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.