Fatal central nervous system co-infection with SARS-CoV-2 and tuberculosis in a healthy child.

BACKGROUND: Central and peripheral nervous system symptoms and complications are being increasingly recognized among individuals with pandemic SARS-CoV-2 infections, but actual detection of the virus or its RNA in the central nervous system has rarely been sought or demonstrated. Severe or fatal illnesses are attributed to SARS-CoV-2, generally without attempting to evaluate for alternative causes or co-pathogens. CASE PRESENTATION: A five-year-old girl with fever and headache was diagnosed with acute SARS-CoV-2-associated meningoencephalitis based on the detection of its RNA on a nasopharyngeal swab, cerebrospinal fluid analysis, and magnetic resonance imaging findings. Serial serologic tests for SARS-CoV-2 IgG and IgA showed seroconversion, consistent with an acute infection. Mental status and brain imaging findings gradually worsened despite antiviral therapy and intravenous dexamethasone. Decompressive suboccipital craniectomy for brain herniation with cerebellar biopsy on day 30 of illness, shortly before death, revealed SARS-CoV-2 RNA in cerebellar tissue using the Centers for Disease Control and Prevention 2019-nCoV Real-Time Reverse Transcriptase-PCR Diagnostic Panel. On histopathology, necrotizing granulomas with numerous acid-fast bacilli were visualized, and Mycobacterium tuberculosis complex DNA was detected by PCR. Ventricular cerebrospinal fluid that day was negative for mycobacterial DNA. Tracheal aspirate samples for mycobacterial DNA and culture from days 22 and 27 of illness were negative by PCR but grew Mycobacterium tuberculosis after 8 weeks, long after the child's passing. She had no known exposures to tuberculosis and no chest radiographic findings to suggest it. All 6 family members had normal chest radiographs and negative interferon-γ release assay results. The source of her tuberculous infection was not identified, and further investigations by the local health department were not possible because of the State of Michigan-mandated lockdown for control of SARS-CoV-2 spread. CONCLUSION: The detection of SARS-CoV-2 RNA in cerebellar tissue and the demonstration of seroconversion in IgG and IgA assays was consistent with acute SARS-CoV-2 infection of the central nervous infection. However, the cause of death was brain herniation from her rapidly progressive central nervous system tuberculosis. SARS-CoV-2 may mask or worsen occult tuberculous infection with severe or fatal consequences.

Differentiation between intra-axial metastatic tumor progression and radiation injury following fractionated radiation therapy or stereotactic radiosurgery using MR spectroscopy, perfusion MR imaging or volume progression modeling.

OBJECTIVE: To determine the accuracy of magnetic resonance spectroscopy (MRS), perfusion MR imaging (MRP), or volume modeling in distinguishing tumor progression from radiation injury following radiotherapy for brain metastasis. METHODS: Twenty-six patients with 33 intra-axial metastatic lesions who underwent MRS (n=41) with or without MRP (n=32) after cranial irradiation were retrospectively studied. The final diagnosis was based on histopathology (n=4) or magnetic resonance imaging (MRI) follow-up with clinical correlation (n=29). Cho/Cr (choline/creatinine), Cho/NAA (choline/N-acetylaspartate), Cho/nCho (choline/contralateral normal brain choline) ratios were retrospectively calculated for the multi-voxel MRS. Relative cerebral blood volume (rCBV), relative peak height (rPH) and percentage of signal-intensity recovery (PSR) were also retrospectively derived for the MRPs. Tumor volumes were determined using manual segmentation method and analyzed using different volume progression modeling. Different ratios or models were tested and plotted on the receiver operating characteristic curve (ROC), with their performances quantified as area under the ROC curve (AUC). MRI follow-up time was calculated from the date of initial radiotherapy until the last MRI or the last MRI before surgical diagnosis. RESULTS: Median MRI follow-up was 16 months (range: 2-33). Thirty percent of lesions (n=10) were determined to be radiation injury; 70% (n=23) were determined to be tumor progression. For the MRS, Cho/nCho had the best performance (AUC of 0.612), and Cho/nCho >1.2 had 33% sensitivity and 100% specificity in predicting tumor progression. For the MRP, rCBV had the best performance (AUC of 0.802), and rCBV >2 had 56% sensitivity and 100% specificity. The best volume model was percent increase (AUC of 0.891); 65% tumor volume increase had 100% sensitivity and 80% specificity. CONCLUSION: Cho/nCho of MRS, rCBV of MRP, and percent increase of MRI volume modeling provide the best discrimination of intra-axial metastatic tumor progression from radiation injury for their respective modalities. Cho/nCho and rCBV appear to have high specificities but low sensitivities. In contrast, percent volume increase of 65% can be a highly sensitive and moderately specific predictor for tumor progression after radiotherapy. Future incorporation of 65% volume increase as a pretest selection criterion may compensate for the low sensitivities of MRS and MRP.

Brain lesions with elevated lactic acid peaks on magnetic resonance spectroscopy.

Magnetic resonance (MR) spectroscopy is a noninvasive imaging tool that provides information on various metabolite concentrations within brain lesions. The biochemical information obtained with MR spectroscopy, along with the morphologic appearance of a lesion on MR imaging, allows for better characterization and improved diagnostic ability. Lactic acid is an end product of anaerobic metabolism. Under conditions of anaerobic metabolism or inflammation, lactate levels become elevated and a characteristic peak at 1.3 ppm is detected on MR spectroscopy. This review will discuss the significance of lactate as a metabolite and will describe various brain lesions and disease conditions in which elevated lactate levels are detected.

West nile virus encephalitis involving the substantia nigra: neuroimaging and pathologic findings with literature review.

West Nile virus has become a medically important arbovirus in the continental United States with its debut in 1999 in the New York City area. We present neuroimaging features and pathologic findings in 2 patients who were severely affected out of the more that 100 documented cases at our institution. Both patients showed striking involvement of the substantia nigra, a finding not previously reported for West Nile virus.