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Accuracy of initial stroke subtype diagnosis. a decision analysis.

BACKGROUND: The clinical diagnosis of stroke subtype is often inaccurate during the first 24 h after stroke onset. Several candidate diagnostic tests might be useful for early determination of subtype, but there is no consensus on what level of accuracy is required to be useful in the selection of patients for subtype-specific studies or therapies. METHODS: A decision analysis was developed to explore the treatment options and estimate the requisite threshold of diagnostic accuracy. Four management strategies were considered: treat all (TA), treat based on new test (TBNT), treat based on clinical diagnosis (TBCD) and treat none (TN). Sensitivity analyses were performed over a wide range of the assumptions in the model. RESULTS: The preferred treatment strategy was dependent on the probability and severity of adverse effects and the positive predictive value (PPV) of the proposed diagnostic test. For a potential therapy with infrequent (7.5%) but severe side effects, TN was preferable, but TBNT dominated if the PPV of the new test was at least 81%. For a therapy with frequent (25%) but mild adverse effects, TBNT was preferable. TA was favored for a therapy with infrequent and mild side effects and TN for a therapy with severe and frequent adverse events. TBCD was never the preferred option unless the PPV of the new test was less accurate than clinical diagnosis alone. CONCLUSIONS: Clinical diagnosis of stroke subtype is insufficient for patient selection, but a new diagnostic test with PPV >/=81% may be useful for early subtype diagnosis and patient selection for stroke subtype-specific clinical trials.

Decision Support Techniques↗

Signal transduction pathways associated with alpha1-adrenoceptor subtypes in cells and tissues including human prostate.

The complexity of the signal transduction pathways linked to alpha1A-adrenoceptors are becoming clearer. At one time it was thought that the alpha1A-subtype was linked to the influx of extracellular Ca2+ while the alpha1B-subtype was linked via inositol phosphate formation to the release of intracellular Ca2. However the coupling of the alpha1-adrenoceptors to G-proteins leads to the activation of a number of different effector enzymes which produce intracellular second messengers and alterations in biological activity. One area of diversity is in the many forms of the Galpha, beta, gamma heterotrimeric G-proteins which confer specificity towards certain effectors. All alpha1-adrenoceptor subtypes have been shown to couple to phospholipase C in many cells and tissues leading to the breakdown of PiP2 to give IP3, which releases intracellular Ca2+, and diacylglycerol, which stimulates protein kinase C. Additional effectors which can couple to alpha1-adrenoceptors include phospholipase D, adenylate cyclase and the mitogen-activated protein kinase pathway. The latter involves a longer term response and causes increased cell growth and may be important in, for example, the prostate as well as in vascular smooth muscle and the heart. In human prostate alpha1-adrenoceptor activation leads to the release of intracellular Ca2+ from ryanodine-sensitive store followed by an influx of extracellular Ca2+, a mechanism different from that linked to the same receptor subtype in several other smooth muscles. Therefore a given alpha1-subtype may be coupled to a variety of different signal transduction mechanisms in different systems. Further, there may be different effector mechanisms linked to alpha1-subtypes in a given cell or tissue e.g. phospholipase C and mitogen-activated protein kinase. An increased understanding of the complexity of signal transduction mechanisms and the elucidation of the details in a particular tissue will open up new possibilities for therapeutic interventions.

Animals↗

Somatostatin receptor subtypes 2 and 5 inhibit corticotropin-releasing hormone-stimulated adrenocorticotropin secretion from AtT-20 cells.

Somatostatin (SRIH) regulates pituitary adrenocorticotropin (ACTH) secretion by interacting with a family of homologous G protein-coupled membrane receptors. The SRIH receptor subtypes (sst(1)-sst(5)) that control ACTH release remain unknown. Using novel, subtype-selective SRIH analogs, we have identified the SRIH receptor subtypes involved in regulating ACTH release from AtT-20 cells, a model for cell line pituitary corticotropes. Radioligand-binding studies with (125)I-SRIH-14 and (125)I-SRIH-28 showed that SRIH-14 and SRIH-28 recognized specific, high-affinity and saturable membrane-binding sites. Nonpeptidyl agonists with selectivity for the sst(2) (L-779,976; compound 2) or sst(1)/sst(5)) (L-817,818; compound 5) receptor subtypes potently displaced (125)I-SRIH-28 from AtT-20 cell membranes, while agonists selective for the sst(1) (L-779,591; compound 1), sst(3) (L-796,778; compound 3) or sst(4) (L-803,087; compound 4) subtypes were inactive. Tyr(11)-SRIH-14, compound 2 (sst(2)) or compound 5 (sst(5)) inhibited forskolin and corticotropin-releasing hormone (CRH)-induced increases in intracellular cAMP. Furthermore, the sst(2) and sst(5) agonists potently inhibited CRH-induced ACTH release from AtT-20 cells. These results provide the first evidence that sst(2) and sst(5) receptor subtypes, but not sst(1), sst(3) or sst(4), inhibit cAMP accumulation and regulate ACTH secretion in the AtT-20 cell model of the rodent corticotrope.

Adrenocorticotropic Hormone↗

Apolipoprotein E polymorphism and stroke subtypes in an Italian cohort.

BACKGROUND: Studies have indicated that apolipoprotein E (ApoE)-epsilon4 is a risk factor for ischemic cerebrovascular diseases (ICVD), but the existence of this association is still controversial. The aims of this study were: (1) to compare ApoE genotype and allele frequencies in Italian cases with ICVD and in healthy control subjects and (2) to compare ApoE allele frequencies among ischemic stroke subtypes. METHODS: A hospital-based cohort of 302 Italian subjects with ICVD and 228 healthy subjects have been recruited to investigate the role of ApoE polymorphisms as risk factors for ICVD. TOAST criteria were employed to stratify ICVD cases by subtypes. RESULTS: No significant differences in ApoE genotype and allele frequencies were found between cases and control subjects. The frequency of ApoE-epsilon4 was lower in cases than in control subjects (6% vs. 10.1%), although not significantly. No differences in ApoE genotype and allele frequencies were evident among ICVD subtypes. However, out of 36 ApoE-epsilon4 alleles 23 (3.7%) were found in subjects with ICVD related to primary degenerative arterial disease related to large vessel disease and small vessel disease, and 13 (2.1%) in remaining subjects. Using logistic regression analysis we assessed whether ApoE-epsilon4 allele was independently associated with risk of ICVD related to a primary degenerative arterial disease compared to other ICVD subtypes. While classical risk factors were significantly associated with higher risk for ICVD due to large vessel disease and small vessel disease than other ICVD subtypes, the role of ApoE-epsilon4 allele was not significant (OR 1.25, 95% CI 0.57-2.74). CONCLUSION: Our study shows similar ApoE-epsilon4 genotype and allele frequencies in patients with ICVD and in control subjects. No differences were found among different ICVD subtypes either.

Adult↗

A new algorithm for deduction of hepatitis B surface antigen subtype determinants from the amino acid sequence.

OBJECTIVE: We have reexamined hepatitis B virus subtypes to determine the role of specific HBsAg amino acids in serologic reactivity because of problematic genotype/subtype associations seen in a set of geographically diverse serum specimens. METHODS: We obtained DNA sequences for 491 HBsAg-positive specimens from geographically distinct locations, determined their genotypes through phylogenetic analysis, and subtyped the specimens using an algorithm derived from published data on the molecular basis of HBsAg subtype reactivity. Problematic samples were subtyped serologically to resolve conflicts based on the amino acid sequence alone. RESULTS: Three isolates were found to have unusual genotype/subtype associations. Examination of the isolates' amino acid sequences suggested amino acid positions 122, 127, 140, 159 and 160 can be used to determine subtype reactivity from HBsAg amino acid sequences, while position 134, previously thought to play a role, is no longer important. CONCLUSIONS: This re-examination of hepatitis B virus subtypes shows the involvement of amino acid positions 122, 127, 140, 159 and 160 in HBsAg reactivity. While d, y, and r reactivities are controlled by single amino acid changes, w reactivity is determined by positions 122, 127, 140, and 159.

Algorithms↗

Serological identification of HLA-B13 subtypes.

A serological approach is used to confirm subtypes of HLA-B13 originally observed by one-dimensional isoelectric focusing (1D-IEF). Sixty anti-B13 alloantibody sera were screened against Chinese panel cells. Two clusters of sera showing distinct reactive patterns were identified. One is a shorter reactive pattern than the other. Using these serological reaction patterns, the B13 antigen can be divided into two subtypes, B13.1 and B13.2, in the Chinese population. These serological subtypes appear to correlate well with the 1D-IEF patterns of B13 subtypes. The serological subtyping is also in agreement with the differences in nucleotide sequence previously determined to exist in B13 antigen subtypes. Family studies show that both B13.1 and B13.2 segregate as HLA-B locus alleles. Gene frequencies for B13.1 and B13.2 were 0.0676 and 0.0612, respectively, in our study population of 337 southern Han Chinese.

Alleles↗

[Therapeutic response of various histological osteosarcoma subtypes to high-dose methotrexate treatment].

The successful or unsuccessful chemotherapy of osteosarcoma has given rise to the division of these tumors into responders and non responders from the clinical point of view. In order to work out drug sensitive tumor components we studied 9 osteosarcomas by a histological subdivision of the osteosarcoma tissue into 6 subtypes. Seven of the 9 osteosarcoma patients had developed lung metastases under adjuvant high dosage methotrexate (HDMTX) therapy. The aim was to identify the components of the primary tumors which had endured HDMTX-therapy as lung metastases. As HDMTX-sensitive histologic differentiation form of osteosarcoma tissue we regarded the no matrix producing-subtype (III), because it did not occur in the lung metastases. The classical subtype (IV) seems to be only partially sensitive because the corresponding lung metastases showed a higher osteoblastic differentiation with increased osteoid production. No therapeutic effect could be observed in the chondromatous (I) and in the sarcomatous (II) subtypes as well as in the two subtypes with intensive osteoid production being termed trabecularly sclerosing (V) and massively osteoid producing subtypes (VI).

Adolescent↗

Cloning of cDNAs for new subtypes of murine low-affinity Fc receptor for IgE (Fc epsilon RII/CD23).

In humans, two subtypes of the low-affinity Fc receptor for IgE, Fc epsilon RIIa and Fc epsilon RIIb, have been identified. The two forms differ only in a short stretch of amino acids at the cytoplasmic amino terminus. On the other hand, only one Fc epsilon RIIa-like receptor was reported in the mouse, although the existence of another subtype of transcript has been suggested. A new cDNA subtype for murine Fc epsilon RII that has amino acid homology to the human subtype b at the amino terminus was cloned by polymerase chain reaction. When expressed transiently in COS cells, the cDNA is capable of generating a functional cell surface protein that is recognized by an anti-Fc epsilon RII antibody and that has affinity to IgE. In the spleen, although the expression level is considerably lower than that of subtype a, the transcript appears in B cells and in non-B cells upon stimulation with IL-4 and LPS, in contrast to the constitutive expression of the conventional Fc epsilon RII transcript. It is also detectable in several cell lines of B- or T-cell lineages. These results suggest that this gene may be the murine counterpart of human Fc epsilon RII subtype b. Another cDNA clone for the distinct Fc epsilon RII transcript has also been isolated. The cDNA also encodes a surface protein functional on COS cells, but its human counterpart has not been found.

Amino Acid Sequence↗

Selective silencing of angiotensin receptor subtype 1a (AT1aR) by RNA interference.

Angiotensin II exerts its physiological effects by activating multiple subtypes of its receptor such as AT1a-, AT1b-, and AT2-receptors. Because of a high degree of similarity among these G-protein-coupled receptors, it has been difficult to assign diverse physiological actions of angiotensin II through these receptor subtypes. We have developed small interfering RNAs to selectively inhibit the expression of the AT1a receptor (AT1aR) subtype. A dsRNA, AT1 47, was found to be highly selective and efficient in reducing the levels of AT1aR subtype. Transfection of AT1aR-expressing CHO cells with dsRNA AT1 47 resulted in an 80% decrease in the AT1aR expression. In contrast, dsRNA AT1 47 showed no significant effects on both AT1bR and AT2R subtypes. Thus, AT1 47 provides us with a powerful tool to selectively silence this subtype of receptor to investigate its role in cardiovascular physiology.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Role of angiotensin subtype 2 receptor in neointima formation after vascular injury.

The role of angiotensin receptor subtypes 1 and 2 was assessed on neointima formation after injury in rat carotid artery. The effects of angiotensin converting enzyme inhibition by perindopril (3 mg.kg-1 x day-1 p.o.) and selective blockade of angiotensin subtype 1 receptors by DuP 753 (5 and 30 mg.kg-1 x day-1 p.o.) were compared on proliferative response to balloon injury. In rats treated 6 days before and for 14 days after injury, perindopril significantly reduced (-76%, p < 0.01) myointimal hyperplasia. In contrast, DuP 753 at 5 mg.kg-1 x day-1 did not modify the hyperplastic response to balloon catheterization. Only at 30 mg.kg-1 x day-1 was DuP 753 able to reduce neointima formation (-47%, p < 0.05). This dose was equipotent to perindopril on the renin-angiotensin system as assessed by the pressor response to angiotensin II and angiotensin I. Therefore, blockade of subtype 1 receptors was a less effective means of suppression of myointimal growth than angiotensin converting enzyme inhibition, suggesting that another angiotensin receptor subtype or converting enzyme substrates are involved in this process. For the determination of whether angiotensin subtype 2 receptors were implicated, the specific subtype 2 receptor antagonist CGP 42112A (1 mg.kg-1 x day-1) was continuously infused perivascularly for 14 days in the vicinity of the injured carotid artery. CGP 42112A was as effective in preventing neointima formation as perindopril (-73%, p < 0.01, versus -76%, p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Specific alpha 1-adrenergic receptor subtypes modulate catecholamine-induced increases and decreases in ventricular automaticity.

Fifty percent of adult canine Purkinje fibers manifest a decrease in automaticity in response to alpha 1-adrenergic stimulation with 10(-10)-10(-8) M norepinephrine (NE), and 50% manifest an increase. In contrast, most neonatal Purkinje fibers show an increase in automaticity in response to these concentrations of NE. We studied the modulation of NE effects, using the subtype selective alpha 1-adrenergic antagonists chloroethylclonidine (CEC) and WB 4101. CEC selectively antagonized the decrease in automatically such that, in both age groups, all Purkinje fibers showed NE-induced increases in automaticity. In Purkinje fibers from dogs treated with pertussis toxin, NE no longer induced a CEC-sensitive decrease in automaticity. In contrast, WB 4101 selectively antagonized the NE-induced increase in automaticity in both age groups. In the presence of WB 4101, NE decreased automaticity uniformly in adult Purkinje fibers and tended to induce no change in automaticity in neonatal Purkinje fibers. In the presence of prazosin (10(-6) M) or combined CEC (10(-7) M) and WB 4101 (10(-7) M), no alpha-agonist-induced increase or decrease in rate was observed. Pretreatment of membranes from newborn and adult dog and rat ventricles with CEC resulted in a selective and irreversible inactivation of 25% of specific binding sites labeled with [125I]IBE2254. In cultured neonatal rat ventricular myocytes, exposure to CEC resulted in a 35% decrease in the density of specific binding sites labeled with [125I]IBE2254 but did not influence alpha-adrenergic stimulation of inositol phosphate accumulation. In contrast, WB 4101 inactivated NE-stimulated inositol phosphate accumulation. Our results suggest that 1) at least two distinct alpha 1-adrenergic receptor subtypes are present in neonatal and adult cardiac tissue, 2) the CEC-sensitive subtype is linked to a decrease in automaticity via a pertussis toxin-sensitive substrate, 3) the WB 4101-sensitive subtype is linked to an increase in automaticity (possibly via a mechanism related to phosphoinositide breakdown), and 4) although CEC- and WB 4101-sensitive alpha 1-adrenergic receptor subtypes are present in the neonate, only the WB 4101-sensitive subtype is expressed functionally to induce effects on ventricular automaticity.

Age Factors↗

Serum C-reactive protein concentration and genotype in relation to ischemic stroke subtype.

BACKGROUND AND PURPOSE: C-reactive protein (CRP) has evolved as an inflammatory risk marker of cardiovascular disease. Several single-nucleotide polymorphisms at the CRP locus have been found to be associated with CRP levels. The aim of the present study was to investigate CRP levels and genetic variants in etiological subtypes of ischemic stroke. METHODS: The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) comprises 600 consecutive ischemic stroke cases (18 to 69 years) and 600 matched controls from western Sweden. Stroke subtypes were defined by the TOAST classification. Serum CRP levels were determined by a high-sensitivity immunometric assay. RESULTS: CRP levels were significantly higher for all ischemic stroke subtypes compared with controls, both in the acute phase and at the 3-month follow-up. After adjustment for traditional risk factors, CRP at follow-up was related to higher odds ratios (ORs) of overall ischemic stroke (OR, 1.25; 95% CI, 1.09 to 1.43) and large-vessel disease (OR, 1.48; 95% CI, 1.09 to 2.00). The CRP -286C>T>A, 1059G>C, and 1444C>T single-nucleotide polymorphisms showed significant associations with CRP levels. However, neither CRP genotypes nor haplotypes showed an association to overall ischemic stroke. CONCLUSIONS: This is the first large study on CRP in different TOAST subtypes in a young ischemic stroke population. CRP levels differed between etiological subtypes of ischemic stroke both in the acute phase and at the 3-month follow-up. CRP at follow-up was associated with overall ischemic stroke and the large-vessel disease subtype. Genetic variants at the CRP locus were associated with CRP levels, but no association was detected for overall ischemic stroke.

Adult↗

Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment.

BACKGROUND AND PURPOSE: The etiology of ischemic stroke affects prognosis, outcome, and management. Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke. A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST). METHODS: A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies. "Possible" and "probable" diagnoses can be made based on the physician's certainty of diagnosis. The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria. The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients, first based only on clinical features and then after reviewing the results of diagnostic tests. RESULTS: The TOAST classification denotes five subtypes of ischemic stroke: 1) large-artery atherosclerosis, 2) cardioembolism, 3) small-vessel occlusion, 4) stroke of other determined etiology, and 5) stroke of undetermined etiology. Using this rating system, interphysician agreement was very high. The two physicians disagreed in only one patient. They were both able to reach a specific etiologic diagnosis in 11 patients, whereas the cause of stroke was not determined in nine. CONCLUSIONS: The TOAST stroke subtype classification system is easy to use and has good interobserver agreement. This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke. Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke.

Anticoagulants↗

Role of angiotensin receptor subtypes in the response of rabbit brain arterioles to angiotensin.

BACKGROUND AND PURPOSE: Angiotensin II has been reported to induce either constriction or dilation in the cerebral microcirculation. The goal of this study was to determine whether binding to different angiotensin II receptor subtypes may account for the divergent responses. METHODS: Pial arterioles ranging a diameter from 28 to 136 microns were observed through a microscope in a closed cranial window preparation in anesthetized rabbits. Arteriolar responses to topical application of 10(-5) mol/L angiotensin II or the vasoactive angiotensin II degradation products L-arginine/angiotensin-(3-8) were measured by videometry. The effect of the subtype 1 receptor antagonist losartan and the subtype 2 antagonist PD 123319 on these responses was examined in separate groups of animals. RESULTS: Topical coapplication of 10(-5) mol/L losartan or 10(-5) mol/L PD 123319 produced 55% and 62% inhibition of the dilator response to 10(-5) mol/L angiotensin II, respectively. Combined application of the antagonists caused 79% inhibition. Each of the antagonists almost completely blocked the response to L-arginine/angiotensin-(3-8). Acetylcholine-induced dilation of rabbit brain arterioles was unaffected by the antagonists. CONCLUSIONS: Both of the known angiotensin II receptor subtypes appear to be involved in angiotensin II-induced dilation of rabbit cerebral arterioles. These results argue against the assumption that vasodilation is a specific function of one of these receptor subtypes, which might have explained the equivocal effects of angiotensin II by predominance of a certain receptor subtype in a given vascular bed.

Angiotensin II↗

Subtypes of ischemic stroke. A hospital-based stroke registry in Taiwan (SCAN-IV).

BACKGROUND AND PURPOSE: To better understand the clinical pattern and further elucidate the risk factors and outcome in different subtypes of cerebral infarction (CI) of the Chinese in Taiwan, we analyzed the National Taiwan University Hospital Stroke Registry in 1995 and performed an ethnic comparison with similar data banks. METHODS: From the National Taiwan University Hospital Stroke Registry in 1995, 676 patients (383 men and 293 women; mean age, 64.9 years; SD, 13.8 years; range, 1 to 98 years) with CI were recruited for this analysis. CI was classified into five subtypes based on clinical manifestations, ultrasonographic studies, and neuroimaging findings: large-artery atherosclerosis, lacunae, cardioembolism, other less common determined causes, and undetermined cause. Vascular risk factors, extracranial carotid artery atherosclerosis, and 30-day case-fatality rates were investigated in each subtype of CI. RESULTS: Of all CI patients, 17%, 29%, 20%, 6%, and 29% were classified as large-artery atherosclerosis, lacunae, cardioembolism, other determined causes, and undetermined cause subtypes, respectively. The present results were compared with those from eight similar Western stroke registries. The relative incidence of lacunar CI in Chinese patients was more common, but large-artery atherosclerotic CI was less common than in whites. Hypertension was frequently seen in CI patients, especially in those with lacunae (85%) and large-artery atherosclerosis (69%). Patients with cardioembolism had a higher percentage of atrial fibrillation (69%), left ventricular hypertrophy, and ischemic heart disease than the other patients. Patients with large-artery atherosclerosis had more vascular risk factors, such as hypertension, diabetes mellitus, smoking, and carotid stenosis. Cardioembolic patients had higher case-fatality rates than other CI patients. Of the cardioembolic patients, 17.3% and 21.8% died within 30 days and during hospitalization, respectively. CONCLUSIONS: The proportion of CI subtypes varied in different stroke registries. This may be partly due to applied classification criteria and racial-ethnic differences. Awareness of the risk factors and outcome in each subtype of stroke may afford further insights into the surveillance and treatment of cerebrovascular disease.

Adolescent↗

Ischemic stroke subtypes: a population-based study of incidence and risk factors.

BACKGROUND AND PURPOSE: There is scant population-based information on incidence and risk factors for ischemic stroke subtypes. METHODS: We identified all 454 residents of Rochester, Minn, with a first ischemic stroke between 1985 and 1989 from the Rochester Epidemiology Project medical records linkage system. We used Stroke Data Bank criteria to assign infarct subtypes after reviewing medical records and brain imaging. We adjusted average annual incidence rates by age and sex to the US 1990 population and compared the age-adjusted frequency of stroke risk factors across ischemic stroke subtypes. RESULTS: Age- and sex-adjusted incidence rates (per 100 000 population) were as follows: large-vessel cervical or intracranial atherosclerosis with >50% stenosis, 27; cardioembolic, 40; lacuna, 25; uncertain cause, 52; other or uncommon cause, 4. Sex differences in incidence rates were detected only for atherosclerosis with stenosis (47 [95% CI, 34 to 61] for men; 12 [95% CI, 7 to 17] for women). There was no difference in prior transient ischemic attack and hypertension among subtypes, and diabetes was not more common among patients with lacunar infarction than other common subtypes. CONCLUSIONS: The age-adjusted incidence rate of stroke due to stenosis of the large cervicocephalic vessels is nearly 4 times higher for men than for women. There is no association between preceding transient ischemic attack and stroke mechanism. Diabetes and hypertension are not more common among patients with lacunae. Age- and sex-adjusted incidence rates for ischemic stroke subtypes in this population can be compared with similarly determined rates from other populations.

Adult↗

Incidence of the major stroke subtypes: initial findings from the North East Melbourne stroke incidence study (NEMESIS).

BACKGROUND AND PURPOSE: Population-based stroke incidence studies are the only accurate way to determine the number of strokes that occur in a given society. Because the major stroke subtypes have different patterns of incidence and outcome, information on the natural history of stroke subtypes is essential. The purpose of the present study was to determine the incidence and case-fatality rate of the major stroke subtypes in a geographically defined region of Melbourne, Australia. METHODS: All suspected strokes that occurred among 133 816 residents of suburbs north and east of Melbourne, Australia, during a 12-month period of 1996 and 1997 were identified and assessed. Multiple overlapping sources were used to ascertain cases, and standard criteria for stroke and case-fatality were used. Stroke subtypes were defined by CT, MRI, and autopsy. RESULTS: Three hundred eighty-one strokes occurred among 353 persons during the study period, with 276 (72%) being first-ever-in-a-lifetime strokes. Of these, 72.5% (95% CI 67.2% to 77.7%) were cerebral infarction, 14.5% (95% CI 10.3% to 18.6%) were intracerebral hemorrhage, 4.3% (95% CI 1.9% to 6.8%) were subarachnoid hemorrhage, and 8.7% (95% CI 5.4% to 12.0%) were stroke of undetermined type. The 28-day case-fatality rate was 12% (95% CI 7% to 16%) for cerebral infarction, 45% (95% CI 30% to 60%) for intracerebral hemorrhage, 50% (95% CI 22% to 78%) for subarachnoid hemorrhage, and 38% (95% CI 18% to 57%) for stroke of undetermined type. CONCLUSIONS: The overall distribution of stroke subtypes and 28-day case-fatality rates are not significantly different from those of most European countries or the United States. There may, however, be some differences in the incidence of subtypes within Australia.

Adolescent↗

Should stroke subtype influence anticoagulation decisions to prevent recurrence in stroke patients with atrial fibrillation?

BACKGROUND AND PURPOSE: Long-term anticoagulation is routinely used for secondary stroke prevention in atrial fibrillation, often regardless of stroke subtype. Although the role of warfarin in cardioembolic stroke is established, it may not prevent recurrence in other stroke subtypes, even in the presence of atrial fibrillation. METHODS: This was a 2-year, prospective, intervention study conducted in a district general hospital. Participants included 386 acute stroke patients with atrial fibrillation. Subjects were characterized for stroke subtype on clinical, neuroimaging, carotid ultrasonographic, and echocardiographic criteria. Eligible patients were treated with adjusted-dose warfarin (international normalized ratio, 2.0 to 3.0). Aspirin (75 to 300 mg/d) was used in patients with contraindications or those who refused anticoagulation. The main outcome measures were rate of recurrent stroke by subtype and major and minor bleeding complications. RESULTS: The aspirin group (n=172) was comparable to the warfarin group (n=214) in terms of age, sex, risk factors, and initial stroke subtype. The rate of recurrent stroke was higher (9.5% versus 4.9%, P<0.02) but that of major bleeding was lower (0.6% versus 2.5%, P<0.05) with aspirin. The increased stroke rate with aspirin was due predominantly to cardioembolic recurrence in patients presenting initially with cardioembolic stroke (8.4% versus 1.9%, P<0.01). The recurrence rate in aspirin-treated patients who presented with lacunar stroke and atrial fibrillation was similar to that seen in patients receiving warfarin (8.8% versus 8.9%). CONCLUSIONS: In this cohort of stroke patients with atrial fibrillation, anticoagulation was superior to aspirin in preventing cardioembolic but not lacunar recurrence. Determination of stroke subtype may be important in anticoagulation decisions for secondary prevention, and further studies are required.

Aged↗