Identification of rare stroke etiologic subtypes through histopathological examination of thrombectomy material

Introduction: Together with intravenous thrombolysis, mechanical thrombectomy is the gold-standard treatment within the first 6 hours of acute ischemic stroke. Histopathological evaluation of the clot retrieved during the endovascular procedure can provide information about etiology and, in particular, can help identify clots of cardiac origin. At our clinic, thrombectomy for acute ischemic stroke has been performed for more than 20 years, and for the last 8 years thrombectomy material has been sent to the pathology laboratory. Here we discuss two cases in whom diseases that only rarely cause stroke were diagnosed solely through histopathological examination of the thrombectomy material, in the absence of any other clinical clue.Methods: The hospital records and the pathology and radiology data of the two reported patients were reviewed retrospectively. No statistical analysis was performed.Case 1- A 68-year-old woman was brought to the emergency department with sudden-onset loss of consciousness and hemiparesis. She had a history of hypertension, DM, and COVID-19 pneumonia four months earlier. She was taking aspirin 100 mg, nebivolol 5 mg, irbesartan 150 mg, and metformin 2×1000 mg. On examination she was somnolent and globally aphasic, with leftward gaze deviation, right central facial palsy, plegia of the right arm, and 1–2/5 paresis of the leg. Her NIHSS score was 21. CT showed a hyperdense artery sign on the left; with an ASPECT score of 8, she was taken for emergent endovascular intervention. Successful recanalization (TICI 2c) was achieved at 230 minutes after symptom onset. The next day, NIHSS was 16, and a type 1 parenchymal hematoma developed. Work-up for stroke etiology showed no arrhythmia, intracardiac thrombus, left atrial myopathy, or carotid stenosis. Three days later, the pathology laboratory reported that the thrombectomy material showed dense, organized groups of fungal hyphae within fibrin (a fungus ball) (Figure 1), and Aspergillus infection was suspected. Chest CT showed central necrotic cavitary lesions in the lower lobes of both lungs. Aspergillus fumigatus grew in tracheal aspirate culture. She received intravenous liposomal amphotericin B for 45 days, followed by oral voriconazole for six months. After 60 days in the Neurology Intensive Care Unit and 12 days on the Neurology ward, she was discharged with an mRS of 4. Once clinical improvement was observed, a 6×6 mm saccular aneurysm in the cavernous segment of the left ICA was treated endovascularly with coiling 6 months later. She was discharged on aspirin and dual antihypertensive therapy, and levetiracetam was started at month 10 because of seizures. She is on a physiotherapy program. She is currently still aphasic and able to take food orally, with a plegic arm and 3/5 muscle strength in the leg; she can walk with a cane and is followed as incontinent (using diapers).Case 1- A 68-year-old woman was brought to the emergency department with sudden-onset loss of consciousness and hemiparesis. She had a history of hypertension, DM, and COVID-19 pneumonia four months earlier. She was taking aspirin 100 mg, nebivolol 5 mg, irbesartan 150 mg, and metformin 2×1000 mg. On examination she was somnolent and globally aphasic, with leftward gaze deviation, right central facial palsy, plegia of the right arm, and 1–2/5 paresis of the leg. Her NIHSS score was 21. CT showed a hyperdense artery sign on the left; with an ASPECT score of 8, she was taken for emergent endovascular intervention. Successful recanalization (TICI 2c) was achieved at 230 minutes after symptom onset. The next day, NIHSS was 16, and a type 1 parenchymal hematoma developed. Work-up for stroke etiology showed no arrhythmia, intracardiac thrombus, left atrial myopathy, or carotid stenosis. Three days later, the pathology laboratory reported that the thrombectomy material showed dense, organized groups of fungal hyphae within fibrin (a fungus ball) (Figure 1), and Aspergillus infection was suspected. Chest CT showed central necrotic cavitary lesions in the lower lobes of both lungs. Aspergillus fumigatus grew in tracheal aspirate culture. She received intravenous liposomal amphotericin B for 45 days, followed by oral voriconazole for six months. After 60 days in the Neurology Intensive Care Unit and 12 days on the Neurology ward, she was discharged with an mRS of 4. Once clinical improvement was observed, a 6×6 mm saccular aneurysm in the cavernous segment of the left ICA was treated endovascularly with coiling 6 months later. She was discharged on aspirin and dual antihypertensive therapy, and levetiracetam was started at month 10 because of seizures. She is on a physiotherapy program. She is currently still aphasic and able to take food orally, with a plegic arm and 3/5 muscle strength in the leg; she can walk with a cane and is followed as incontinent (using diapers).Case 2- A 46-year-old woman was brought to the emergency department with sudden-onset left-sided weakness. She had no known systemic disease, but during a pregnancy 20 years earlier she had had a pulmonary embolism and had temporarily used enoxaparin. On examination she was alert and mildly dysarthric. She had left central facial palsy, left hemiplegia, a left Babinski sign, and left hemihypoesthesia. Her NIHSS score was 16. DWI showed a patchy, incompletely established infarct in the right middle cerebral artery territory. With no contraindication, she was taken to the angiography suite and, under general anesthesia, successful TICI 3 recanalization was achieved by aspiration at 150 minutes after symptom onset (Figure 2). The next day her muscle strength had largely recovered and she began to walk. By the end of the first week, NIHSS was 0. She was monitored for 2 nights in the Neurology intensive care unit and for 4 days on the ward. Rhythm Holter monitoring, transthoracic echocardiography, and transesophageal echocardiography were normal, and there were no radiological findings suggestive of carotid disease or intracranial atherosclerosis. After 15 days, the pathology laboratory reported that the thrombectomy material showed fibrin fragments densely infiltrated by polymorphonuclear leukocytes. In the young stroke work-up, lupus anticoagulant was elevated on two occasions four months apart (L1: 56.1-59, L2: 43.8-53.9), and the lupus ratio was 1.04. ANA and cANCA were also positive on repeat testing, at titers between 1/10 and 1/320. Rheumatological evaluation found no other evidence of systemic SLE involvement. Evaluated together with the pathological findings, the findings led to a diagnosis of “antiphospholipid antibody syndrome,” and colchicine and chloroquine were added to warfarin. Two years later, warfarin was switched to rivaroxaban because of vaginal bleeding, and four months after this she developed sudden vision loss in one eye; she was diagnosed with “paracentral acute middle maculopathy (PAMM)” secondary to small vessel occlusion in the superficial and middle layers of the retina. She was switched back to warfarin. She continues to be followed with no sequelae and an mRS of 0.Case 2- A 46-year-old woman was brought to the emergency department with sudden-onset left-sided weakness. She had no known systemic disease, but during a pregnancy 20 years earlier she had had a pulmonary embolism and had temporarily used enoxaparin. On examination she was alert and mildly dysarthric. She had left central facial palsy, left hemiplegia, a left Babinski sign, and left hemihypoesthesia. Her NIHSS score was 16. DWI showed a patchy, incompletely established infarct in the right middle cerebral artery territory. With no contraindication, she was taken to the angiography suite and, under general anesthesia, successful TICI 3 recanalization was achieved by aspiration at 150 minutes after symptom onset (Figure 2). The next day her muscle strength had largely recovered and she began to walk. By the end of the first week, NIHSS was 0. She was monitored for 2 nights in the Neurology intensive care unit and for 4 days on the ward. Rhythm Holter monitoring, transthoracic echocardiography, and transesophageal echocardiography were normal, and there were no radiological findings suggestive of carotid disease or intracranial atherosclerosis. After 15 days, the pathology laboratory reported that the thrombectomy material showed fibrin fragments densely infiltrated by polymorphonuclear leukocytes. In the young stroke work-up, lupus anticoagulant was elevated on two occasions four months apart (L1: 56.1-59, L2: 43.8-53.9), and the lupus ratio was 1.04. ANA and cANCA were also positive on repeat testing, at titers between 1/10 and 1/320. Rheumatological evaluation found no other evidence of systemic SLE involvement. Evaluated together with the pathological findings, the findings led to a diagnosis of “antiphospholipid antibody syndrome,” and colchicine and chloroquine were added to warfarin. Two years later, warfarin was switched to rivaroxaban because of vaginal bleeding, and four months after this she developed sudden vision loss in one eye; she was diagnosed with “paracentral acute middle maculopathy (PAMM)” secondary to small vessel occlusion in the superficial and middle layers of the retina. She was switched back to warfarin. She continues to be followed with no sequelae and an mRS of 0.Discussion/Conclusion: Thrombus material removed with retrievable stents or aspiration catheters can be distinguished according to its source by its content of fibrin/platelet aggregates, erythrocytes, and leukocytes. Clots that contain leukocytes together with fibrin and platelet clusters are generally accepted as cardiac in origin, and erythrocyte-rich clots as originating from non-cardiac sources. Cerebral emboli arising from infective endocarditis can also be identified by histopathological examination of thrombectomy material. Our two patients show how necessary it is to examine the clot removed by thrombectomy with microscopic