The current study aimed to investigate whether diffusion-weighted imaging-positive (DWI+) lesions after acute intracerebral hemorrhage (ICH) are associated with underlying small vessel disease (SVD... Show moreThe current study aimed to investigate whether diffusion-weighted imaging-positive (DWI+) lesions after acute intracerebral hemorrhage (ICH) are associated with underlying small vessel disease (SVD) or linked to the acute ICH. We included patients >= 18 years with spontaneous ICH confirmed on neuroimaging and performed 3T MRIs after a median of 11 days (interquartile range [IQR] 6-43). DWI+ lesions were assessed in relation to the hematoma (perihematomal vs. distant and ipsilateral vs. contralateral). Differences in clinical characteristics, ICH characteristics, and MRI markers of SVD between participants with or without DWI+ lesions were investigated using non-parametric tests. We observed 54 DWI+ lesions in 30 (22%) of the 138 patients (median age [IQR] 65 [55-73] years; 71% men, 59 lobar ICH) with available DWI images. We found DWI+ lesions ipsilateral (54%) and contralateral (46%) to the ICH, and 5 (9%) DWI+ lesions were located in the immediate perihematomal region. DWI+ lesion presence was associated with probable CAA diagnosis (38 vs. 15%, p = 0.01) and larger ICH volumes (37 [8-47] vs. 12 [6-24] ml, p = 0.01), but not with imaging features of SVD. Our findings suggest that DWI+ lesions after ICH are a feature of both the underlying SVD and ICH-related mechanisms. Show less
Background: Whether certain activities can trigger spontaneous intracerebral hemorrhage (ICH) remains unknown. Insights into factors that trigger vessel rupture resulting in ICH improves knowledge... Show moreBackground: Whether certain activities can trigger spontaneous intracerebral hemorrhage (ICH) remains unknown. Insights into factors that trigger vessel rupture resulting in ICH improves knowledge on the pathophysiology of ICH. We assessed potential trigger factors and their risk for ICH onset. Methods: We included consecutive patients diagnosed with ICH between July 1, 2013, and December 31, 2019. We interviewed patients on their exposure to 12 potential trigger factors (eg, Valsalva maneuvers) in the (hazard) period soon before onset of ICH and their normal exposure to these trigger factors in the year before the ICH. We used the case-crossover design to calculate relative risks (RR) for potential trigger factors. Results: We interviewed 149 patients (mean age 64, 66% male) with ICH. Sixty-seven (45%) had a lobar hemorrhage, 60 (40%) had a deep hemorrhage, 19 (13%) had a cerebellar hemorrhage, and 3 (2%) had an intraventricular hemorrhage. For ICH in general, there was an increased risk within an hour after caffeine consumption (RR=2.5 [95% CI=1.8-3.6]), within an hour after coffee consumption alone (RR=4.8 [95% CI=3.3-6.9]), within an hour after lifting >25 kg (RR=6.6 [95% CI=2.2-19.9]), within an hour after minor head trauma (RR=10.1 [95% CI=1.7-60.2]), within an hour after sexual activity (RR=30.4 [95% CI=16.8-55.0]), within an hour after straining for defecation (RR=37.6 [95% CI=22.4-63.4]), and within an hour after vigorous exercise (RR=21.8 [95% CI=12.6-37.8]). Within 24 hours after flu-like disease or fever, the risk for ICH was also increased (RR=50.7 [95% CI=27.1-95.1]). Within an hour after Valsalva maneuvers, the RR for deep ICH was 3.5 (95% CI=1.7-6.9) and for lobar ICH the RR was 2.0 (95% CI=0.9-4.2). Conclusions: We identified one infection and several blood pressure related trigger factors for ICH onset, providing new insights into the pathophysiology of vessel rupture resulting in ICH. Show less
Aim To investigate whether there is a topographical and temporal pattern of index and recurrent intracerebral hemorrhages (ICH) in Dutch-type hereditary Cerebral Amyloid Angiopathy (D-CAA) to... Show moreAim To investigate whether there is a topographical and temporal pattern of index and recurrent intracerebral hemorrhages (ICH) in Dutch-type hereditary Cerebral Amyloid Angiopathy (D-CAA) to increase our understanding on CAA-related ICH development. Methods We included patients with DNA confirmed D-CAA or a history with >= 1 lobar ICH and >= 1 first-degree relative with D-CAA. Topographical pattern was studied by location (proportion frontal/parietal/temporal/occipital; infra/supratentorial and occurrence ratios relative to lobe volume) and volume of index and recurrent ICHs were determined on CT. Temporal pattern was examined by time between recurrent ICHs was retrieved from medical records. Results We included 72 patients with D-CAA (mean age at index ICH 55 years) with in total 214 ICH. The median follow-up time was 7 years (range 0.8 to 28 years). All ICH were lobar and supratentorial. The index ICH was most frequently located in the occipital lobe (34% vs. 22% in the other three lobes; with index ICH occurrence ratios relative to lobe volume of 1.9 for occipital, 1.0 for temporal, 1.2 for parietal, and 0.5 for frontal, p = 0.001). In 16/47 (34%) patients with multiple ICH, the second ICH was located in the same lobe as the index ICH. The median time-interval between subsequent ICH was #1-2 ICH 27 months, #2-3 ICH 14 months, and #3-4 ICH 7 months (p = 0.6) There was no difference in volume between index and recurrent ICHs. Conclusions We found that index and recurrent ICHs in D-CAA have a preference for the occipital lobe and are least frequent in the frontal lobe, which adds to the existing knowledge of histopathological studies on amyloid load in CAA. Surprisingly, there was no acceleration in time nor gradual increase of hematoma volume between subsequent ICHs. Show less
Background and Purpose:Cortical calcifications have been reported in patients with cerebral amyloid angiopathy (CAA), although their prevalence and pathophysiology are unknown. We investigated the... Show moreBackground and Purpose:Cortical calcifications have been reported in patients with cerebral amyloid angiopathy (CAA), although their prevalence and pathophysiology are unknown. We investigated the frequency of calcifications on computed tomography, their association with intracerebral hemorrhage (ICH) and their coexistence with a striped pattern of the occipital cortex reflecting microcalcifications on ultra-high-field 7T-magnetic resonance imaging in Dutch-type hereditary CAA (D-CAA) and sporadic CAA.Methods:We included D-CAA mutation carriers with a proven APP (amyloid precursor protein) mutation or >= 1 lobar ICH and >= 1 first-degree relative with D-CAA and sporadic CAA patients with probable CAA according to the modified Boston criteria. D-CAA carriers were regarded symptomatic when they had a history of symptomatic ICH. We assessed the presence, location, and progression of calcifications and their association with ICH and the striped occipital cortex.Results:We found cortical calcifications in 15/81 (19% [95% CI, 11-29]) D-CAA mutation carriers (15/69 symptomatic and 0/12 presymptomatic) and in 1/59 (2% [95% CI, 0-9]) sporadic CAA patients. Calcifications were all bilateral located in the occipital lobes. In 3/15 (20%) of the symptomatic D-CAA patients the calcifications progressed over a period up to 10 years. There was evidence of an association between cortical calcifications and new ICH development (hazard ratio, 7.1 [95% CI, 0.9-54.9], log-rank P=0.03). In 7/25 D-CAA symptomatic carriers in whom a 7T-magnetic resonance imaging was performed, a striped pattern of the occipital cortex was present; in 3/3 (100%) of those with calcifications on computed tomography and 4/22 (18%) of those without calcifications.Conclusions:Occipital cortical calcifications are frequent in D-CAA but seem to be rare in sporadic CAA. Their absence in presymptomatic carriers and their association with ICH might suggest that they are a marker for advanced CAA. Cortical calcifications on computed tomography seem to be associated with the striped occipital cortex on 7T-magnetic resonance imaging which may possibly represent an early stage of calcification. Show less
Koemans, E.A.; Voigt, S.; Rasing, I.; Jolink, W.M.T.; Harten, T.W. van; Grond, J. van der; ... ; Wermer, M.J.H. 2021
Background and aimTo investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary... Show moreBackground and aimTo investigate whether a striped occipital cortex and intragyral hemorrhage, two markers recently detected on ultra-high-field 7-tesla-magnetic resonance imaging in hereditary cerebral amyloid angiopathy (CAA), also occur in sporadic CAA (sCAA) or non-sCAA intracerebral hemorrhage (ICH).MethodsWe performed 7-tesla-magnetic resonance imaging in patients with probable sCAA and patients with non-sCAA-ICH. Striped occipital cortex (linear hypointense stripes perpendicular to the cortex) and intragyral hemorrhage (hemorrhage restricted to the juxtacortical white matter of one gyrus) were scored on T-2*-weighted magnetic resonance imaging. We assessed the association between the markers, other CAA-magnetic resonance imaging markers and clinical features.ResultsWe included 33 patients with sCAA (median age 70 years) and 29 patients with non-sCAA-ICH (median age 58 years). Striped occipital cortex was detected in one (3%) patient with severe sCAA. Five intragyral hemorrhages were found in four (12%) sCAA patients. The markers were absent in the non-sCAA-ICH group. Patients with intragyral hemorrhages had more lobar ICHs (median count 6.5 vs. 1.0), lobar microbleeds (median count >50 vs. 15), and lower median cognitive scores (Mini Mental State Exam: 20 vs. 28, Montreal Cognitive Assessment: 18 vs. 24) compared with patients with sCAA without intragyral hemorrhage. In 12 (36%) patients, sCAA diagnosis was changed to mixed-type small vessel disease due to deep bleeds previously unobserved on lower field-magnetic resonance imaging.ConclusionWhereas a striped occipital cortex is rare in sCAA, 12% of patients with sCAA have intragyral hemorrhages. Intragyral hemorrhages seem to be related to advanced disease and their absence in patients with non-sCAA-ICH could suggest specificity for CAA. Show less
Background and Purpose:The Edinburgh computed tomography and genetic criteria enable diagnosis of cerebral amyloid angiopathy (CAA) associated lobar intracerebral hemorrhage (ICH) but have not been... Show moreBackground and Purpose:The Edinburgh computed tomography and genetic criteria enable diagnosis of cerebral amyloid angiopathy (CAA) associated lobar intracerebral hemorrhage (ICH) but have not been validated in living patients. We assessed the sensitivity of the Edinburgh criteria in patients with acute lobar ICH due to Dutch-type hereditary CAA; a genetic and pure form of CAA.Methods:We retrospectively analyzed computed tomography-scans from a cohort of consecutive Dutch-type hereditary CAA patients who presented with >= 1 episode(s) of acute lobar ICH at the Leiden University Medical Center. Presence of subarachnoid hemorrhage (SAH) and finger-like projections (FLP) were determined. Association of SAH and FLP with ICH volume was analyzed using multivariate linear regression.Results:We included 55 Dutch-type hereditary CAA patients (mean age 56 years, 55% men) with a total of 107 episodes of acute lobar ICH. SAH was present in 82/107 (76%) and FLP in 62/107 (58%), resulting in a sensitivity of 76% for SAH and 58% for FLP. In 56 (52%), both markers were present. Nineteen (18%) lobar ICH showed no SAH extension or FLP. ICH volume was significantly associated with presence of SAH (median volume 4 versus 28 mL; P=0.001) and presence of FLP (median volume 7 versus 39 mL; P<0.001). With an ICH volume of >= 40 mL, the sensitivity of the presence of both SAH and FLP was >81% (95% CI, 70%-92%), whereas in ICH volumes Conclusions:The computed tomography-based Edinburgh criteria seem to be a sensitive diagnostic test for CAA-associated lobar ICH, although they should be used with caution in small-sized lobar ICH. Show less
Background and Purpose-To determine whether migraine, which has often been described as an inaugural manifestation in monogenic cerebrovascular syndromes, is associated with cerebral amyloid... Show moreBackground and Purpose-To determine whether migraine, which has often been described as an inaugural manifestation in monogenic cerebrovascular syndromes, is associated with cerebral amyloid pathology, we assessed migraine and its correlation with magnetic resonance imaging markers in Hereditary Dutch-Type Cerebral Amyloid Angiopathy (D-CAA or Hereditary Cerebral Hemorrhage With Amyloidosis-Dutch type).Methods-All D-CAA mutation carriers who visited our clinic between 2012 and 2018 were included. Migraine was diagnosed by an interview and classified according to the International Classification of Headache Disorders. Magnetic resonance imaging scans were scored for intracerebral hemorrhage (ICH) location(s) and presence of cortical superficial siderosis. Kaplan Meier survival analysis was used for age of ICH onset in carriers with and without migraine. Correlation with ICH location(s) and cortical superficial siderosis were calculated with Poisson regression analysis adjusted for confounders.Results-We included 86 D-CAA mutation carriers (57% women, mean age 57 years), 48 (56%) suffered from migraine, all with aura. Prevalence was higher than expected compared with the general population (women, P<0.05; men, P<0.001). Migraine was the inaugural symptom in 77% and an isolated symptom in 35% of the carriers. Carriers with and without migraine did not differ for age of first ICH, cortical superficial siderosis prevalence, or occipital ICH. Time between migraine onset and first ICH was 8.5 years. Aura attacks lasting >= 60 minutes signaled acute ICH in 55%.Conclusions-Migraine with aura is an important, often inaugural, symptom in D-CAA. Aura attacks lasting >= 60 minutes may signal acute ICH in D-CAA. Migraine with aura may be regarded as an early marker of disease in hereditary CAA preceding the occurrence of symptomatic ICH by several years. Show less
Background and purpose: To determine whether migraine, which has often been described as an inaugural manifestation in monogenic cerebrovascular syndromes, is associated with cerebral amyloid... Show moreBackground and purpose: To determine whether migraine, which has often been described as an inaugural manifestation in monogenic cerebrovascular syndromes, is associated with cerebral amyloid pathology we assessed migraine and its correlation with MRI markers in Hereditary Dutch-type Cerebral Amyloid Angiopathy (D-CAA or HCHWA-D).Methods: All D-CAA mutation carriers who visited our clinic between 2012-2018 were included. Migraine was diagnosed by an interview and classified according to the International Classification of Headache Disorders. MRIs were scored for intracerebral hemorrhage (ICH) location(s) and presence of cortical superficial siderosis (cSS). Kaplan Meier survival analysis was used for age of ICH onset in carriers with and without migraine. Correlation with ICH location(s) and cSS were calculated with Poisson regression analysis adjusted for confounders.Results: We included 86 D-CAA mutation carriers (57% women, mean age 57 years), 48 (56%) suffered from migraine, all with aura. Prevalence was higher than expected compared with the general population (women p<0.05; men p<0.001). Migraine was the inaugural symptom in 77% and an isolated symptom in 35% of the carriers. Carriers with and without migraine did not differ for age of first ICH, cSS prevalence or occipital ICH. Time between migraine onset and first ICH was 8.5 years. Aura attacks lasting ≥60 minutes signaled acute ICH in 55%.Conclusions: Migraine with aura is an important, often inaugural symptom in D-CAA. Aura attacks lasting ≥60 minutes may signal acute ICH in D-CAA. Migraine with aura may be regarded as an early marker of disease in hereditary CAA preceding the occurrence of symptomatic ICH by several years. Show less
Gooskens, C.; Heuven, V.J.J.P. van; Golubović, J.; Schüppert, A.; Swarte, F.; Voigt, S. 2017
By means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language... Show moreBy means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language families in Europe. We first present the results of a selection of 1833 listeners representing the mutual intelligibility between young, educated Europeans from the same 16 countries where the test languages are spoken. Next, we present the data from a sub-group of listeners who had not learned the test language and had had minimal exposure to it. This allows us to investigate how well the listeners understand the test language on the basis of structural similarities between their own language and the test languages. Finally, we compare the results of the two data sets to the traditional genealogic characterisation of the three language groups. We expect the intelligibility results from the second group of listeners who had had minimal exposure to the test language to be a better reflection of the genealogical characterisation than the results from the larger group who had sometimes been exposed to the test language or had learned it at school. Show less
Gooskens, C.; Heuven, V.J.J.P. van; Golubović, J.; Schüppert, A.; Swarte, F.; Voigt, S. 2017
By means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language... Show moreBy means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language families in Europe. We first present the results of a selection of 1833 listeners representing the mutual intelligibility between young, educated Europeans from the same 16 countries where the test languages are spoken. Next, we present the data from a sub-group of listeners who had not learned the test language and had had minimal exposure to it. This allows us to investigate how well the listeners understand the test language on the basis of structural similarities between their own language and the test languages. Finally, we compare the results of the two data sets to the traditional genealogic characterisation of the three language groups. We expect the intelligibility results from the second group of listeners who had had minimal exposure to the test language to be a better reflection of the genealogical characterisation than the results from the larger group who had sometimes been exposed to the test language or had learned it at school. Show less
Gooskens, C.; Heuven, V.J.J.P. van; Golubović, J.; Schüppert, A.; Swarte, F.; Voigt, S. 2017
By means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language... Show moreBy means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language families in Europe. We first present the results of a selection of 1833 listeners representing the mutual intelligibility between young, educated Europeans from the same 16 countries where the test languages are spoken. Next, we present the data from a sub-group of listeners who had not learned the test language and had had minimal exposure to it. This allows us to investigate how well the listeners understand the test language on the basis of structural similarities between their own language and the test languages. Finally, we compare the results of the two data sets to the traditional genealogic characterisation of the three language groups. We expect the intelligibility results from the second group of listeners who had had minimal exposure to the test language to be a better reflection of the genealogical characterisation than the results from the larger group who had sometimes been exposed to the test language or had learned it at school. Show less
Gooskens, C.; Heuven, V.J.J.P. van; Golubović, J.; Schüppert, A.; Swarte, F.; Voigt, S. 2017
By means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language... Show moreBy means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language families in Europe. We first present the results of a selection of 1833 listeners representing the mutual intelligibility between young, educated Europeans from the same 16 countries where the test languages are spoken. Next, we present the data from a sub-group of listeners who had not learned the test language and had had minimal exposure to it. This allows us to investigate how well the listeners understand the test language on the basis of structural similarities between their own language and the test languages. Finally, we compare the results of the two data sets to the traditional genealogic characterisation of the three language groups. We expect the intelligibility results from the second group of listeners who had had minimal exposure to the test language to be a better reflection of the genealogical characterisation than the results from the larger group who had sometimes been exposed to the test language or had learned it at school. Show less
Gooskens, C.; Heuven, V.J.J.P. van; Golubović, J.; Schüppert, A.; Swarte, F.; Voigt, S. 2017
By means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language... Show moreBy means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language families in Europe. We first present the results of a selection of 1833 listeners representing the mutual intelligibility between young, educated Europeans from the same 16 countries where the test languages are spoken. Next, we present the data from a sub-group of listeners who had not learned the test language and had had minimal exposure to it. This allows us to investigate how well the listeners understand the test language on the basis of structural similarities between their own language and the test languages. Finally, we compare the results of the two data sets to the traditional genealogic characterisation of the three language groups. We expect the intelligibility results from the second group of listeners who had had minimal exposure to the test language to be a better reflection of the genealogical characterisation than the results from the larger group who had sometimes been exposed to the test language or had learned it at school. Show less
Gooskens, C.; Heuven, V.J.J.P. van; Golubović, J.; Schüppert, A.; Swarte, F.; Voigt, S. 2017
By means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language... Show moreBy means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language families in Europe. We first present the results of a selection of 1833 listeners representing the mutual intelligibility between young, educated Europeans from the same 16 countries where the test languages are spoken. Next, we present the data from a sub-group of listeners who had not learned the test language and had had minimal exposure to it. This allows us to investigate how well the listeners understand the test language on the basis of structural similarities between their own language and the test languages. Finally, we compare the results of the two data sets to the traditional genealogic characterisation of the three language groups. We expect the intelligibility results from the second group of listeners who had had minimal exposure to the test language to be a better reflection of the genealogical characterisation than the results from the larger group who had sometimes been exposed to the test language or had learned it at school. Show less
Gooskens, C.; Heuven, V.J.J.P. van; Golubović, J.; Schüppert, A.; Swarte, F.; Voigt, S. 2017
By means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language... Show moreBy means of a large-scale web-based investigation, we established the degree of mutual intelligibility of 16 closely related spoken languages within the Germanic, Slavic and Romance language families in Europe. We first present the results of a selection of 1833 listeners representing the mutual intelligibility between young, educated Europeans from the same 16 countries where the test languages are spoken. Next, we present the data from a sub-group of listeners who had not learned the test language and had had minimal exposure to it. This allows us to investigate how well the listeners understand the test language on the basis of structural similarities between their own language and the test languages. Finally, we compare the results of the two data sets to the traditional genealogic characterisation of the three language groups. We expect the intelligibility results from the second group of listeners who had had minimal exposure to the test language to be a better reflection of the genealogical characterisation than the results from the larger group who had sometimes been exposed to the test language or had learned it at school. Show less
