Noa Molshatzki

Chronic Kidney Disease in Patients with Acute Intracerebral Hemorrhage: Association with Large Hematoma Volume and Poor Outcome

Background: Chronic kidney disease (CKD) is associated with both a risk of adverse vascular outcome and a risk of bleeding. We have tested the hypothesis that in the setting of an acute intracerebral hemorrhage (ICH), CKD is associated with poor outcome and with larger hematoma volume. Methods: We examined the association between CKD and ICH characteristics and outcome within a prospective cohort study of consecutive patients hospitalized with an acute stroke and followed for 1 year. CKD was categorized by the estimated baseline glomerular filtration rate into moderate/severe impairment (<45), mild impairment (45–60) and no impairment (>60 ml/min/1.73 m2). Results: Among 128 patients with an ICH (mean age = 71.7 ± 12.3 years, 41.4% women) 46.1% had CKD (23.4% mild and 22.7% moderate/severe). Patients with moderate/severe impairment had >4-fold adjusted hazard ratio for mortality over 1 year (4.29; 95% CI = 1.69–10.90) compared to patients with no impairment. The hematoma volumes [median (25–75%)] were 15.3 ml (5.4–37.5) in patients with no impairment, 16.6 (6.8–36.9) in mild impairment and 50.2 (10.4–109.1) in moderate/severe impairment (p = 0.009). The location of the hematoma was lobar in 12% with no impairment, 17% with mild impairment and 39% with moderate/severe impairment (p = 0.02). Patients with moderate/severe impairment exhibited a 2.3-fold higher hematoma volume (p = 0.04) and a >6-fold higher odds of lobar location (95% CI = 1.59–24.02) as compared to no impairment. Further adjustment for antiplatelet use and for presence of leukoaraiosis attenuated the association with hematoma volume (p = 0.15), while moderate/severe impairment was associated with an adjusted OR of 5.35 (95% CI = 1.18–24.14) for lobar location. Conclusions: Presence of moderate/severe CKD among patients with ICH is associated with larger, lobar hematomas and with poor outcome.

Anemia status, hemoglobin concentration and outcome after acute stroke: a cohort study

BackgroundIn the setting of an acute stroke, anemia has the potential to worsen brain ischemia, however, the relationship between the entire range of hemoglobin to long-term outcome is not well understood.MethodsWe examined the association between World Health Organization-defined admission anemia status (hemoglobin<13 in males, <12 g/dl in women) and hemoglobin concentration and 1-year outcome among 859 consecutive patients with acute stroke (ischemic or intracerebral hemorrhage).ResultsThe mean baseline hemoglobin concentration was 13.8 ± 1.7 g/dl (range 8.1 - 18.7). WHO-defined anemia was present in 19% of patients among both women and men. After adjustment for differences in baseline characteristics, patients with admission anemia had an adjusted OR for all-cause death at 1-month of 1.90 (95% CI, 1.05 to 3.43) and at 1-year of 1.72 (95% CI, 1.00 to 2.93) and for the combined end-point of disability, nursing facility care or death of 2.09 (95% CI, 1.13 to 3.84) and 1.83 (95% CI, 1.02 to 3.27) respectively. The relationship between hemoglobin quartiles and all-cause death revealed a non-linear association with increased risk at extremes of both low and high concentrations. In logistic regression models developed to estimate the linear and quadratic relation between hemoglobin and outcomes of interest, each unit increment in hemoglobin squared was associated with increased adjusted odds of all-cause death [at 1-month 1.06 (1.01 to 1.12; p = 0.03); at 1-year 1.09 (1.04 to 1.15; p < 0.01)], confirming that extremes of both low and high levels of hemoglobin were associated with increased mortality.ConclusionsWHO-defined anemia was common in both men and women among patients with acute stroke and predicted poor outcome. Moreover, the association between admission hemoglobin and mortality was not linear; risk for death increased at both extremes of hemoglobin.

Neurological outcome in cerebrotendinous xanthomatosis treated with chenodeoxycholic acid: early versus late diagnosis.

ObjectiveTo present the long-term neurological outcome of Jewish Israeli patients with cerebrotendinous xanthomatosis (CTX) after several years of chenodeoxycholic acid (CDCA) treatment. MethodsA cross sectional observational study of all patients with a diagnosis of CTX followed in a referral outpatient clinic during the years 2003–2012. ResultsEighteen patients (10 men) from 11 families were enrolled. Sixteen patients were included in the analysis (2 patients had low compliance for treatment). The mean ± SD age at last evaluation was 35.0 ± 9.2 years (range, 16–45 years). After their diagnosis, at age 22.6 ± 10.8 years, all patients were treated with CDCA. Patients who started treatment after the age of 25 years had worse outcome and were significantly more limited in ambulation (P = 0.004) and more cognitively impaired (P = 0.047). Five patients who started treatment after 25 years of age continued to deteriorate despite CDCA treatment. ConclusionsBeginning CDCA treatment as early as possible is crucial to preventing neurological damage and deterioration in CTX. After significant neurological pathology is established, the effect of treatment is limited and deterioration may continue.

Low Cholesterol, Statins and Outcomes in Patients with First-Ever Acute Ischemic Stroke

Background: High cholesterol has been associated with better stroke outcomes. Conversely, a protective effect of prestroke statin use in the acute phase of stroke has been reported. The effect of low cholesterol on outcome in patients with and without prestroke statin treatment has not been studied. We assessed the association between low cholesterol and ischemic stroke short- and long-term outcomes and studied potential interactions with statin treatment in patients with a first-ever ischemic stroke in a prospective national registry. Methods: Ischemic stroke patients in the National Acute Stroke Israeli (NASIS) registry with a first-ever stroke and no previous disability, dementia or cancer admitted in all hospitals nationwide during 2-month periods in 2004, 2007 and 2010 were included (n = 1,895). Cholesterol levels ≤155 mg/dl (1st quintile) were defined as low cholesterol and patients treated with statins for at least 7 days before stroke onset were categorized as prestroke statin treated. Severe stroke (NIHSS ≥11), total anterior circulation infarction, poor functional outcome (defined as discharged to a nursing facility or modified Rankin Scale >3 or death), and mortality at discharge and at 3 years were the study outcomes. Associations between low cholesterol and outcomes at discharge were assessed separately in patients with and without prestroke statin treatment using multiple logistic regression analyses. Mortality at 3 years was assessed in a subset of 681 patients with Cox proportional hazard models. Results: Patients were 67.4 ± 13.5 years old on average; 43.1% were women. Low cholesterol was associated with higher rates of stroke risk factors. Controlling for age, sex, hypertension, diabetes, current smoking, ischemic heart disease, congestive heart failure and atrial fibrillation, low cholesterol was significantly associated with severe stroke, total anterior circulation infarction and poor functional outcome in patients with and without statin treatment. There were no interactions between low cholesterol and prestroke statin therapy in association with outcomes. Short- and long-term mortality rates were increased for patients with low cholesterol (5.2% at discharge and 35% at 3-years) compared with higher levels (2.5% at discharge and 20.5% at 3 years). Adjusted mortality risks were increased for patients with low cholesterol; however, this finding was statistically significant only for patients not on statins before the stroke. Conclusions: Low cholesterol is associated with increased stroke severity and poorer functional outcome in patients with and without prestroke statin use. Low-cholesterol statin-naive patients show increased risks of mortality. ‘Reverse epidemiology’ in the association between cholesterol and outcome is possible in patients with ischemic stroke.

The Frontal Assessment Battery as a Tool for Evaluation of Frontal Lobe Dysfunction in Patients With Parkinson Disease

Background: Frontal-type cognitive deficits are common in patients with Parkinson disease (PD). The Frontal Assessment Battery (FAB) was developed to assess frontal lobe functions. However, many studies found that it also correlated with a variety of other general neuropsychological tests. Objectives: To evaluate whether the FAB has an added value over the Mini-Mental State Examination (MMSE) and other bedside neuropsychological tests in reflecting cognitive deficits in patients with PD. Methods: Seventy-two consecutive patients with PD underwent cognitive assessment including the FAB, the MMSE, and a variety of other neuropsychological tests. Correlations were examined using the Spearman’s r. Results: Highly significant correlations were found between the total FAB score and tests of attention, executive functions, and memory. To evaluate the contribution of the FAB beyond that of the MMSE, partial correlation was used. Analyses revealed that the FAB still correlated with most of the tests. Dividing the patients according to the median MMSE score revealed that the high correlation between the FAB and the MMSE was preserved in the low MMSE group, while in the high MMSE group the correlation was relatively low. In the high MMSE group, the FAB correlated with 11 tests compared to the MMSE that correlated with one (P < .001), while in the low MMSE group the number of correlations was 13 versus 7, respectively (P = .05). Conclusions: In our sample of patients with PD, the FAB correlated with dysfunction in a variety of cognitive domains including attention, memory, and executive functions. The FAB has an added value over the MMSE, particularly among nondemented patients, an advantage that can be used in clinical practice.

Cerebral artery calcification in patients with acute cerebrovascular diseases: determinants and long‐term clinical outcome

Background and purpose:  Coronary artery calcium is an independent predictor of all‐cause mortality. We sought to examine the determinants of intracranial cerebral artery calcification (CAC) and its association with long‐term outcome in a large prospective cohort of stroke patients.

Recovery of self-rated health as a predictor of recurrent ischemic events after first myocardial infarction: a 13-year follow-up.

OBJECTIVE Following the trajectory hypothesis for the validity of self-rated health (SRH), we tested whether subjective recovery of health, that is, return to the same or higher level of SRH after a major health event, independently predicts better long-term prognosis. METHODS Participants were 640 patients (≤ 65 years) admitted to the eight medical centers in central Israel with incident MI in a 1-year period (mean age 54, 17% female). Baseline data were collected within days of the index MI. SRH in the preceding year was assessed at baseline, and current SRH was assessed 3-6 months later. Recurrent ischemic events (recurrent MI, hospitalization with unstable angina pectoris, or cardiac death) were recorded during a mean follow-up of 13 years. RESULTS A reduced risk of recurrent events was associated with an upward change of one level (e.g., from 3 at T1 to 4 at T2) in SRH (HR = 0.76, 95%CI: 0.69-0.85), controlling for baseline retrospective SRH. Risk was still significantly lower for each unit of improvement after adjusting for sociodemographics, preevent comorbidity, cardiac risk factors, MI severity, and early post-MI events (HR = 0.85, 95% CI 0.75-0.95). CONCLUSIONS Individuals who perceived themselves 3-6 months after a first MI to be healthier than they had been in the year preceding the MI were more likely to survive event-free throughout the next 13 years, controlling for baseline retrospective SRH and multiple cardiac risk factors. Failure to experience such subjective recovery of ones health is a serious risk factor, which indicates that SRH should be monitored regularly after a MI.

Serum calcium levels and long-term mortality in patients with acute stroke.

Background: Calcium concentrations in serum are maintained within an exquisitely narrow range. Our aim was to examine the association between serum calcium and albumin-adjusted calcium (calciumadj) levels and stroke outcome in a cohort of unselected patients with acute stroke. Methods: Consecutive patients hospitalized due to acute stroke (ischemic or intracerebral hemorrhage) throughout a large medical center were systematically assessed and followed for 1 year. Baseline total calcium and calciumadj levels were collapsed into groups of low (<8.6 mg/dl), normal (8.7–9.9 mg/dl) and high (>10 mg/dl) levels and linear and quadratic relations with outcome were examined. Result: Among 784 patients (mean age 70.7 ± 12.5 years, 42.5% females), the mean ± SD total calcium level was 9.3 ± 0.6 mg/dl. For total calcium, the adjusted hazard ratio (HR) for all-cause death over 1 year was 1.83 [95% confidence interval (CI) 1.22–2.75] among patients with low versus normal levels. For calciumadj, the adjusted HR for all-cause death among women was over 3-fold higher among patients with high calciumadj levels versus those with normal levels (3.31; 95% CI 1.70–6.46), while no such associations were observed among men. In models developed to estimate the linear and quadratic relations, each unit increment in total calcium squared was associated with an increased adjusted HR of all-cause death over 1 year (p = 0.02) confirming nonlinear associations, and each unit increment in calciumadj squared was associated with an increased adjusted HR of all-cause death over 1 year among women (p < 0.001) but not among men (p = 0.70). Conclusions: Serum calcium concentrations are a marker of mortality in acute stroke patients, but the associations are not linear, increasing at both extremes of calcium levels. Our findings suggest that long-term survival is optimal in a distinct range of serum calcium levels.

The LRRK2 G2019S mutation status does not affect the outcome of subthalamic stimulation in patients with Parkinson's disease

BACKGROUND Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established therapy for advanced Parkinsons disease (PD). The most common genetic mutation associated with PD identified to date is the G2019S mutation of the LRRK2 gene, which is highly prevalent in the Ashkenazi Jewish population. The effect of STN-DBS surgery in patients carrying this mutation has not been systematically studied. We therefore performed a case-control study to evaluate the impact of the G2019S mutation status on the outcomes of bilateral STN-DBS. METHODS The study sample included 39 Jewish PD patients with bilateral STN-DBS. Thirteen patients (5 females) were G2019S mutation heterozygous. The control group consisted of 26 PD patients with bilateral STN-DBS, negative for the mutation, matched (2:1) for gender, age at PD onset, and disease duration at surgery. Clinical data including the Unified PD Rating Scale scores (UPDRS), levodopa equivalent daily dose (LEDD), and clinical global impression of change (CGIC) concerning both motor and neuropsychiatric outcome- were available at 3 time points (preoperative baseline, 6-12 months and 3 years postoperatively). RESULTS Implementing a linear mixed model, a significant improvement (p < 0.05) was found for the whole group concerning reduction in motor UPRDS (off state) and LEDD pre- vs. postoperatively, as expected. No difference in clinical outcome was found between carriers and matched non-carriers at baseline or at postoperative follow-up (up to 3 years). CONCLUSIONS In our study, STN-DBS outcomes were not influenced by the LRRK2 G2019S mutation, and thus knowledge of carrier status may not be relevant to the considerations of patient selection for surgery.

Serum Uric Acid and Subsequent Cognitive Performance in Patients with Pre-Existing Cardiovascular Disease

High serum uric acid (UA) levels are associated with numerous vascular risk factors, and vascular disease, that predispose patients to cognitive impairment, yet UA is also a major natural antioxidant and higher levels have been linked to slower progression of several neurodegenerative disease. In-order to test the association between UA and subsequent cognitive performance among patients that carry a high vascular burden, UA levels were determined by calorimetric enzymatic tests in a sub-cohort of patients with chronic cardiovascular disease who previously participating in a secondary prevention trial. After an average of 9.8±1.7 years, we assessed cognitive performance (Neurotrax Computerized Cognitive Battery) as well as cerebrovascular reactivity (CVR) and common carotid intima-media thickness (IMT). Among 446 men (mean age 62.3±6.4 yrs) mean UA levels were 5.8±1.1 mg/dL. Adjusted linear regression models revealed that low UA levels (bottom quintile) were associated with poorer cognitive performance. Adjusted differences between the bottom quintile and grouped top UA quintiles were (B coefficient±SE) −4.23±1.28 for global cognitive scores (p = 0.001), −4.69±1.81 for memory scores (p = 0.010), −3.32±1.43 for executive scores (p = 0.020) and −3.43±1.97 for visual spatial scores (p = 0.082). Significant difference was also found for attention scores (p = 0.015). Additional adjustment for impaired CVR and high common carotid IMT slightly attenuated the relationship. Stronger UA effect on cognitive performance was found for older (age>65) patients with significant age interaction for global cognitive score (p = 0.016) and for executive (p = 0.018) and attention domains (p<0.001). In conclusion, we demonstrate that low UA levels in patients with preexisting cardiovascular disease are associated with poorer cognitive function a decade later. These findings lend support to the hypothesis that oxidative stress may be involved in the pathogenesis of age-associated cognitive impairment.