Neurological manifestations of COVID-19: a systematic review.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global spread of coronavirus disease (COVID-19). Our understanding of the impact this virus has on the nervous system is limited. Our review aims to inform and improve decision-making among the physicians treating COVID-19 by presenting a systematic analysis of the neurological manifestations experienced within these patients. METHODS: Any study, released prior to May 20, 2020, that reported neurological manifestations in patients infected by SARS-CoV-2 was systematically reviewed using the PRISMA (Preferred Reporting Items for Systemic review and Meta-Analysis) statement. RESULTS: Our systematic review included data from 37 articles: twelve retrospective studies, two prospective studies, and the rest case reports/series. The most commonly reported neurological manifestations of COVID-19 were myalgia, headache, altered sensorium, hyposmia, and hypogeusia. Uncommonly, COVID-19 can also present with central nervous system manifestations such as ischemic stroke, intracerebral hemorrhage, encephalo-myelitis, and acute myelitis, peripheral nervous manifestations such as Guillain-Barré syndrome and Bell's palsy, and skeletal muscle manifestations such as rhabdomyolysis. CONCLUSION: While COVID-19 typically presents as a self-limiting respiratory disease, it has been reported in up to 20% of patients to progress to severe illness with multi-organ involvement. The neurological manifestations of COVID-19 are not uncommon, but our study found most resolve with treatment of the underlying infection. Although the timeliness of this review engages current challenges posed by the COVID-19 pandemic, readers must not ignore the limitations and biases intrinsic to an early investigation.

Spatiotemporal expression of NDRG2 in the human fetal brain.

N-myc downstream-regulated gene 2 (NDRG2) has been implicated in the development of central nervous system and brain diseases such as brain tumors, ischemic stroke and neurodegenerative disorders. However, it remains unclear that the spatiotemporal distribution of NDRG2 in the human fetal brain. In this study, we examined the expression pattern of NDRG2 in different regions of human fetal brain at 16-28 gestational weeks (GWs) by using RT-PCR, western blot and immunohistochemistry. Firstly, RT-PCR revealed that mRNA of NDRG2 was detected in the human brain regions of fetuses at 16-28 GWs such as medulla oblongata (MdO), mesencephalon (MeE), cerebellum (Cbl), frontal lobe (Fr), ventricular (VZ)/subventricular zone (SVZ) and hippocampus (hip), and the expressions of NDRG2 mRNA in these human fetal brain regions were increased with gestational maturation. Furthermore, western blot and immunohistochemistry results revealed that at 28 GWs, the expression of NDRG2 protein was restricted to the MdO's olivary nucleus, MeE's aqueduct, cerebellar internal granular layers, cerebral cortex of the Fr, VZ/SVZ of lateral ventricle, and hippocampal dentate gyrus, and highest expression in the VZ/SVZ, and lowest in the MeE. Finally, double immunohistochemistry results showed that NDRG2 in the MdO, Cbl and VZ/SV at 28 GWS was mainly expressed in neurons (NeuN positive cells), and in some astrocytes (GFAP positive cells). Taken together, these results suggest that NDRG2 is mainly expressed in human fetal neurons of various brain regions during development, which may be involved in neuronal growth and maturation.

Proteomic analysis and comparison of intra­ and extracranial cerebral atherosclerosis responses to hyperlipidemia in rabbits.

The present study aimed to investigate protein expression levels of intra­ and extracranial atherosclerosis in rabbits following administration of a high­fat diet. Rabbits were randomly divided into control (group A; n=9) and high­fat diet (group B; n=9) groups. At week 12, tissues were sectioned from the common carotid artery (CCA) and middle cerebral artery (MCA). Pathological analysis was performed. Differential protein expression levels were examined by 2­D gel electrophoresis (2­DE) and mass spectrometry (MS) analysis and validated by western blotting. Serum lipid levels, the intima­media thickness (IMT) and degree of atherosclerosis of the CCA and MCA were increased at week 12 in the high­fat diet group compared with rabbits that received a normal diet. 2­DE and MS analysis of the protein extracted from CCA and MCA detected >439 different proteins; the expression of 25 proteins was altered, and 8 proteins [albumin A chain, tropomyosin α­1 chain (TPM1), heat shock protein 70 (HSP70), α­smooth muscle actin, ß­galactose binding agglutinin, TPM4 isoform 2, cell keratin 9, single octylic acid glyceride ß­2) demonstrated significant alterations in expression levels. Due to limited antibody sources, only three differentially expressed proteins (TPM1, HSP70 and α­smooth muscle actin) were examined by western blotting. The results of our previous study demonstrated that hyperlipidemia affected the IMT of intracranial and extracranial cerebral arteries. In the present study, protein expression levels of TPM1 and α­smooth muscle actin from extracranial cerebral arteries were significantly increased compared with intracranial cerebral arteries; however, protein expression levels of HSP70 from intracranial cerebral arteries was increased compared with extracranial cerebral arteries. The differences may be closely associated with cell proliferation and metastasis, and oxidoreduction, in intra­ and extracranial cerebral atherosclerosis. HSP70 may have protective properties against atherosclerosis via underlying anti­inflammatory mechanisms, furthermore, differential protein expression levels (TPM1, HSP70 and α­smooth muscle actin) between intra­ and extracranial cerebral arteries may facilitate the identification of novel biological markers for the diagnosis and treatment of cerebral arteriosclerosis.