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Geriatr Gerontol Int 2015; 15: 811–815
LETTERS TO THE EDITOR CASE REPORT
Alzheimer’s disease associated with sporadic cerebral amyloid angiopathy in an elderly patient
Dear Editor, A 67-year-old woman was hospitalized for ischemic stroke. The computed tomography scan and cerebral magnetic resonance imaging (MRI) showed right frontoparietal hypodensity, suggestive of a recent ischemic stroke. Cerebral MRI also found three other similar small lesions in the frontal and left parietal white matter as well as biparietal cortical atrophy, right hippocampal atrophy and hyperintensity as a result of a microangiopathy, without hemosiderin deposition. Magnetic resonance angiography found no significant stenosis of large arteries or aneurysm. Clopidogrel was given for the secondary prevention of stroke. The clinical course was characterized by several ischemic strokes causing epilepsy, for which valproate was started. Rapid cognitive decline appeared with a Mini-Mental State Examination score of 15/30. Valproate-induced encephalopathy was suspected and confirmed by cognitive improvement (increase in Mini-Mental State Examination score up to 27/30) after stopping the treatment. However, 1 year later, a progressive cognitive decline reappeared, with loss of autonomy, compatible with Alzheimer’s disease (AD), given the neuropsychological assessment. Cerebral MRI showed frontal lacunar syndrome, hemosiderosis, cortical and right hippocampal atrophy, microbleeds, and focal subarachnoid hemorrhage (FSAH). Because of the risk of increased bleeding, clopidrogel was stopped. Mixed hippocampal and vascular dementia was suspected. Phasic
disorders progressively increased; 2 years later, the patient had difficulty understanding complex instructions, and apraxia appeared. In addition to atrophy (cortex and corpus callosum), cerebral MRI (Fig. 1) showed microangiopathy of the semi-oval centers and lateral ventricles, the after-effects of subarachnoid hemorrhage, and cerebellar punctiform areas of hemosiderin, suggesting cerebral amyloid angiopathy (CAA). Magnetic resonance angiography showed bilateral atheroma in both C4 segments and possible stenosis of the C5 segment of the right carotid. Analysis of the cerebrospinal fluid showed an increase in levels of protein, tau protein and phosphorylated tau protein, and a decrease in amyloid-β-peptide-1–42 level. The significant increase in tau protein and phosphorylated tau protein levels associated with a reduction in the amyloid-β-peptide-1–42 rate in the cerebrospinal fluid consolidated the hypothesis of probable AD associated with sporadic CAA. CAA is observed in more than 80% of cases of AD.1 It is classically secondary to an aneurysm or trauma. However, neither aneurysm nor a history or mark of trauma was found in the present patient. The cognitive decline was initially attributed to valproate, as cognition improved rapidly after stopping the drug.2 However, this improvement lasted for only 1 year. The cognitive disorders were also compatible with AD, but we suspected mixed dementia in view of the association of dysexecutive symptoms with cortical signs.3 The follow-up brain MRI showed new lesions
Figure 1 Bilateral superficial siderosis in the temporal and parietal lobes with bilateral supra- and subtentorial microbleeds.
© 2015 Japan Geriatrics Society
doi: 10.1111/ggi.12460
| 811
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N Watanabe et al.
evocative of CAA. The lesions were hemosiderin deposits on the one hand and probable FSAH on the other.4 Indeed, cortical superficial hemosiderosis is a common and characteristic feature of CAA, and hemorrhage into the subarachnoid space could also contribute to hemosiderosis in CAA.4 Finally, the patient’s age (6th decade) was compatible with reports for CAA.5 However, FSAH is not in the Boston criteria.6 Usually, the subarachnoid hemorrhage is a result of lobar hematoma.7 Some authors suggest that FSAH be included in the diagnostic criteria for sporadic CAA in the elderly.8 The increase in tau protein and phosphorylated tau protein levels in the cerebrospinal fluid coupled with a decrease in amyloid-β-peptide-1–42 rate were in favor of AD (in addition to hippocampal atrophy) and sporadic CAA.9 The clinician should consider the possibility of CAA in the elderly, which is a contraindication to anticoagulant therapy.10
Acknowledgment The authors are grateful to Mr Philip Bastable.
Disclosure The authors declare no conflict of interest. Odile Guaquière-Bernard,1 Olivier Rouaud2 and Patrick Manckoundia3,4 1 Nursing Home «Valmy, Résidalya», Departments of 2Neurology, 3 Geriatrics and Internal Medicine, Hospital of Champmaillot, University Hospital, and 4Inserm/U1093 Motricity-Plasticity, University of Burgundy, Dijon, France
References 1 Feldman HH, Maia LF, Mackenzie IR, Forster BB, Martzke J, Woolfenden A. Superficial siderosis: a potential diagnostic marker of cerebral amyloid angiopathy in Alzheimer disease. Stroke 2008; 39: 2894–2897. 2 Manckoundia P, Disson-Dautriche A, Rouaud O, Richard D, Tavernier-Vidal B, Pfitzenmeyer P. Syndrome démentiel du sujet âgé lié à un traitement par acide valproïque : à propos d’un cas. Rev Med Interne 2008; 29: 827–829. 3 McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984; 34: 939–944. 4 Charidimou A, Jäger RH, Fox Z et al. Prevalence and mechanisms of cortical superficial siderosis in cerebral amyloid angiopathy. Neurology 2013; 81: 626–632. 5 Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012; 83: 124–137. 6 Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy. Validation of the Boston criteria. Neurology 2001; 56: 537–539. 7 Linn J, Wollenweber FA, Lummel N et al. Superficial siderosis is warning sign for future intracranial hemorrhage. J Neurol 2013; 260: 176–181. 8 Linn J, Halpin A, Demaerel P et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010; 74: 1346–1350. 9 Alonzo NC, Hyman BT, Rebeck GW, Greenberg SM. Progression of cerebral amyloid angiopathy: accumulation of amyloid-béta40 in affected vessels. J Neuropathol Exp Neurol 1998; 57: 353–359. 10 McCarron MO, Hoffmann KL, DeLong DM, Gray L, Saunders AM, Alberts MJ. Intracerebral hemorrhage outcome: apolipoprotein E genotype, hematoma, and edema volumes. Neurology 1999; 53: 2176–2179.
Reactivation of hepatitis B virus during treatment with hydroxyurea in an elderly patient with essential thrombocythemia Dear Editor, A 72-year-old woman with JAK2V617F mutationpositive essential thrombocythemia (ET) came to Juntendo University Hospital, Tokyo, Japan, in March 2003. She had been treated with 500 mg/day of hydroxyurea (HU) and low-dose aspirin since 1996 at another hospital. On first medical examination, hepatitis B surface (HBs) antigen (Ag) and antihepatitis B envelope (HBe) antibody (Ab) were positive, HBeAg was negative and hepatitis B virus (HBV)-DNA levels were undetect812 |
doi: 10.1111/ggi.12461
able, and she was observed as an inactive HBV carrier. The dose of HU was gradually increased at our hospital, maximized at 1500 mg/day. In April 2012, a slight increase of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of 64 IU/L and 48 IU/L was seen, respectively, and persisted at around the same levels thereafter. In February 2013, a further rise of AST and ALT of 276 IU/L and 139 IU/L was observed, respectively, and HU and aspirin administration were discontinued under the suspicion of drug-induced liver dysfunction. However, liver dysfunction exacerbated, © 2015 Japan Geriatrics Society
Geriatr Gerontol Int 2015; 15: 811–815
LETTERS TO THE EDITOR CASE REPORT
Alzheimer’s disease associated with sporadic cerebral amyloid angiopathy in an elderly patient
Dear Editor, A 67-year-old woman was hospitalized for ischemic stroke. The computed tomography scan and cerebral magnetic resonance imaging (MRI) showed right frontoparietal hypodensity, suggestive of a recent ischemic stroke. Cerebral MRI also found three other similar small lesions in the frontal and left parietal white matter as well as biparietal cortical atrophy, right hippocampal atrophy and hyperintensity as a result of a microangiopathy, without hemosiderin deposition. Magnetic resonance angiography found no significant stenosis of large arteries or aneurysm. Clopidogrel was given for the secondary prevention of stroke. The clinical course was characterized by several ischemic strokes causing epilepsy, for which valproate was started. Rapid cognitive decline appeared with a Mini-Mental State Examination score of 15/30. Valproate-induced encephalopathy was suspected and confirmed by cognitive improvement (increase in Mini-Mental State Examination score up to 27/30) after stopping the treatment. However, 1 year later, a progressive cognitive decline reappeared, with loss of autonomy, compatible with Alzheimer’s disease (AD), given the neuropsychological assessment. Cerebral MRI showed frontal lacunar syndrome, hemosiderosis, cortical and right hippocampal atrophy, microbleeds, and focal subarachnoid hemorrhage (FSAH). Because of the risk of increased bleeding, clopidrogel was stopped. Mixed hippocampal and vascular dementia was suspected. Phasic
disorders progressively increased; 2 years later, the patient had difficulty understanding complex instructions, and apraxia appeared. In addition to atrophy (cortex and corpus callosum), cerebral MRI (Fig. 1) showed microangiopathy of the semi-oval centers and lateral ventricles, the after-effects of subarachnoid hemorrhage, and cerebellar punctiform areas of hemosiderin, suggesting cerebral amyloid angiopathy (CAA). Magnetic resonance angiography showed bilateral atheroma in both C4 segments and possible stenosis of the C5 segment of the right carotid. Analysis of the cerebrospinal fluid showed an increase in levels of protein, tau protein and phosphorylated tau protein, and a decrease in amyloid-β-peptide-1–42 level. The significant increase in tau protein and phosphorylated tau protein levels associated with a reduction in the amyloid-β-peptide-1–42 rate in the cerebrospinal fluid consolidated the hypothesis of probable AD associated with sporadic CAA. CAA is observed in more than 80% of cases of AD.1 It is classically secondary to an aneurysm or trauma. However, neither aneurysm nor a history or mark of trauma was found in the present patient. The cognitive decline was initially attributed to valproate, as cognition improved rapidly after stopping the drug.2 However, this improvement lasted for only 1 year. The cognitive disorders were also compatible with AD, but we suspected mixed dementia in view of the association of dysexecutive symptoms with cortical signs.3 The follow-up brain MRI showed new lesions
Figure 1 Bilateral superficial siderosis in the temporal and parietal lobes with bilateral supra- and subtentorial microbleeds.
© 2015 Japan Geriatrics Society
doi: 10.1111/ggi.12460
| 811
bs_bs_banner
N Watanabe et al.
evocative of CAA. The lesions were hemosiderin deposits on the one hand and probable FSAH on the other.4 Indeed, cortical superficial hemosiderosis is a common and characteristic feature of CAA, and hemorrhage into the subarachnoid space could also contribute to hemosiderosis in CAA.4 Finally, the patient’s age (6th decade) was compatible with reports for CAA.5 However, FSAH is not in the Boston criteria.6 Usually, the subarachnoid hemorrhage is a result of lobar hematoma.7 Some authors suggest that FSAH be included in the diagnostic criteria for sporadic CAA in the elderly.8 The increase in tau protein and phosphorylated tau protein levels in the cerebrospinal fluid coupled with a decrease in amyloid-β-peptide-1–42 rate were in favor of AD (in addition to hippocampal atrophy) and sporadic CAA.9 The clinician should consider the possibility of CAA in the elderly, which is a contraindication to anticoagulant therapy.10
Acknowledgment The authors are grateful to Mr Philip Bastable.
Disclosure The authors declare no conflict of interest. Odile Guaquière-Bernard,1 Olivier Rouaud2 and Patrick Manckoundia3,4 1 Nursing Home «Valmy, Résidalya», Departments of 2Neurology, 3 Geriatrics and Internal Medicine, Hospital of Champmaillot, University Hospital, and 4Inserm/U1093 Motricity-Plasticity, University of Burgundy, Dijon, France
References 1 Feldman HH, Maia LF, Mackenzie IR, Forster BB, Martzke J, Woolfenden A. Superficial siderosis: a potential diagnostic marker of cerebral amyloid angiopathy in Alzheimer disease. Stroke 2008; 39: 2894–2897. 2 Manckoundia P, Disson-Dautriche A, Rouaud O, Richard D, Tavernier-Vidal B, Pfitzenmeyer P. Syndrome démentiel du sujet âgé lié à un traitement par acide valproïque : à propos d’un cas. Rev Med Interne 2008; 29: 827–829. 3 McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984; 34: 939–944. 4 Charidimou A, Jäger RH, Fox Z et al. Prevalence and mechanisms of cortical superficial siderosis in cerebral amyloid angiopathy. Neurology 2013; 81: 626–632. 5 Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012; 83: 124–137. 6 Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy. Validation of the Boston criteria. Neurology 2001; 56: 537–539. 7 Linn J, Wollenweber FA, Lummel N et al. Superficial siderosis is warning sign for future intracranial hemorrhage. J Neurol 2013; 260: 176–181. 8 Linn J, Halpin A, Demaerel P et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010; 74: 1346–1350. 9 Alonzo NC, Hyman BT, Rebeck GW, Greenberg SM. Progression of cerebral amyloid angiopathy: accumulation of amyloid-béta40 in affected vessels. J Neuropathol Exp Neurol 1998; 57: 353–359. 10 McCarron MO, Hoffmann KL, DeLong DM, Gray L, Saunders AM, Alberts MJ. Intracerebral hemorrhage outcome: apolipoprotein E genotype, hematoma, and edema volumes. Neurology 1999; 53: 2176–2179.
Reactivation of hepatitis B virus during treatment with hydroxyurea in an elderly patient with essential thrombocythemia Dear Editor, A 72-year-old woman with JAK2V617F mutationpositive essential thrombocythemia (ET) came to Juntendo University Hospital, Tokyo, Japan, in March 2003. She had been treated with 500 mg/day of hydroxyurea (HU) and low-dose aspirin since 1996 at another hospital. On first medical examination, hepatitis B surface (HBs) antigen (Ag) and antihepatitis B envelope (HBe) antibody (Ab) were positive, HBeAg was negative and hepatitis B virus (HBV)-DNA levels were undetect812 |
doi: 10.1111/ggi.12461
able, and she was observed as an inactive HBV carrier. The dose of HU was gradually increased at our hospital, maximized at 1500 mg/day. In April 2012, a slight increase of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of 64 IU/L and 48 IU/L was seen, respectively, and persisted at around the same levels thereafter. In February 2013, a further rise of AST and ALT of 276 IU/L and 139 IU/L was observed, respectively, and HU and aspirin administration were discontinued under the suspicion of drug-induced liver dysfunction. However, liver dysfunction exacerbated, © 2015 Japan Geriatrics Society
