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Domino-Style Cerebral Bleeding in a Patient With Immune Thrombocytopenic Purpura

Domino-Style Cerebral Bleeding in a Patient With Immune Thrombocytopenic Purpura A woman in her mid to late 70s who had previously received a diagnosis of immune thrombocytopenic purpura was admitted to the hospital with disturbed activity, ataxic gait, and subacute onset of apathy. She had severe disturbance of consciousness with quadriplegia and global dysphagia, and her National Institutes of Health Stroke Scale score was 28 (range, 0-42, with 0 indicating no stroke symptom and 21-42 indicating severe stroke). She had severe thrombocytopenia (platelet count, <5 × 103/µL [to convert to ×109 per liter, multiply by 1.0]) right before hospitalization. Computed tomography of her brain revealed bleeding throughout the brain (Figure, A-C). Susceptibility weighted imaging with 3-T magnetic resonance imaging revealed abundant microbleeds and macrobleeds in the lobar area in particular. These bleeds included lesions that were visible and lesions that were invisible to computed tomography (Figure, D-F). Cerebral spinal fluid analysis revealed a remarkable decrease in the Aβ40 level (929 pg/mL; mean [SD] level, 4003 [1185] pg/mL) and in the Aβ40/Aβ42 ratio (1.56; mean [SD] ratio, 4.91 [1.13]).1 Thus, the radiological and biochemical findings suggested underlying arteriopathy related to cerebral amyloid angiopathy (CAA), albeit combined with some hypertensive arteriopathy. The administration of high doses of corticosteroids and γ-globulin rapidly brought her platelet count back to normal levels. Notably, she also quickly regained her consciousness, and she was discharged from the hospital a month later, with no neurological deficits; her National Institutes of Health Stroke Scale score was 0. For 2 years after being discharged, her platelet count was maintained at the level of 10 to 20 × 103/µL, and the numbers of microbleeds and macrobleeds detected by use of susceptibility weighted imaging with 3-T magnetic resonance imaging have not increased. Figure. Computed Tomographic (CT) and Susceptibility Weighted Imaging (SWI)/Magnetic Resonance Imaging Scans of Patient’s Brain View LargeDownload The magnetic resonance imaging was performed at 3-T field strength (MAGNETOM TrioTim; Siemens) on the third hospital day. Susceptibility weighted imaging was performed using the following parameters: repetition time, 27 milliseconds; echo time, 20 milliseconds; slice thickness, 3 mm; gap width, 0 mm. Discussion It is well known that spontaneous cerebral macrobleeds or microbleeds vary in terms of pathology depending on their anatomical location; those that occur in deep or infratentorial regions are characterized by hypertensive microangiopathy, whereas those that strictly occur in lobar areas are associated with CAA.2 Her multiple cerebral microbleeds were characterized by a myriad of fresh and chronic bleeds with neurological symptoms of subacute onset. They might be “domino-style cerebral bleeds,”2 which occur when bleeding from 1 ruptured small vessel causes secondary bleeding in other small vessels. Neurons secrete Aβ, and some of it is trapped in the cerebral vasculature before drainage. Cerebral amyloid angiopathy is characterized by increased vascular deposition and decreased Aβ levels in cerebral spinal fluid, the major isoform of which is Aβ40.1 Therefore, the decreases in the Aβ40 level and in the Aβ40/Aβ42 ratio in her cerebral spinal fluid suggest that her lobar-dominant cerebral microbleeds were characterized by CAA in addition to immune thrombocytopenic purpura, although the association of CAA and immune thrombocytopenic purpura remains to be elucidated. Although the incidence of intracerebral hemorrhage in patients with immune thrombocytopenic purpura is believed to be only 1% to 2%,3 the accompanying inflammatory endothelial damage and thrombosis due to CAA could induce domino-style multiple macrobleeds or microbleeds, similar to what was observed in a case of paroxysmal cold hemoglobinuria.4 The fact that corticosteroids and γ-globulin dramatically ameliorated her condition supports this hypothesis. Back to top Article Information Corresponding Author: Takero Shindo, MD, PhD, Department of Hematology, Respiratory Medicine and Oncology, Saga University School of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan (takeros@cc.saga-u.ac.jp). Published Online: February 22, 2016. doi:10.1001/jamaneurol.2015.4508. Conflict of Interest Disclosures: None reported. References 1. Verbeek MM, Kremer BP, Rikkert MO, Van Domburg PH, Skehan ME, Greenberg SM. Cerebrospinal fluid amyloid β40 is decreased in cerebral amyloid angiopathy. Ann Neurol. 2009;66(2):245-249.PubMedGoogle ScholarCrossref 2. Greenberg SM, Vernooij MW, Cordonnier C, et al; Microbleed Study Group. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 2009;8(2):165-174.PubMedGoogle ScholarCrossref 3. Lee MS, Kim WC. Intracranial hemorrhage associated with idiopathic thrombocytopenic purpura: report of seven patients and a meta-analysis. Neurology. 1998;50(4):1160-1163.PubMedGoogle ScholarCrossref 4. Kim GM, Kim CH, Kim BS. Multiple cerebral infarction and microbleeds associated with adult-onset paroxysmal cold hemoglobinuria. J Clin Neurosci. 2009;16(2):348-349. PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Neurology American Medical Association

Domino-Style Cerebral Bleeding in a Patient With Immune Thrombocytopenic Purpura

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Publisher
American Medical Association
Copyright
Copyright © 2016 American Medical Association. All Rights Reserved.
ISSN
2168-6149
eISSN
2168-6157
DOI
10.1001/jamaneurol.2015.4508
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Abstract

A woman in her mid to late 70s who had previously received a diagnosis of immune thrombocytopenic purpura was admitted to the hospital with disturbed activity, ataxic gait, and subacute onset of apathy. She had severe disturbance of consciousness with quadriplegia and global dysphagia, and her National Institutes of Health Stroke Scale score was 28 (range, 0-42, with 0 indicating no stroke symptom and 21-42 indicating severe stroke). She had severe thrombocytopenia (platelet count, <5 × 103/µL [to convert to ×109 per liter, multiply by 1.0]) right before hospitalization. Computed tomography of her brain revealed bleeding throughout the brain (Figure, A-C). Susceptibility weighted imaging with 3-T magnetic resonance imaging revealed abundant microbleeds and macrobleeds in the lobar area in particular. These bleeds included lesions that were visible and lesions that were invisible to computed tomography (Figure, D-F). Cerebral spinal fluid analysis revealed a remarkable decrease in the Aβ40 level (929 pg/mL; mean [SD] level, 4003 [1185] pg/mL) and in the Aβ40/Aβ42 ratio (1.56; mean [SD] ratio, 4.91 [1.13]).1 Thus, the radiological and biochemical findings suggested underlying arteriopathy related to cerebral amyloid angiopathy (CAA), albeit combined with some hypertensive arteriopathy. The administration of high doses of corticosteroids and γ-globulin rapidly brought her platelet count back to normal levels. Notably, she also quickly regained her consciousness, and she was discharged from the hospital a month later, with no neurological deficits; her National Institutes of Health Stroke Scale score was 0. For 2 years after being discharged, her platelet count was maintained at the level of 10 to 20 × 103/µL, and the numbers of microbleeds and macrobleeds detected by use of susceptibility weighted imaging with 3-T magnetic resonance imaging have not increased. Figure. Computed Tomographic (CT) and Susceptibility Weighted Imaging (SWI)/Magnetic Resonance Imaging Scans of Patient’s Brain View LargeDownload The magnetic resonance imaging was performed at 3-T field strength (MAGNETOM TrioTim; Siemens) on the third hospital day. Susceptibility weighted imaging was performed using the following parameters: repetition time, 27 milliseconds; echo time, 20 milliseconds; slice thickness, 3 mm; gap width, 0 mm. Discussion It is well known that spontaneous cerebral macrobleeds or microbleeds vary in terms of pathology depending on their anatomical location; those that occur in deep or infratentorial regions are characterized by hypertensive microangiopathy, whereas those that strictly occur in lobar areas are associated with CAA.2 Her multiple cerebral microbleeds were characterized by a myriad of fresh and chronic bleeds with neurological symptoms of subacute onset. They might be “domino-style cerebral bleeds,”2 which occur when bleeding from 1 ruptured small vessel causes secondary bleeding in other small vessels. Neurons secrete Aβ, and some of it is trapped in the cerebral vasculature before drainage. Cerebral amyloid angiopathy is characterized by increased vascular deposition and decreased Aβ levels in cerebral spinal fluid, the major isoform of which is Aβ40.1 Therefore, the decreases in the Aβ40 level and in the Aβ40/Aβ42 ratio in her cerebral spinal fluid suggest that her lobar-dominant cerebral microbleeds were characterized by CAA in addition to immune thrombocytopenic purpura, although the association of CAA and immune thrombocytopenic purpura remains to be elucidated. Although the incidence of intracerebral hemorrhage in patients with immune thrombocytopenic purpura is believed to be only 1% to 2%,3 the accompanying inflammatory endothelial damage and thrombosis due to CAA could induce domino-style multiple macrobleeds or microbleeds, similar to what was observed in a case of paroxysmal cold hemoglobinuria.4 The fact that corticosteroids and γ-globulin dramatically ameliorated her condition supports this hypothesis. Back to top Article Information Corresponding Author: Takero Shindo, MD, PhD, Department of Hematology, Respiratory Medicine and Oncology, Saga University School of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan (takeros@cc.saga-u.ac.jp). Published Online: February 22, 2016. doi:10.1001/jamaneurol.2015.4508. Conflict of Interest Disclosures: None reported. References 1. Verbeek MM, Kremer BP, Rikkert MO, Van Domburg PH, Skehan ME, Greenberg SM. Cerebrospinal fluid amyloid β40 is decreased in cerebral amyloid angiopathy. Ann Neurol. 2009;66(2):245-249.PubMedGoogle ScholarCrossref 2. Greenberg SM, Vernooij MW, Cordonnier C, et al; Microbleed Study Group. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol. 2009;8(2):165-174.PubMedGoogle ScholarCrossref 3. Lee MS, Kim WC. Intracranial hemorrhage associated with idiopathic thrombocytopenic purpura: report of seven patients and a meta-analysis. Neurology. 1998;50(4):1160-1163.PubMedGoogle ScholarCrossref 4. Kim GM, Kim CH, Kim BS. Multiple cerebral infarction and microbleeds associated with adult-onset paroxysmal cold hemoglobinuria. J Clin Neurosci. 2009;16(2):348-349. PubMedGoogle ScholarCrossref

Journal

JAMA NeurologyAmerican Medical Association

Published: Apr 1, 2016

Keywords: cerebral amyloid angiopathy,neuroimaging,cerebral hemisphere hemorrhage,purpura, thrombocytopenic, idiopathic,gait ataxia

References