Neurol Sci DOI 10.1007/s10072-014-1814-5
QUIZ CASES
Acute cerebral infarction in watershed distribution in a patient with hypereosinophilic syndrome without cardiac lesion Xiaoli Wu • Yang Guo • Xiaoping Tan
Received: 24 February 2014 / Accepted: 23 April 2014 Ó Springer-Verlag Italia 2014
Abstract We here in describe a case of hypereosinophilic syndrome (HES) with acute cerebral infarction in a watershed distribution with lesions of the carotid artery but no damage to the endocardium or myocardium. A 62-yearold Chinese man complained of left-sided hemiparesis. Brain MR showed multiple areas of acute ischemia. The eosinophil count was 4.84 3 109/L, or 41.7 % of all white blood cells. Doppler ultrasound showed multiple medium– high echo plaques in the bilateral carotid bifurcation with reduction in diameter of 10-15 %. Transthoracic echocardiography was normal. A short course of glucocorticoids and aspirin were administered to the patient, and he was discharged with significant improvement of his neurological symptoms and eosinophil count. The patient refused to take prednisone thereafter; however, 6 months later, his eosinophil count was 1.57 9 109/L, or 15.3 % of all white blood cells. Transthoracic echocardiography continued to be normal, but vascular ultrasound demonstrated many bilateral carotid low-medium echo plaques. This case describes a patient HES with acute cerebral infarction in a watershed distribution with lesions of the carotid artery but no cardiac damage. HES should be considered to be a cause of multiple cerebral infarctions. Keywords Hypereosinophilic syndrome Cerebral infarction Color Doppler ultrasound Carotid atherosclerosis
X. Wu (&) Y. Guo X. Tan Department of Neurology, Shengjing Hospital of China Medical University, Shenyang 110021, China e-mail: [email protected]
Introduction Hypereosinophilic syndrome (HES) is a rare disorder characterized by marked and persistent eosinophilia with organ system dysfunction. HES has substantial clinical heterogeneity and a highly variable prognosis. We report a case of HES presenting with multiple bilateral watershed cerebral infarctions with lesions of carotid artery instead of damage to the endocardium or myocardium.
Case report A 62-year-old Chinese man was admitted to our hospital with left-sided hemiparesis. The clinical examination was unremarkable except for left hemiparesis with 4/5 strength in his left upper and lower limbs and brisk left deep tendon reflexes. He had no history of vascular risk factors. There was no history of fever, diarrhea, skin rash, joint pains, bleeding diathesis, or viral exanthema. There was no history of parasitic infection, neoplasm, or vasculitis. There was no history suggestive of allergic rhinitis or asthma. Diffusion-weighted magnetic resonance imaging (MRI) showed posterior fossa and multiple bilateral acute cerebral ischemia in watershed distribution. MR angiography showed no evidence of arterial abnormalities (Fig. 1). Doppler ultrasound showed two proximal medium–high echo plaques at 5.7 9 2.3 mm and 12.5 9 3.3 mm in the right carotid bifurcation with a 15-20 % reduction in diameter, as well as a high echo plaque at 9.0 9 2.6 mm in the left carotid artery with a 10-15 % reduction in diameter (Figs. 2, 3). A cardiac source of microembolism was investigated via transthoracic echocardiography in light of the bilateral border zone infarctions without proximal large vessel occlusion, but the echocardiography was negative.
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Neurol Sci
Fig. 1 Hypereosinophilia with multiple cerebral infarcts in a 62-year-old man. Diffusion-weighted imaging (a-e) reveals multiple acute infarcts in bilateral border zones. f MR angiography is normal.
MRI 6 months later showed multiple areas of cerebromalacia in the parietal lobe (g, h). MR angiography is normal (i)
Etiological workup for stroke, including lipid profile, glucose, serum homocysteine, electrocardiogram and tests for disseminated intravascular coagulation, was nonrevealing. Laboratory testing demonstrated a white blood cell count of 11.6 3 109/L, with eosinophils of 4.84 3 109/L (0.04-0.49 3 109/L), or 41.7 % of all white blood cells. Stool examination for ova and parasites was negative. Autoimmune markers for antineutrophil antibody, antineutrophil cytoplasmic antibody, rheumatoid factor, and anticardiolipin antibodies (immunoglobulin G and immunoglobulin M) were negative. Other laboratory parameters, including erythrocyte sedimentation rate, high-sensitivity C-reactive protein, and troponin were within normal limits. Bone marrow examination revealed increased marrow cellularity with increased eosinophilic component. Under the diagnosis of acute HES, the patient received oral aspirin 100 mg per day and intravenous methylprednisolone
40 mg per day for 7 days, and he continued oral prednisone 60 mg per day for 1 week. His eosinophil count remained within the normal range, and he had significant improvement of his neurological symptoms. He was then discharged, and he refused to take prednisone thereafter. The patient continued oral aspirin for about 3 months after the first visit then he stopped the medicine. Six months later, the patient came back for a second visit and was noted to have full recovery of his general condition and no neurologic deficits. Magnetic resonance imaging showed multiple areas of cerebromalacia in the parietal lobe, and MR angiography showed no abnormalities (Fig. 1). Transthoracic echocardiography continued to be normal. His eosinophil count was 1.57 9 109/L, or 15.3 % of all white blood cells. What was most unexpected was the result of his carotid ultrasound, which showed bilateral internal carotid intimamedia thickening. There were two low-medium echo
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Neurol Sci Fig. 2 Color Doppler ultrasound of the right carotid artery 6 months prior (a, b) and 6 months later (c, d)
Fig. 3 Color Doppler ultrasound of the left carotid artery 6 months prior (a, b) and 6 months later (c2e)
plaques at 13.7 9 3.1 and 24.1 9 2.9 mm in the left common carotid artery with a 20-40 % reduction in diameter, and a high echo plaque at 10.5 9 2.4 mm at the
right carotid bifurcation, as well as a low echo plaque at 23.2 9 2.0 mm in the right common carotid artery with a 10-20 % reduction in diameter (Figs. 2, 3).
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Neurol Sci
Discussion HES is a rare myeloid disease characterized by the presence of persistent eosinophilia (for over 6 months) [1,500/mm3 and associated with organ involvement and dysfunction [1]. There are many other diseases that can cause extreme eosinophilia and multiple cerebra vascular lesions, such as Churg-Strauss syndrome (CSS). CSS also known as eosinophilic granulomatosis with polyangiitis is a form of vasculitis characterized mainly by inflammation of the smaller blood vessels such as arteries, arterioles and venules. CSS consists of eosinophilia, asthma and allergic vasculitis of various organ systems [2]. Vasculitis lesions in brain can lead to multiple cerebral infarctions. So CSS should be always considered in patients with hypereosinophilia and stroke. In our case, the patient had no clinical history of allergic rhinitis or asthma. Furthermore, autoimmune markers were negative. These results didnot support the diagnosis of CSS. Neurological manifestations are often observed in HES. Moore et al. documented neurologic dysfunction in 65 % of their 52 patients with HES. Of these, 12 % had stroke. The characteristic features of stroke in HES include the occurrence of multiple strokes in different vascular territories at different times. The etiology may be due to direct eosinophilic damage to the endocardium and myocardium or due to the release of eosinophilic basic proteins that initiate endomyocardial necrosis. This makes the heart a potential source of these multiple emboli [3]. In our patient, however, no cardiac thrombus or structural anomaly was found after transthoracic echocardiography was performed twice; thus there seemed to be a low possibility of cardioembolism causing the stroke. Furthermore, we found carotid atherosclerosis that progressed rapidly over 6 months without adequate treatment. Bilateral carotid artery atherosclerosis as evidenced on vascular ultrasound indicated a primary vascular lesion as a result of hypereosinophilia. So we considered the bilateral small infarcts over the anterior and posterior circulations were caused by multiple cerebrovascular damages just like in carotid arteries even if with no abnormalities with MR angiography. In our patient, eosinophils seemed to have direct cytotoxicity on the carotid wall instead of the endocardium and myocardium.
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Most previous studies have emphasized that the cytotoxic effect of proteins released by circulating eosinophils, subsequent endothelial damage, and thrombus formation are responsible for brain infarction [4]. In cerebral arteries, both thromboembolic infarction and direct eosinophilic toxicity may be caused by hypereosinophilia. Microthromboemboli preferentially embolize along vessels to the border zones. This was proved by a prior experimental report and was related to the size of the embolic particles [5]. The main mechanism of eosinophilic toxicity to cerebral arteriolar endothelial cells was thought to be through the production of the tumor necrosis factor (TNF)-a mediated by eosinophil cationic granular protein [6]. Such evidence suggested that imperceptible eosinophilic infiltrates in the vascular wall caused intima damage and eventually led to thrombosis.
Conclusions This case demonstrated a patient with hypereosinophilic syndrome with acute cerebral infarction in a watershed distribution with lesions of carotid artery but no cardiac damage. HES should be considered to be a cause of multiple cerebral infarctions.
References 1. Weller PF, Bubley GJ (1994) The idiopathic hypereosinophilic syndrome. Blood 83:2759–2779 2. Churg J, Strauss L (1951) Allergic granulomatosis, allergic angitis, and periarteritis nodosa. Am J Pathol 27:277–301 3. Ogbogu PU, Rosing DR, Horne MK (2007) Cardiovascular manifestations of hypereosinophilic syndromes. Immunol Allergy Clin North Am 27:457–475 4. Prick JJ, Gabree¨ls-Festen AA, Korten JJ, van der Wiel TW (1988) Neurological manifestations of the hypereosinophic syndrome (HES). Clin Neurol Neurosurg 90:269–273 5. Pollanen MS, Deck JH (1990) The mechanism of embolic watershed infarction: experimental studies. Can J Neurol Sci 17:395–398 6. Slungaard A, Vercellotti GM, Walker G, Nelson RD, Jacob HS (1990) Tumor necrosis factor alpha/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium. J Exp Med 171:2025–2041
QUIZ CASES
Acute cerebral infarction in watershed distribution in a patient with hypereosinophilic syndrome without cardiac lesion Xiaoli Wu • Yang Guo • Xiaoping Tan
Received: 24 February 2014 / Accepted: 23 April 2014 Ó Springer-Verlag Italia 2014
Abstract We here in describe a case of hypereosinophilic syndrome (HES) with acute cerebral infarction in a watershed distribution with lesions of the carotid artery but no damage to the endocardium or myocardium. A 62-yearold Chinese man complained of left-sided hemiparesis. Brain MR showed multiple areas of acute ischemia. The eosinophil count was 4.84 3 109/L, or 41.7 % of all white blood cells. Doppler ultrasound showed multiple medium– high echo plaques in the bilateral carotid bifurcation with reduction in diameter of 10-15 %. Transthoracic echocardiography was normal. A short course of glucocorticoids and aspirin were administered to the patient, and he was discharged with significant improvement of his neurological symptoms and eosinophil count. The patient refused to take prednisone thereafter; however, 6 months later, his eosinophil count was 1.57 9 109/L, or 15.3 % of all white blood cells. Transthoracic echocardiography continued to be normal, but vascular ultrasound demonstrated many bilateral carotid low-medium echo plaques. This case describes a patient HES with acute cerebral infarction in a watershed distribution with lesions of the carotid artery but no cardiac damage. HES should be considered to be a cause of multiple cerebral infarctions. Keywords Hypereosinophilic syndrome Cerebral infarction Color Doppler ultrasound Carotid atherosclerosis
X. Wu (&) Y. Guo X. Tan Department of Neurology, Shengjing Hospital of China Medical University, Shenyang 110021, China e-mail: [email protected]
Introduction Hypereosinophilic syndrome (HES) is a rare disorder characterized by marked and persistent eosinophilia with organ system dysfunction. HES has substantial clinical heterogeneity and a highly variable prognosis. We report a case of HES presenting with multiple bilateral watershed cerebral infarctions with lesions of carotid artery instead of damage to the endocardium or myocardium.
Case report A 62-year-old Chinese man was admitted to our hospital with left-sided hemiparesis. The clinical examination was unremarkable except for left hemiparesis with 4/5 strength in his left upper and lower limbs and brisk left deep tendon reflexes. He had no history of vascular risk factors. There was no history of fever, diarrhea, skin rash, joint pains, bleeding diathesis, or viral exanthema. There was no history of parasitic infection, neoplasm, or vasculitis. There was no history suggestive of allergic rhinitis or asthma. Diffusion-weighted magnetic resonance imaging (MRI) showed posterior fossa and multiple bilateral acute cerebral ischemia in watershed distribution. MR angiography showed no evidence of arterial abnormalities (Fig. 1). Doppler ultrasound showed two proximal medium–high echo plaques at 5.7 9 2.3 mm and 12.5 9 3.3 mm in the right carotid bifurcation with a 15-20 % reduction in diameter, as well as a high echo plaque at 9.0 9 2.6 mm in the left carotid artery with a 10-15 % reduction in diameter (Figs. 2, 3). A cardiac source of microembolism was investigated via transthoracic echocardiography in light of the bilateral border zone infarctions without proximal large vessel occlusion, but the echocardiography was negative.
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Neurol Sci
Fig. 1 Hypereosinophilia with multiple cerebral infarcts in a 62-year-old man. Diffusion-weighted imaging (a-e) reveals multiple acute infarcts in bilateral border zones. f MR angiography is normal.
MRI 6 months later showed multiple areas of cerebromalacia in the parietal lobe (g, h). MR angiography is normal (i)
Etiological workup for stroke, including lipid profile, glucose, serum homocysteine, electrocardiogram and tests for disseminated intravascular coagulation, was nonrevealing. Laboratory testing demonstrated a white blood cell count of 11.6 3 109/L, with eosinophils of 4.84 3 109/L (0.04-0.49 3 109/L), or 41.7 % of all white blood cells. Stool examination for ova and parasites was negative. Autoimmune markers for antineutrophil antibody, antineutrophil cytoplasmic antibody, rheumatoid factor, and anticardiolipin antibodies (immunoglobulin G and immunoglobulin M) were negative. Other laboratory parameters, including erythrocyte sedimentation rate, high-sensitivity C-reactive protein, and troponin were within normal limits. Bone marrow examination revealed increased marrow cellularity with increased eosinophilic component. Under the diagnosis of acute HES, the patient received oral aspirin 100 mg per day and intravenous methylprednisolone
40 mg per day for 7 days, and he continued oral prednisone 60 mg per day for 1 week. His eosinophil count remained within the normal range, and he had significant improvement of his neurological symptoms. He was then discharged, and he refused to take prednisone thereafter. The patient continued oral aspirin for about 3 months after the first visit then he stopped the medicine. Six months later, the patient came back for a second visit and was noted to have full recovery of his general condition and no neurologic deficits. Magnetic resonance imaging showed multiple areas of cerebromalacia in the parietal lobe, and MR angiography showed no abnormalities (Fig. 1). Transthoracic echocardiography continued to be normal. His eosinophil count was 1.57 9 109/L, or 15.3 % of all white blood cells. What was most unexpected was the result of his carotid ultrasound, which showed bilateral internal carotid intimamedia thickening. There were two low-medium echo
123
Neurol Sci Fig. 2 Color Doppler ultrasound of the right carotid artery 6 months prior (a, b) and 6 months later (c, d)
Fig. 3 Color Doppler ultrasound of the left carotid artery 6 months prior (a, b) and 6 months later (c2e)
plaques at 13.7 9 3.1 and 24.1 9 2.9 mm in the left common carotid artery with a 20-40 % reduction in diameter, and a high echo plaque at 10.5 9 2.4 mm at the
right carotid bifurcation, as well as a low echo plaque at 23.2 9 2.0 mm in the right common carotid artery with a 10-20 % reduction in diameter (Figs. 2, 3).
123
Neurol Sci
Discussion HES is a rare myeloid disease characterized by the presence of persistent eosinophilia (for over 6 months) [1,500/mm3 and associated with organ involvement and dysfunction [1]. There are many other diseases that can cause extreme eosinophilia and multiple cerebra vascular lesions, such as Churg-Strauss syndrome (CSS). CSS also known as eosinophilic granulomatosis with polyangiitis is a form of vasculitis characterized mainly by inflammation of the smaller blood vessels such as arteries, arterioles and venules. CSS consists of eosinophilia, asthma and allergic vasculitis of various organ systems [2]. Vasculitis lesions in brain can lead to multiple cerebral infarctions. So CSS should be always considered in patients with hypereosinophilia and stroke. In our case, the patient had no clinical history of allergic rhinitis or asthma. Furthermore, autoimmune markers were negative. These results didnot support the diagnosis of CSS. Neurological manifestations are often observed in HES. Moore et al. documented neurologic dysfunction in 65 % of their 52 patients with HES. Of these, 12 % had stroke. The characteristic features of stroke in HES include the occurrence of multiple strokes in different vascular territories at different times. The etiology may be due to direct eosinophilic damage to the endocardium and myocardium or due to the release of eosinophilic basic proteins that initiate endomyocardial necrosis. This makes the heart a potential source of these multiple emboli [3]. In our patient, however, no cardiac thrombus or structural anomaly was found after transthoracic echocardiography was performed twice; thus there seemed to be a low possibility of cardioembolism causing the stroke. Furthermore, we found carotid atherosclerosis that progressed rapidly over 6 months without adequate treatment. Bilateral carotid artery atherosclerosis as evidenced on vascular ultrasound indicated a primary vascular lesion as a result of hypereosinophilia. So we considered the bilateral small infarcts over the anterior and posterior circulations were caused by multiple cerebrovascular damages just like in carotid arteries even if with no abnormalities with MR angiography. In our patient, eosinophils seemed to have direct cytotoxicity on the carotid wall instead of the endocardium and myocardium.
123
Most previous studies have emphasized that the cytotoxic effect of proteins released by circulating eosinophils, subsequent endothelial damage, and thrombus formation are responsible for brain infarction [4]. In cerebral arteries, both thromboembolic infarction and direct eosinophilic toxicity may be caused by hypereosinophilia. Microthromboemboli preferentially embolize along vessels to the border zones. This was proved by a prior experimental report and was related to the size of the embolic particles [5]. The main mechanism of eosinophilic toxicity to cerebral arteriolar endothelial cells was thought to be through the production of the tumor necrosis factor (TNF)-a mediated by eosinophil cationic granular protein [6]. Such evidence suggested that imperceptible eosinophilic infiltrates in the vascular wall caused intima damage and eventually led to thrombosis.
Conclusions This case demonstrated a patient with hypereosinophilic syndrome with acute cerebral infarction in a watershed distribution with lesions of carotid artery but no cardiac damage. HES should be considered to be a cause of multiple cerebral infarctions.
References 1. Weller PF, Bubley GJ (1994) The idiopathic hypereosinophilic syndrome. Blood 83:2759–2779 2. Churg J, Strauss L (1951) Allergic granulomatosis, allergic angitis, and periarteritis nodosa. Am J Pathol 27:277–301 3. Ogbogu PU, Rosing DR, Horne MK (2007) Cardiovascular manifestations of hypereosinophilic syndromes. Immunol Allergy Clin North Am 27:457–475 4. Prick JJ, Gabree¨ls-Festen AA, Korten JJ, van der Wiel TW (1988) Neurological manifestations of the hypereosinophic syndrome (HES). Clin Neurol Neurosurg 90:269–273 5. Pollanen MS, Deck JH (1990) The mechanism of embolic watershed infarction: experimental studies. Can J Neurol Sci 17:395–398 6. Slungaard A, Vercellotti GM, Walker G, Nelson RD, Jacob HS (1990) Tumor necrosis factor alpha/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium. J Exp Med 171:2025–2041
![[Multiple cerebral infarctions in a patient with hypereosinophilic syndrome with Löffler endocarditis: a case report].](/assets/img/hold.png)
