Embedded Files
Welcome to the Academic and Educational pages of the
Department of Radiology
Seth G.S. Medical College and K.E.M. Hospital, Mumbai , India
Case of the Month
Case of the Month
Clinical Profile:
Clinical Profile:
A 16 year old boy presented to the emergency department with three day's history of cough, fever, and altered mental status. His disease deteriorated and suddenly progressed to confusion and altered sensorium.
A 16 year old boy presented to the emergency department with three day's history of cough, fever, and altered mental status. His disease deteriorated and suddenly progressed to confusion and altered sensorium.
Radiological Investigations:
Radiological Investigations:
Plain and contrast enhanced CT scans of the brain show well defined hypodensity in both substantia nigra and middle cerebral peduncles with no significant post contrast enhancement
Plain and contrast enhanced CT scans of the brain show well defined hypodensity in both substantia nigra and middle cerebral peduncles with no significant post contrast enhancement
During this active COVID pandemic, as a routine practice, chest CT were being done; but in this patient - especially to rule out CNS involvement.The HRCT of the chest shows multifocal diffuse ground glass opacities in both lungs .
During this active COVID pandemic, as a routine practice, chest CT were being done; but in this patient - especially to rule out CNS involvement.The HRCT of the chest shows multifocal diffuse ground glass opacities in both lungs .
MRI of the brain shows T2/FLAIR hyperintensity in both substantia nigra and cerebral peduncles without restricted diffusion or susceptibility on SWI. However, the lesion shows T2 shine through and peripheral patchy rim enhancement on post contrast study
MRI of the brain shows T2/FLAIR hyperintensity in both substantia nigra and cerebral peduncles without restricted diffusion or susceptibility on SWI. However, the lesion shows T2 shine through and peripheral patchy rim enhancement on post contrast study
Radiological diagnosis:
Radiological diagnosis:
In current scenario of COVID-19, HRCT findings are suggestive of COVID-19 infection.
In current scenario of COVID-19, HRCT findings are suggestive of COVID-19 infection.
On correlation between CT and MRI findings ,features are suggestive of COVID encephalitis
On correlation between CT and MRI findings ,features are suggestive of COVID encephalitis
Laboratory workup
Laboratory workup
Initial Initial laboratory work-up was negative for influenza, with the diagnosis of COVID-19 made by detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) viral nucleic acid in a nasopharyngeal swab specimen using the U.S. Centers for Disease Control and Prevention (CDC) 2019-Novel Coronavirus (2019-nCoV) Real-Time Reverse Transcriptase-Polymerase Chain Reaction assay. The assay was performed on a Roche thermocycler at our institution following “emergency use authorization” from the CDC.
Initial Initial laboratory work-up was negative for influenza, with the diagnosis of COVID-19 made by detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) viral nucleic acid in a nasopharyngeal swab specimen using the U.S. Centers for Disease Control and Prevention (CDC) 2019-Novel Coronavirus (2019-nCoV) Real-Time Reverse Transcriptase-Polymerase Chain Reaction assay. The assay was performed on a Roche thermocycler at our institution following “emergency use authorization” from the CDC.
Laboratory tests with CSF showed WBC (0.001 × 109/L), protein (0.27 g/L), ADA (0.17 U/L) and sugar (3.14 mmol/L) contents within normal limits. CSF bacterial culture showed no growth after 3 days, and tests for herpes simplex virus 1 and 2, varicella zoster virus were negative.
Laboratory tests with CSF showed WBC (0.001 × 109/L), protein (0.27 g/L), ADA (0.17 U/L) and sugar (3.14 mmol/L) contents within normal limits. CSF bacterial culture showed no growth after 3 days, and tests for herpes simplex virus 1 and 2, varicella zoster virus were negative.
Testing for presence of SARS-CoV-2 in CSF was performed and it shows positive results.
Testing for presence of SARS-CoV-2 in CSF was performed and it shows positive results.
Course in the hospital:
Course in the hospital:
The patient was admitted in Medical Intensive Care Unit , routine supportive therapy was started for COVID. The patient's saturation continued to fall on nasal oxygen, so he was intubated and is now on a ventilator.
The patient was admitted in Medical Intensive Care Unit , routine supportive therapy was started for COVID. The patient's saturation continued to fall on nasal oxygen, so he was intubated and is now on a ventilator.
He has been given IVIg , HCQ, Oseltamivir and steroids; but with little improvement.
He has been given IVIg , HCQ, Oseltamivir and steroids; but with little improvement.
His GCS is 7
His GCS is 7
Discussion:
Discussion:
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome (SARS-CoV-2). It was first identified in December 2019 in Wuhan, China, and has resulted in an ongoing pandemic. The first confirmed case has been traced back to 17 November 2019 in Hubei. Traces of the virus have been found in the wastewater that was collected from Milan, Turin and Italy. As of 30 June 2020,more than 10.2 million cases have been reported across 188 countries and territories, resulting in more than 504,000, deaths. More than 5.2 million people have recovered. Common symptoms include fever , cough , fatigue , shortness of breath and loss of smell and taste. While the majority of cases result in mild symptoms, some progress to acute respiratory distress syndrome(ARDS) possibly precipitated by cytokines storm, multiorgan failure, septic shock, and blood clots. The time from exposure to onset of symptoms is typically around five days, but may range from two to fourteen days.
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome (SARS-CoV-2). It was first identified in December 2019 in Wuhan, China, and has resulted in an ongoing pandemic. The first confirmed case has been traced back to 17 November 2019 in Hubei. Traces of the virus have been found in the wastewater that was collected from Milan, Turin and Italy. As of 30 June 2020,more than 10.2 million cases have been reported across 188 countries and territories, resulting in more than 504,000, deaths. More than 5.2 million people have recovered. Common symptoms include fever , cough , fatigue , shortness of breath and loss of smell and taste. While the majority of cases result in mild symptoms, some progress to acute respiratory distress syndrome(ARDS) possibly precipitated by cytokines storm, multiorgan failure, septic shock, and blood clots. The time from exposure to onset of symptoms is typically around five days, but may range from two to fourteen days.
The lungs are the organs most affected by COVID‑19 because the virus accesses host cells via the enzyme angiotensin converting enzyme 2 (ACE2), which is most abundant in type II alveolar cells of the lungs. The virus uses a special surface glycoprotein called a "spike" (peplomer) to connect to ACE2 and enter the host cell. The density of ACE2 in each tissue correlates with the severity of the disease in that tissue and some have suggested decreasing ACE2 activity might be protective, though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective. As the alveolar disease progresses, respiratory failure might develop and death may follow.
The lungs are the organs most affected by COVID‑19 because the virus accesses host cells via the enzyme angiotensin converting enzyme 2 (ACE2), which is most abundant in type II alveolar cells of the lungs. The virus uses a special surface glycoprotein called a "spike" (peplomer) to connect to ACE2 and enter the host cell. The density of ACE2 in each tissue correlates with the severity of the disease in that tissue and some have suggested decreasing ACE2 activity might be protective, though another view is that increasing ACE2 using angiotensin II receptor blocker medications could be protective. As the alveolar disease progresses, respiratory failure might develop and death may follow.
SARS-CoV-2 may also cause respiratory failure through affecting the brainstem as other coronaviruses have been found to invade the central nervous system. While the virus has been detected in cerebrospinal fluid at autopsies, the exact mechanism by which it invades the CNS remains unclear and may first involve invasion of peripheral nerves given the low levels of ACE2 in the brain.
SARS-CoV-2 may also cause respiratory failure through affecting the brainstem as other coronaviruses have been found to invade the central nervous system. While the virus has been detected in cerebrospinal fluid at autopsies, the exact mechanism by which it invades the CNS remains unclear and may first involve invasion of peripheral nerves given the low levels of ACE2 in the brain.
The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium as well as endothelial cells and enterocytes of small intestine
The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelium as well as endothelial cells and enterocytes of small intestine
The virus can cause acute myocardial injury and chronic damage to the cardiovascular system.An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China and is more frequent in severe disease. Rates of cardiovascular symptoms are high, owing to the systemic inflammatory response and immune system disorders during disease progression, but acute myocardial injuries may also be related to ACE2 receptors in the heart. ACE2 receptors are highly expressed in the heart and are involved in heart function. A high incidence of thrombosis (31%) and venous thromboembolism (25%) have been found in ICU patients with COVID‑19 infections, and may be related to poor prognosis. Blood vessel dysfunction and clot formation (as suggested by high D-dimer levels) are thought to play a significant role in mortality, incidences of clots leading to pulmonary embolisms, and ischaemic events within the brain have been noted as complications leading to death in patients infected with SARS-CoV-2. Infection appears to set off a chain of vasoconstriction responses within the body, constriction of blood vessels within the pulmonary circulation has also been posited as a mechanism in which oxygenation decreases alongside the presentation of viral pneumonia.
The virus can cause acute myocardial injury and chronic damage to the cardiovascular system.An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China and is more frequent in severe disease. Rates of cardiovascular symptoms are high, owing to the systemic inflammatory response and immune system disorders during disease progression, but acute myocardial injuries may also be related to ACE2 receptors in the heart. ACE2 receptors are highly expressed in the heart and are involved in heart function. A high incidence of thrombosis (31%) and venous thromboembolism (25%) have been found in ICU patients with COVID‑19 infections, and may be related to poor prognosis. Blood vessel dysfunction and clot formation (as suggested by high D-dimer levels) are thought to play a significant role in mortality, incidences of clots leading to pulmonary embolisms, and ischaemic events within the brain have been noted as complications leading to death in patients infected with SARS-CoV-2. Infection appears to set off a chain of vasoconstriction responses within the body, constriction of blood vessels within the pulmonary circulation has also been posited as a mechanism in which oxygenation decreases alongside the presentation of viral pneumonia.
Another common cause of death is complications related to the kidneys. Early reports show that up to 30% of hospitalized patients in both China and New York have experienced some injury to their kidneys, including some persons with no previous kidney problems.
Another common cause of death is complications related to the kidneys. Early reports show that up to 30% of hospitalized patients in both China and New York have experienced some injury to their kidneys, including some persons with no previous kidney problems.
Autopsies of people who died of COVID‑19 have found diffuse alveolar damage (DAD), and lymphocyte-containing inflammatory infiltrates within the lung.
Autopsies of people who died of COVID‑19 have found diffuse alveolar damage (DAD), and lymphocyte-containing inflammatory infiltrates within the lung.
Based on the CT findings, the level of suspicion of COVID-19 infection is graded from very low or CO-RADS 1 up to very high or CO-RADS 5 and the severity and stage of the disease is determined with remarks on comorbidity and a differential diagnosis.
Based on the CT findings, the level of suspicion of COVID-19 infection is graded from very low or CO-RADS 1 up to very high or CO-RADS 5 and the severity and stage of the disease is determined with remarks on comorbidity and a differential diagnosis.
CORADS-1 has a high negative predictive value in patients with complaints for four or more days.
CORADS-1 has a high negative predictive value in patients with complaints for four or more days.
CORADS 5 has a very high positive predictive value given the high a priori-chance in this epidemic.
CORADS 5 has a very high positive predictive value given the high a priori-chance in this epidemic.
The interobserver variation of CORADS 2-4 is still high and has a poor negative and predictive value.
The interobserver variation of CORADS 2-4 is still high and has a poor negative and predictive value.
The interpretation of the CT findings has to be combined with the clinical symptoms and the duration of the symptoms as a CT can be negative in the first few days of a mild infection.
The interpretation of the CT findings has to be combined with the clinical symptoms and the duration of the symptoms as a CT can be negative in the first few days of a mild infection.
Acute necrotizing encephalopathy (ANE) is a rare complication of influenza and other viral infections and has been related to intracranial cytokine storms, which result in blood-brain- barrier breakdown, but without direct viral invasion or parainfectious demyelination (3). Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome (4). While predominantly described in the pediatric population, ANE is known to occur in adults as well. The most characteristic imaging feature includes symmetric, multifocal lesions with invariable thalamic involvement (5). Other commonly involved locations include the brain stem, cerebral white matter, and cerebellum (5). Lesions appear hypoattenuating on CT images and MRI demonstrates T2 FLAIR hyperintense signal with internal hemorrhage. Postcontrast images may demonstrate a ring of contrast enhancement (5).Including acute stroke (6%) and altered mental status (15%) (1). Neurotropism of coronavirus may account for the relatively high percentage of neurologic involvement (6, 7). In addition to neurotropism, another potential mechanism for neurologic manifestations might be related to cytokine storm syndrome (2,8).
Acute necrotizing encephalopathy (ANE) is a rare complication of influenza and other viral infections and has been related to intracranial cytokine storms, which result in blood-brain- barrier breakdown, but without direct viral invasion or parainfectious demyelination (3). Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome (4). While predominantly described in the pediatric population, ANE is known to occur in adults as well. The most characteristic imaging feature includes symmetric, multifocal lesions with invariable thalamic involvement (5). Other commonly involved locations include the brain stem, cerebral white matter, and cerebellum (5). Lesions appear hypoattenuating on CT images and MRI demonstrates T2 FLAIR hyperintense signal with internal hemorrhage. Postcontrast images may demonstrate a ring of contrast enhancement (5).Including acute stroke (6%) and altered mental status (15%) (1). Neurotropism of coronavirus may account for the relatively high percentage of neurologic involvement (6, 7). In addition to neurotropism, another potential mechanism for neurologic manifestations might be related to cytokine storm syndrome (2,8).
In addition to findings of encephalitis, increased thrombosis rates in coronavirus infection has been reported. In patients with SARS-CoV, increased incidence of deep venous thrombosis and pulmonary embolism was observed despite optimal anticoagulant therapy (9). Additionally, intracranial arterial stroke cases have been reported in SARS patients receiving IVIG treatment (9).
In addition to findings of encephalitis, increased thrombosis rates in coronavirus infection has been reported. In patients with SARS-CoV, increased incidence of deep venous thrombosis and pulmonary embolism was observed despite optimal anticoagulant therapy (9). Additionally, intracranial arterial stroke cases have been reported in SARS patients receiving IVIG treatment (9).
The most common imaging finding was cortical signal abnormalities on FLAIR images, accompanied by cortical diffusion restriction, leptomeningeal enhancement or cortical blooming artifact in some of these cases. The main differential diagnosis for this constellation of findings is infectious or autoimmune encephalitis, seizure, hypoglycemia and hypoxia. (10-16) The cases with bilateral frontal involvement may have hypoxia as underlying pathogenesis given the underlying respiratory distress and frontotemporal hypoperfusion as demonstrated by Helms et al., in COVID-19 patients admitted to ICU (5). Cortical microhemorrhages and breakdown of blood-brain barrier can accompany hypoxia which can result in such an imaging pattern. Postictal state is also a plausible etiology for our imaging findings, however the relative symmetry and deep white matter involvement in our cases don’t support postictal changes.
The most common imaging finding was cortical signal abnormalities on FLAIR images, accompanied by cortical diffusion restriction, leptomeningeal enhancement or cortical blooming artifact in some of these cases. The main differential diagnosis for this constellation of findings is infectious or autoimmune encephalitis, seizure, hypoglycemia and hypoxia. (10-16) The cases with bilateral frontal involvement may have hypoxia as underlying pathogenesis given the underlying respiratory distress and frontotemporal hypoperfusion as demonstrated by Helms et al., in COVID-19 patients admitted to ICU (5). Cortical microhemorrhages and breakdown of blood-brain barrier can accompany hypoxia which can result in such an imaging pattern. Postictal state is also a plausible etiology for our imaging findings, however the relative symmetry and deep white matter involvement in our cases don’t support postictal changes.
References:
References:
1. Mao L, Wang M, Chen S, et al. Neurological Manifestations of Hospitalized Patients with
1. Mao L, Wang M, Chen S, et al. Neurological Manifestations of Hospitalized Patients with
COVID-19 in Wuhan, China: a retrospective case series study. JAMA Neurol 2020. doi:
COVID-19 in Wuhan, China: a retrospective case series study. JAMA Neurol 2020. doi:
10.1001/jamaneurol.2020.1127
10.1001/jamaneurol.2020.1127
2. Desforges M, Le Coupanec A, Stodola JK, et al. Human coronaviruses: viral and cellular factors involved in neuro invasiveness and neuropathogenesis. Virus Res 2014;194:145-158. doi: 10.1016/j.virusres.2014.09.011
2. Desforges M, Le Coupanec A, Stodola JK, et al. Human coronaviruses: viral and cellular factors involved in neuro invasiveness and neuropathogenesis. Virus Res 2014;194:145-158. doi: 10.1016/j.virusres.2014.09.011
3. Moriguchi T, Harii N, Goto J, et al. A first Case of Meningitis/Encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020. doi: 10.1016/j.ijid.2020.03.062
3. Moriguchi T, Harii N, Goto J, et al. A first Case of Meningitis/Encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020. doi: 10.1016/j.ijid.2020.03.062
4. Poyiadji N, Shahin G, Noujaim D, et al. COVID-19–associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology 2020:201187. doi: 10.1148/radiol.2020201187
4. Poyiadji N, Shahin G, Noujaim D, et al. COVID-19–associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology 2020:201187. doi: 10.1148/radiol.2020201187
5. Helms J, Kremer S, Merdji H, et al. Neurologic Features in Severe SARS-CoV-2 Infection. N Eng J Med 2020. doi: 10.1056/NEJMc2008597
5. Helms J, Kremer S, Merdji H, et al. Neurologic Features in Severe SARS-CoV-2 Infection. N Eng J Med 2020. doi: 10.1056/NEJMc2008597
6. Morfopoulou S, Brown JR, Davies EG, et al. Human Coronavirus OC43 Associated with Fatal Encephalitis. N Eng J Med 2016;375(5):497-498. doi: 10.1056/NEJMc1509458
6. Morfopoulou S, Brown JR, Davies EG, et al. Human Coronavirus OC43 Associated with Fatal Encephalitis. N Eng J Med 2016;375(5):497-498. doi: 10.1056/NEJMc1509458
7. Tsai LK, Hsieh ST, Chang YC. Neurological manifestations in severe acute respiratory syndrome. Acta Neurol Taiwan 2005;14(3):113-119.
7. Tsai LK, Hsieh ST, Chang YC. Neurological manifestations in severe acute respiratory syndrome. Acta Neurol Taiwan 2005;14(3):113-119.
8. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0
8. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0
In Press
In Press
9. Umapathi T, Kor AC, Venketasubramanian N, et al. Large artery ischaemic stroke in severe acute respiratory syndrome (SARS). J Neurol 2004;251(10):1227-1231. doi: 10.1007/s00415- 004-0519-8
9. Umapathi T, Kor AC, Venketasubramanian N, et al. Large artery ischaemic stroke in severe acute respiratory syndrome (SARS). J Neurol 2004;251(10):1227-1231. doi: 10.1007/s00415- 004-0519-8
10. Koeller KK, Shih RY. Viral and Prion Infections of the Central Nervous System: Radiologic- Pathologic Correlation: From the Radiologic Pathology Archives. Radiographics 2017;37(1):199-233. doi: 10.1148/rg.2017160149
10. Koeller KK, Shih RY. Viral and Prion Infections of the Central Nervous System: Radiologic- Pathologic Correlation: From the Radiologic Pathology Archives. Radiographics 2017;37(1):199-233. doi: 10.1148/rg.2017160149
11. Kelley BP, Patel SC, Marin HL, et al. Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis. AJNR Am J Neuroradiol 2017;38(6):1070-1078. doi: 10.3174/ajnr.A5086
11. Kelley BP, Patel SC, Marin HL, et al. Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis. AJNR Am J Neuroradiol 2017;38(6):1070-1078. doi: 10.3174/ajnr.A5086
12. Cianfoni A, Caulo M, Cerase A, et al. Seizure-induced brain lesions: a wide spectrum of variably reversible MRI abnormalities. Eur J Radiol 2013;82(11):1964-1972. doi: 10.1016/j.ejrad.2013.05.020
12. Cianfoni A, Caulo M, Cerase A, et al. Seizure-induced brain lesions: a wide spectrum of variably reversible MRI abnormalities. Eur J Radiol 2013;82(11):1964-1972. doi: 10.1016/j.ejrad.2013.05.020
13. Muttikkal TJ, Wintermark M. MRI patterns of global hypoxic-ischemic injury in adults. J Neuroradiol 2013;40(3):164-171. doi: 10.1016/j.neurad.2012.08.002
13. Muttikkal TJ, Wintermark M. MRI patterns of global hypoxic-ischemic injury in adults. J Neuroradiol 2013;40(3):164-171. doi: 10.1016/j.neurad.2012.08.002
14. Bathla G, Policeni B, Agarwal A. Neuroimaging in patients with abnormal blood glucose levels. AJNR Am J Neuroradiol 2014;35(5):833-840. doi: 10.3174/ajnr.A3486
14. Bathla G, Policeni B, Agarwal A. Neuroimaging in patients with abnormal blood glucose levels. AJNR Am J Neuroradiol 2014;35(5):833-840. doi: 10.3174/ajnr.A3486
15. McKinney AM, Sarikaya B, Gustafson C, et al. Detection of microhemorrhage in posterior reversible encephalopathy syndrome using susceptibility-weighted imaging. AJNR Am J Neuroradiol 2012;33(5):896-903. doi: 10.3174/ajnr.A2886
15. McKinney AM, Sarikaya B, Gustafson C, et al. Detection of microhemorrhage in posterior reversible encephalopathy syndrome using susceptibility-weighted imaging. AJNR Am J Neuroradiol 2012;33(5):896-903. doi: 10.3174/ajnr.A2886
16. Fanou EM, Coutinho JM, Shannon P, et al. Critical Illness-Associated Cerebral Microbleeds.
16. Fanou EM, Coutinho JM, Shannon P, et al. Critical Illness-Associated Cerebral Microbleeds.
.
.
Google Sites
Report abuse