Posterior white matter disease distribution as a predictor of amyloid angiopathy

Thanprasertsuk, Sekh; Martínez-Ramírez, Sergi; Pontes-Neto, Octávio Marques; Ni, Jun; Ayres, Alison; Reed, Anne; Swords, Kyleen; Gurol, M. Edip; Greenberg, Steven M.; Viswanathan, Anand

doi:10.1212/wnl.0000000000000732

Cited by 87 publications

(81 citation statements)

References 30 publications

(34 reference statements)

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“…The most involved vascular territory in CAA has been reported to be middle cerebral artery territory [5], as also seen in our case, which is not surprising since it is one of the major vessels that supply cortical areas. Additionally, microinfarct, another probably underestimated MRI inding [6], were more frequently seen in the occipital cortex in the scenario of CAA [7], and similarly the high correlation between posterior distribution of white matter disease and CAA have been seen [8]. It remains unclear what causes the unusual features of the multiple microhemorrhages con ined to one hemisphere, as discovered in our case.…”

Section: Discussionsupporting

confidence: 53%

Lateralized Cerebral Amyloid Angiopathy presenting with recurrent Lacunar Ischemic Stroke

Li¹

2017

J Neurosci Neurol Disord

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An 84-year-old woman with history of diabetes, hypothyroidism, and hyperlipidemia presented with acute onset of paresis of left arm and paresthesia of left face and arm. She had a similar prior episode two weeks ago with only left arm paresthesia. She had a similar prior episode two weeks ago with only left arm paresthesia. On the initial encounter, the patient exam revealed BP of 150/46 and normal sinus rhythm. Neurological exam showed reduced pinprick and light touch sensations over the left side of the face, arm and leg, and mild weakness on the scale of 4/5 of the left upper extremity. The above symptoms resolved within two hours. Her workup including glucose level, vasculitis panel, ECHO and EKG, which were all normal. Carotid duplex revealed mild stenosis of the ICA bilaterally. CT angiogram of head and neck showed no hemodynamically signi icant stenosis, aneurysm, dissection or vascular malformation of the head and neck. No focal or multifocal segmental narrowing of vessels were seen. EEG did now show any abnormalities. Telemetry did not reveal an evidence of atrial ibrillation. Lumbar puncture was not performed.The MRI revealed different stages of lacunar ischemic lesions. Interestingly, the SWAN sequences showed lateralized rather than global multiple microhemorrhages over the right MCA and PCA territory, and the sulcal hyperintensity on FLAIR was also seen with no associated susceptibility effect and minimal enhancement (Figure 1 AbstractHere we reported an interesting case of an 84-year-old woman with acute onset of paresis of left arm and paresthesia of left face and arm. The symptoms resolved within two hours. She also had a similar prior episode two weeks ago with only left arm paresthesia. Her MRI revealed different stages of lacunar ischemic lesions. Interestingly, the SWAN sequences showed lateralized rather than global multiple microhemorrhages over the right MCA and PCA territory, and the sulcal hyperintensity on FLAIR was also seen with no associated susceptibility effect and minimal enhancement, indicating probable cerebral amyloid angiopathy (CAA) based on Boston Criteria.It has been acknowledged that the CAA could manifest with certain localization preference. Cerebral microinfarct and white matter disease in CAA have been more often observed in the posterior circulation territory, however the restricted lateralization reported in our case has not been seen. Since CAA is often diagnosed when the characteristic MRI fi ndings are picked up incidentally, recognizing this as a potential "TIA mimic" will be important for guiding treatment due to its higher risk of bleeding. In summary, this case highlights that the CAA could present as restricted lateralized lesions and occur as transient neurologic defi cits, which to our knowledge has not be reported before. Recognition of it as a potential manifestation of CAA will be valuable in the clinical diagnosis process.

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Section: Discussionsupporting

confidence: 53%

Lateralized Cerebral Amyloid Angiopathy presenting with recurrent Lacunar Ischemic Stroke

Li¹

2017

J Neurosci Neurol Disord

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“…The predominantly parieto-occipital location of the WMH further supports the hypothesis that they relate to CAA. CAA, which is present to at least some degree in 70%e100% of AD brains at postmortem (Bergeron et al, 1987;Ellis et al, 1996), has a particular predilection for the occipital lobes (Alafuzoff et al, 2009;Thal et al, 2002), and a posterior distribution of WMH has been shown to predict pathologically confirmed CAA (Thanprasertsuk et al, 2014). Although only one of the APP subjects had a mutation within the Ab coding domain, their ARWMC score was considerably higher than the median for the APP group, consistent with pathological reports of severe CAA in cases with intradomain APP mutations.…”

Section: Discussionmentioning

confidence: 99%

Genetic determinants of white matter hyperintensities and amyloid angiopathy in familial Alzheimer's disease

Ryan

Biessels

Kim

et al. 2015

Neurobiology of Aging

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Familial Alzheimer's disease (FAD) treatment trials raise interest in the variable occurrence of cerebral amyloid angiopathy (CAA); an emerging important factor in amyloid-modifying therapy. Previous pathological studies reported particularly severe CAA with postcodon 200 PSEN1 mutations and amyloid beta coding domain APP mutations. As CAA may manifest as white matter hyperintensities (WMH) on magnetic resonance imaging, particularly posteriorly, we investigated WMH in 52 symptomatic FAD patients for associations with mutation position. WMH were visually rated in 39 PSEN1 (18 precodon 200); 13 APP mutation carriers and 25 healthy controls. Ten PSEN1 mutation carriers (5 precodon 200) had postmortem examination. Increased WMH were observed in the PSEN1 postcodon 200 group and in the single APP patient with an amyloid beta coding domain (p.Ala692Gly, Flemish) mutation. WMH burden on MRI correlated with severity of CAA and cotton wool plaques in several areas. The precodon 200 group had younger ages at onset, decreased axonal density and/or integrity, and a greater T-lymphocytic response in occipital deep white matter. Mutation site contributes to the phenotypic and pathological heterogeneity witnessed in FAD.

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“…21 Supporting this, others have shown that a more prominent posterior WMH distribution is an independent predictor of pathologic evidence of CAA. 22 In addition, parietal and occipital lobar CMB counts have been shown to be increased in those with greater WMH burden. 23 Conversely, occipital PVWMH in the NC subgroup were less strongly associated with biomarkers of elevated amyloid.…”

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confidence: 99%

Periventricular hyperintensities are associated with elevated cerebral amyloid

Marnane¹,

Aljawadi²,

Mortazavi³

et al. 2016

Neurology

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Objective: To investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral b-amyloid (Ab) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study. Methods:The burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Ab, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET.Results: Increased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p , 0.01) and low CSF-Ab (p , 0.01).In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p , 0.05). In a similar logistic regression model, parietal and occipital (p , 0.05) but not frontal (p 5 0.05) PVWMH were independently associated with CSF-Ab. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p , 0.05) and occipital PVWMH and elevated CSF-phospho-tau (p , 0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Ab levels (p , 0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements.Conclusions: Increased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified. Pathologic and imaging studies have shown that in Alzheimer disease (AD), cerebral small vessel disease (SVD) is coexistent in up to 80% and hastens cognitive deterioration.1 Whether this reflects parallel neuronal injury or synergistic worsening of AD pathogenic mechanisms remains unclear. 2There has been recent interest in the putative role of SVD in disruption of physiologic interstitial fluid bulk flow and paravascular mechanisms of b-amyloid (Ab) clearance.3 If SVD is an

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Posterior white matter disease distribution as a predictor of amyloid angiopathy

Cited by 87 publications

References 30 publications

Lateralized Cerebral Amyloid Angiopathy presenting with recurrent Lacunar Ischemic Stroke

Lateralized Cerebral Amyloid Angiopathy presenting with recurrent Lacunar Ischemic Stroke

Genetic determinants of white matter hyperintensities and amyloid angiopathy in familial Alzheimer's disease

Periventricular hyperintensities are associated with elevated cerebral amyloid

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