Sensitivity of the Boston criteria version 2.0 in Dutch-type hereditary cerebral amyloid angiopathy.

BACKGROUND AND AIM: The revised Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) add two radiological markers to the existing criteria: severe visible perivascular spaces in the centrum semiovale and white matter hyperintensities (WMHs) in a multispot pattern. This study aims to determine the sensitivity of the updated criteria in mutation carriers with Dutch-type hereditary CAA (D-CAA) in an early and later disease stage. METHODS: In this cross-sectional study, we included presymptomatic and symptomatic D-CAA mutation carriers from our prospective natural history study (AURORA) at the Leiden University Medical Center between 2018 and 2021. 3-Tesla scans were assessed for CAA-related magnetic resonance imaging (MRI) markers. We compared the sensitivity of the Boston criteria v2.0 to the previously used modified Boston criteria v1.5. RESULTS: We included 64 D-CAA mutation carriers (mean age 49 years, 55% women, 55% presymptomatic). At least one white matter (WM) feature was seen in 55/64 mutation carriers (86%: 74% presymptomatic, 100% symptomatic). Fifteen (23%) mutation carriers, all presymptomatic, showed only WM features and no hemorrhagic markers. The sensitivity for probable CAA was similar between the new and the previous criteria: 11/35 (31%) in presymptomatic mutation carriers and 29/29 (100%) in symptomatic mutation carriers. The sensitivity for possible CAA in presymptomatic mutation carriers increased from 0/35 (0%) to 15/35 (43%) with the new criteria. CONCLUSION: The Boston criteria v2.0 increase the sensitivity for detecting possible CAA in presymptomatic D-CAA mutation carriers and, therefore, improve the detection of the early phase of CAA.

Cerebellar hemorrhages in patients with Dutch-type hereditary cerebral amyloid angiopathy.

BACKGROUND: Recent studies suggest that superficially located cerebellar intracerebral hemorrhage (ICH) and microbleeds might point towards sporadic cerebral amyloid angiopathy (CAA). AIMS: We investigated the proportion of cerebellar ICH and asymptomatic macro- and microbleeds in Dutch-type hereditary CAA (D-CAA), a severe and essentially pure form of CAA. METHODS: Symptomatic patients with D-CAA (defined as ≥1 symptomatic ICH) and presymptomatic D-CAA mutation-carriers were included. We assessed magnetic resonance imaging scans for symptomatic (cerebellar) ICH and asymptomatic cerebellar macro- and microbleeds according to the STRIVE-criteria. Location was assessed as superficial-cerebellar (cortex, vermis or juxta-cortical) or deep-cerebellar (white matter, pedunculi cerebelli and gray nuclei). RESULTS: We included 63 participants (mean age 58 years, 60% women, 42 symptomatic). In total, the 42 symptomatic patients with D-CAA had 107 symptomatic ICH (range 1-7). None of these ICH were located in the cerebellum. Six of 42 (14%, 95%CI 4-25%) symptomatic patients and none of the 21 (0%, 95%CI 0-0%) presymptomatic carriers had ≥ 1 asymptomatic cerebellar macrobleed(s). All macrobleeds were superficially located. Cerebellar microbleeds were found in 40 of 63 (64%, 95%CI 52-76) participants (median 1.0, range 0-159), 81% in symptomatic patients and 29% in presymptomatic carriers. All microbleeds were strictly or predominantly superficially (ratio superficial versus deep 15:1) located. CONCLUSIONS: Superficially located asymptomatic cerebellar macrobleeds and microbleeds are common in D-CAA. Cerebellar microbleeds are already present in the presymptomatic stage. Despite the high frequency of cerebellar micro and macrobleeds, CAA pathology did not result in symptomatic cerebellar ICH in patients with D-CAA.

Striped occipital cortex and intragyral hemorrhage: Novel magnetic resonance imaging markers for cerebral amyloid angiopathy.

BACKGROUND AND AIM: To 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). METHODS: We 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 T2*-weighted magnetic resonance imaging. We assessed the association between the markers, other CAA-magnetic resonance imaging markers and clinical features. RESULTS: We 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. CONCLUSION: Whereas 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.

Middle cerebral artery diameter changes during rhythmic handgrip exercise in humans.

Transcranial Doppler (TCD) sonography is a frequently employed technique for quantifying cerebral blood flow by assuming a constant arterial diameter. Given that exercise increases arterial pressure by sympathetic activation, we hypothesized that exercise might induce a change in the diameter of large cerebral arteries. Middle cerebral artery (MCA) cross-sectional area was assessed in response to handgrip exercise by direct magnetic resonance imaging (MRI) observations. Twenty healthy subjects (11 female) performed three 5 min bouts of rhythmic handgrip exercise at 60% maximum voluntary contraction, alternated with 5 min of rest. High-resolution 7 T MRI scans were acquired perpendicular to the MCA. Two blinded observers manually determined the MCA cross-sectional area. Sufficient image quality was obtained in 101 MCA-scans of 19 subjects (age-range 20-59 years). Mixed effects modelling showed that the MCA cross-sectional area decreased by 2.1 ± 0.8% (p = 0.01) during handgrip, while the heart rate increased by 11 ± 2% (p < 0.001) at constant end-tidal CO2 (p = 0.10). In conclusion, the present study showed a 2% decrease in MCA cross-sectional area during rhythmic handgrip exercise. This further strengthens the current concept of sympathetic control of large cerebral arteries, showing in vivo vasoconstriction during exercise-induced sympathetic activation. Moreover, care must be taken when interpreting TCD exercise studies as diameter constancy cannot be assumed.