Discussion
A novel coronavirus was first identified in China causing human
respiratory disease.[3] As the virus is spreading and causing a
worldwide pandemic, our understanding of the disease spectrum is
evolving.
Accumulating evidence shows that SARS-COV-2 is not limited to the
respiratory system but also has a deleterious effect on other organs and
systems like the cardiovascular, gastrointestinal, and nervous system.
[1,4]
Both glial and neuronal cells express ACE2 receptors, making them
susceptible to SARS-COV-2 attack. [5-7] The virus makes the access
to the brain either by the cerebral circulation, where ACE2 receptors
are expressed in the endothelial lining of the cerebral vessels, or the
retrograde path from the olfactory bulb through the cribriform plate.
[5-8]
Both central and peripheral nervous system manifestations have been
reported either as COVID-19 specific or related to critical
illness.[2] Disease spectrum may range from anosmia, ageusia,
headache and dizziness without other clinical features to more severe
involvement like encephalitis, acute disseminated encephalomyelitis,
myelitis, cerebrovascular manifestations, peripheral and muscle
disease.[2]
Cerebrovascular disease is an important complication of COVID-19, with a
reported incidence of 2-6 % of hospitalized patients. The
hypercoagulable state with the inflammatory cascade leading to
endothelial damage predispose to acute cerebrovascular events. [2]
Intracerebral haemorrhage is not a common event in general intensive
care unit (ICU) patients. Hematologic malignancies, severe
thrombocytopenia, sepsis complicated by renal and hepatic dysfunction,
mechanical ventilation with high inspiratory pressures, and high CO2,
all could be associated with increased risk of intracranial haemorrhage
(ICH) in critical illness. [9]
Few case reports and case series reported intracranial haemorrhage as a
complication of COVID-19, [4,10-18] while only one report showed
that ICH happened before the respiratory manifestations.[4]
The presence of ACE2 receptors in the endothelium of cerebral vessels,
makes them a target for SARS-COV-2, which leads to endothelial
dysfunction and dysregulation of local blood pressure and flow,
resulting in vessel wall rupture. [12-13,17] In a series of COVID-19
non survivors, post-mortem brain MRI suggests vasculopathic changes that
could be related to the viral damaging effect on the
endothelium.[19]
In some reports, the intracerebral bleeding was secondary to the
haemorrhagic transformation of cerebral stroke,[12] haemorrhagic
transformation of cerebral venous thrombosis, [18]
meningoencephalitis complicated with ICH.[15]
In one small series of 3 patients, the cause of ICH was uncertain either
secondary to therapeutic anticoagulation or as a complication of
COVID-19. They also shared a common finding on brain imaging showing
anoxic brain injury.[20]
Diffuse brain oedema and multifocal haemorrhages support the speculation
that anoxic brain injury and cytokine storm rather than anticoagulation
led to ICH in COVID-19 patients. [6-7,10] In case series of COVID-19
non survivors, brain post-mortem histopathological examination revealed
hypoxic injury without evidence of encephalitis.[21]
Spontaneous Corpus callosum hematoma is rarely described in
literature.[22] Possible causes are traumatic brain injury,
hypertension, ruptured anterior communicating artery or peri callosal
artery aneurysm, bleeding associated with tumours or
encephalitis,[23] which was not the case in our patient who did not
have any of the risk factors.
One series of 11 patients describes diffuse leukoencephalopathy with
micro-haemorrhages. In 4/11 patients the location of the micro
haemorrhages was in the corpus callosum, all patients were on mechanical
ventilation and on monitored anticoagulation, but no bleeding elsewhere
in the body, brain hypoxia was proposed as the mechanism of the brain
findings.[14]
SARS-COV-2 does not appear to be thrombogenic by itself. Rather, the
coagulation abnormalities are secondary to the intense inflammatory
reaction. The abnormal coagulation profile early in the infection is not
translated to clinical bleeding as compared to other RNA viruses causing
haemorrhagic fevers.[24]
The risk of venous thromboembolism (VTE) in critically ill patients due
to COVID-19 is higher compared to the general ICU population, and the
risk of VTE is still there even with prophylactic dose of
anticoagulation. [24-25]
Our patient was having severe COVID-19 pneumonia and ARDS that required
prolonged. mechanical ventilation with evidence of cytokine storm and
hypercoagulability state. The course was complicated by corpus callosum
hematoma, which is an uncommon site of ICH, despite the improvement in
the respiratory manifestation the clinical picture became more
complicated by developing pulmonary embolism.
In our patient, the endothelial dysfunction secondary to the intense
inflammatory condition could explain the cerebral vessel damage causing
ICH rather than a manifestation of bleeding tendency, as the
hypercoagulability state resulted in PE. COVID-19 could be the umbrella
under which all the events can be explained.
Reporting such a case might help to increase the understanding of the
neurological complications associated with COVID-19 and will increase
the awareness of possible challenges emerging while treating COVID-19
patients.