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Epileptogenicity of cortical dysplasia in temporal lobe dual pathology: an electrophysiological study with invasive recordings.

Hippocampal sclerosis is often associated with macroscopic or microscopic dysplasia in the temporal neocortex (TN). The relevance of such a dual pathology with regard to epileptogenesis is unclear. This study investigates the role of both pathologies in the generation of ictal and interictal activity. Ictal (113 seizures) and interictal data from invasive EEG recordings with simultaneous depth electrodes in the hippocampus and subdural electrodes over the TN were analysed retrospectively in 12 patients with variable degrees of hippocampal sclerosis and different types of histologically confirmed temporal cortical dysplasia [all male, age at epilepsy onset <1-29 years (mean 9.6 years), age when invasive recordings were performed 6-50 years (mean 28.2 years)]. Of the seizures 41.3% arose from the amygdala/hippocampus complex (AHC), 34.7% from the TN, 22% were simultaneously recorded from AHC and TN (indeterminate seizure onset), and 2% from other regions. In three patients, seizure onset was recorded only from the AHC. In patients with severe hippocampal sclerosis only 12% of the seizures arose from the TN, whereas in patients with mild hippocampal sclerosis 58% arose from the TN. The type of cortical dysplasia, however, did not predict seizure onset in the AHC or TN. Propagation time from the TN to the AHC tended to be shorter (mean 7.4 s) than vice versa (mean 13.7 s). The most common initial ictal patterns in the AHC were rhythmic beta activity (<25 Hz) and repetitive sharp waves, and in the TN were fast activity (>25 Hz) and repetitive sharp waves. The interictal patterns over the TN were similar to those seen over extratemporal focal cortical dysplasias. Simultaneous recordings from the hippocampus and the TN strongly suggest that dysplastic tissue in the TN is often epileptogenic. The quantitative contribution of the hippocampus to seizure generation corresponded with the degree of hippocampal pathology, whereas different subtypes of cortical dysplasia did not affect its relative contribution to seizure generation and even mild forms of dysplasia were epileptogenic.

Adolescent↗

Characteristics of advantages of positron emission tomography over computed tomography for N-staging in lung cancer patients.

OBJECTIVE: We analyzed the characteristics of advantages of positron emission tomography (PET) over computed tomography (CT) for N-staging in lung cancer patients. METHODS: Preoperative PET and CT scans were performed for 2057 lymph node stations in 205 patients with peripheral-type lung cancer. The advantages of PET over CT for N-staging were analyzed among lymph node locations and histological subtypes. RESULTS: The pathological N-stages were N0 in 143 patients, N1 in 31, N2 in 24 and N3 in 7. PET was able to diagnose N0, N2 and N3 diseases more accurately than CT (P=0.03, 0.01 and 0.02, respectively), but there was no significant difference between the two modalities for N1 disease. In the upper mediastinal lymph node stations, both false-negative and false-positive were significantly less frequent with PET than with CT (P=0.001). In the lower mediastinal and supra clavicle lymph nodes, PET showed a lower frequency of false-negative than CT (P=0.04 and 0.003, respectively), but there was no significant difference in the frequency of false-positive between the two modalities. Among histological types, PET could stage adenocarcinoma with less frequent false-negative and squamous cell carcinoma with less frequent false-positive than CT (P=0.02 and 0.005, respectively). CONCLUSION: For N-staging, PET was superior to CT for the following: (1) more accurate for N0, N2 and N3 diseases but not for N1; (2) lower frequency of false-positive in the upper mediastinal nodes; and (3) lower frequencies of false-negative in adenocarcinoma and false-positive in squamous cell carcinoma. Recognizing these advantages of PET could make the N-staging of lung cancer more accurate.

Adenocarcinoma↗

Occipital lobe developmental malformations and epilepsy: clinical spectrum, treatment, and outcome.

PURPOSE: Cortical developmental malformations (CDM) are increasingly recognized in association with epilepsy. We describe 10 patients (age range 14-35 years) with symptomatic occipital lobe epilepsy and CDM. METHODS: Neurologic, neuroophthalmologic and electrophysiologic studies were performed. Patients had MRI, SPECT, and in some cases intracranial EEG investigators. RESULTS: Mean age of seizure onset was 8 years. We noted strong correlations between the presence of visual auras, the scalp EEG pattern, and the subtype of underlying pathology. Magnetic resonance imaging (MRI) showed CDM in all patients, with polymicrogyria and focal dysplasia being the most frequent malformations. Despite the presence of occipital lobe structural malformations in all patients, visual field deficits were present in only 2. Those who underwent cortical resections were seizure-free or showed major improvement at a mean follow-up of 3.5 years. CONCLUSIONS: Intracranial stimulation studies and the low frequency of pre- and postoperative deficits suggest that some degree of cortical visual reorganization may occur in patients with occipital lobe malformations. Occipital lobe CDM should be sought as a cause of symptomatic occipital lobe epilepsy even though they may become symptomatic after childhood.

Adolescent↗

Does apolipoprotein E genotype influence the risk of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage? Systematic review and meta-analyses of 31 studies among 5961 cases and 17,965 controls.

BACKGROUND AND PURPOSE: Apolipoprotein E genotype (APOE) is associated with cholesterol metabolism, ischemic heart disease, and cerebral amyloid angiopathy, and so may affect risk of both ischemic and hemorrhagic stroke. METHODS: We comprehensively sought and identified studies of the association of apoE with ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). We did meta-analyses to assess the evidence for an association between APOE and the various pathological types and subtypes of stroke, and assessed the effects of several methodological criteria. RESULTS: We analyzed data from 31 eligible studies (26 IS, 8 ICH, and 3 SAH) in 5961 cases and 17 965 controls. epsilon4 allele-containing (epsilon4+) genotypes were significantly associated with IS (odds ratio [OR], 1.11; 95% CI, 1.01 to 1.22) and SAH (OR, 1.42; 95% CI, 1.01 to 1.99) and nonsignificantly with ICH (OR, 1.16; 95% CI, 0.93 to 1.44), whereas epsilon2+ genotypes were associated with ICH (OR, 1.32; 95% CI, 1.01 to 1.74). Associations appeared stronger with epsilon4+ genotypes for large artery compared with other IS subtypes and for Asian compared with white populations, and with epsilon2+ genotypes for lobar compared with deep hemorrhages. However, we found no association between epsilon4+ genotypes and IS when we analyzed only larger studies (>200 cases; OR, 0.99; 95% CI, 0.88 to 1.11) or studies without control selection bias (OR, 0.99; 95% CI, 0.85 to 1.17). CONCLUSIONS: Publication and selection biases make existing studies of APOE and stroke unreliable. Further, very large, methodologically rigorous studies are needed.

Adult↗

Estimates of the prevalence of acute stroke impairments and disability in a multiethnic population.

BACKGROUND AND PURPOSE: The goals of the present study were to estimate the prevalence of acute impairments and disability in a multiethnic population of first-ever stroke and to identify differences in impairment and early disability between pathological and Bamford subtypes. Associations between impairments and death and disability at 3 months were identified. METHODS: Impairments that occur at the time of maximum neurological deficit were recorded, and disability according to the Barthel Index (BI) was assessed 1 week and 3 months after stroke in patients in the South London Stroke Register: RESULTS: Of 1259 registered patients, 6% had 1 or 2, 31.1% had 3 to 5, 50.6% had 6 to 10, and 10.6% had >10 impairments. Common impairments were weakness (upper limb, 77.4%), urinary incontinence (48.2%), impaired consciousness (44.7%), dysphagia (44.7%), and impaired cognition (43.9%). Patients with total anterior circulation infarcts had the highest age-adjusted prevalence of weakness, dysphagia, urinary incontinence, cognitive impairment, and disability. Patients with subarachnoid hemorrhage had the highest rates of coma. Patients with lacunar stroke had the high prevalence of weakness but were least affected by disability, incontinence, and cognitive dysfunction. Blacks had higher age- and sex-adjusted rates of disability in ischemic stroke (BI <20, odds ratio 2.76, 95% CI 1.47 to 5.21, P=0.002; BI <15, odds ratio 1.8, 95% CI 1.45 to 2.81, P=0.01) but impairment rates similar to those of whites. On multivariable analysis, incontinence, coma, dysphagia, cognitive impairment, and gaze paresis were independently associated with severe disability (BI <10) and death at 3 months. CONCLUSIONS: The extent of these findings indicates that an acute assessment of impairments and disability is necessary to determine the appropriate nursing and rehabilitation needs of patients with stroke.

Age Distribution↗

A psychometric typology of U.K. domestic violence offenders.

A number of studies have described subtypes of domestically violent men, and the heterogeneity of domestically violent men is well established. The aim of the current study was to investigate the distribution of subtypes using psychometric measures in convicted domestically violent offenders in England. Four subtypes of offenders were identified: low pathology, borderline, narcissistic, and antisocial. These subtypes were broadly comparable with the family-only, dysphoric/borderline, and generally violent/antisocial types proposed by Holtzworth-Munroe and Stuart. The majority of the sample (60%) best fit the generally violent/antisocial profile. However, the reliance on psychometric measurement and lack of corroborative evidence from partners means that further research is necessary to test these findings.

Adult↗

Creutzfeldt-Jakob disease associated with the R208H mutation in the prion protein gene.

The authors investigated a patient who died of apparent sporadic Creutzfeldt-Jakob disease (CJD) but carried a R208H substitution in the prion protein (PrP). The patient phenotype was indistinguishable from typical sporadic CJD (i.e., MM1 subtype). In addition, pathologic PrP, PrP(Sc), originated from both the normal and the mutated PRNP allele and had the same characteristics as PrP(Sc) type 1. The authors propose that the R208H mutation influences disease susceptibility without significantly affecting PrP(Sc) properties or disease phenotype.

14-3-3 Proteins↗

The role of sodium channels in disease.

Native sodium channels exist as polypeptide multimers of an alpha-subunit (260 kDa) and subsidiary and smaller beta-subunits, which are divided into at least three subtypes--beta(1), beta(2) and beta(3). The alpha-subunits are structurally diverse, arising from multiple sodium channel genes and alternative splicing events. Recent progress has led to a good understanding of the molecular structure of sodium channels, how they work and the significance of their expression in particular cell types. This, coupled with experimental studies linking particular isoforms with particular disease states and the discovery of distinct human sodium channelopathies (specific mutations in specific isoforms that cause a variety of diseases, including paralysis, long QT syndrome and epilepsy), is beginning to reveal how particular sodium channel subtypes underlie specific pathologies. All this provides great potential for the development of new therapies. The first generation of sodium channel blockers has led to a broad-spectrum anticonvulsant that is now widely used (lamotrigine) and an impressive neuroprotective agent that is in clinical trials for stroke (sipatrigine). The development of the next generation of sodium channel blockers will be greatly facilitated by elaboration of the pharmacology of the various isoforms, which itself is dependent upon the existence of reliable, rapid and high-throughput assays for sodium channel activity.

Journal Article↗

High molecular weight corticotropin measured with immunoradiometric assay in a patient with asymptomatic pituitary corticotropinoma.

A 57-yr-old female with corticotropinoma showing no Cushingoid stigmata is reported. Basal plasma levels of ACTH measured with immunoradiometric assay and beta-endorphin were high, 12.6-15.9 pmol/l and 3.5 pmol/l, respectively. Plasma cortisol level and urinary free cortisol excretion were normal, 303-359 nmol/l and 171-226 nmol/day, respectively. Plasma ACTH markedly increased to 70.5 pmol/l with intravenous administration of 100 microg CRH. Diurnal rhythm of plasma ACTH was seen, but its level in the night was still high. Plasma ACTH suppression with dexamethasone was insufficient. CRH stimulation after dexamethasone suppression increased plasma ACTH level from 4.4 to 13.7 pmol/l. Intravenous administration of 4 microg desmopressin increased plasma ACTH from 15.6 to 19.6 pmol/l. Oral administration of 16 mg lepramide insufficiently decreased plasma ACTH from 7.3 to 5.3 pmol/l. However, plasma cortisol responses in these conditions were normal. Postoperative pathological study revealed subtype 1 corticotropinoma immunohistochemically and electron-microscopically. Postoperative basal plasma ACTH decreased to 3.9 pmol/l, although plasma cortisol did not change. Diurnal rhythm and dexamethasone suppressibility of plasma ACTH became normal. Plasma sample was chromatographed on a Sephadex G-75 column. The elution profile showed two peaks of ACTH, one of which was compatible with 1-39 ACTH and another with higher molecular weight ACTH which was probably secreted from corticotropinoma. Anomaly in processing of proopiomelanocortin was suspected.

Adenoma↗

Malignant lymphoma. A study of 75 cases presenting in soft tissue.

We report 75 cases of malignant lymphoma presenting in soft tissue taken from the files of the Armed Forces Institute of Pathology. All histologic subtypes with the exception of lymphoblastic lymphoma were represented. Our findings indicate that virtually any soft tissue site may be involved; there is no sex predilection; and size is not helpful in predicting survival. Among the 55 patients for which race was known, there were no black patients. Thirty-three patients with extensive evaluations at the time of diagnosis had no evidence of disseminated disease, but eight of these exhibited widespread disease within 3 months of diagnosis, and seven of the eight died of disease (median survival, 4 months). The remaining 25 patients had much better outcomes; 18 of 19 with intermediate and high-grade lymphomas were alive and well at a median of 74 months after diagnosis. Some tumors exhibited a propensity for involvement of remote soft tissue sites.

Humans↗

Endometrial carcinosarcomas have a different prognosis and pattern of spread compared to high-risk epithelial endometrial cancer.

OBJECTIVE: The endometrial origin of uterine carcinosarcoma has recently been well established. The current study investigates whether uterine carcinosarcomas can be included in protocols on high-risk endometrial cancer, given the similarities in biologic behavior of both entities. METHODS: Pathological and surgical notes of patients diagnosed with grade 3 endometrioid, carcinosarcoma, serous and clear cell endometrial cancer subtypes were retrospectively analyzed with special attention to the spread pattern of the different subtypes. Information on site of relapse and time to recurrence was obtained. RESULTS: We traced 146 patients of which 9 patients were ineligible. Histological subtypes of the remaining 137 patients were as follows: 50 (37%) grade 3 endometrioid carcinoma, 54 (39%) serous or clear cell carcinoma (non-endometrioid carcinoma), and 33 (24%) carcinosarcomas. Distribution of early stage disease (I and II) was 67, 46, and 78% for grade 3 endometrioid, non-endometrioid, and carcinosarcoma, respectively. Although we could not trace differences in hematogenic and transperitoneal spread among the three subtypes, non-endometrioid and carcinosarcomas were more likely to spread to pelvic and paraaortic lymph nodes (P < 0.01). Using univariate analysis, both stage (P < 0.006, Wald statistic) and histological type appear to determine the outcome, whereas lymphovascular space infiltration (P < 0.25) and age (P < 0.07) were not significantly different between the three histological subtypes. Cox Regression multivariate analysis on 127 women suffering from the three histological subtypes suggested that both stage III-IV disease (P < 0.00001) and histological type (carcinosarcoma) (P < 0.003) were of prognostic significance [hazard ratio (CI 95%) were, respectively, 3.8 (2.1-7.0) and 3.2 (1.7-5.9)]. Analyzing cases limited to stage I-II endometrial cancer, 24/28 (86%) grade 3 endometrioid, 18/24 (75%) non-endometrioid, and 11/25 (44%) carcinosarcomas survived, suggesting a worse outcome for endometrial carcinosarcoma when compared to the other subtypes (P < 0.008, Log Rank). A higher incidence of pulmonary metastases explained the worse outcome for early stage carcinosarcoma (P < 0.006), whereas the incidence of liver metastasis, transperitoneal spread, or recurrences in lymph nodes or vagina were comparable between the three pathologic subtypes. CONCLUSIONS: Although endometrial carcinosarcoma originates from epithelial cancer, the intrinsic more aggressive tumor biology suggests that this subtype should not be incorporated in studies on high-risk epithelial endometrial cancer.

Adenocarcinoma, Clear Cell↗

Differences in oxidative stress dependence between gastric adenocarcinoma subtypes.

AIM: To investigate the extent of oxidative stress in pre-neoplastic and neoplastic gastric mucosa in relation to their pathological criteria and histological subtypes. METHODS: A total of 104 gastric adenocarcinomas from 98 patients (88 infiltrative and 16 intraepithelial tumors) were assessed immunohistochemically for expression of iNOS and occurrence of nitrotyrosine (NTYR)-containing proteins and 8-hydroxy-2'-deoxyguanosine (8-OH-dG)-containing DNA, as markers of NO production and damages to protein and DNA. RESULTS: Tumor cells staining for iNOS, NTYR and 8-OH-dG were detected in 41%, 62% and 50% of infiltrative carcinoma, respectively. The three markers were shown for the first time in intraepithelial carcinoma. The expression of iNOS was significantly more frequent in tubular carcinoma (TC) compared to diffuse carcinoma (DC) (54% vs 18%; P = 0.008) or in polymorphous carcinoma (PolyC) (54% vs 21%; P = 0.04). NTYR staining was obviously more often found in TC than that in PolyC (72% vs 30%; P = 0.03). There was a tendency towards a higher rate of iNOS staining when distant metastasis (pM) was present. In infiltrative TC, the presence of oxidative stress markers was not significantly correlated with histological grade, density of inflammation, the depth of infiltration (pT), lymph nodes dissemination (pN) and pathological stages (pTNM). CONCLUSION: The iNOS-oxidative pathway may play an important role in TC, but moderately in PolyC and DC. DNA oxidation and protein nitration occur in the three subtypes. Based on the significant differences of NTYR levels, TC and PolyC appear as two distinct subtypes.

Adenocarcinoma↗

The pathology of primary progressive multiple sclerosis.

The present review will focus on the current knowledge of the pathology of primary progressive multiple sclerosis lesions. Multiple sclerosis (MS) is an inflammatory demyelinating disease with a broad clinical variability. The main disease courses are relapsing-remitting, secondary progressive and primary progressive MS. Pathological studies examining the specific underlying pathology of a defined clinical subtype are rare. Here, we focus on the pathological characteristics of the MS lesions and summarize the current findings of the pathology of primary progressive MS with respect to inflammation, oligodendrocyte myelin pathology, axon destruction and immunopathology of the lesions.

Alleles↗

Expression patterns of proliferating cell nuclear antigen in the small intestine of mice infected with Metagonimus yokogawai and Metagonimus Miyata type.

Genus Metagonimus has been a subject of taxonomic debates for several years. In morphological aspects, M. yokogawai has been thought to have three subtypes, namely Yokogawa type (M. yokogawai in strict sense), Miyata type and Koga type, But differences in the intestinal pathology induced by these subtypes have not been studied yet. In this study we compared the pathological reactions induced by M. yokogawai and Metagonimus Miyata type using proliferating cell nuclear antigen (PCNA) index. Metacercariae (Mc) of M. yokogawai were collected by artificial digestion of Plecoglossus altivelis and Mc of Metagonimus Miyata type were collected from Zacco platypus. Three hundreds Mc of each species were infected orally to ICR mice. The mice were sacrificed at 3, 6, 10, 16 and 23 days after infection and the small intestines were resected into three portions (proximal, middle, and distal). Immunohistochemical staining for PCNA was done using PC-10 (DAKO-PCNA, CA, USA). The PCNA indices in M. yokogawai infected group on the 6th and 23rd day after infection were lower than in the control and Miyata type infected groups (p < 0.05) from all of the three intestinal regions. On the other hand, the control group and Metagonimus Miyata type infected group did not make any differences in PCNA indices. The villus/crypt (V/C) ratio was also decreased significantly in M. yokogawai infected mice but not in Metagonimus Miyata type infected ones. It is suggested that M. yokogawai induce villous atrophy through a decrease in the cell proliferation at the crypt. The results of this study suggested that M. yokogawai induce more serious intestinal pathology than Metagonimus Miyata type.

Animals↗

Differentiation of multiple sclerosis subtypes: implications for treatment.

There has been tremendous progress in the immunomodulatory treatment of multiple sclerosis (MS) during recent years. With the introduction of interferon-beta, glatiramer acetate and mitoxantrone (recently registered for MS in the US), there are at least three therapeutic strategies that have proven effective in large phase III studies. However, not all patients with MS respond well to treatment with these drugs. This may largely be a consequence of disease heterogeneity. From a clinical perspective, patients with different disease courses show different treatment responses. Patients with relapsing-remitting MS are more likely to respond to immunomodulatory therapy than those with a progressive disease course. Studies of patients with secondary progressive MS have yielded inconsistent results and, so far, there has been no positive phase III study of immunomodulatory therapy in patients with primary progressive MS. Pathological evidence indicates that subtyping based on clinical findings alone does not reflect actual disease heterogeneity. In a large series of biopsy and autopsy specimens, at least four subtypes could be identified with respect to oligodendrocyte/myelin pathology and immunopathology. As long as the only method of identifying subtypes of disease is histopathology, differential therapy will remain a future goal. Thus, there is an urgent need for in vivo markers of immunopathogenesis in an individual patient that would allow treatment to be specifically directed towards a given pathological focus. However, at least from a theoretical point of view, some therapeutic approaches appear very attractive. Plasmapheresis and/or intravenous immunoglobulins could most plausibly be the best approach for the immunopathological subtype of MS, which is characterised by antibody and complement deposition next to demyelinated axons, in order to remove antibodies. The subtype of MS that is associated with heavy macrophage activation, T cell infiltration and expression of inflammatory mediator molecules, including tumour necrosis factor-alpha, may be most likely to respond to immunomodulation with interferon-beta or glatiramer acetate. There are other subtypes of MS in which viral infection or oligodendrocyte degeneration, rather than autoimmunity, appear to play a role. It is possible that these could benefit from antiviral therapy, oligodendrocyte protection or oligodendrocyte transplantation, although therapies based on these latter approaches have yet to be developed.

Adrenal Cortex Hormones↗

Relevance of pathologic classifications and diagnosis of acute myeloid leukemia to clinical trials and clinical practice.

Many new insights into the diagnosis, pathogenesis, clinical manifestation, treatment and prognosis of patients with AML reflect the heterogeneity of the disease. The initial descriptions of the various subtypes of AML, established by the FAB classification, were based on morphology and cytochemical stains. Although morphology remains the foundation for the diagnosis, additional diagnostic studies including immunophenotyping, cytogenetic evaluation, and molecular genetic studies have become critical, and in some specific cases, mandatory, complementary tools. Several specific subtypes of AML are now treated with directed or targeted therapy. Acute promyelocytic leukemia is currently the only example of a subtype of AML to which specific therapy targeted to a molecular genetic abnormality is available and this subtype now is highly curable. Future studies will address newly identified prognostic factors and gene mutations such as FLT3, Wilm's tumor (WTI), and CEBPA which will enable the further pathologic classification of patients with AML. Finally, microarray analysis will likely identify genes critically involved in the pathogenesis of specific pathologic subtypes.

Acute Disease↗

Atypical glandular cells of undetermined significance: a five-year retrospective histopathologic study.

OBJECTIVE: Our purpose was to ascertain the types and frequency of pathologic conditions associated with atypical glandular cells of undetermined significance on Papanicolaou smears. STUDY DESIGN: A 5-year retrospective review of screening cervical cytologic examinations diagnosed as atypical glandular cells of undetermined significance was performed at the University of Virginia to determine pathologic findings associated with atypical glandular cells of undetermined significance on Papanicolaou smears stratified by subtype and overall. RESULTS: Pathologic findings for the respective Papanicolaou smears with the diagnosis of atypical glandular cells of undetermined significance not otherwise specified, favor benign, squamous intraepithelial lesions, and favor neoplasia through the follow-up interval were as follows: squamous intraepithelial lesions in 11%, 8%, 38%, and 20%; adenocarcinoma in situ in 3%, 0%, 0%, and 10%; endometrial hyperplasia in 3%, 5%, 1%, and 2%; and cancer in 8%, 3%, 1%, and 7%. Overall, 63 patients (32%) had preinvasive or invasive lesions. CONCLUSIONS: Atypical glandular cells of undetermined significance on Papanicolaou smears were correlated with significant findings in 45% of patients (32% with preinvasive or invasive lesions and 13% with benign lesions). A prompt and aggressive workup is recommended.

Adolescent↗

Predicting survival for 1 year among different subtypes of stroke. Results from the Perth Community Stroke Study.

BACKGROUND AND PURPOSE: Few studies have evaluated the factors influencing or predicting long-term survival after stroke in an unselected series of patients in whom the underlying cerebrovascular pathology is clearly defined. Moreover, the relative importance of risk factors for stroke, including sociodemographic and premorbid variables, has not been described in detail. METHODS: The study cohort consisted of 492 patients with stroke who were registered with a population-based study of acute cerebrovascular disease undertaken in Perth, Western Australia, during an 18-month period in 1989 and 1990. Objective evidence of the pathological basis of the stroke was obtained in 86% of cases, and all deaths among patients during a follow-up of 1 year were reviewed. RESULTS: One hundred twenty patients (24%) died within 28 days of the onset of stroke. Among the different subtypes of stroke, the 1-year case fatality (mean, 38%) varied from 6% and 16% for boundary zone infarction and lacunar infarction, respectively, to 42% and 46% for subarachnoid hemorrhage and primary intracerebral hemorrhage, respectively. Using Cox proportional-hazards analysis, a predictive model was developed on 321 patients with acute stroke (test sample). The best model contained five baseline variables that were independent predictors of death within 1 year: coma (relative risk [RR], 3.0; 95% confidence interval [CI], 1.1 to 8.4), urinary incontinence (RR, 3.9; 95% CI, 1.4 to 10.6), cardiac failure (RR, 6.5; 95% CI, 2.8 to 15.1), severe paresis (RR, 4.9; 95% CI, 1.6 to 15.5), and atrial fibrillation (RR, 2.0; 95% CI, 1.1 to 3.5). The sensitivity, specificity, and negative predictive value of this model for predicting death were 90%, 83%, and 95%, respectively. When applied to a second randomly selected validation sample of 171 events, sensitivity was 94%, specificity 62%, and negative predictive value 92%, indicating stability of the model. CONCLUSIONS: Although the case fatality, timing, and cause of death vary considerably among the different pathological subtypes of stroke, simple clinical measures that reflect the severity of the neurological deficit and associated cardiac disease at onset independently predict death by 1 year and may help to direct management.

Adolescent↗