Kazuma Nakagawa

Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials.

Objectives:Randomized trials have suggested that hypertonic saline solutions may be superior to mannitol for the treatment of elevated intracranial pressure, but their impact on clinical practice has been limited, partly by their small size. We therefore combined their findings in a meta-analysis. Data Sources:We searched for relevant studies in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and ISI Web of Knowledge. Study Selection:Randomized trials were included if they directly compared equiosmolar doses of hypertonic sodium solutions to mannitol for the treatment of elevated intracranial pressure in human subjects undergoing quantitative intracranial pressure measurement. Data Extraction:Two investigators independently reviewed potentially eligible trials and extracted data using a preformed data collection sheet. Disagreements were resolved by consensus or by a third investigator if needed. We collected data on patient demographics, type of intracranial pathology, baseline intracranial pressure, osms per treatment dose, quantitative change in intracranial pressure, and prespecified adverse events. Our primary outcome was the proportion of successfully treated episodes of elevated intracranial pressure. Data Synthesis:Five trials comprising 112 patients with 184 episodes of elevated intracranial pressure met our inclusion criteria. In random-effects models, the relative risk of intracranial pressure control was 1.16 (95% confidence interval, 1.00–1.33), and the difference in mean intracranial pressure reduction was 2.0 mm Hg (95% confidence interval, −1.6 to 5.7), with both favoring hypertonic saline over mannitol. A mild degree of heterogeneity was present among the included trials. There were no significant adverse events reported. Conclusions:We found that hypertonic saline is more effective than mannitol for the treatment of elevated intracranial pressure. Our meta-analysis is limited by the small number and size of eligible trials, but our findings suggest that hypertonic saline may be superior to the current standard of care and argue for a large, multicenter, randomized trial to definitively establish the first-line medical therapy for intracranial hypertension.

Autoregulation in the posterior circulation is altered by the metabolic state of the visual cortex

Background and Purpose— Previous studies suggest that dynamic autoregulation in the posterior cerebral artery (PCA) is less efficient compared to the middle cerebral artery (MCA). We examined the role of cerebral vasodilation caused by metabolic activation (ie, visual stimulus) on autoregulatory characteristics in the 2 vascular territories. Methods— Blood flow velocity in the PCA and MCA and mean arterial pressure were measured continuously in 45 healthy volunteers (62±3 years) while seated with eyes open. Additional 20 subjects (60±5 years) were examined with eyes closed and open. Autoregulation was assessed using transfer function gains in both the PCA and MCA territories in the low (0.03–0.07 Hz), high (0.07–0.15 Hz), and cardiac (≈1 Hz) frequency ranges. Results— With eyes open, gains were significantly higher in the PCA compared to the MCA in the low (PCA: 1.41±0.09 vs MCA: 1.18±0.07; P=0.003) and high (PCA: 2.06±0.12 vs MCA: 1.61±0.08; P=0.0001) frequencies. Opening eyes increased blood flow velocity and reduced cerebrovascular resistance index in the PCA but not in MCA. This vasodilation in the PCA was associated with increased gain in the low (autoregulatory) frequency, whereas MCA gain did not change (PCA: 0.89±0.14 vs 1.31±0.17, MCA: 1.24±0.16 vs 1.16±0.11; P=0.02). Conclusions— Dilation of the PCA territory during visual cortex activation resulted in increased PCA transfer function gain without changing MCA gain. Thus, impaired autoregulation in the PCA reported in previous literature is likely the result of metabolic vasodilation and not an inherent difference in the autoregulatory characteristics of the posterior circulation.

Accuracy of Neurovascular Fellows' Prognostication of Outcome After Subarachnoid Hemorrhage

Background and Purpose— The purpose of this study was to determine the accuracy and optimal timing of physician prognostication in patients with subarachnoid hemorrhage, a prototypical neurological disease characterized by variable outcomes and frequent disability. Methods— From October 2009 to April 2010, treating neurologists at a tertiary care academic medical center made daily predictions of the modified Rankin Scale at 6 months for consecutive patients with subarachnoid hemorrhage. Actual functional outcomes at 6 months were determined by phone interview and dichotomized into good (modified Rankin Scale 0–2) and poor (modified Rankin Scale 3–6) outcomes. Descriptive statistics were used to assess the accuracy of prognostications. Multiple logistic regression and generalized estimating equations were used to assess changes in prognostication accuracy over time and the relationship between prognostication accuracy and clinical factors. Results— Physicians made 648 prognostications for 66 patients. Overall accuracy ranged from 78% to 88%. Among patients predicted to have a good outcome, 81% (95% CI, 71%–92%) actually had a good outcome, whereas 88% (95% CI, 77%–99%) of patients predicted to do poorly had poor outcomes. No significant trends were seen in prognostication accuracy over time during the hospital course (P=0.72). Increasing age, infection, mechanical ventilation, hydrocephalus, and seizures all significantly worsened physician accuracy. Conclusions— Neurologists were generally but not perfectly accurate in their prognostications of functional outcomes. The accuracy of prognoses did not correlate with the hospital day on which they were made but was affected by clinical factors that can cloud the neurological examination.

Dynamic cerebral autoregulation after intracerebral hemorrhage: A case-control study

BackgroundDynamic cerebral autoregulation after intracerebral hemorrhage (ICH) remains poorly understood. We performed a case-control study to compare dynamic autoregulation between ICH patients and healthy controls.MethodsTwenty-one patients (66 ± 15 years) with early (< 72 hours) lobar or basal ganglia ICH were prospectively studied and compared to twenty-three age-matched controls (65 ± 9 years). Continuous measures of mean flow velocity (MFV) in the middle cerebral artery and mean arterial blood pressure (MAP) were obtained over 5 min. Cerebrovascular resistance index (CVRi) was calculated as the ratio of MAP to MFV. Dynamic cerebral autoregulation was assessed using transfer function analysis of spontaneous MAP and MFV oscillations in the low (0.03-0.15 Hz) and high (0.15-0.5 Hz) frequency ranges.ResultsThe ICH group demonstrated higher CVRi compared to controls (ipsilateral: 1.91 ± 1.01 mmHg·s·cm-1, p = 0.04; contralateral: 2.01 ± 1.24 mmHg·s·cm-1, p = 0.04; vs. control: 1.42 ± 0.45 mmHg·s·cm-1). The ICH group had higher gains than controls in the low (ipsilateral: 1.33 ± 0.58%/mmHg, p = 0.0005; contralateral: 1.47 ± 0.98%/mmHg, p = 0.004; vs. control: 0.82 ± 0.30%/mmHg) and high (ipsilateral: 2.11 ± 1.31%/mmHg, p < 0.0001; contralateral: 2.14 ± 1.49%/mmHg, p < 0.0001; vs. control: 0.66 ± 0.26%/mmHg) frequency ranges. The ICH group also had higher coherence in the contralateral hemisphere than the control (ICH contralateral: 0.53 ± 0.38, p = 0.02; vs. control: 0.38 ± 0.15) in the high frequency range.ConclusionsPatients with ICH had higher gains in a wide range of frequency ranges compared to controls. These findings suggest that dynamic cerebral autoregulation may be less effective in the early days after ICH. Further study is needed to determine the relationship between hematoma size and severity of autoregulation impairment.

A new Thr49Pro transthyretin gene mutation associated with leptomeningeal amyloidosis.

Leptomeningeal amyloidosis is a rare central nervous system manifestation of systemic amyloidosis from transthyretin (TTR) mutation. Ten TTR gene mutations associated with this condition have been described. We report the clinical, radiological, and pathological features of a case of leptomeningeal amyloidosis from a novel Thr49Pro TTR gene mutation. A 53 year-old man presented with recurrent episodes of transient aphasia and right hand stiffness, headaches, and peripheral neuropathy. A surgical biopsy of the leptomeninges and superficial cortex, and DNA sequences of the TTR gene were analyzed. Elevated cerebrospinal fluid (CSF) protein and diffuse leptomeningeal enhancement of the neuraxis from the cortical sulci to the cauda equina on contrast MRI were the defining clinical features. A surgical biopsy revealed TTR amyloid deposition in the subpia and within the leptomeningeal blood vessels. DNA sequencing showed a proline-for-threonine substitution at codon 49 of the TTR gene in one allele. A novel Thr49Pro TTR gene mutation is associated with leptomeningeal amyloidosis resulting in recurrent CNS symptoms.

Cardiac Rupture After Intravenous t-PA Administration in Acute Ischemic Stroke

BackgroundVentricular free wall rupture is a fatal complication of myocardial infarction (MI). Although described in MI patients who receive thrombolytic therapy, this complication is not well known in ischemic stroke patients who receive intravenous (IV) t-PA.MethodsCase report.ResultsWe present a 93-year-old woman with an acute onset of a right middle cerebral artery syndrome in the setting of subacute MI. IV t-PA was administered and she subsequently developed asystolic arrest and died. Autopsy showed subacute MI, hemopericardium, and rupture of the left ventricle.ConclusionsThis case illustrates a fatal cardiac complication of IV thrombolytic therapy for stroke. The speculated mechanism is hemorrhage into the infarcted myocardium.

Sex Differences in the Use of Early Do-Not-Resuscitate Orders After Intracerebral Hemorrhage

Background and Purpose— Studies show that women are more likely to receive do-not-resuscitate (DNR) orders after acute medical illnesses than men. However, the sex differences in the use of DNR orders after acute intracerebral hemorrhage (ICH) have not been described. Methods— We conducted a retrospective study of consecutive patients hospitalized for acute ICH at a tertiary stroke center between 2006 and 2010. Unadjusted and multivariable logistic regression analyses were performed to test for associations between female sex and early (<24 hours of presentation) DNR orders. Results— A total of 372 consecutive ICH patients without preexisting DNR orders were studied. Overall, 82 (22%) patients had early DNR orders after being hospitalized with ICH. In the fully adjusted model, early DNR orders were more likely in women (odds ratio, 3.18; 95% confidence interval, 1.51–6.70), higher age (odds ratio, 1.09 per year; 95% confidence interval, 1.05–1.12), larger ICH volume (odds ratio, 1.01 per cm3; 95% confidence interval, 1.01–1.02), and lower initial GCS score (odds ratio, 0.76 per point; 95% confidence interval, 0.69–0.84). Early DNR orders were less likely when the patients were transferred from another hospital (odds ratio, 0.28, 95% confidence interval, 0.11–0.76). Conclusions— Women are more likely to receive early DNR orders after ICH than men. Further prospective studies are needed to determine factors contributing to the sex variation in the use of early DNR order after ICH.

Racial disparities among Native Hawaiians and Pacific Islanders with intracerebral hemorrhage

Objectives: To evaluate disparities in stroke risk factors and outcome among the Native Hawaiians and other Pacific Islanders (NHPI) in Hawaii who are hospitalized with intracerebral hemorrhage (ICH). Methods: We performed a retrospective study on consecutive patients hospitalized for acute ICH at a single tertiary center on Oahu between 2004 and 2010. Clinical data were obtained from the Get With the Guidelines–Stroke database. Multivariable logistic regression was used to assess the predictors for young ICH (age <45). Results: A total of 562 patients hospitalized for acute ICH (Asian 63%, NHPI 18%, white 16%, other 3%) were studied. The NHPI were younger (mean ages, NHPI 55 ± 16 vs white 66 ± 16 years, p < 0.0001), and had higher prevalence of diabetes (NHPI 35% vs white 20%, p = 0.01) and history of hypertension (NHPI 77% vs white 64%, p = 0.04) compared to white patients. Independent predictors for young ICH were NHPI race (odds ratio [OR] 3.55; 95% confidence interval [CI] 1.33–9.45), being transferred from another hospital (OR 2.03; 95% CI 1.05–3.93), hypertension (OR 0.49; 95% CI 0.27–0.91), previous stroke or TIA (OR 0.21; 95% CI 0.05–0.91), and dyslipidemia (OR 0.15; 95% CI 0.05–0.50). Conclusions: NHPI with ICH are younger and have higher burden of risk factors compared to white patients. Further studies controlling for socioeconomic modifiers are needed to determine factors contributing to the younger age at presentation in this racial group.

Disparities among Asians and Native Hawaiians and Pacific Islanders with ischemic stroke

Objectives: To evaluate disparities in cardiovascular risk factors among Asians and Native Hawaiians and other Pacific Islanders (NHPI) in Hawaii who are hospitalized with ischemic stroke. Methods: We performed a retrospective study on consecutive patients hospitalized for ischemic stroke at a single tertiary center in Honolulu between 2004 and 2010. The prevalence of cardiovascular risk factors was compared for NHPI, Asians, and whites who were hospitalized for ischemic stroke. Results: A total of 1,921 patients hospitalized for ischemic stroke were studied. NHPI were less likely to be older (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.94–0.96), more likely to be female (OR 1.55, 95% CI 1.07–2.24), and more likely to have diabetes (OR 2.74, 95% CI 1.87–4.00), hypertension (OR 1.98, 95% CI 1.27–3.10), and obesity (OR 1.82, 95% CI 1.25–2.65) than whites. NHPI had higher low-density lipoprotein levels (114 ± 50 mg/dL vs 103 ± 45 mg/dL, p = 0.001) and lower high-density lipoprotein levels (38 ± 11 mg/dL vs 45 ± 15 mg/dL, p < 0.0001) than whites. Compared with Asians, NHPI were less likely to be older (OR 0.95, 95% CI 0.94–0.97) and more likely to have diabetes (OR 1.88, 95% CI 1.35–2.61), previous stroke or TIA (OR 1.57, 95% CI 1.09–2.25), and obesity (OR 6.05, 95% CI 4.31–8.48). Conclusions: Asians, NHPI, and whites with ischemic stroke have substantially different cardiovascular risk factors. Targeted secondary prevention will be important in reducing disparities among these racial groups.

Ultra-Early Magnetic Resonance Imaging Findings of Eclampsia

OBJECTIVE To report the very early magnetic resonance imaging features of eclampsia. DESIGN Case report. SETTING Inpatient neurology service. PATIENT A 35-year-old woman who developed late postpartum eclampsia with cerebral edema, caudate hemorrhage, and ischemic strokes. Main Outcome Measure Very early magnetic resonance imaging features. RESULTS Magnetic resonance imaging with gadolinium showed posterior sulcal hyperintensity and leptomeningeal enhancement preceding the development of posterior reversible encephalopathy syndrome, hemorrhage, and ischemic strokes by days. CONCLUSION Magnetic resonance imaging with gadolinium shows early characteristic findings that precede the more classic clinical presentation of eclampsia.