Original Paper Eur Neurol 2014;71:283–287 DOI: 10.1159/000357426
Received: July 23, 2013 Accepted: November 17, 2013 Published online: February 26, 2014
The Importance of Amyloid β Protein in Cerebrospinal Fluid when You Recognize Convexal Subarachnoid Hemorrhage Ryota Tamura Hideyuki Tomita Katsuhiro Mizutani Tomoru Miwa Department of Neurosurgery, Ashikaga Red Cross Hospital, Ashikaga City, Japan
Abstract Background: Convexal subarachnoid hemorrhage (cSAH) is sometimes experienced in cerebral amyloid angiopathy (CAA), but ones that are repeated within a brief time period are not common. Also, it is often difficult to diagnose CAA when you experience a case of cSAH. Methods: We examined the clinical course of 2 cases that showed cSAH repeatedly. We examined cerebrospinal fluid (CSF) concentrations of amyloid β protein (Aβ) 40 and 42 and tau protein as additional evidence for a diagnosis of CAA. Results: Case 1 presented with transient motor paresis of the left hand and case 2 with transient sensory disturbance of the left hand. CT scans showed cSAH on the right central sulcus in both patients. Case 1 showed development of intracerebral hemorrhage on the frontal lobe near the right central sulcus. Case 2 showed relapse of cSAH with recurrence of the same symptoms. These cases could not be diagnosed by image analysis, but were considered CAA by Aβ40, Aβ42 and tau protein in CSF. Conclusion: Aβ in CSF can be presented here as support for the diagnosis of CAA that is difficult to diagnose by Boston criteria. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 0014–3022/14/0716–0283$39.50/0 E-Mail [email protected] www.karger.com/ene
Introduction
In the elderly, cerebral amyloid angiopathy (CAA)-associated intracerebral hemorrhage (ICH) tends to be lobar in location, but CAA patients sometimes present with atraumatic localized convexal subarachnoid hemorrhage (cSAH). However, there are no reports mentioning that cSAH is repeated within a short time period. The Boston criteria were used as a means of making a presumptive diagnosis of CAA clinically [1]. How should we identify the causative disease if there are no specific observations in angiography, magnetic resonance imaging (MRI) and so on? We report the clinical findings from 2 patients who presented with repetitive cSAH caused by CAA, and the importance and technique involved in the diagnosis using cerebrospinal fluid (CSF) concentrations of amyloid β peptide (Aβ) [2].
Methods Two cases, each with cSAH on the right central sulcus, were seen at our hospital in 2012. We examined the unusual clinical course and transition on computed tomography (CT) and MRI for the 2 cases that showed repetitive cSAH caused by CAA. We reviewed and compared our findings with those from previously published reports.
Hideyuki Tomita, MD Department of Neurosurgery Ashikaga Red Cross Hospital 284-1 Yobe-cho, Ashikaga City 326-0843 (Japan) E-Mail h.tomita-jns @ ashikaga.jrc.or.jp
Downloaded by: University of Tokyo 157.82.153.40 - 6/1/2015 1:39:34 AM
Key Words Cerebral amyloid angiopathy · Alzheimer’s disease · Convexal subarachnoid hemorrhage · Reversible cerebral vasoconstriction syndrome · Amyloid β
a
b
c
d
Fig. 1. Unenhanced head CT showed cSAH (a) on the right central sulcus at the time of first admission, ICH (b) on the frontal lobe
We did not use biopsy, but instead examined CSF concentrations of Aβ40, Aβ42 and tau protein as additional means of diagnosing CAA. In addition, we investigated whether the patients were suffering from Alzheimer’s disease (AD) by examination with single-photon emission computed tomography (SPECT) and Z scores of voxel-based specific regional analysis system for AD (VSRAD) on MRI [3].
Results
Case 1 Unenhanced head CT showed cSAH on the right central sulcus of a 63-year-old woman who presented with transient motor paresis of her left hand; the patient was thus admitted to our hospital (fig. 1a). Vital signs were normal. The Glasgow Coma Scale score was 14 (E4V4M6). Her neck was supple, and the neurologic examination was 284
Eur Neurol 2014;71:283–287 DOI: 10.1159/000357426
unremarkable except for a left Barre’s sign. Blood analysis was normal. There were no thrombotic risks (protein S, protein C, etc.). There were no abnormal findings on 3-dimensional CT angiography. Susceptibility-weighted imaging of MRI on day 2 showed cSAH, single superficial siderosis and 1 microbleed involving the right frontal lobe. There were no acute cerebral infarctions or neoplastic lesions. On the same day, we performed brain angiography, but there were no aneurysms, arteriovenous malformations or fistulas, thromboses or spasms. In the evening after brain angiography, the patient was suddenly in a semidelirious state. CT showed ICH on the frontal lobe near the right central sulcus (fig. 1b). Hemiparesis was temporarily severer, but it gradually improved. On day 22, the patient was discharged. On day 57, MRI was performed in our outpatient department and showed recurrent multiple cSAH in the right frontal, parietal and temporal lobes Tamura/Tomita/Mizutani/Miwa
Downloaded by: University of Tokyo 157.82.153.40 - 6/1/2015 1:39:34 AM
near the right central sulcus on day 2 and ICH (d) on the frontal lobe in the same position as on day 2. c Unenhanced head MRI showed recurrent multiple cSAH in the right frontal, parietal and temporal lobe on day 57.
a
b
c
d
Fig. 2. Unenhanced head CT showed cSAH (a) on the right central sulcus at the time of first admission, cSAH (b) on the right cen-
(fig. 1c). She remained free of symptoms. A brain angiography was performed again, but there were no abnormal findings. On day 90, the patient was taken to our hospital by ambulance with left hemiplegia. Her Glasgow Coma Scale score was 14 (E4V4M6). A CT showed massive ICH in the frontal lobe in the same position as on day 2 (fig. 1d). She did not report having a headache. MRI showed no abnormal findings. Her cognitive symptoms worsened, so we examined SPECT and her Z score of VSRAD on MRI. SPECT showed diminished blood flow to the parietal lobes bilaterally, and the hippocampus had become atrophic. Her Z score of VSRAD was 3.2 [3]. Thus, she was suspected of having AD, and we prescribed donepezil hydrochloride. She received rehabilitation and her paralysis improved (modified Rankin scale grade 2). We were able to keep dementia from worsening, and she was discharged on day 155.
We could not diagnose CAA actively using the Boston criteria, because no multiple microbleeds were found on the MRI. So we examined CSF concentrations of Aβ40, Aβ42 and tau protein to support a diagnosis. The level of Aβ40 was 1,790 pmol/l, Aβ42 was 63.7 pmol/l and total tau protein (t-tau) was 546 pg/ml. Concentrations of Aβ40 and Aβ42 were lower than control levels, while that of t-tau was higher than control levels. These results suggested the possibility of CAA with AD [2].
Aβ Protein in Cerebrospinal Fluid and cSAH
Eur Neurol 2014;71:283–287 DOI: 10.1159/000357426
Case 2 A 76-year-old woman presented to our hospital with transient sensory disturbance of the left hand, involving numbness over a few minutes. She did not report having a headache. Unenhanced head CT showed cSAH on the right central sulcus as in case 1 (fig. 2a). Vital signs were normal. Her Glasgow Coma Scale score was 14 (E4V4M6). Her neck was supple. Blood analysis was normal. 285
Downloaded by: University of Tokyo 157.82.153.40 - 6/1/2015 1:39:34 AM
tral sulcus and other frontal and parietal sulci on day 5, a small amount of relapse (c) of cSAH on the right central sulcus on day 7, and relapses (d) of cSAH on the right central sulcus with headache and vomiting on day 26.
Discussion
Here, we present 2 cases of repetitive cSAH that were likely caused by CAA. First, acute cSAH is sometimes seen, has seldom been described and is associated with a variety of causes, including cerebral venous thrombosis, vascular malformations, reversible cerebral vasoconstriction syndrome, posterior reversible encephalopathy syndrome and CAA, among others [4]. In principle, biopsy provides pathologic confirmation of CAA. Findings from MRI such as leukoaraiosis, hemispheric microbleeds and superficial siderosis are clearly important for diagnosis. More microbleeds are scattered on the cerebral cortex of CAA patients compared to controls (47.4 vs. 22.4%). Thus, frequent asymptomatic microbleeds may be one means of characterizing CAA. More than 60.5% of CAA patients showed superficial siderosis on MRI, compared to the absence of siderosis in controls. As stated by Linn et al. [5], the sensitivity of the Boston criteria for diagnosing CAA is 89.5%, but the sen286
Eur Neurol 2014;71:283–287 DOI: 10.1159/000357426
sitivity is improved up to 94.7% with the evaluation of superficial siderosis. However, how should we identify causative disease if there are no specific observations in angiography, MRI and so on? In those cases, Aβ in the CSF can be a key to diagnosing. We examined the CSF concentrations of Aβ40, Aβ42 and tau protein as auxiliary diagnostic tools. The control value of Aβ42 is 838 ± 253 pg/ml, that of Aβ40 is 4,003 ± 1,185 pg/ml, and t-tau is 215 ± 78.3 pg/ml. Compared with control subjects, decreased CSF Aβ42 is found in both AD and CAA patients; it is lower in CAA patients than in AD patients. Among CAA patients, Aβ42 is found at a mean level of 42.4% that of control values, while in AD patients, it is 51.6% that of control values. In contrast, the concentration of Aβ40 in CSF is decreased only in CAA patients compared with AD patients and controls. Both CSF t-tau and phosphorylated tau protein concentrations are significantly higher in AD patients compared with CAA patients, although the concentrations in CAA patients are higher than those in controls. Sensitivity and specificity for Aβ40 are 87.5 and 47.1%, respectively; those for Aβ42 are 86.2 and 94.1%, respectively; those for t-tau are 96.5 and 52.9%, respectively, and those for phosphorylated tau are 77.6 and 58.8%, respectively [2]. In both cases, Aβ40 and Aβ42 concentrations were lower than in the controls, while t-tau concentrations were higher than control values. These results suggest the possibility of an association between CAA and AD, especially in case 1, where SPECT and the Z score of VSRAD showed complications related to AD [3]. Generally CAA is associated with AD in 80% of cases [6, 7]. When comparing MRI and Aβ in CSF, Aβ in CSF has a higher sensitivity and specificity. As seen in these cases, MRI could not diagnose CAA, but CSF made the diagnosis possible. So we think CSF analysis is important for CAA. cSAH in these cases are typical for the location and symptoms. In general, the majority of cases of cSAH (51%) are localized to the frontal lobe and 21% are localized to the parietal lobe. Patients often present with transient motor or sensory symptoms, as in both of the cases described here. Patients may not report suffering from a headache or they may report a mild headache. At first glance, symptoms of cSAH, like those seen in the present cases, may be handled as recurring complaints on an outpatient basis. We believe that there may be a large number of patients with cSAH that escape clinical recognition. It is difficult to diagnose CAA at that stage of cSAH [8]. Tamura/Tomita/Mizutani/Miwa
Downloaded by: University of Tokyo 157.82.153.40 - 6/1/2015 1:39:34 AM
No abnormal findings were revealed by 3-dimensional CT angiography and brain angiography on day 2. On day 5, enhanced MRI showed exacerbated cSAH on the right central sulcus and other frontal and parietal sulci with no symptoms (fig. 2b). There were no microbleeds and superficial siderosis in the right cerebral hemisphere on the T2*-weighted phase. On day 7, the patient was discharged. On that same day, the patient presented to our hospital again with transient sensory disturbance of the left hand. A CT scan showed a minor relapse of cSAH on the right central sulcus (fig. 2c). Symptoms improved after a few minutes, and the patient returned home. On day 22, she returned to our hospital again with the same symptoms. A CT scan showed no hemorrhage, but she was admitted for follow-up. On day 26, she complained of a mild headache and vomited. The CT scan showed relapse of cSAH on the right central sulcus (fig. 2d). Subsequently, she became asymptomatic, and CT showed no increase in cSAH. On day 31, she was discharged. In case 2, SPECT did not show a pattern consistent with AD. The Z score of VSRAD was 1.33, so AD was interpreted as negative [3]. However, the level of Aβ40 was 2,430 pmol/l, Aβ42 was 155 pmol/l and t-tau was 645 pg/ ml in CSF. Aβ40 and Aβ42 concentrations were lower than control levels, while that of t-tau was higher than control levels. These results suggest the possibility of CAA with AD [2].
However, it has never been reported that cSAH happens repeatedly within a short time period. These cases are both diagnosed as CAA. So cSAH caused by CAA can happen repeatedly within a short time period and finally become ICH of lobar location like in case 1. In other words, cSAH caused by CAA may act as a warning of progression to ICH, so a careful follow-up is vitally important.
Conclusions
Aβ protein in CSF can be presented here as support for the diagnosis of CAA that is difficult to diagnose by Boston criteria. cSAH repeated within a short time period is not so seen and since there is a possibility of CAA, it may act as a warning of progression to ICH, so a careful follow-up is vitally important.
References
Aβ Protein in Cerebrospinal Fluid and cSAH
4 Cuvinciuc V, Viguier A, Calviere L, et al: Isolated acute nontraumatic cortical subarachnoid hemorrhage. Am J Neuroradiol 2010;31: 1355–1362. 5 Linn J, Halpin A, Demaerel P, et al: Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010;74: 1346–1350.
6 Arvanitakis Z, Leurgans SE, Wang Z, et al: Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann Neurol 2011;69:320–327. 7 Yamada M: Risk factors for cerebral amyloid angiopathy in the elderly. Ann NY Acad Sci 2002;977:37–44. 8 Kumar S, Goddeau RP, Selim MH, et al: Atraumatic convexal subarachnoid hemorrhage: clinical presentation, imaging patterns, and etiologies. Neurology 2010; 74: 893–899.
Eur Neurol 2014;71:283–287 DOI: 10.1159/000357426
287
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1 Knudsen KA, Rosand J, Karluk D, et al: Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston Criteria. Neurology 2001;56:537–539. 2 Verbeek MM, Kremer BPH, Rikkert MO, et al: Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy. Ann Neurol 2009;66:245–249. 3 Li X, Shimizu S, Jikiki I, et al: Correlations between Z-score of VSRAD and regional cerebral blood flow of SPECT in patients with Alzheimer’s disease and mild cognitive impairment. Psychiatry Clin Neurosci 2010;64:284–292.
Received: July 23, 2013 Accepted: November 17, 2013 Published online: February 26, 2014
The Importance of Amyloid β Protein in Cerebrospinal Fluid when You Recognize Convexal Subarachnoid Hemorrhage Ryota Tamura Hideyuki Tomita Katsuhiro Mizutani Tomoru Miwa Department of Neurosurgery, Ashikaga Red Cross Hospital, Ashikaga City, Japan
Abstract Background: Convexal subarachnoid hemorrhage (cSAH) is sometimes experienced in cerebral amyloid angiopathy (CAA), but ones that are repeated within a brief time period are not common. Also, it is often difficult to diagnose CAA when you experience a case of cSAH. Methods: We examined the clinical course of 2 cases that showed cSAH repeatedly. We examined cerebrospinal fluid (CSF) concentrations of amyloid β protein (Aβ) 40 and 42 and tau protein as additional evidence for a diagnosis of CAA. Results: Case 1 presented with transient motor paresis of the left hand and case 2 with transient sensory disturbance of the left hand. CT scans showed cSAH on the right central sulcus in both patients. Case 1 showed development of intracerebral hemorrhage on the frontal lobe near the right central sulcus. Case 2 showed relapse of cSAH with recurrence of the same symptoms. These cases could not be diagnosed by image analysis, but were considered CAA by Aβ40, Aβ42 and tau protein in CSF. Conclusion: Aβ in CSF can be presented here as support for the diagnosis of CAA that is difficult to diagnose by Boston criteria. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 0014–3022/14/0716–0283$39.50/0 E-Mail [email protected] www.karger.com/ene
Introduction
In the elderly, cerebral amyloid angiopathy (CAA)-associated intracerebral hemorrhage (ICH) tends to be lobar in location, but CAA patients sometimes present with atraumatic localized convexal subarachnoid hemorrhage (cSAH). However, there are no reports mentioning that cSAH is repeated within a short time period. The Boston criteria were used as a means of making a presumptive diagnosis of CAA clinically [1]. How should we identify the causative disease if there are no specific observations in angiography, magnetic resonance imaging (MRI) and so on? We report the clinical findings from 2 patients who presented with repetitive cSAH caused by CAA, and the importance and technique involved in the diagnosis using cerebrospinal fluid (CSF) concentrations of amyloid β peptide (Aβ) [2].
Methods Two cases, each with cSAH on the right central sulcus, were seen at our hospital in 2012. We examined the unusual clinical course and transition on computed tomography (CT) and MRI for the 2 cases that showed repetitive cSAH caused by CAA. We reviewed and compared our findings with those from previously published reports.
Hideyuki Tomita, MD Department of Neurosurgery Ashikaga Red Cross Hospital 284-1 Yobe-cho, Ashikaga City 326-0843 (Japan) E-Mail h.tomita-jns @ ashikaga.jrc.or.jp
Downloaded by: University of Tokyo 157.82.153.40 - 6/1/2015 1:39:34 AM
Key Words Cerebral amyloid angiopathy · Alzheimer’s disease · Convexal subarachnoid hemorrhage · Reversible cerebral vasoconstriction syndrome · Amyloid β
a
b
c
d
Fig. 1. Unenhanced head CT showed cSAH (a) on the right central sulcus at the time of first admission, ICH (b) on the frontal lobe
We did not use biopsy, but instead examined CSF concentrations of Aβ40, Aβ42 and tau protein as additional means of diagnosing CAA. In addition, we investigated whether the patients were suffering from Alzheimer’s disease (AD) by examination with single-photon emission computed tomography (SPECT) and Z scores of voxel-based specific regional analysis system for AD (VSRAD) on MRI [3].
Results
Case 1 Unenhanced head CT showed cSAH on the right central sulcus of a 63-year-old woman who presented with transient motor paresis of her left hand; the patient was thus admitted to our hospital (fig. 1a). Vital signs were normal. The Glasgow Coma Scale score was 14 (E4V4M6). Her neck was supple, and the neurologic examination was 284
Eur Neurol 2014;71:283–287 DOI: 10.1159/000357426
unremarkable except for a left Barre’s sign. Blood analysis was normal. There were no thrombotic risks (protein S, protein C, etc.). There were no abnormal findings on 3-dimensional CT angiography. Susceptibility-weighted imaging of MRI on day 2 showed cSAH, single superficial siderosis and 1 microbleed involving the right frontal lobe. There were no acute cerebral infarctions or neoplastic lesions. On the same day, we performed brain angiography, but there were no aneurysms, arteriovenous malformations or fistulas, thromboses or spasms. In the evening after brain angiography, the patient was suddenly in a semidelirious state. CT showed ICH on the frontal lobe near the right central sulcus (fig. 1b). Hemiparesis was temporarily severer, but it gradually improved. On day 22, the patient was discharged. On day 57, MRI was performed in our outpatient department and showed recurrent multiple cSAH in the right frontal, parietal and temporal lobes Tamura/Tomita/Mizutani/Miwa
Downloaded by: University of Tokyo 157.82.153.40 - 6/1/2015 1:39:34 AM
near the right central sulcus on day 2 and ICH (d) on the frontal lobe in the same position as on day 2. c Unenhanced head MRI showed recurrent multiple cSAH in the right frontal, parietal and temporal lobe on day 57.
a
b
c
d
Fig. 2. Unenhanced head CT showed cSAH (a) on the right central sulcus at the time of first admission, cSAH (b) on the right cen-
(fig. 1c). She remained free of symptoms. A brain angiography was performed again, but there were no abnormal findings. On day 90, the patient was taken to our hospital by ambulance with left hemiplegia. Her Glasgow Coma Scale score was 14 (E4V4M6). A CT showed massive ICH in the frontal lobe in the same position as on day 2 (fig. 1d). She did not report having a headache. MRI showed no abnormal findings. Her cognitive symptoms worsened, so we examined SPECT and her Z score of VSRAD on MRI. SPECT showed diminished blood flow to the parietal lobes bilaterally, and the hippocampus had become atrophic. Her Z score of VSRAD was 3.2 [3]. Thus, she was suspected of having AD, and we prescribed donepezil hydrochloride. She received rehabilitation and her paralysis improved (modified Rankin scale grade 2). We were able to keep dementia from worsening, and she was discharged on day 155.
We could not diagnose CAA actively using the Boston criteria, because no multiple microbleeds were found on the MRI. So we examined CSF concentrations of Aβ40, Aβ42 and tau protein to support a diagnosis. The level of Aβ40 was 1,790 pmol/l, Aβ42 was 63.7 pmol/l and total tau protein (t-tau) was 546 pg/ml. Concentrations of Aβ40 and Aβ42 were lower than control levels, while that of t-tau was higher than control levels. These results suggested the possibility of CAA with AD [2].
Aβ Protein in Cerebrospinal Fluid and cSAH
Eur Neurol 2014;71:283–287 DOI: 10.1159/000357426
Case 2 A 76-year-old woman presented to our hospital with transient sensory disturbance of the left hand, involving numbness over a few minutes. She did not report having a headache. Unenhanced head CT showed cSAH on the right central sulcus as in case 1 (fig. 2a). Vital signs were normal. Her Glasgow Coma Scale score was 14 (E4V4M6). Her neck was supple. Blood analysis was normal. 285
Downloaded by: University of Tokyo 157.82.153.40 - 6/1/2015 1:39:34 AM
tral sulcus and other frontal and parietal sulci on day 5, a small amount of relapse (c) of cSAH on the right central sulcus on day 7, and relapses (d) of cSAH on the right central sulcus with headache and vomiting on day 26.
Discussion
Here, we present 2 cases of repetitive cSAH that were likely caused by CAA. First, acute cSAH is sometimes seen, has seldom been described and is associated with a variety of causes, including cerebral venous thrombosis, vascular malformations, reversible cerebral vasoconstriction syndrome, posterior reversible encephalopathy syndrome and CAA, among others [4]. In principle, biopsy provides pathologic confirmation of CAA. Findings from MRI such as leukoaraiosis, hemispheric microbleeds and superficial siderosis are clearly important for diagnosis. More microbleeds are scattered on the cerebral cortex of CAA patients compared to controls (47.4 vs. 22.4%). Thus, frequent asymptomatic microbleeds may be one means of characterizing CAA. More than 60.5% of CAA patients showed superficial siderosis on MRI, compared to the absence of siderosis in controls. As stated by Linn et al. [5], the sensitivity of the Boston criteria for diagnosing CAA is 89.5%, but the sen286
Eur Neurol 2014;71:283–287 DOI: 10.1159/000357426
sitivity is improved up to 94.7% with the evaluation of superficial siderosis. However, how should we identify causative disease if there are no specific observations in angiography, MRI and so on? In those cases, Aβ in the CSF can be a key to diagnosing. We examined the CSF concentrations of Aβ40, Aβ42 and tau protein as auxiliary diagnostic tools. The control value of Aβ42 is 838 ± 253 pg/ml, that of Aβ40 is 4,003 ± 1,185 pg/ml, and t-tau is 215 ± 78.3 pg/ml. Compared with control subjects, decreased CSF Aβ42 is found in both AD and CAA patients; it is lower in CAA patients than in AD patients. Among CAA patients, Aβ42 is found at a mean level of 42.4% that of control values, while in AD patients, it is 51.6% that of control values. In contrast, the concentration of Aβ40 in CSF is decreased only in CAA patients compared with AD patients and controls. Both CSF t-tau and phosphorylated tau protein concentrations are significantly higher in AD patients compared with CAA patients, although the concentrations in CAA patients are higher than those in controls. Sensitivity and specificity for Aβ40 are 87.5 and 47.1%, respectively; those for Aβ42 are 86.2 and 94.1%, respectively; those for t-tau are 96.5 and 52.9%, respectively, and those for phosphorylated tau are 77.6 and 58.8%, respectively [2]. In both cases, Aβ40 and Aβ42 concentrations were lower than in the controls, while t-tau concentrations were higher than control values. These results suggest the possibility of an association between CAA and AD, especially in case 1, where SPECT and the Z score of VSRAD showed complications related to AD [3]. Generally CAA is associated with AD in 80% of cases [6, 7]. When comparing MRI and Aβ in CSF, Aβ in CSF has a higher sensitivity and specificity. As seen in these cases, MRI could not diagnose CAA, but CSF made the diagnosis possible. So we think CSF analysis is important for CAA. cSAH in these cases are typical for the location and symptoms. In general, the majority of cases of cSAH (51%) are localized to the frontal lobe and 21% are localized to the parietal lobe. Patients often present with transient motor or sensory symptoms, as in both of the cases described here. Patients may not report suffering from a headache or they may report a mild headache. At first glance, symptoms of cSAH, like those seen in the present cases, may be handled as recurring complaints on an outpatient basis. We believe that there may be a large number of patients with cSAH that escape clinical recognition. It is difficult to diagnose CAA at that stage of cSAH [8]. Tamura/Tomita/Mizutani/Miwa
Downloaded by: University of Tokyo 157.82.153.40 - 6/1/2015 1:39:34 AM
No abnormal findings were revealed by 3-dimensional CT angiography and brain angiography on day 2. On day 5, enhanced MRI showed exacerbated cSAH on the right central sulcus and other frontal and parietal sulci with no symptoms (fig. 2b). There were no microbleeds and superficial siderosis in the right cerebral hemisphere on the T2*-weighted phase. On day 7, the patient was discharged. On that same day, the patient presented to our hospital again with transient sensory disturbance of the left hand. A CT scan showed a minor relapse of cSAH on the right central sulcus (fig. 2c). Symptoms improved after a few minutes, and the patient returned home. On day 22, she returned to our hospital again with the same symptoms. A CT scan showed no hemorrhage, but she was admitted for follow-up. On day 26, she complained of a mild headache and vomited. The CT scan showed relapse of cSAH on the right central sulcus (fig. 2d). Subsequently, she became asymptomatic, and CT showed no increase in cSAH. On day 31, she was discharged. In case 2, SPECT did not show a pattern consistent with AD. The Z score of VSRAD was 1.33, so AD was interpreted as negative [3]. However, the level of Aβ40 was 2,430 pmol/l, Aβ42 was 155 pmol/l and t-tau was 645 pg/ ml in CSF. Aβ40 and Aβ42 concentrations were lower than control levels, while that of t-tau was higher than control levels. These results suggest the possibility of CAA with AD [2].
However, it has never been reported that cSAH happens repeatedly within a short time period. These cases are both diagnosed as CAA. So cSAH caused by CAA can happen repeatedly within a short time period and finally become ICH of lobar location like in case 1. In other words, cSAH caused by CAA may act as a warning of progression to ICH, so a careful follow-up is vitally important.
Conclusions
Aβ protein in CSF can be presented here as support for the diagnosis of CAA that is difficult to diagnose by Boston criteria. cSAH repeated within a short time period is not so seen and since there is a possibility of CAA, it may act as a warning of progression to ICH, so a careful follow-up is vitally important.
References
Aβ Protein in Cerebrospinal Fluid and cSAH
4 Cuvinciuc V, Viguier A, Calviere L, et al: Isolated acute nontraumatic cortical subarachnoid hemorrhage. Am J Neuroradiol 2010;31: 1355–1362. 5 Linn J, Halpin A, Demaerel P, et al: Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010;74: 1346–1350.
6 Arvanitakis Z, Leurgans SE, Wang Z, et al: Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann Neurol 2011;69:320–327. 7 Yamada M: Risk factors for cerebral amyloid angiopathy in the elderly. Ann NY Acad Sci 2002;977:37–44. 8 Kumar S, Goddeau RP, Selim MH, et al: Atraumatic convexal subarachnoid hemorrhage: clinical presentation, imaging patterns, and etiologies. Neurology 2010; 74: 893–899.
Eur Neurol 2014;71:283–287 DOI: 10.1159/000357426
287
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1 Knudsen KA, Rosand J, Karluk D, et al: Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston Criteria. Neurology 2001;56:537–539. 2 Verbeek MM, Kremer BPH, Rikkert MO, et al: Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy. Ann Neurol 2009;66:245–249. 3 Li X, Shimizu S, Jikiki I, et al: Correlations between Z-score of VSRAD and regional cerebral blood flow of SPECT in patients with Alzheimer’s disease and mild cognitive impairment. Psychiatry Clin Neurosci 2010;64:284–292.
