novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from Wuhan, China, in December 2019, resulting in a severe outbreak of pneumonia 1 ; SARS-CoV-2 causes a clinical syndrome, coronavirus disease 2019 (COVID-19), and its pulmonary manifestations have been well described. There is growing evidence of neurological complications and disease in patients with COVID-19. Two similar human coronaviruses (CoV), Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1), have also been associated with neurological disease in rare cases. This raises the questions of whether SARS-CoV-2 is neurotropic and whether it contributes to postinfectious neurologic complications. A handful of case reports have described neurological complications in patients with COVID-19. 1-4 However, it remains unknown to what extent SARS-CoV-2 damages the central nervous system (CNS) or if neurological symptoms are attributable to secondary mechanisms. Search Strategy and Selection Criteria References for this review were identified by searches of PubMed from April to May 2020 for articles published between 1969 and April 2020, as well as references from relevant articles. The search terms COVID-19, SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43, neurotropism, neuroinvasion, and coronavirus were used. There were no language restrictions. The final list of included articles was generated on the basis of relevance to the topics covered in this review. Neurotropic Coronaviruses Coronaviruses (CoV) are large, enveloped, positive-sense RNA viruses divided into 3 genera: alphacoronavirus, betacoronavirus, and gammacoronavirus. 5 These viruses infect humans and numerous animal species, generally causing upper or lower respiratory tract, IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing human coronavirus disease 2019 (COVID-19), which has now spread into a worldwide pandemic. The pulmonary manifestations of COVID-19 have been well described in the literature. Two similar human coronaviruses that cause Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1) are known to cause disease in the central and peripheral nervous systems. Emerging evidence suggests COVID-19 has neurologic consequences as well. OBSERVATIONS This review serves to summarize available information regarding coronaviruses in the nervous system, identify the potential tissue targets and routes of entry of SARS-CoV-2 into the central nervous system, and describe the range of clinical neurological complications that have been reported thus far in COVID-19 and their potential pathogenesis. Viral neuroinvasion may be achieved by several routes, including transsynaptic transfer across infected neurons, entry via the olfactory nerve, infection of vascular endothelium, or leukocyte migration across the blood-brain barrier. The most common neurologic complaints in COVID-19 are anosmia, ageusia, and headache, but other diseases, such as s...

To identify and characterize otherwise occult inter-individual spatial variation of white matter abnormalities across mild traumatic brain injury (mTBI) patients. After informed consent and in compliance with Health Insurance Portability and Accountability Act (HIPAA), Diffusion tensor imaging (DTI) was performed on a 3.0 T MR scanner in 34 mTBI patients (19 women; 19-64 years old) and 30 healthy control subjects. The patients were imaged within 2 weeks of injury, 3 months after injury, and 6 months after injury. Fractional anisotropy (FA) images were analyzed in each patient. To examine white matter diffusion abnormalities across the entire brain of individual patients, we applied Enhanced Z-score Microstructural Assessment for Pathology (EZ-MAP), a voxelwise analysis optimized for the assessment of individual subjects. Our analysis revealed areas of abnormally low or high FA (voxel-wise P-value < 0.05, cluster-wise P-value < 0.01(corrected for multiple comparisons)). The spatial pattern of white matter FA abnormalities varied among patients. Areas of low FA were consistent with known patterns of traumatic axonal injury. Areas of high FA were most frequently detected in the deep and subcortical white matter of the frontal, parietal, and temporal lobes, and in the anterior portions of the corpus callosum. The number of both abnormally low and high FA voxels changed during follow up. Individual subject assessments reveal unique spatial patterns of white matter abnormalities in each patient, attributable to inter-individual differences in anatomy, vulnerability to injury and mechanism of injury. Implications of high FA remain unclear, but may evidence a compensatory mechanism or plasticity in response to injury, rather than a direct manifestation of brain injury.