A method to isolate and cryopreserve cerebrospinal fluid mononuclear cells from external ventricular drains to investigate immunological processes in acute brain injuries.

The inflammatory response to acute brain injuries is a key contributor to subsequent outcome. The study of local central nervous system inflammatory responses is hindered by raised intracranial pressure precluding cerebrospinal fluid sampling by lumbar puncture. External ventricular drains are sited in some acute brain injury patients to divert cerebrospinal fluid and thus reduce intracranial pressure, and represent a potential route to safely gather large volumes of cerebrospinal fluid for immunological studies. In this manuscript we show that mononuclear cells can be isolated from cerebrospinal fluid collected from external ventricular drains, and that the large volumes of cerebrospinal fluid available yield sufficient mononuclear cells to allow cryopreservation. Prolonged storage of cerebrospinal fluid in the external ventricular drain collection bag can alter the phenotype of cells recovered, but the predicted effect of this can be estimated for a given flow cytometry panel by assessing the changes in peripheral blood mononuclear cells exposed to the same conditions. The described method will allow clinical studies of acute brain injuries to investigate the immunological processes occurring within the central nervous system compartment, rather than relying on changes in the peripheral circulation.

Neurological update: COVID-19.

Coronavirus Disease 2019 is predominantly a disorder of the respiratory system, but neurological complications have been recognised since early in the pandemic. The major pathophysiological processes leading to neurological damage in COVID-19 are cerebrovascular disease, immunologically mediated neurological disorders and the detrimental effects of critical illness on the nervous system. It is still unclear whether direct invasion of the nervous system by the Severe Acute Respiratory Syndrome Coronavirus 2 occurs; given the vast numbers of people infected at this point, this uncertainty suggests that nervous system infection is unlikely to represent a significant issue if it occurs at all. In this review, we explore what has been learnt about the neurological complications of COVID-19 over the course of the pandemic, and by which mechanisms these complications most commonly occur.