A review of methamphetamine use and stroke in the young

Methamphetamine (meth) is a potent and addictive central nervous system stimulant with increasing use. Stroke is one severe possible complication of meth use. Due to high levels of manufacturing in Mexico, the western United States has experienced greater consequences of meth use. The literature reviewed herein is comprised of case studies and series, and it suggests that hemorrhagic stroke (including hypertensive-like intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage), as opposed to ischemic stroke, is the more common type of neurovascular complication of meth use. Meth-related strokes are a particular concern for younger patients with stroke and may be a partial explanation for increasing stroke rates in this age group. We describe two cases (one intraparenchymal hemorrhage and one ischemic stroke) in young patients (<50 years old) with recent meth use to illustrate clinical characteristics and therapeutic considerations. There are several proposed pathophysiological explanations for meth-associated hemorrhagic stroke including an induced hypertensive surge, vasospasm, blood brain barrier breakdown, chronic hypertension, aneurysm development and rupture, and very rarely associated vasculitis. The increased risk of ischemic stroke related to meth use is less well supported in the literature, but this may, in part, be related to a lack of appropriately designed and powered research studies. Proposed mechanisms for ischemic stroke complications of meth use include those affecting blood vessels such as accelerated atherosclerosis, chronic hypertension, vasospasm, and vasculitis, plus mechanisms that affect the heart including cardiomyopathy, arrhythmias, and infective endocarditis (especially with injection drug use). Standard therapeutic interventions for acute stroke and approaches to secondary stroke prevention seem appropriate for meth-associated strokes, with the addition of abstinence from continued meth use. There is no evidence for any meth-specific stroke treatments. Finally, the prolonged duration of meth withdrawal is described. Larger, prospective studies of meth-related strokes are needed to allow for a better understanding and improved care for this often-devastating consequence of an increasingly prevalent cause of strokes in young patients

Wide variation and rising utilization of stroke magnetic resonance imaging: Data from 11 States

Objective: Neuroimaging is an essential component of the acute stroke evaluation. Magnetic resonance imaging (MRI) is more accurate than computed tomography (CT) for the diagnosis of stroke, but is more costly and time‐consuming. We sought to describe changes in MRI utilization from 1999 to 2008. Methods: We performed a serial cross‐sectional study with time trends of neuroimaging in patients with a primary International Classification of Diseases, 9th Edition, Clinical Modification discharge diagnosis of stroke admitted through the emergency department in the State Inpatient Databases from 10 states. MRI utilization was measured by Healthcare Cost and Utilization Project criteria. Data were included for states from 1999 to 2008 where MRI utilization could be identified. Results: A total of 624,842 patients were hospitalized for stroke in the period of interest. MRI utilization increased in all states. Overall, MRI absolute utilization increased 38%, and relative utilization increased 235% (28% of strokes in 1999 to 66% in 2008). Over the same interval, CT utilization changed little (92% in 1999 to 95% in 2008). MRI use varied widely by state. In 2008, MRI utilization ranged from a low of 55% of strokes in Oregon to a high of 79% in Arizona. Diagnostic imaging was the fastest growing component of total hospital costs (213% increase from 1999 to 2007). Interpretation: MRI utilization during stroke hospitalization increased substantially, with wide geographic variation. Rather than replacing CT, MRI is supplementing it. Consequently, neuroimaging has been the fastest growing component of hospitalization cost in stroke. Recent neuroimaging practices in stroke are not standardized and may represent an opportunity to improve the efficiency of stroke care. Ann Neurol 2012;71:179–185Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90061/1/22698_ftp.pd

Prehospital score for acute disease: a community-based observational study in Japan

<p>Abstract</p> <p>Background</p> <p>Ambulance usage in Japan has increased consistently because it is free under the national health insurance system. The introduction of refusal for ambulance transfer is being debated nationally. The purpose of the present study was to investigate the relationship between prehospital data and hospitalization outcome for acute disease patients, and to develop a simple prehospital evaluation tool using prehospital data for Japan's emergency medical service system.</p> <p>Methods</p> <p>The subjects were 9,160 consecutive acute disease patients aged ≥ 15 years who were transferred to hospital by Kishiwada City Fire Department ambulance between July 2004 and March 2006. The relationship between prehospital data (age, systolic blood pressure, pulse rate, respiration rate, level of consciousness, SpO₂level and ability to walk) and outcome (hospitalization or non-hospitalization) was analyzed using logistic regression models. The prehospital score component of each item of prehospital data was determined by beta coefficients. Eligible patients were scored retrospectively and the distribution of outcome was examined. For patients transported to the two main hospitals, outcome after hospitalization was also confirmed.</p> <p>Results</p> <p>A total of 8,330 (91%) patients were retrospectively evaluated using a prehospital score with a maximum value of 14. The percentage of patients requiring hospitalization rose from 9% with score = 0 to 100% with score = 14. With a cut-off point score ≥ 2, the sensitivity, specificity, positive predictive value and negative predictive value were 97%, 16%, 39% and 89%, respectively. Among the 6,498 patients transported to the two main hospitals, there were no deaths at scores ≤ 1 and the proportion of non-hospitalization was over 90%. The proportion of deaths increased rapidly at scores ≥ 11.</p> <p>Conclusion</p> <p>The prehospital score could be a useful tool for deciding the refusal of ambulance transfer in Japan's emergency medical service system.</p

Regional variation in hospitalization for stroke among Asians/Pacific Islanders in the United States: a nationwide retrospective cohort study

BACKGROUND: In Asia, stroke incidence varies dramatically from country to country. Little is known about stroke incidence in Asians/Pacific Islanders in the US, where regional heterogeneity in Asian/Pacific Islander sub-populations is great. We sought to characterize both the national and regional incidences of first and recurrent hospitalized acute ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage in Asians/Pacific Islanders compared to non-Hispanic whites. METHODS: We used the National Inpatient Sample of the 1997 Healthcare Cost and Utilization Project. It is a 20% stratified sample of hospitalizations to nonfederal hospitals in the US. National and regional projections were made using sampling weights specific for patients and hospitals. We identified stroke subtypes using previously validated ICD-9 codes. Age-adjusted incidence rates were calculated using the direct method with the US population in 2000 as the standard. RESULTS: There were 169,386 stroke hospitalizations in the database. Nationally, compared to whites, Asians/Pacific Islanders were more likely to have subarachnoid hemorrhage (incidence rate ratio {RR} female: 1.53, 95% CI 1.41–1.65; male RR: 1.13, 95% CI 1.00–1.27) and intracerebral hemorrhage (female RR 1.29, 95% CI 1.22–1.36; male RR: 1.58, 95% CI 1.50–1.67). However, when examined by geographic regions, Asians/Pacific Islanders had higher incidence rates of subarachnoid hemorrhage and intracerebral hemorrhage predominantly in the West, and lower rates of stroke elsewhere. CONCLUSION: Stroke incidence varies 3-fold among Asians/Pacific Islanders residing in different US regions. Geographic variation is less dramatic in whites. Whether genetic or cultural differences are responsible for dramatic heterogeneity among Asian/Pacific Islander populations is unclear and deserves further study

Genome-wide association study of cerebral small vessel disease reveals established and novel loci

Intracerebral haemorrhage and small vessel ischaemic stroke (SVS) are the most acute manifestations of cerebral small vessel disease, with no established preventive approaches beyond hypertension management. Combined genome-wide association study (GWAS) of these two correlated diseases may improve statistical power to detect novel genetic factors for cerebral small vessel disease, elucidating underlying disease mechanisms that may form the basis for future treatments. Because intracerebral haemorrhage location is an adequate surrogate for distinct histopathological variants of cerebral small vessel disease (lobar for cerebral amyloid angiopathy and non-lobar for arteriolosclerosis), we performed GWAS of intracerebral haemorrhage by location in 1813 subjects (755 lobar and 1005 non-lobar) and 1711 stroke-free control subjects. Intracerebral haemorrhage GWAS results by location were meta-analysed with GWAS results for SVS from MEGASTROKE, using 'Multi-Trait Analysis of GWAS' (MTAG) to integrate summary data across traits and generate combined effect estimates. After combining intracerebral haemorrhage and SVS datasets, our sample size included 241 024 participants (6255 intracerebral haemorrhage or SVS cases and 233 058 control subjects). Genome-wide significant associations were observed for non-lobar intracerebral haemorrhage enhanced by SVS with rs2758605 [MTAG P-value (P) = 2.6 x 10(-8)] at 1q22;rs72932727 (P = 1.7 x 10(-8)) at 2q33;and rs9515201 (P = 5.3 x 10(-10)) at 13q34. In the GTEx gene expression library, rs2758605 (1q22), rs72932727 (2q33) and rs9515201 (13q34) are significant cis-eQTLs for PMF1 (P = 1 x 10(-4) in tibial nerve), NBEAL1, FAM117B and CARF (P<2.1 x 10(-7) in arteries) and COL4A2 and COL4A1 (P<0.01 in brain putamen), respectively. Leveraging S-PrediXcan for gene-based association testing with the predicted expression models in tissues related with nerve, artery, and non-lobar brain, we found that experiment-wide significant (P<8.5 x 10(-7)) associations at three genes at 2q33 including NBEAL1, FAM117B and WDR12 and genome-wide significant associations at two genes including ICA1L at 2q33 and ZCCHC14 at 16q24. Brain cell-type specific expression profiling libraries reveal that SEMA4A, SLC25A44 and PMF1 at 1q22 and COL4A1 and COL4A2 at 13q34 were mainly expressed in endothelial cells, while the genes at 2q33 (FAM117B, CARF and NBEAL1) were expressed in various cell types including astrocytes, oligodendrocytes and neurons. Our cross-phenotype genetic study of intracerebral haemorrhage and SVS demonstrates novel genome-wide associations for non-lobar intracerebral haemorrhage at 2q33 and 13q34. Our replication of the 1q22 locus previous seen in traditional GWAS of intracerebral haemorrhage, as well as the rediscovery of 13q34, which had previously been reported in candidate gene studies with other cerebral small vessel disease-related traits strengthens the credibility of applying this novel genome-wide approach across intracerebral haemorrhage and SVS

Rare missense functional variants at COL4A1 and COL4A2 in sporadic intracerebral Hhmorrhage

Objective: To test the genetic contribution of rare missense variants in COL4A1 and COL4A2 in which common variants are genetically associated with sporadic intracerebral hemorrhage (ICH), we performed rare variant analysis in multiple sequencing data for the risk for sporadic ICH. Methods: We performed sequencing across 559Kbp at 13q34 including COL4A1 and COL4A2 among 2,133 individuals (1,055 ICH cases; 1,078 controls) in US-based and 1,492 individuals (192 ICH cases; 1,189 controls) from Scotland-based cohorts, followed by sequence annotation, functional impact prediction, genetic association testing, and in silico thermodynamic modeling. Results: We identified 107 rare nonsynonymous variants in sporadic ICH, of which two missense variants, rs138269346 (COL4A1I110T) and rs201716258 (COL4A2H203L), were predicted to be highly functional and occurred in multiple ICH cases but not in controls from the US-based cohort. The minor allele of rs201716258 was also present in Scottish ICH patients, and rs138269346 was observed in two ICH-free controls with a history of hypertension and myocardial infarction. Rs138269346 was nominally associated with non-lobar ICH risk (P=0.05), but not with lobar ICH (P=0.08), while associations between rs201716258 and ICH subtypes were non-significant (P&gt;0.12). Both variants were considered pathogenic based on minor allele frequency (&lt;0.00035 in EUR), predicted functional impact (deleterious or probably damaging), and in silico modeling studies (substantially altered physical length and thermal stability of collagen). Conclusions: We identified rare missense variants in COL4A1/A2 in association with sporadic ICH. Our annotation and simulation studies suggest that these variants are highly functional and may represent targets for translational follow-up

Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage

Background and Purpose-Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. Methods-We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. Results-No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score. Conclusion-Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN. (Stroke. 2012; 43: 2877-2883.