Cerebral deep venous thrombosis and COVID-19: case report

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  • 1 Department of Neurological Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
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Herein, the authors present the case of a 54-year-old male diagnosed with coronavirus disease 2019 (COVID-19) during a screening test. The patient was asked to self-isolate at home and report with any exacerbations of symptoms. He presented later with pneumonia complicated by encephalopathy at days 14 and 15 from initial diagnosis, respectively. MRI of the brain showed bithalamic and gangliocapsular FLAIR signal abnormality with mild right-sided thalamic and periventricular diffusion restriction. A CT venogram was obtained given the distribution of edema and demonstrated deep venous thrombosis involving the bilateral internal cerebral veins and the vein of Galen. CSF workup was negative for encephalitis, as the COVID-19 polymerase chain reaction (PCR) test and bacterial cultures were negative. A complete hypercoagulable workup was negative, and the venous thrombosis was attributed to a hypercoagulable state induced by COVID-19. The mental decline was attributed to bithalamic and gangliocapsular venous infarction secondary to deep venous thrombosis. Unfortunately, the patient’s condition continued to decline, and care was withdrawn.

ABBREVIATIONS

COVID-19 = coronavirus disease 2019; CSF = cerebrospinal fluid; EVD = external ventricular drain; ICP = intracranial pressure; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Herein, the authors present the case of a 54-year-old male diagnosed with coronavirus disease 2019 (COVID-19) during a screening test. The patient was asked to self-isolate at home and report with any exacerbations of symptoms. He presented later with pneumonia complicated by encephalopathy at days 14 and 15 from initial diagnosis, respectively. MRI of the brain showed bithalamic and gangliocapsular FLAIR signal abnormality with mild right-sided thalamic and periventricular diffusion restriction. A CT venogram was obtained given the distribution of edema and demonstrated deep venous thrombosis involving the bilateral internal cerebral veins and the vein of Galen. CSF workup was negative for encephalitis, as the COVID-19 polymerase chain reaction (PCR) test and bacterial cultures were negative. A complete hypercoagulable workup was negative, and the venous thrombosis was attributed to a hypercoagulable state induced by COVID-19. The mental decline was attributed to bithalamic and gangliocapsular venous infarction secondary to deep venous thrombosis. Unfortunately, the patient’s condition continued to decline, and care was withdrawn.

On March 11, 2020, the World Health Organization declared that coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a pandemic.1 The virus has a high reproduction number (2.0–2.5) allowing it to infect a large number of the world population.2 The primary organ affected is the respiratory system; however, neurological manifestations have been reported.3 Herein, we describe a case of COVID-19 infection with pulmonary manifestations and encephalopathy due to cerebral venous infarction secondary to deep venous thrombosis.

Case Report

History and Examination

A 54-year-old male, with a medical history notable only for hypertension, tested positive for COVID-19 at another institution during a screening examination conducted due to close contact with a COVID-19–positive individual on April 5, 2020. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) assay. The patient was asked to self-quarantine; however, 9 days after testing positive, he presented with shortness of breath and cough. The patient was diagnosed with pneumonia and started on oxygen, ceftriaxone, and azithromycin. The patient’s mental status declined (day 15 after the initial diagnosis), for which he required mechanical ventilation. CT imaging of the brain showed bithalamic and gangliocapsular hypodensity with mass effect and approximately 6 mm of rightward midline shift, as well as prominence of the bilateral temporal horns. Subsequent MRI of the brain showed bithalamic and gangliocapsular FLAIR signal abnormality with mild right-sided thalamic and periventricular diffusion restriction. The temporal horns were prominent with evidence of transependymal flow. He was transferred to our institution for further management.

Upon admission to Thomas Jefferson University Hospital, the patient was obtunded, opening his eyes and grimacing only to deep noxious stimulation, localizing his bilateral upper extremities weakly, and withdrawing his bilateral lower extremities (Glasgow Coma Scale [GCS] E2V2M5). His pupils were equal and reactive, and protective brainstem reflexes were intact. Auscultation of his lungs revealed coarse breath sounds bilaterally, consistent with his known COVID-19 pulmonary pathology. Given his poor mental status and concern for obstructive hydrocephalus, a right external ventricular drain (EVD) was placed for cerebrospinal fluid (CSF) diversion, intracranial pressure (ICP) monitoring, and CSF studies. The CSF opening pressure was 30 cm H2O (Fig. 1). A CT venogram, obtained given the distribution of edema, demonstrated deep venous thrombosis involving the bilateral internal cerebral veins and the vein of Galen (Fig. 2), as well as progressive deep cerebral edema. Pertinent laboratory findings on admission to the intensive care unit are summarized in Table 1. Notable findings included elevated levels of D-dimer, erythrocyte sedimentation rate, lactate dehydrogenase, and serum ferritin. A complete hypercoagulable workup did not identify the provocative cause for the venous thrombosis, and the venous thrombosis was attributed to a hypercoagulable state induced by COVID-19 (antithrombin III, antiphospholipid antibodies, etc.). Also, CSF studies showed a markedly increased protein content and white blood cell count, initially suggesting the possibility of COVID-19 encephalitis. However, SARS-CoV-2 RNA was not detected in the CSF, and bacterial cultures remained negative.

FIG. 1.
FIG. 1.

A: Axial FLAIR MRI showing hyperintense signal in the bilateral thalami (white arrows) and basal ganglia region (worse on the patient’s right). Note the transependymal flow at the right frontal horn (blue arrow). B: Coronal CT scan showing the EVD in the right frontal horn (thick arrow). Note the dilated right temporal horn (small arrow) indicating hydrocephalus. Figure is available in color online only.

FIG. 2.
FIG. 2.

Sagittal CT venogram showing filling defects in the internal cerebral vein (top arrow) and vein of Galen (bottom arrow) consistent with thrombosis.

TABLE 1.

Demographic and clinical characteristics and laboratory findings

FactorDescription
Demographic characteristics
 Age (yrs)54
 SexM
Initial findings
 Medical historyHypertension
 Symptoms at disease onsetShortness of breath, cough
 Imaging featuresLt lower lobe pneumonia
 Treatment before admission to ICUO2, ceftriaxone, & azithromycin
 No. of days from disease onset to thrombotic events15
Findings on admission to ICU
 No. of days since disease onset15
 Disease severitySevere
 Laboratory findings
  WBC (B/L)7.8
  Differential count (B/L)
   Total neutrophils6.42
   Total lymphocytes1.09
   Total monocytes0.17
  Platelet count (B/L)372
  Hemoglobin (g/dl)14.4
  Albumin (g/dl)3.7
  ALT (IU/L)67
  AST (IU/L)44
  LDH (IU/L)382
  Creatinine (mg/dl)1.06
  Creatine kinase (IU/L)190
  EGFR (ml/min/1.73 m2)>60
  hs-cTnT (ng/L)14
  Prothrombin time (sec)11.8
  aPTT (sec)25
  Fibrinogen (mg/dl)429
  Antithrombin III (%)99
  D-dimer (ng/ml)3151
  Serum ferritin (ng/ml)508
  Procalcitonin (ng/ml)0.2
  High-sensitivity CRP (mg/dl)0.60
  ESR (mm/hr)47
 CSF studies
  RBC count (cell/μl)401
  WBC (cell/μl)10
  Glucose (mg/dl)38
  Protein (mg/dl)1104
 Imaging featuresEncephalitis w/ midline shift; venous infarct involving bithalamic & basal ganglia; deep venous thrombosis involving straight sinus, vein of Galen, bilat internal cerebral veins, & rt basal vein of Rosenthal

ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate aminotransferase; B/L = billion per liter; CRP = C-reactive protein; EGFR = estimated glomerular filtration rate; ESR = erythrocyte sedimentation rate; hs-cTnT = high-sensitivity cardiac troponin T; LDH = lactate dehydrogenase; RBC = red blood cell; WBC = white blood cell.

Bold values indicate higher than normal range.

Treatment and Posttreatment Course

The patient was started on hydroxychloroquine for COVID-19 treatment. A heparin infusion was initiated given the cerebral deep venous thrombosis, and a 3% hypertonic saline infusion was administered given concerns over increasing mass effect due to cerebral edema. Serial CT scans revealed a punctate focus of hemorrhage in the right basal ganglia that remained stable. The patient had an episode of ICP crisis with a dilated right pupil that was responsive to 23.4% hypertonic saline administration. His right frontal ventricular drain was not draining CSF at this point. A subsequent CT scan showed the ventricle collapsed around the catheter tip, a dilated left ventricle, and progressive deep cerebral edema. The heparin infusion was temporarily held and a left-sided ventricular drain was placed. These measures allowed for transient control of ICP, but unfortunately he developed progressive bilateral deep venous infarctions involving critical structures and sustained elevated ICPs, and care was withdrawn on the 9th day of the hospital stay.

Discussion

Neurological manifestations caused by COVID-19 range from mild to severe symptoms. Several published reports have noted severe headache, anosmia, encephalopathy, encephalitis, meningitis, and acute cerebrovascular disease such as ischemic and hemorrhagic stroke.3–5 The coronavirus family has previously shown the ability to directly infect the central nervous system, and this may be the cause of some such presentations. Additionally, some severe presentations are thought to be at least partly attributable to an unusually intense inflammatory response, which has been widely reported in pulmonary tissue.3 Such a response may predispose to a hypercoagulable state, putting patients at risk for stroke due to either arterial occlusion or venous congestion. There are numerous reports documenting an increased risk of thromboembolic events in COVID-19–positive patients.6,7 Cerebral infarcts secondary to antiphospholipid antibodies in COVID-19 patients have also been reported.7 It is paramount to keep a high index of suspicion of venous thrombosis when faced with an encephalitis picture in the setting of COVID-19. The management is completely different, in which anticoagulation may improve outcomes.

Conclusions

SARS-CoV-2 may induce a hypercoagulable state causing cerebral venous thrombosis. The radiological features may share similarities with several differential diagnoses, including encephalitis. It is paramount to perform a complete workup because the management is completely different, and this affects the patient’s outcome. It is crucial to account for such manifestations when managing patients with COVID-19.

Disclosures

Dr. Jabbour is a consultant for Medtronic and MicroVention. Drs. Tjoumakaris and Gooch are consultants for Stryker.

Author Contributions

Conception and design: Al Saiegh. Acquisition of data: Ghosh, Keppetipola. Drafting the article: Hoelscher, Sweid, Ghosh, Al Saiegh. Critically revising the article: Shah, Hoelscher, Sweid, Ghosh. Reviewed submitted version of manuscript: Shah, Farrell, Jallo, Jabbour, Tjoumakaris, Gooch, Rosenwasser. Approved the final version of the manuscript on behalf of all authors: Shah. Administrative/technical/material support: Keppetipola, Rosenwasser.

References

  • 1

    Bedford J , Enria D , Giesecke J , et al. COVID-19: towards controlling of a pandemic . Lancet . 2020 ;395 (10229 ):1015 1018 .

  • 2

    Akhmerov A , Marbán E . COVID-19 and the heart . Circ Res . 2020 ;126 (10 ):1443 1455 .

  • 3

    Mao L , Jin H , Wang M , et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China . JAMA Neurol . 2020 ;77 (6 ):683 690 .

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Moriguchi T , Harii N , Goto J , et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2 . Int J Infect Dis . 2020 ;94 :55 58 .

  • 5

    Poyiadji N , Shahin G , Noujaim D , et al. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features . Radiology . 2020 ;296 (2 ):E119 E120 .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Connors JM , Levy JH . Thromboinflammation and the hypercoagulability of COVID-19 . J Thromb Haemost . 2020 ;18 (7 ):1559 1561 .

  • 7

    Zhang Y , Xiao M , Zhang S , et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19 . N Engl J Med . 2020 ;382 (17 ):e38 .

Illustrations from Marx and Schroeder (pp 318–326). Copyright Henry W. S. Schroeder. Published with permission.
  • View in gallery

    A: Axial FLAIR MRI showing hyperintense signal in the bilateral thalami (white arrows) and basal ganglia region (worse on the patient’s right). Note the transependymal flow at the right frontal horn (blue arrow). B: Coronal CT scan showing the EVD in the right frontal horn (thick arrow). Note the dilated right temporal horn (small arrow) indicating hydrocephalus. Figure is available in color online only.

  • View in gallery

    Sagittal CT venogram showing filling defects in the internal cerebral vein (top arrow) and vein of Galen (bottom arrow) consistent with thrombosis.

  • 1

    Bedford J , Enria D , Giesecke J , et al. COVID-19: towards controlling of a pandemic . Lancet . 2020 ;395 (10229 ):1015 1018 .

  • 2

    Akhmerov A , Marbán E . COVID-19 and the heart . Circ Res . 2020 ;126 (10 ):1443 1455 .

  • 3

    Mao L , Jin H , Wang M , et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China . JAMA Neurol . 2020 ;77 (6 ):683 690 .

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Moriguchi T , Harii N , Goto J , et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2 . Int J Infect Dis . 2020 ;94 :55 58 .

  • 5

    Poyiadji N , Shahin G , Noujaim D , et al. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features . Radiology . 2020 ;296 (2 ):E119 E120 .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Connors JM , Levy JH . Thromboinflammation and the hypercoagulability of COVID-19 . J Thromb Haemost . 2020 ;18 (7 ):1559 1561 .

  • 7

    Zhang Y , Xiao M , Zhang S , et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19 . N Engl J Med . 2020 ;382 (17 ):e38 .

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