Olfactory nerve: from ugly duckling to swan.

BACKGROUND: The olfactory nerve has never been the shining star of neurological examination. Quite the contrary, examining the first cranial nerve is often an overlooked step. As cases of anosmia secondary to COVID-19 infection continue to rise, the 2020 pandemic has shed new light on this much-forgotten nerve, its value as an aid to diagnosis of several diseases and its central role in our daily lives. OBJECTIVE: We aimed to emphasize how essential and simple clinical examination of the olfactory system can be by highlighting practical techniques and clinical tips for its assessment. We also share pearls and pitfalls in localization and differential diagnosis, which may prove valuable to busy clinicians. METHODS: A broad review of the literature was conducted by searching PubMed, Cochrane and Google Scholar for articles and books containing topics regarding examination of the olfactory nerve and its anatomy, physiology and pathology. No particular inclusion or exclusion criteria were used. RESULTS: Forty different works were found, between books and articles, from which 20 were selected after careful analysis. CONCLUSIONS: Despite the tragedy and adversity that followed the COVID-19 pandemic, its legacy has taught us a crystal-clear lesson: olfaction should no longer be neglected in clinical practice.

Cerebrospinal fluid findings in neurological diseases associated with COVID-19 and insights into mechanisms of disease development.

OBJECTIVES: To analyze the cerebrospinal fluid (CSF) of patients with SARS-CoV-2 infection and neurological manifestations to provide evidence for the understanding of mechanisms associated with central nervous system (CNS) involvement in COVID-19. METHODS: Patients (n = 58) were grouped according to their main neurological presentation: headache (n = 14); encephalopathy (n = 24); inflammatory neurological diseases, including meningoencephalitis (n = 4), acute myelitis (n = 3), meningitis (n = 2), acute disseminated encephalomyelitis (ADEM) (n = 2), encephalitis (n = 2), and neuromyelitis optica (n = 1); and Guillain-Barré syndrome (n = 6). Data regarding age, sex, cerebrovascular disease, and intracranial pressure were evaluated in combination with CSF profiles defined by cell counts, total protein and glucose levels, concentration of total Tau and neurofilament light chain (NfL) proteins, oligoclonal band patterns, and detection of SARS-CoV-2 RNA. RESULTS: CSF of patients with inflammatory neurological diseases was characterized by pleocytosis and elevated total protein and NfL levels. Patients with encephalopathy were mostly older men (mean age of 61.0 ± 17.6 years) with evidence of cerebrovascular disease. SARS-CoV-2 RNA in CSF was detected in 2 of 58 cases: a patient with refractory headache, and another patient who developed ADEM four days after onset of COVID-19 symptoms. Three patients presented intrathecal IgG synthesis, and four had identical oligoclonal bands in CSF and serum, indicating systemic inflammation. CONCLUSION: Patients with neurological manifestations associated with COVID-19 had diverse CSF profiles, even within the same clinical condition. Our findings indicate a possible contribution of viral replication on triggering CNS infiltration by immune cells and the subsequent inflammation promoting neuronal injury.

Patients with COVID-19 and neurological manifestations show undetectable SARS-CoV-2 RNA levels in the cerebrospinal fluid.

We report that patients with COVID-19 displaying distinct neurological disorders have undetectable or extremely low levels of SARS-CoV-2 RNA in the cerebrospinal fluid, indicating that viral clearance precede the neurological involvement. This finding points to the need for the development of more sensitive molecular tests and the investigation of other neurotropic pathogens to exclude concurrent neuroinfection.