COVID-19: Neurological manifestations

Since the Chinese health authorities confirmed the first case of novel coronavirus infection, almost all of the clinical focus has been on the viral's prodromal symptoms and severe life-threatening adverse effects such as ARDS. However, neurologists all over the world have been reporting the neurological manifestations of COVID-19 such as, ataxia, encephalopathy, myelitis among others. One neurological symptom in particular received inordinate attention, anosmia, even though it barely has any diagnostic relevance. It is safe to say that the neurological deficits are ongoing in this pandemic without getting noticed appropriately. However, since we are in the early phases of understanding the clinical conundrum of the COVID-19, such relative blindness is expected.

How does SARS-CoV-2 enter the CNS?

Two pathways have been postulated:
1. Through the cribriform plate
2. Systemic circulatory dissemination after infecting the lungs.

Reported neurological manifestations:

1. Anosmia - Can be explained by the proximity of the olfactory bulb to the cribriform plate
2. Hypoguesia, dysguesia
3. Headache, malaise
4. Unstable walking or ataxia, dizziness
These four can occur in the early phase of the disease.

5. Cerebral hemorrhage - This has been hypothesized to be due to decrease in expression and function of ACE2 proteins, especially in hypertensive patients in whom the expression of ACE2 is already low. Given that ACE2 signaling lowers BP, lack of ACE2 function would lead to higher BP which might precipitate cerebral hemorrhage.
6. Cerebral infarction (acute cerebrovascular disease causing stroke)
7. Ondine's curse - The central respiratory centres lose their function, which consequently impairs involuntary respiration severely.
8. Acute encephalopathy - headache, altered mental status, convulsions.
9. Myopathy

Interestingly, the CSF in the patients were normal, which implies that COVID-19 does not cross the blood brain barrier and hence cannot cause meningitis or encephalitis. We should keep in mind that the neurological manifestations could be secondary to hypoxia, respiratory or metabolic acidosis and other complications of the COVID-19 infection.

Thank you!

-Vinayak

References:

1. Necrotizing Encephalopathy: CT and MRI Features

https://pubs.rsna.org/doi/10.1148/radiol.2020201187

2. Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy

https://www.cureus.com/articles/29414-neurological-complications-of-coronavirus-disease-covid-19-encephalopathy

3. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study

https://www.medrxiv.org/content/10.1101/2020.02.22.20026500v1