospinal fluid

et al. 2022

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Background VZV infection can involve every level of the neurologic system: from the central nervous system (CNS) to the peripheral nervous system (PNS), including aseptic meningitis. Prognosis seems to differ between these neurological involvements. Prognostic factors remain unknown. Methods This is a retrospective multicenter study including all patients with a positive VZV polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) from eight centers in Paris (France) between 2011 and 2018. Unfavorable outcome was defined as mortality linked to VZV or incomplete recovery. Modified Rankin Scale (mRS) evaluated disability before and after the infection, with the difference designated as Rankin Delta. Results Seventy‐two patients were included (53% male, median age 51 years, median mRS 0). Immunosuppression was reported in 42%. The clinical spectrum included 26 cases of meningitis, 27 instances of CNS involvement, 16 of PNS involvement, and 3 isolated replications (positive PCR but no criteria for neurological complications from VZV). Antiviral treatment was administered to 69 patients (96%). Sixty‐two patients completed follow‐up. Death linked to VZV occurred in eight cases. Unfavorable outcome (UO) occurred in 60% and was significantly associated with a higher prior mRS (Odd‐ratio (OR) 3.1 [1.4–8.8] p = .012) and the presence of PNS or CNS manifestations (OR 22 [4–181] p = .001, OR 6.2 [1.3–33] p = .03, respectively, compared to meningitis). In the CSF, higher protein level (p < .0001) was also significantly associated with a higher Rankin Delta. Conclusions Neurological complications of VZV with evidence of CSF viral replication are heterogeneous: aseptic meningitis has a good prognosis, whereas presence of CNS and PNS involvement is associated with a higher risk of mortality and of sequelae, respectively.

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“…These results support other studies showing that WNV nucleic acid is usually undetectable in CSF by clinical PCR (23, 45) or mNGS (18), though it may be observed in immunocompromised subjects (15, 45–48). Similarly, CSF mycoplasma nucleic acid was not detected clinically or by mNGS from three subjects with positive mycoplasma serology, supporting interpretations that CNS complications of mycoplasma infections likely reflect a para-infectious antibody-mediated response, rather than direct infection (49).…”

Section: Discussionmentioning

confidence: 53%

Enhanced virus detection and metagenomic sequencing in patients with meningitis and encephalitis

Piantadosi

Mukerji

et al. 2020

Preprint

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Meningitis and encephalitis are leading causes of central nervous system (CNS) disease and often result in severe neurological compromise or death. Traditional diagnostic workflows largely rely on pathogen-specific diagnostic tests, sometimes over days to weeks. Metagenomic next-generation sequencing (mNGS) is a high-throughput platform that profiles all nucleic acid in a sample. We prospectively enrolled 68 patients from New England with known or suspected CNS infection and performed mNGS from both RNA and DNA to identify potential pathogens. Using a computational metagenomic classification pipeline based on KrakenUniq and BLAST, we detected pathogen nucleic acid in cerebrospinal fluid (CSF) from 22 subjects. This included some pathogens traditionally diagnosed by serology or not typically identified in CSF, including three transmitted by Ixodes scapularis ticks (Powassan virus, Borrelia burgdorferi, Anaplasma phagocytophilum). Among 24 subjects with no clinical diagnosis, we detected enterovirus in two subjects and Epstein Barr virus in one subject. We also evaluated two methods to enhance detection of viral nucleic acid, hybrid capture and methylated DNA depletion. Hybrid capture nearly universally increased viral read recovery. Although results for methylated DNA depletion were mixed, it allowed detection of varicella zoster virus DNA in two samples that were negative by standard mNGS. Overall, mNGS is a promising approach that can test for multiple pathogens simultaneously, with similar efficacy to pathogen-specific tests, and can uncover geographically relevant infectious CNS disease, such as tick-borne infections in New England. With further laboratory and computational enhancements, mNGS may become a mainstay of workup for encephalitis and meningitis.ImportanceMeningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures. Despite intensive diagnostic efforts, 40-60% of people with meningitis or encephalitis have no clear cause of their CNS disease identified. As diagnostic uncertainty often leads to costly inappropriate therapies, the need for novel pathogen detection methods is paramount. Metagenomic next-generation sequencing (mNGS) offers the unique opportunity to circumvent these challenges using unbiased laboratory and computational methods. Here, we performed comprehensive mNGS from 68 patients with suspected CNS infection, and define enhanced methods to improve the detection of CNS pathogens, including those not traditionally identified in the CNS by nucleic acid detection. Overall, our work helps elucidate how mNGS can become a mainstay in the diagnostic toolkit for CNS infections.

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Central nervous system (CNS) enterovirus infections: A single center retrospective study on clinical features, diagnostic studies, and outcome

Cited by 7 publications

References 20 publications

Enhanced Virus Detection and Metagenomic Sequencing in Patients with Meningitis and Encephalitis

Enhanced Virus Detection and Metagenomic Sequencing in Patients with Meningitis and Encephalitis

Neurological complications of varicella zoster virus reactivation: Prognosis, diagnosis, and treatment of 72 patients with positive PCR in the cerebrospinal fluid

Enhanced virus detection and metagenomic sequencing in patients with meningitis and encephalitis

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