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*It is only for medical professionals to read for reference.
When you encounter these symptoms, don't forget the cause
.
Today, I will introduce a 74-year-old woman who was hospitalized due to ischemic stroke.
The common possible causes of stroke were ruled out.
The patient was found to have embolism in other organs at the same time (highly suggesting hypercoagulable state).
After investigation, it was found that there was an occult lung tumor.
The condition deteriorated rapidly.
Despite the anticoagulation treatment, repeated embolism occurred, which eventually led to the death of the patient [1]
.
I hope I can bring you some gains
.
Case review: A 74-year-old female was admitted to the hospital with “sudden language disorder, skewed speech, and weakness of the right limb for 12 hours”
.
Physical examination: fever, aphasia, left central facial paralysis, and positive left Babinksi sign
.
Past history: Hypertension and dyslipidemia are well controlled
.
Auxiliary examinations: 1) Computed tomography (CT) of the head showed bilateral ischemic infarcts in the basal ganglia and subcortical frontal lobe-parietal lobe, the time is unknown
.
2) Electrocardiogram (ECG) showed sinus rhythm, chest X-ray showed a small amount of left pleural effusion
.
Blood analysis showed 14400 white blood cells/μl, C-reactive protein 217.
8 mg/l, LDH 459 U/l and INR 1.
57
.
3) Doppler ultrasonography and transthoracic echocardiography of neck vessels showed no change
.
4) DWI shows acute cerebral infarction in the left and right cerebral hemispheres, anterior and posterior circulation with multiple bloodsheds (Figure 1)
.
FIG 1: DWI consider the possibility of cardioembolic etiology, enoxaparin started in the first seven days of hospitalization, but transesophageal echocardiography revealed no patent foramen ovale, valvular disease and other abnormalities
.
On the day of the start of anticoagulation, the neurological deficit worsened, leading to failure
.
Repeated head CT examination, found a huge solid hematoma in the left frontal area, and stopped enoxaparin
.
After excluding common causes of stroke, the following examinations were performed, but they did not show any abnormalities: lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I antibody, antithrombin III, protein S and C, antineutrophil Cytoplasmic autoantibodies, prothrombin gene and factor V Leiden mutations and HIV, HBV, HCV and VDRL serology
.
The antinuclear antibody was positive (1:160), D-dimer was 1644μg/l (normal <230μg/l), and fibrinogen was 1.
4 g/l (normal 2-4 g/l)
.
The whole body CT scan showed solid lesions in the left lower lobe of the left lung, multiple pathological lymph nodes in the mediastinum, peripheral pulmonary thromboembolism, right femoral popliteal vein thrombosis, spleen and renal infarction (Figure 2-4)
.
Figure 2: Contrast-enhanced CT scan of the abdomen showing abdominal infarction (red arrow) Figure 3: Contrast-enhanced CT scan of the abdomen showing renal infarction (red arrow) Figure 4: Contrast-enhanced CT scan of the thoracic cavity showing the left lower lobe lung cancer (red arrow) Unable to restore anticoagulation immediately, a filter was placed in the inferior vena cava
.
Cerebral angiography showed occlusion of the right internal carotid artery (review of previous normal cervical vascular Doppler ultrasonography), and vasculitis was ruled out
.
Endoscopic ultrasound-guided transesophageal mediastinal lymph node biopsy revealed non-small cell lung cancer
.
The results of immunohistochemical tests for lung cancer subtypes are inconclusive
.
Diffuse intravascular coagulation (DIC) with multiple brain and systemic thrombotic events is considered as a paraneoplastic syndrome of occult lung tumors
.
Due to the continuous progression of hemorrhagic stroke, enoxaparin was resumed 2 weeks after the incident
.
However, despite the reintroduction of anticoagulation therapy, new thromboembolic events still occurred, and as thrombocytopenia gradually worsened, anticoagulation therapy was eventually suspended
.
During the hospitalization, the patient still had fever and high inflammatory parameters, but no source of infection was found, and the microbial culture was negative.
This change may be related to systemic thrombosis
.
Later, the patient was unable to speak and was quadriplegic.
According to the scoring standard of the Eastern Cooperative Oncology Group (ECOG) of the physical status, the patient scored 4
.
Taking into account the advanced tumor (stage IIIB/IV) and high dependence, it is not expected to produce any benefits, and it was decided not to initiate the use of cytostatics in a multidisciplinary consultation
.
The patient was referred to palliative care and died a few days later
.
Discussion of stroke and venous thrombosis may be the first manifestation of occult malignancies, and may appear several months before the malignancy [2,3]
.
The most common cause of stroke in patients with malignant tumors is related to traditional cerebrovascular risk factors, but cryptogenic stroke is more common in this population [4]
.
Stroke has certain characteristics in some patients with malignant tumors, indicating that its underlying pathophysiological mechanism is different from the traditional pathophysiological mechanism, indicating that malignant tumors may play a more direct role in the occurrence of stroke [3,4]
.
This patient has a variety of malignant tumor-related ischemic stroke characteristics: cryptogenic stroke with fewer traditional cardiovascular risk factors, multiple acute ischemic lesions in different cerebrovascular regions, elevated D-dimer, and coexistence Other embolic events [3,4]
.
Studies have shown that the presence of high inflammatory parameters seems to be one of the characteristics of patients with tumor-related ischemic stroke [5]
.
Therefore, stroke patients with these characteristics should suspect occult malignancies
.
The hypercoagulable state associated with malignant tumors seems to be the most important mechanism in the occurrence of malignant tumor-related ischemic stroke, which may be the most serious DIC, which is a poor prognostic factor of lung cancer [2,4,6]
.
In this patient, paraneoplastic DIC caused venous thrombosis and multiple arterial thrombosis in the brain, kidney, and spleen
.
Although enoxaparin may cause cerebral hemorrhage, DIC certainly played a key role, not only causing thrombosis, but also causing bleeding through the consumption of platelets and clotting factors [2]
.
Anticoagulation may be beneficial; however, the safety and effectiveness of this strategy in patients with malignant tumors and DIC have not been evaluated in large clinical trials.
This case illustrates that this therapy may be difficult to manage [1,3] The treatment of tumor formation is crucial to the solution of DIC[2,6]
.
It also reminds us that although patients with malignant tumors are particularly vulnerable, guidelines for stroke prevention and treatment in this population should still be developed [3]
.
Key points 1.
Stroke can be the primary manifestation of occult malignancies
.
2.
For occult stroke cases, if there are the following conditions: elevated D-dimer, multiple infarcts in different vascular distribution areas, and embolic events in other organs, the possibility of occult malignant tumors should be considered
.
3.
Malignant tumors have not been cured, and anticoagulation therapy may be insufficient
.
References: [1]Costa JA, Rodrigues M, Montero M, et al.
CT- proven ischaemic stroke as the first manifestation of occult lung cancer.
Eur J Case Rep Intern Med, 2019, 6 (1):001007.
[2 ]Levi M.
Management ofcancer-associated disseminated intravascular coagulation.
Thromb Res.
2016;140(Suppl 1):S66–70.
[3]Wang JY, Zhang GJ, Zhuo SX, Wang K, HuXP, Zhang H, et al.
D-dimer >2.
785 μg/ml and multiple infarcts ≥3 vascular territories are two characteristics of identifying cancer-associated ischemicstroke patients.
Neurol Res.
2018;40:948–954.
[4]Dearborn JL, Urrutia VC, Zeiler SR.
Stroke and cancer-a complicated relationship.
J Neurol TranslNeurosci.
2014;2:1039.
[5]Lee EJ, Nah HW, Kwon JY, Kang DW, KwonSU, Kim JS.
Ischemic stroke in patients with cancer: is it different from usualstrokes? Int J Stroke.
2014;9:406–412.
[6]Kanaji N, Mizoguchi H, Inoue T,Tadokoro A,Watanabe N, Ishii T, et al.
Clinical features of patients with lungcancer accompanied by thromboembolism or disseminated intravascular coagulation.
Ther Clin Risk Manag.
2018;14:1361–1368.
[6]Costa JA, Rodrigues M, Montero M, et al.
CT- proven ischaemic stroke as the first manifestation of occult lung cancer.
Eur J Case Rep Intern Med, 2019, 6 (1):001007.
When you encounter these symptoms, don't forget the cause
.
Today, I will introduce a 74-year-old woman who was hospitalized due to ischemic stroke.
The common possible causes of stroke were ruled out.
The patient was found to have embolism in other organs at the same time (highly suggesting hypercoagulable state).
After investigation, it was found that there was an occult lung tumor.
The condition deteriorated rapidly.
Despite the anticoagulation treatment, repeated embolism occurred, which eventually led to the death of the patient [1]
.
I hope I can bring you some gains
.
Case review: A 74-year-old female was admitted to the hospital with “sudden language disorder, skewed speech, and weakness of the right limb for 12 hours”
.
Physical examination: fever, aphasia, left central facial paralysis, and positive left Babinksi sign
.
Past history: Hypertension and dyslipidemia are well controlled
.
Auxiliary examinations: 1) Computed tomography (CT) of the head showed bilateral ischemic infarcts in the basal ganglia and subcortical frontal lobe-parietal lobe, the time is unknown
.
2) Electrocardiogram (ECG) showed sinus rhythm, chest X-ray showed a small amount of left pleural effusion
.
Blood analysis showed 14400 white blood cells/μl, C-reactive protein 217.
8 mg/l, LDH 459 U/l and INR 1.
57
.
3) Doppler ultrasonography and transthoracic echocardiography of neck vessels showed no change
.
4) DWI shows acute cerebral infarction in the left and right cerebral hemispheres, anterior and posterior circulation with multiple bloodsheds (Figure 1)
.
FIG 1: DWI consider the possibility of cardioembolic etiology, enoxaparin started in the first seven days of hospitalization, but transesophageal echocardiography revealed no patent foramen ovale, valvular disease and other abnormalities
.
On the day of the start of anticoagulation, the neurological deficit worsened, leading to failure
.
Repeated head CT examination, found a huge solid hematoma in the left frontal area, and stopped enoxaparin
.
After excluding common causes of stroke, the following examinations were performed, but they did not show any abnormalities: lupus anticoagulant, anticardiolipin and anti-β2-glycoprotein I antibody, antithrombin III, protein S and C, antineutrophil Cytoplasmic autoantibodies, prothrombin gene and factor V Leiden mutations and HIV, HBV, HCV and VDRL serology
.
The antinuclear antibody was positive (1:160), D-dimer was 1644μg/l (normal <230μg/l), and fibrinogen was 1.
4 g/l (normal 2-4 g/l)
.
The whole body CT scan showed solid lesions in the left lower lobe of the left lung, multiple pathological lymph nodes in the mediastinum, peripheral pulmonary thromboembolism, right femoral popliteal vein thrombosis, spleen and renal infarction (Figure 2-4)
.
Figure 2: Contrast-enhanced CT scan of the abdomen showing abdominal infarction (red arrow) Figure 3: Contrast-enhanced CT scan of the abdomen showing renal infarction (red arrow) Figure 4: Contrast-enhanced CT scan of the thoracic cavity showing the left lower lobe lung cancer (red arrow) Unable to restore anticoagulation immediately, a filter was placed in the inferior vena cava
.
Cerebral angiography showed occlusion of the right internal carotid artery (review of previous normal cervical vascular Doppler ultrasonography), and vasculitis was ruled out
.
Endoscopic ultrasound-guided transesophageal mediastinal lymph node biopsy revealed non-small cell lung cancer
.
The results of immunohistochemical tests for lung cancer subtypes are inconclusive
.
Diffuse intravascular coagulation (DIC) with multiple brain and systemic thrombotic events is considered as a paraneoplastic syndrome of occult lung tumors
.
Due to the continuous progression of hemorrhagic stroke, enoxaparin was resumed 2 weeks after the incident
.
However, despite the reintroduction of anticoagulation therapy, new thromboembolic events still occurred, and as thrombocytopenia gradually worsened, anticoagulation therapy was eventually suspended
.
During the hospitalization, the patient still had fever and high inflammatory parameters, but no source of infection was found, and the microbial culture was negative.
This change may be related to systemic thrombosis
.
Later, the patient was unable to speak and was quadriplegic.
According to the scoring standard of the Eastern Cooperative Oncology Group (ECOG) of the physical status, the patient scored 4
.
Taking into account the advanced tumor (stage IIIB/IV) and high dependence, it is not expected to produce any benefits, and it was decided not to initiate the use of cytostatics in a multidisciplinary consultation
.
The patient was referred to palliative care and died a few days later
.
Discussion of stroke and venous thrombosis may be the first manifestation of occult malignancies, and may appear several months before the malignancy [2,3]
.
The most common cause of stroke in patients with malignant tumors is related to traditional cerebrovascular risk factors, but cryptogenic stroke is more common in this population [4]
.
Stroke has certain characteristics in some patients with malignant tumors, indicating that its underlying pathophysiological mechanism is different from the traditional pathophysiological mechanism, indicating that malignant tumors may play a more direct role in the occurrence of stroke [3,4]
.
This patient has a variety of malignant tumor-related ischemic stroke characteristics: cryptogenic stroke with fewer traditional cardiovascular risk factors, multiple acute ischemic lesions in different cerebrovascular regions, elevated D-dimer, and coexistence Other embolic events [3,4]
.
Studies have shown that the presence of high inflammatory parameters seems to be one of the characteristics of patients with tumor-related ischemic stroke [5]
.
Therefore, stroke patients with these characteristics should suspect occult malignancies
.
The hypercoagulable state associated with malignant tumors seems to be the most important mechanism in the occurrence of malignant tumor-related ischemic stroke, which may be the most serious DIC, which is a poor prognostic factor of lung cancer [2,4,6]
.
In this patient, paraneoplastic DIC caused venous thrombosis and multiple arterial thrombosis in the brain, kidney, and spleen
.
Although enoxaparin may cause cerebral hemorrhage, DIC certainly played a key role, not only causing thrombosis, but also causing bleeding through the consumption of platelets and clotting factors [2]
.
Anticoagulation may be beneficial; however, the safety and effectiveness of this strategy in patients with malignant tumors and DIC have not been evaluated in large clinical trials.
This case illustrates that this therapy may be difficult to manage [1,3] The treatment of tumor formation is crucial to the solution of DIC[2,6]
.
It also reminds us that although patients with malignant tumors are particularly vulnerable, guidelines for stroke prevention and treatment in this population should still be developed [3]
.
Key points 1.
Stroke can be the primary manifestation of occult malignancies
.
2.
For occult stroke cases, if there are the following conditions: elevated D-dimer, multiple infarcts in different vascular distribution areas, and embolic events in other organs, the possibility of occult malignant tumors should be considered
.
3.
Malignant tumors have not been cured, and anticoagulation therapy may be insufficient
.
References: [1]Costa JA, Rodrigues M, Montero M, et al.
CT- proven ischaemic stroke as the first manifestation of occult lung cancer.
Eur J Case Rep Intern Med, 2019, 6 (1):001007.
[2 ]Levi M.
Management ofcancer-associated disseminated intravascular coagulation.
Thromb Res.
2016;140(Suppl 1):S66–70.
[3]Wang JY, Zhang GJ, Zhuo SX, Wang K, HuXP, Zhang H, et al.
D-dimer >2.
785 μg/ml and multiple infarcts ≥3 vascular territories are two characteristics of identifying cancer-associated ischemicstroke patients.
Neurol Res.
2018;40:948–954.
[4]Dearborn JL, Urrutia VC, Zeiler SR.
Stroke and cancer-a complicated relationship.
J Neurol TranslNeurosci.
2014;2:1039.
[5]Lee EJ, Nah HW, Kwon JY, Kang DW, KwonSU, Kim JS.
Ischemic stroke in patients with cancer: is it different from usualstrokes? Int J Stroke.
2014;9:406–412.
[6]Kanaji N, Mizoguchi H, Inoue T,Tadokoro A,Watanabe N, Ishii T, et al.
Clinical features of patients with lungcancer accompanied by thromboembolism or disseminated intravascular coagulation.
Ther Clin Risk Manag.
2018;14:1361–1368.
[6]Costa JA, Rodrigues M, Montero M, et al.
CT- proven ischaemic stroke as the first manifestation of occult lung cancer.
Eur J Case Rep Intern Med, 2019, 6 (1):001007.
