Multidisciplinary care is considered the standard of care for both adult and pediatric neuromuscular disorders and has been associated with improved quality of life, resource utilization, and health outcomes. Multidisciplinary care is delivered in multidisciplinary clinics that coordinate care across multiple specialties by reducing travel burden and streamlining care. In addition, the multidisciplinary care setting facilitates the integration of clinical research, patient advocacy, and care innovation (e.g., telehealth). Yet, multidisciplinary care requires substantial commitment of staff time and resources. We calculated personnel costs in our ALS clinic in 2015 and found an average cost per patient visit of $580, of which only 45% was covered by insurance reimbursement. In this review, we will describe classic and emerging concepts in multidisciplinary care models for adult and pediatric neuromuscular disease. We will then explore the financial impact of multidisciplinary care with emphasis on sustainability and metrics to demonstrate quality and value. Muscle Nerve 56: 848–858, 2017

Multidisciplinary care is considered the standard of care for both adult and pediatric neuromuscular disorders and has been associated with improved quality of life, resource utilization, and health outcomes. Multidisciplinary care is delivered in multidisciplinary clinics that coordinate care across multiple specialties by reducing travel burden and streamlining care. In addition, the multidisciplinary care setting facilitates the integration of clinical research, patient advocacy, and care innovation (e.g., telehealth). Yet, multidisciplinary care requires substantial commitment of staff time and resources. We calculated personnel costs in our ALS clinic in 2015 and found an average cost per patient visit of $580, of which only 45% was covered by insurance reimbursement. In this review, we will describe classic and emerging concepts in multidisciplinary care models for adult and pediatric neuromuscular disease. We will then explore the financial impact of multidisciplinary care with emphasis on sustainability and metrics to demonstrate quality and value.

OBJECTIVE:To evaluate whether the burden of deep and lobar lacunes differs between patients with intracerebral hemorrhage (ICH) with definite/probable cerebral amyloid angiopathy (CAA) per the Boston criteria and hypertensive small vessel disease (HTN-SVD; ICH in basal ganglia, thalami, brainstem).METHODS:We defined lobar and deep lacunes similar to the topographic distribution used for ICH and cerebral microbleeds (CMBs). We then compared their distribution between patients with CAA-ICH and those with strictly deep CMB and ICH (HTN-ICH). The independent associations of lacune location with the diagnosis of CAA-ICH and HTN-ICH were evaluated with multivariable models. The relationship between lobar lacunes and white matter hyperintensity (WMH) volume was evaluated by means of partial correlation analyses adjusted for age and a validated visual scale.RESULTS:In our final cohort of 316 patients with ICH, lacunes were frequent (24.7%), with similar rates in 191 patients with CAA and 125 with HTN-ICH (23% vs 27.2%, p = 0.4). Lobar lacunes were more commonly present in CAA (20.4% vs 5.7%, p < 0.001), while deep lacunes were more frequent in HTN-ICH (15.2% vs 2.1%, p < 0.001). After correction for demographics and clinical and neuroimaging markers of SVD, lobar lacunes were associated with CAA (p = 0.003) and deep lacunes with HTN-ICH (p < 0.001). Lobar lacunes in 80% of the cases were at least in contact with WMH, and after adjustment for age, they were highly correlated to WMH volume (r = 0.42, p < 0.001).CONCLUSIONS:Lobar lacunes are associated with CAA, whereas deep lacunes are more frequent in HTN-SVD. Lobar lacunes seem to have a close relationship with WMH, suggesting a possible common origin.

Objective: To assess MRI-visible enlarged perivascular spaces (EPVS) burden and different topographical patterns (in the centrum semiovale [CSO] and basal ganglia [BG]) in 2 common microangiopathies: cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA). Methods: Consecutive patients with spontaneous intracerebral hemorrhage (ICH) from a prospective MRI cohort were included. Small vessel disease MRI markers, including cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), and white matter hyperintensities (WMH), were rated. CSO-EPVS/BG-EPVS were assessed on a validated 4-point visual rating scale (0 = no EPVS, 1 = <10, 2 = 11–20, 3 = 21–40, and 4 = >40 EPVS). We tested associations of predefined high-degree (score >2) CSO-EPVS and BG-EPVS with other MRI markers in multivariable logistic regression. We subsequently evaluated associations with CSO-EPVS predominance (i.e., CSO-EPVS > BG-EPVS) and BG-EPVS predominance pattern (i.e., BG-EPVS > CSO-EPVS) in adjusted multinomial logistic regression (reference group, BG-EPVS = CSO-EPVS). Results: We included 315 patients with CAA-ICH and 137 with HA-ICH. High-degree CSO-EPVS prevalence was greater in CAA-related ICH vs HA-related ICH (43.8% vs 17.5%, p < 0.001). In multivariable logistic regression, high-degree CSO-EPVS was associated with lobar CMB (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.10–1.61, p = 0.003) and cSS (OR 2.08, 95% CI 1.30–3.32, p = 0.002). Deep CMBs (OR 2.85, 95% CI 1.75–4.64, p < 0.0001) and higher WMH volume (OR 1.02, 95% CI 1.01–1.04, p = 0.010) were predictors of high-degree BG-EPVS. A CSO-EPVS–predominant pattern was more common in CAA-ICH than in HA-ICH (75.9% vs 39.4%, respectively, p < 0.0001). CSO-PVS predominance was associated with lobar CMB burden and cSS, while BG-EPVS predominance was associated with HA-ICH and WMH volumes. Conclusions: Different patterns of MRI-visible EPVS provide insights into the dominant underlying microangiopathy type in patients with spontaneous ICH.

Background: The predominant type of cerebral small vessel disease (SVD) and clinical outcomes of patients who present with a combination of lobar and deep intracerebral hemorrhage (ICH)/microbleed (MB) locations (Mixed-ICH, see figure) is unknown. Methods: Out of 391 consecutive ICH, 75 (19%) had Mixed-ICH, and their demographics, clinical/laboratory features, and SVD neuroimaging markers were compared to 191 probable Cerebral Amyloid Angiopathy (CAA-ICH) and 125 strictly deep-MB and ICH (Deep-ICH) patients. ICH-recurrence on follow up was also analyzed. Results: Mixed-ICH patients had a higher prevalence of hypertension, diabetes, left ventricular hypertrophy rates, higher creatinine values, as well as more prevalent lacunes and basal ganglia (BG) enlarged perivascular spaces (EPVS) than CAA-ICH (all p<0.05). When compared to Deep-ICH, Mixed-ICH patients were older, had higher WMH volumes and MB count, and more prevalent lacunes and centrum semiovale EPVS (all p<0.05). In multivariable models, Mixed-ICH diagnosis was associated with higher creatinine, more lacunes and BG EPVS, than CAA-ICH (all p<0.05). When compared to Deep-ICH, Mixed-ICH patients were older and had more lacunes and MBs in multivariable models (all p<0.05). Annual risk of ICH-recurrence was 5.1% for Mixed-ICH, higher compared to Strictly Deep-ICH but lower than CAA-ICH (1.6% and 10.4%, respectively). Conclusions: Mixed-ICH, commonly seen when MRI obtained during etiologic workup, appears to be mostly driven by vascular risk factors similar to Strictly Deep-ICH, but demonstrates more severe parenchymal damage and higher ICH-recurrence risk.

Objective: In order to explore the mechanisms of cortical superficial siderosis (cSS) multifocality and its clinical implications for recurrent intracerebral hemorrhage (ICH) risk in patients with cerebral amyloid angiopathy (CAA), we used a new rating method that we developed specifically to evaluate cSS extent at spatially separated foci. Methods: Consecutive patients with CAA-related ICH according to Boston criteria from a single-center prospective cohort were analyzed. The new score that assesses cSS multifocality (total range 0–4) showed excellent interrater reliability (k = 0.87). The association of cSS with markers of CAA and acute ICH was investigated. Patients were followed prospectively for recurrent symptomatic ICH. Results: The cohort included 313 patients with CAA. Multifocal cSS prevalence was 21.1%. APOE ε2 allele prevalence was higher in patients with multifocal cSS. In probable/definite CAA, cSS multifocality was independently associated with neuroimaging markers of CAA severity, including lobar microbleeds, but not with acute ICH features, which conversely, were determinants of cSS in possible CAA. During a median follow-up of 2.6 years (interquartile range 0.9–5.1 years), the annual ICH recurrence rates per cSS scores (0–4) were 5%, 6.5%, 13.5%, 16.2%, and 26.9%, respectively. cSS multifocality (presence and spread) was the only independent predictor of increased symptomatic ICH risk (hazard ratio 3.19; 95% confidence interval 1.77–5.75; p < 0.0001). Conclusions: The multifocality of cSS correlates with disease severity in probable CAA; therefore cSS is likely to be caused by discrete hemorrhagic foci. The new cSS scoring system might be valuable for clinicians in determining annual risk of ICH recurrence.

Fazit Die zerebrale Amyloidangiopathie und die hypertensive Arteriopathie wiesen in der MRT unterschiedliche Leukoaraiose-Muster auf. Der Rarefizierungstyp auf den Scans könne laut den Autoren auf die Ursache der Gefäßerkrankung und auf den Grund für die Gehirnblutung hindeuten.

Objective:To identify different white matter hyperintensity (WMH) patterns between 2 hemorrhage-prone cerebral small vessel diseases (SVD): cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA).Methods:Consecutive patients with SVD-related intracerebral hemorrhage (ICH) from a single-center prospective cohort were analyzed. Four predefined subcortical WMH patterns were compared between the CAA and HA groups. These WMH patterns were (1) multiple subcortical spots; (2) peri-basal ganglia (BG); (3) large posterior subcortical patches; and (4) anterior subcortical patches. Their associations with other imaging (cerebral microbleeds [CMBs], enlarged perivascular spaces [EPVS]) and clinical markers of SVD were investigated using multivariable logistic regression.Results:The cohort included 319 patients with CAA and 137 patients with HA. Multiple subcortical spots prevalence was higher in the CAA compared to the HA group (29.8% vs 16.8%; p = 0.004). Peri-BG WMH pattern was more common in the HA- vs the CAA-ICH group (19% vs 7.8%; p = 0.001). In multivariable logistic regression, presence of multiple subcortical spots was associated with lobar CMBs (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.01-1.50, p = 0.039) and high degree of centrum semiovale EPVS (OR 2.43; 95% CI 1.56-3.80, p < 0.0001). By contrast, age (OR 1.05; 95% CI 1.02-1.09, p = 0.002), deep CMBs (OR 2.46; 95% CI 1.44-4.20, p = 0.001), total WMH volume (OR 1.02; 95% CI 1.01-1.04, p = 0.002), and high BG EPVS degree (OR 8.81; 95% CI 3.37-23.02, p < 0.0001) were predictors of peri-BG WMH pattern.Conclusion:Different patterns of subcortical leukoaraiosis visually identified on MRI might provide insights into the dominant underlying microangiopathy type as well as mechanisms of tissue injury in patients with ICH.

Objective: We aim to further define predictive factors of survival, disease progression, and complications of ALS patients after gastrostomy tube placement. Background: Gastrostomy tube (G-tube) placement is often considered to supplement nutrition in ALS patients. Current AAN guidelines only risk-stratify patients based on respiratory status. Little evidence guides the appropriate timing of G-tube placement, details procedure-related complications, or provides data on survival after the intervention. Design/Methods: Approximately 500 ALS patients underwent G-tube placement at Massachusetts General Hospital from 1999 to 2014. Comprehensive data regarding baseline and procedure characteristics, disease progression, and survival is being collected. Indications for G-tube placement were categorized as bulbar dysfunction, weight loss, respiratory decline, appetite decline, and inability to feed self. Procedure-related complications were categorized as perioperative (e.g within 7 days), within 30 days (e.g. day 8 to day 30), and greater than 30 days after G-tube. An interim analysis of 75 randomly-selected subjects is presented. Results: 81[percnt] of patients had more than one indication for G-tube placement; bulbar dysfunction was the leading indication. The average time from dysphagia onset to G-tube placement was 10.8 months. Average vital capacity and ALSFRS-R total score proximate to the procedure were 51[percnt] of predicted normal and 31, respectively. Median survival after G-tube placement was 9.9 months; 58[percnt] of patients passed away within 1 year of the procedure. 75[percnt] of patients experienced at least one post-procedure complication. 33[percnt] of total complications occurred within 1 week of the procedure, the most frequent of which were abdominal pain, respiratory distress, and aspiration pneumonia. Conclusions: Further evaluation of predictive factors of survival and disease progression, gastrostomy methodology, and post-procedural complications is needed in a large clinic-based ALS population. Completion of this data analysis and assessment of matched controls may help guide clinical practice.

Introduction: Mechanisms of cortical superficial siderosis (cSS) in cerebral amyloid angiopathy (CAA) are unknown, but might include in situ bleeding from amyloid laden superficial vessels or blood products redistribution from acute lobar intracerebral hemorrhage (ICH). Hypothesis: We aimed to identify factors related to the extent and multifocality of cSS. Methods: We analyzed consecutive CAA-related ICH patients diagnosed with Boston criteria from a prospective cohort. cSS multifocality, was rated for spatially distinct foci involvement and bi-hemispheric distribution on a 0-4 scale (1 point: 1 sulcus or focal immediately adjacent sulci, 2 points: 2 or more non-adjacent sulci OR more than 3 adjacent sulci, in each hemisphere) with excellent interrater reliability (k=0.87). Radiological markers of CAA and ICH characteristics were assessed using quantitative methods or validated visual scales, and their association with cSS multifocality was investigated in multivariable regression. Results: The cohort included 312 CAA patients (53% male; mean age 71.7). cSS was found in 34.6%: unifocal in 42 patients (13.5%), multifocal in 66 (23.1%). Presence and multifocality of cSS were not related with characteristics of the acute ICH such as ICH volume, ICH side or areas of acute subarachnoid blood on initial CT. ICH side did not predict cSS side or multifocality at that side. cSS multifocality was related to the presence of IVH in patients who had a single ICH without microbleeds (MB), but not in patients with multiple hemorrhagic lesions (ICH and/or MBs). In ordinal logistic regression, cSS multifocality was related to lobar microbleeds burden (OR: 1.57; 95%CI: 1.27-1.94; p<0.0001) and MRI centrum semiovale perivascular spaces (PVS, OR: 2.05; 95%CI: 1.26-3.33; p=0.004) but not basal ganglia PVS or leukoaraiosis volume. A secondary analysis using Cox regression showed that cSS multifocality was an independent risk factor for recurrent ICH (HR: 2.21; 95%CI: 1.09-4.52 and 3.91; 95%CI: 1.40-10.9 for multifocality presence and severity) after adjusting for other confounders. Conclusion: Extent and multifocality of cSS appear to be markers of CAA severity and independent predictors of ICH recurrence, and can provide insights potential into pathomechanisms.

Background: Interactions between intracranial arterial pathologies (IAP) and cerebral small vessel disease (SVD) are an increasingly debated topic. Hypothesis: We analyzed associations between the type/severity of SVD and two IAPs, the intracranial arterial calcifications (ICAC) and intracranial stenosis (ICS) in intracerebral hemorrhage (ICH) patients. Methods: Consecutive ICH patients from a prospective cohort were included. Patients were divided into those meeting Boston criteria for cerebral amyloid angiopathy (CAA) and those with strictly deep hypertensive ICH consistent with hypertensive SVD (HTN-SVD). White matter hyperintensity volume (WMH) and microbleed count (MB) were quantitatively measured on MRI as markers of SVD severity. Head CT angiography was rated for presence of ICAC and for presence of >50% intracranial arterial stenosis (ICS). Associations of IAPs with the type of SVD (CAA vs HTN) as well as imaging markers of SVD severity were analyzed in multivariate models. We also explored the association between IAPs and presence of pre-ICH dementia. Results: The cohort included 253 CAA patients and 90 HTN-SVD. CAA patients were older (73.5 vs 64.8, p<0.001), demonstrating higher WMH (25ml vs 16ml, p<0.001) but lower prevalence of hypertension than HTN-ICH. In univariate comparisons between CAA and HTN-SVD, the presence of ICACs (74% vs 72%, p=0.7) and ICS (7% vs 7.8%, p=0.8) were not different. ICS was not related to the type of SVD in multivariate models either. Using multivariate logistic regression, HTN-SVD was independently associated with presence of ICAC (adjusted OR = 2.56 [95% CI 1.1-6.2, p=0.002), as well as older age, male gender and hypercholesterolemia. We found no association between IAPs and parenchymal markers of SVD severity (WMH and MB) (all p>0.2) and no association with presence of dementia before ICH (p>0.2). Conclusions: HTN-SVD is associated with increased ICAC in multivariate models, suggesting either shared risk factors or direct interactions between SVD and IAP. There is no association of intracranial large artery pathologies (ICAC, ICS) with parenchymal (WMH, MB) or clinical (dementia) consequences of cerebral small vessel diseases.

Background: The association between cerebral small vessel diseases (cSVD) and intracranial atherosclerosis is debated and conflicting results have been reported. We sought to investigate this association in patients with intracerebral hemorrhage (ICH), due to severe cSVD.Methods: Consecutive ICH patients were divided into those meeting criteria for cerebral amyloid angiopathy (CM) and those with deep hypertensive ICH consistent with hypertensive cSVD (HTN-SVD). White matter hyperintensity volumes (WMH) and microbleed counts (MB) were measured on MRI. CTA was rated for severity of intracranial carotid calcifications and for presence of >50% intracranial stenosis (ICS). Associations of intracranial atherosclerosis severity with type of SVD (CAA vs HTN-cSVD) and with imaging and clinical markers of cSVD burden were analyzed.Results: The cohort included 253 CAA and 90 HTN-SVD patients. In multivariable models, the type of cSVD (CAA vs. HTN-cSVD) was not associated with calcification severity (OR = 1.04, 95% CI [0.62-3.5], p = 037) or presence of ICS (OR = 0.84, 95% CI [021-2.74], p = 0.78). We found no association between intracranial atherosclerosis (calcifications and stenoses) and parenchymal markers of cSVD severity (WMH and MB, adjusted p >= 0.2 for all comparisons) and no association with presence of dementia before ICH (adjusted p 0.2 for both comparisons).Conclusions: We found no association between intracranial atherosclerosis and parenchymal or clinical consequences of cSVD, suggesting that cSVDs while sharing some risk factors are not influenced by upstream larger vessel pathologies. (C) 2016 Elsevier B.V. All rights reserved.

IMPORTANCE Hematoma expansion is an important determinant of outcome in spontaneous intracerebral hemorrhage (ICH) due to small vessel disease (SVD), but the association between the severity of the underlying SVD and the extent of bleeding at the acute phase is unknown to date.OBJECTIVE To investigate the association between key magnetic resonance imaging (MRI) markers of SVD (as per the Standards for Reporting Vascular Changes on Neuroimaging [STRIVE] guidelines) and hematoma volume and expansion in patients with lobar or deep ICH.DESIGN, SETTING, AND PARTICIPANTS Analysis of data collected from 418 consecutive patients admitted with primary lobar or deep ICH to a single tertiary care medical center between January 1, 2000, and October 1, 2012. Data were analyzed on March 4, 2016. Participants were consecutive patients with computed tomographic images allowing ICH volume calculation and MRI allowing imaging markers of SVD assessment.MAIN OUTCOMES AND MEASURES The ICH volumes at baseline and within 48 hours after symptom onset were measured in 418 patients with spontaneous ICH without anticoagulant therapy, and hematoma expansion was calculated. Cerebral microbleeds, cortical superficial siderosis, and white matter hyperintensity volume were assessed on MRI. The associations between these SVD markers and ICH volume, as well as hematoma expansion, were investigated using multivariable models.RESULTS This study analyzed 254 patients with lobar ICH (mean [SD] age, 75 [11] years and 140 [55.1%] female) and 164 patients with deep ICH (mean [SD] age 67 [14] years and 71 [43.3%] female). The presence of cortical superficial siderosis was an independent variable associated with larger ICH volume in the lobar ICH group (odds ratio per quintile increase in final ICH volume, 1.49; 95% CI, 1.14-1.94; P = .004). In multivariable models, the absence of cerebral microbleeds was associated with larger ICH volume for both the lobar and deep ICH groups (odds ratios per quintile increase in final ICH volume, 1.41; 95% CI, 1.11-1.81; P = .006 and 1.43; 95% CI, 1.04-1.99; P = .03; respectively) and with hematoma expansion in the lobar ICH group (odds ratio, 1.70; 95% CI, 1.07-2.92; P = .04). The white matter hyperintensity volumes were not associated with either hematoma volume or expansion.CONCLUSIONS AND RELEVANCE In patients admitted with primary lobar or deep ICH to a single tertiary care medical center, the presence of cortical superficial siderosis was an independent variable associated with larger lobar ICH volume, and the absence of cerebral microbleeds was associated with larger lobar and deep ICHs. The absence of cerebral microbleeds was independently associated with more frequent hematoma expansion in patients with lobar ICH. We provide an analytical framework for future studies aimed at limiting hematoma expansion.

Background and Purpose— Lobar microbleeds suggestive of cerebral amyloid angiopathy (CAA) are often identified on MRI in the absence of lobar intracerebral hemorrhage (ICH). We compared the baseline characteristics and risk of subsequent ICH among such patients to those presenting with CAA-related lobar ICH. Methods— Clinical data (demographics, risk factors), apolipoprotein E genotype, neuroimaging markers of CAA severity (microbleed counts, leukoaraiosis volume), and clinical outcomes (incidence rates of ICH and death during a mean follow-up of 5.3±3.8 years) were compared between 63 patients enrolled because of incidentally found microbleeds and 316 with CAA-related ICH, in our prospectively enrolled cohort. Predictors of incident ICH were explored in the microbleed-only patients using multivariable Cox regression models. Results— Microbleed-only patients shared similar demographic, apolipoprotein E, and vascular risk profiles with lobar ICH patients, but had more lobar microbleeds (median, 10 versus 2; P <0.001) and higher leukoaraiosis volumes (median, 31 versus 23 mL; P =0.02). Microbleed-only patients had a nontrivial incidence rate of ICH, not different from patients presenting with ICH (5 versus 8.9 per 100 person-years; adjusted hazard ratio, 0.58; 95% confidence interval, 0.31–1.06; P =0.08). Microbleed-only patients had a higher mortality rate (hazard ratio, 1.67; 95% confidence interval, 1.1–2.6) compared with ICH survivors. Warfarin use and increasing age were independent predictors of future ICH among microbleed-only patients after correction for other covariates. Conclusions— Patients presenting with isolated lobar microbleeds on MRI have a genetic, neuroimaging, and hemorrhagic risk profile suggestive of severe CAA pathology. They have a substantial risk of incident ICH, potentially affecting decisions regarding anticoagulation in clinical situations.

BACKGROUND/OBJECTIVES: Lobar microbleeds (LMB) are increasingly identified on brain MRI of older adults, suggesting a diagnosis of cerebral amyloid angiopathy (CAA) in the absence of intracerebral hemorrhage (ICH). Identifying the baseline characteristics and risk of future ICH of these subjects is important to understand their prognosis and safety of antithrombotic use in this setting. METHODS: Baseline characteristics (demographics, risk factors, APOE genotype), markers of CAA severity (LMB counts, white matter hyperintensity volume), and finally outcomes during a mean follow up of 4 years (incidence rate of ICH and case-fatality) were compared between 62 CAA patients without and 747 with ICH diagnosed using Boston criteria upon enrollment. The association between antithrombotic use and risk of incident ICH was explored in patients presenting with isolated LMBs after adjusting for covariates listed above. RESULTS: Female gender (52% vs. 37% p=0.023) and hypertension (67% vs. 53% p=0.025) were more common in patients presenting with ICH, other baseline characteristics did not differ. Patients presenting without ICH had more LMBs (median 10 vs. 1 p<0.001), and higher white matter hyperintensity volume (38cc±32 vs. 27cc ±24 p=0.008) than patients with ICH even after correction for other covariates. Patients without ICH on enrollment had a lower but non-trivial incidence rate of ICH during follow-up (4.8 per 100 person-years vs. 9 per 100 person-years; RR: 0.56, 95%CI 0.27-0.97). The case-fatality rates were similar between these groups (p=0.5). In patients presenting without ICH, the use of Warfarin was an independent predictor of future ICH (p=0.02) in the multivariate model. Patients using either ASA 325mg/day OR Clopidogrel OR ASA/Dipyridamol had higher risk of future ICH (p=.049) but this association did not remain significant in multivariate model. Use of ASA 81mg daily was not a predictor of incident ICH risk. CONCLUSIONS: Patients presenting with LMBs on MRI have a clinical, genetic, and neuroimaging profile suggestive of severe CAA pathology. They have a considerable risk of incident ICH albeit lower than patients who had a prior lobar ICH. The use of warfarin increases the risk of future ICH in patients with isolated LMBs on MRI.

Intracerebral hemorrhage (ICH, or macrobleeds) and cerebral microbleeds—smaller foci of hemosiderin deposits commonly detected by magnetic resonance imaging of older adults with or without ICH—are both associated with an increased risk of future ICH. These hemorrhagic pathologies also share risk factors with ischemic thromboembolic conditions that may require antithrombotic therapy, requiring specialists in cardiology, internal medicine, and neurology to weigh the benefits vs hemorrhagic risks of antithrombotics in individual patients. This paper will review recent advances in our understanding of hemorrhage prone cerebrovascular pathologies with a particular emphasis on use of these markers in decision making for antithrombotic use.

Objective: We aimed to identify the potential contributions of cerebral amyloid angiopathy (CAA) and hypertensive microvasculopathy on periventricular (PV) and subcortical (SC) white matter disease (WMD). Methods: Total, SC and PV WMD volumes of 359 CAA patients and 102 patients with hypertensive intracerebral hemorrhage (htn-ICH) were quantitatively measured on FLAIR MRI. The presence of 6 different subcortical WMD patterns (detailed under Results and Figure 1) was recorded. The independent predictors of each of these WMD variables were explored using multivariate models that included the diagnosis (CAA vs htn-ICH), age, gender, ApoE genotype, vascular risk factors, total WMD volume as well as lobar and deep microbleed (MB) counts from T2*MRI. Results: CAA patients were older (mean 74 vs 68, p<0.001) with a higher WMD burden (p<0.05 for total, PV and SC WMD) than htn-ICH cases. Older age, higher lobar and deep MB counts were independent predictors of both total and PV WMH (p<0.01 for all predictors) whereas only high lobar MB count was independently associated with SC WMD (p<0.001). CAA-related covariates (CAA diagnosis and/or lobar MB counts) were independently associated with large posterior SC WMD (Fig 1a, frequency 16% in CAA vs 5% in htn-ICH, p<0.001) and anterior SC WMD (Fig 1b, 46% vs 24%, p<0.01). Peri-basal ganglia WMD (Fig 1c) pattern was more frequent in htn-ICH (29% vs 10%, p<0.001) and independently associated with deep MB count. The SC spots (Fig 1d, p=0.16), U-shaped SC WMD pattern (Fig 1e, p=0.17) and severe-coalescent WMD (Fig 1f, p=0.5) were not independently related to CAA or htn-ICH. Conclusions: Our results show that CAA pathology is associated with the severity of both PV and SC WMD as well as presence of severe posterior and anterior SC disease. A pattern of deep peri-basal ganglia WMD is mostly associated with hypertensive disease. Recognition of these patterns might help understand the dominant type of microvasculopathy in older individuals with WMD.