Recurrent versus first cervical artery dissection - a retrospective study of clinical and vascular characteristics.

BACKGROUND AND PURPOSE: Most recurrent cervical artery dissection (CeAD) events occur shortly after the acute first CeAD. This study compared the characteristics of recurrent and first CeAD events and searched for associations between subsequent events of an individual person. METHODS: Cervical artery dissection patients with a new CeAD event occurring during a 3-6 month follow-up were retrospectively selected in seven specialized stroke centers. Clinical and vascular characteristics of the initial and the recurrent CeADs were compared. RESULTS: The study sample included 76 patients. Recurrent CeADs were occlusive in one (1.3%) patient, caused cerebral ischaemia in 13 (17.1%) and were asymptomatic in 39 (51.3%) patients, compared to 29 (38.2%) occlusive, 42 (55.3%) ischaemic and no asymptomatic first CeAD events. In 52 (68.4%) patients, recurrent dissections affected both internal carotid arteries or both vertebral arteries, whilst 24 (31.6%) patients had subsequent dissections in both types of artery. Twelve (28.6%) of 42 patients with an ischaemic first dissection had ischaemic symptoms due to the recurrent CeADs, too. However, only one (1.3%) of 34 patients with a non-ischaemic first CeAD suffered ischaemia upon recurrence. CONCLUSION: Recurrent CeAD typically affects the same site of artery. It causes ischaemic events less often than the first CeAD. The risk that patients who presented with solely non-ischaemic symptoms of a first CeAD will have ischaemic symptoms in the case of a recurrent CeAD seems very small.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Prognostic significance of pulsatile tinnitus in cervical artery dissection.

BACKGROUND AND PURPOSE: Our aim was to investigate whether pulsatile tinnitus (PT) in cervical artery dissection (CeAD) has prognostic significance. METHODS: All CeAD patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study with documentation of PT were analysed. The presence of PT was systematically assessed using a standardized questionnaire. Stroke severity at admission was defined according to the National Institutes of Health Stroke Scale (NIHSS). Excellent outcome after 3 months was defined as a modified Rankin Scale of 0-1. RESULTS: Sixty-three of 778 patients (8.1%) reported PT. PT+ patients presented less often with ischaemic stroke (41.3% vs. 63.9%, P < 0.001), more often with dissection in the internal carotid artery (85.7% vs. 64.2%, P = 0.001), less often with vessel occlusion (19.0% vs. 34.1%, P = 0.017) and more often with excellent outcome at 3 months (92.1% vs. 75.4%, P = 0.002). Logistic regression analysis identified PT as an independent predictor of excellent outcome after 3 months [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.22-12.87] adjusted to significant outcome predictors NIHSS on admission (OR 0.82, 95% CI 0.79-0.86), Horner syndrome (OR 1.95, 95% CI 1.16-3.29) and vessel occlusion (OR 0.62, 95% CI 0.40-0.94) and to non-significant predictors age, sex, pain and location of CeAD. CONCLUSION: The presence of PT in CeAD is associated with a benign clinical course and predicts a favourable outcome.

Anemia in young patients with ischaemic stroke.

BACKGROUND AND PURPOSE: To investigate the association of anemia on admission with ischaemic stroke (IS), stroke severity and early functional outcome in patients with cervical artery dissection (CeAD) or with IS of other causes (non-CeAD-IS patients). METHODS: The study sample comprised all patients from the Cervical Artery Dissection and Ischaemic Stroke Patients (CADISP) study without pre-existing disability and with documentation of stroke severity and hemoglobin (Hb) concentration on admission. Anemia was classified as mild (Hb < 12 g/dl in women and Hb < 13 g/dl in men) or moderate to severe (Hb < 10 g/dl in women and Hb < 11 g/dl in men). Stroke severity on admission was assessed with the National Institutes of Health Stroke Scale (NIHSS). Outcome after 3 months was assessed with the modified Rankin Scale (mRS-3mo). Unfavorable outcome was defined as mRS-3mo ≥ 3. RESULTS: Amongst 1206 study patients (691 CeAD and 515 non-CeAD), 87 (7.2%) had anemia, which was moderate to severe in 18 (1.5%) patients. Anemia was associated with female sex in both study samples, but no further associations with risk factors or comorbidities were observed. In CeAD patients, anemia was associated with occurrence of stroke (P = 0.042). In both study samples, anemic patients had more severe strokes (CeAD, P = 0.023; non-CeAD, P = 0.005). Functional outcome was not associated with anemia in general, but moderate to severe anemia was significantly associated with unfavorable outcome (P = 0.004). CONCLUSION: Anemia on admission was associated with stroke in CeAD patients and with more severe strokes in both study samples. Moderate to severe anemia may predict unfavorable outcome.

Stroke in first-degree relatives of patients with cervical artery dissection.

BACKGROUND AND PURPOSE: Patients with ischaemic stroke (IS) caused by a spontaneous cervical artery dissection (CeAD) worry about an increased risk for stroke in their families. The occurrence of stroke in relatives of patients with CeAD and in those with ischaemic stroke attributable to other (non-CeAD) causes were compared. METHODS: The frequency of stroke in first-degree relatives (family history of stroke, FHS) was studied in IS patients (CeAD patients and age- and sex-matched non-CeAD patients) from the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) database. FHS ≤ 50 and FHS > 50 were defined as having relatives who suffered stroke at the age of ≤50 or >50 years. FHS ≤ 50 and FHS > 50 were studied in CeAD and non-CeAD IS patients and related to age, sex, number of siblings, hypertension, hypercholesterolemia, smoking and body mass index (BMI). RESULTS: In all, 1225 patients were analyzed. FHS ≤ 50 was less frequent in CeAD patients (15/598 = 2.5%) than in non-CeAD IS patients (38/627 = 6.1%) (P = 0.003; odds ratio 0.40, 95% confidence interval 0.22-0.73), also after adjustment for age, sex and number of siblings (P = 0.005; odds ratio 0.42, 95% confidence interval 0.23-0.77). The frequency of FHS > 50 was similar in both study groups. Vascular risk factors did not differ between patients with positive or negative FHS ≤ 50. However, patients with FHS > 50 were more likely to have hypertension and higher BMI. CONCLUSION: Relatives of CeAD patients had fewer strokes at a young age than relatives of non-CeAD IS stroke patients.

Elevated peripheral leukocyte counts in acute cervical artery dissection.

BACKGROUND AND PURPOSE: It has been suggested that inflammation may play a role in the development of cervical artery dissection (CeAD), but evidence remains scarce. METHODS: A total of 172 patients were included with acute (< 24 h) CeAD and 348 patients with acute ischaemic stroke (IS) of other (non-CeAD) causes from the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study, and 223 age- and sex-matched healthy control subjects. White blood cell (WBC) counts collected at admission were compared across the three groups. RESULTS: Compared with healthy control subjects, CeAD patients and non-CeAD stroke patients had higher WBC counts (P < 0.001). Patients with CeAD had higher WBC counts and were more likely to have WBC > 10 000/µl than non-CeAD stroke patients (38.4% vs. 23.0%, P < 0.001) and healthy controls (38.4% vs. 8.5%, P < 0.001). WBC counts were higher in CeAD (9.4 ± 3.3) than in IS of other causes (large artery atherosclerosis, 8.7 ± 2.3; cardioembolism, 8.2 ± 2.8; small vessel disease, 8.4 ± 2.4; undetermined cause, 8.8 ± 3.1; P = 0.022). After adjustment for age, sex, stroke severity and vascular risk factors in a multiple regression model, elevated WBC count remained associated with CeAD, as compared with non-CeAD stroke patients [odds ratio (OR) = 2.56; 95% CI 1.60-4.11; P < 0.001) and healthy controls (OR = 6.27; 95% CI 3.39-11.61; P < 0.001). CONCLUSIONS: Acute CeAD was associated with particularly high WBC counts. Leukocytosis may reflect a pre-existing inflammatory state, supporting the link between inflammation and CeAD.

Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study.

BACKGROUND AND PURPOSE: Risk factors for IS in young adults differ between genders and evolve with age, but data on the age- and gender-specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. METHODS: Stroke etiology was reported in detail for 3331 patients aged 15-49 years with first-ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low- and high-risk sources. Other determined group was divided into dissection and other non-dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. RESULTS: Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high-risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high-risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. CONCLUSIONS: The etiology of IS in young adults has clear gender-specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

Gender and cervical artery dissection.

BACKGROUND AND PURPOSE: To analyze previously established gender differences in cervical artery dissection (CeAD). METHODS: This case-control study is based on the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) population comprising 983 consecutive CeAD patients (mean age: 44.1 ± 9.9 years) and 658 control patients with a non-CeAD ischemic stroke (IS) (44.5 ± 10.5 years). RESULTS: Cervical artery dissection was more common in men (56.7% vs. 43.3%, P < 0.001) and men were older (46.4 vs. 41.0 years, P < 0.001). We assessed putative risk factors for CeAD including vascular risk factors, recent cervical trauma, pregnancies, and infections. All gender differences in the putative risk factors and outcome were similar in the CeAD and the non-CeAD IS groups. CONCLUSION: Our analysis of the largest collection of CeAD patients to date confirms male predominance and differences in age at dissection between men and women. Gender differences in putative risk factors may explain the higher frequency of CeAD in men and their older age, but the putative risk factors are probably not specific for CeAD.

Thrombolysis in cervical artery dissection--data from the Cervical Artery Dissection and Ischaemic Stroke Patients (CADISP) database.

OBJECTIVE: To examine whether thrombolysis for stroke attributable to cervical artery dissection (CeAD(Stroke) ) affects outcome and major haemorrhage rates. METHODS: We used a multicentre CeAD(Stroke) database to compare CeAD(Stroke) patients treated with and without thrombolysis. Main outcome measures were favourable 3-month outcome (modified Rankin Scale 0-2) and 'major haemorrhage' [any intracranial haemorrhage (ICH) and major extracranial haemorrhage]. Adjusted odds ratios [OR (95% confidence intervals)] were calculated on the whole database and on propensity-matched groups. RESULTS: Among 616 CeAD(Stroke) patients, 68 (11.0%) received thrombolysis; which was used in 55 (81%) intravenously. Thrombolyzed patients had more severe strokes (median NIHSS score 16 vs. 3; P < 0.001) and more often occlusion of the dissected artery (66.2% vs. 39.4%; P < 0.001). After adjustment for stroke severity and vessel occlusion, the likelihood for favourable outcome did not differ between the treatment groups [OR(adjusted) 0.95 (95% CI 0.45-2.00)]. The propensity matching score model showed that the odds to recover favourably were virtually identical for 64 thrombolyzed and 64 non-thrombolyzed-matched CeAD(Stroke) patients [OR 1.00 (0.49-2.00)]. Haemorrhages occurred in 4 (5.9%) thrombolyzed patients, all being asymptomatic ICHs. In the non-thrombolysis group, 3 (0.6%) patients had major haemorrhages [asymptomatic ICH (n = 2) and major extracranial haemorrhage (n = 1)]. CONCLUSION: As thrombolysis was neither independently associated with unfavourable outcome nor with an excess of symptomatic bleedings, our findings suggest thrombolysis should not be withheld in CeAD(Stroke) patients. However, the lack of any trend towards a benefit of thrombolysis may indicate the legitimacy to search for more efficient treatment options including mechanical revascularization strategies.

No association of the -105 promoter polymorphism of the selenoprotein S encoding gene SEPS1 with cerebrovascular disease.

A common pro-inflammatory promoter variant of the selenoprotein S encoding gene (SEPS1) was studied in young stroke patients from Italy and Germany and in healthy control subjects. The -105A-allele was found in 56 of 205 (27.3%) patients with ischemic stroke IS because of a spontaneous cervical artery dissection (CAD), and in 69 of 295 (23.4%) patients <50 years with IS of non-CAD origin. The SEPS -105A promoter variant was detected in 87 of 393 healthy control subjects (22.1%) and in 11 of 55 CAD patients without IS (20%). The non-significant differences of SEPS1 allele frequencies between disease groups and healthy controls suggest that the SEPS1 -105A allele is not a major-risk factor for stroke.

MTHFR 677TT genotype increases the risk for cervical artery dissections.

The methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism was studied in 174 German patients with cervical artery dissection (CAD). The results were compared with published data on 927 healthy German controls. In the series of patients, the frequency of T alleles and of TT carriers was slightly higher (13.8%) than among the healthy controls (10.6%). In patients with multiple dissections (n = 50), the proportion of TT carriers (18%) was found to be even higher and correlated with the number of events. The MTHFR C677T polymorphism was suggested to modify the risk for CAD.

Preclinical evaluation of lovastatin.

Administration of lovastatin to animals at high dosage levels produces a broad spectrum of toxicity. This toxicity is expected based on the critical nature of the target enzyme (HMG CoA reductase) and the magnitude of the dosage levels used. The information reviewed in this paper demonstrates that these adverse findings in animals do not predict significant risk in humans. The reason for this derives from the fact that all the available evidence suggests that the adverse effects observed are produced by an exaggeration of the desired biochemical effect of the drug at high dosage levels. The presence of clear and high no-effect doses for these toxic effects along with the fact that most of the changes observed are clearly mechanism-based (directly attributable to inhibition of mevalonate synthesis) indicate that it is unlikely that similar changes will be observed at the therapeutic dosage levels in humans. This hypothesis is supported by the extensive human safety experience described by Tobert in the following report.

Potential benefit of biventricular pacing in patients with congestive heart failure and ventricular tachyarrhythmia.

Treatment of congestive heart failure (CHF) aims for symptomatic relief and reduction of mortality both from sudden death and pump failure. The implantable cardioverter defibrillator (ICD) is highly effective in the prevention of sudden death, but no mortality benefit in advanced CHF has yet been shown. Biventricular pacing may lead to functional improvement in selected patients with CHF. Thus, a biventricular pacemaker with defibrillation capabilities may be ideal for patients with advanced CHF. We retrospectively analyzed the data from 384 patients (age 59 +/- 12 years, 322 male and 62 female) with regard to New York Heart Association (NYHA) CHF class, mean QRS duration, mean PR interval, presence of a QRS > 120 msec and incidence of atrial fibrillation at the time of ICD implantation. Based on eligibility criteria from studies in biventricular pacing, we analyzed how many patients may benefit from biventricular pacing. Patients with CHF were older (NYHA class III: 60.9 +/- 9.7, class II: 61.3 +/- 10 versus class I: 50.8 +/- 13.6 years, p < 0.001 each) and mean QRS duration was longer with advanced CHF (NYHA class III 127.8 +/- 30 msec; class II 119.4 +/- 27.7 msec; class 0-1: 103.9 +/- 17.7 msec, p < 0.001, analysis of variance) as was the mean PR interval (NYHA class III 189.9 +/- 33.5 msec; class II 176.1 +/- 29.3 msec; class 0-1 162.7 +/- 45.9 msec, p < 0.001, analysis of variance). The incidence of atrial fibrillation was higher in class III (25.5%) compared with class 0-1 (16.9%) and class II patients (14.1%, p = 0.043, chi-square test). A total of 28 patients (7.3%) fulfilled eligibility criteria for biventricular pacing if NYHA class III patients were considered candidates and 48 (12.5%) if patients with NYHA II CHF and ejection fraction < or = 30% were included. Thus, biventricular pacing may offer a promising therapeutic approach for a significant proportion of patients with CHF at risk for ventricular tachyarrhythmia.

Electrocardiographic remodeling in patients paced for heart failure.

Congestive heart failure due to advanced coronary artery disease or dilated cardiomyopathy is often associated with intraventricular conduction delays. Electrical resynchronization is an evolving method to improve clinical and functional status. To evaluate whether pacing-induced changes in the electrocardiogram are related to hemodynamic changes, we analyzed electrocardiograms of patients enrolled in the Pacing Therapies in Congestive Heart Failure trial. The study population consisted of 42 patients, New York Heart Association functional class III-IV with a baseline QRS complex of 175 +/- 32 msec and a PR interval of 196 +/- 33 msec. The mean left ventricular ejection fraction was 0.23. Using high-resolution computer scans, we measured QRS duration of intrinsic and paced electrocardiographs at different times during the study. Results of the electrocardiographic measurements were correlated with functional results. During the crossover period, 34 episodes of biventricular pacing, 27 episodes of left ventricular pacing, and 5 episodes of right ventricular pacing occurred, each at an individual optimized atrioventricular (AV) delay. The only significant difference was that right ventricular pacing increased the QRS width by 40 msec as compared with baseline or biventricular pacing. Functional benefit, as indicated by relative increase of peak oxygen uptake (VO2) compared with baseline, was significantly correlated with shortening of paced QRS width (correlation coefficient, r = 0.55; p <0.05). After 12-month follow-up of 28 patients, we saw a slight, nonsignificant decrease of intrinsic QRS width. With regard to the underlying disease, intrinsic QRS width at baseline and at 12 months was also not significantly different between patients with coronary artery disease and dilated cardiomyopathy. This study found that right ventricular pacing causes an increase in QRS duration in patients with left bundle-branch block, whereas in left ventricular and biventricular pacing, QRS width remains unchanged. Shortening of QRS width is correlated with a pronounced relative increase of peak VO2, and thus may become a noninvasive marker of clinical efficacy. There is no evidence of remodeling of the intrinsic electrocardiogram after 12 months of pacing.

Biotransformation of norcocaine to norcocaine nitroxide by rat brain microsomes.

In the mid 1970's, norcocaine was identified as a metabolite of cocaine in rat brain tissue. We extend these studies by demonstrating that rat brain FAD-containing monooxygenase metabolizes norcocaine to N-hydroxynorcocaine. This hydroxylamine is then further oxidized to the nitroxyl free radical norcocaine nitroxide by rat brain cytochrome P-450. Brain microsomal reduction of norcocaine nitroxide leads to the generation of superoxide. Finally, incubation of rat brain microsomes with either N-hydroxynorcocaine or norcocaine nitroxide leads to significant lipid peroxidation as monitored by spin-trapping techniques.

Enhanced semantic priming in thought-disordered schizophrenic patients using a word pronunciation task.

Previous research on semantic priming in schizophrenia has produced contradictory findings. For the present study, it was intended to resolve some of the ambiguities in the literature. Using a semantic priming task with word pronunciation, evidence is provided that thought-disordered schizophrenic (TD) patients exhibit significantly increased semantic priming as compared to healthy and psychiatric controls. Results suggest that enhanced semantic priming is not confined to tasks that require lexical decision. Moreover, results indicate that TD schizophrenic patients suffer from a decay of hierarchical thinking, i.e. TD schizophrenics reveal a tendency to process the less meaningful rather than the dominant aspects of external information. Priming effects for the inferior meaning of homograph words (for example, 'dance' is an inferior, and 'game' is a superior associate of the word 'ball') were significantly greater compared to healthy controls and non-TD schizophrenics. Results were not moderated by sociodemographic background variables, psychomotor slowing and psychopathological symptoms other than thought disorder.

Antibodies to beta2 glycoprotein I are associated with in vitro fertilization implantation failure as well as recurrent miscarriage: results of a prevalence study.

OBJECTIVE: To investigate whether antiphospholipid and related autoantibodies are associated with IVF implantation failure as well as with recurrent spontaneous miscarriage. DESIGN: Prevalence study. SETTING: University teaching hospital and associated IVF unit. PATIENT(S): Patients with at least three consecutive first-trimester miscarriages (n = 97), patients undergoing IVF who had at least 10 embryos transferred without any resulting clinical pregnancy (n = 105), fertile women (n = 106), and patients newly referred for IVF treatment (n = 52). INTERVENTION(S): Antibodies tested included lupus anticoagulant; immunoglobulin (Ig) G and IgM isotypes of each of anticardiolipin antibody, antiphosphatidylserine, antiphosphatidylethanolamine, and antiphosphatidylinositol; beta2 glycoprotein I antibodies; and antinuclear antibodies. Statistical analysis included chi2 and Fisher's exact tests for differences between groups, and multiple linear regression analysis and Spearman's nonparametric tests for relations between results. MAIN OUTCOME MEASURE(S): Seropositivity for autoantibodies tested. RESULT(S): Overall, 84 (23%) of the 360 samples tested positive for at least one autoantibody. Beta2 glycoprotein I IgM antibody and antinuclear antibody were significantly associated with both IVF implantation failure and recurrent miscarriage. CONCLUSION(S): Autoantibodies, particularly beta2 glycoprotein I antibodies and antinuclear antibodies, are associated with IVF implantation failure as well as with recurrent spontaneous abortion, although the mechanism is still unclear. The high seroprevalence of antibodies to beta2 glycoprotein I suggests that it may have an important role in autoimmune reproductive failure that needs to be explored further.

Impact of comorbid depressive symptoms on neuropsychological performance in obsessive-compulsive disorder.

There is indirect evidence from previous research that several executive disturbances in obsessive-compulsive disorder (OCD) are mediated by comorbid depressive symptoms. For the present study, the authors investigated whether OCD patients with elevated Hamilton Rating Scale for Depression (HRSD) scores would exhibit deficits in tasks sensitive to the medial and dorsolateral frontal cortex as well as other executive tasks. The 36 OCD patients were split along the median according to their HRSD scores and compared with matched control subjects. Patients with high HRSD scores performed significantly worse than control subjects and patients with low HRSD scores on the Wisconsin Card Sorting Test, the Trail-Making Test (TMT, Part B), and the TMT difference score. Moreover, patients with high HRSD scores exhibited deficits on a (creative) verbal fluency task. It is suggested that comorbid depressive symptoms may have artificially inflated some executive deficit scores in previous studies.

Histocompatibility antigens and habitual abortion.

Eighty-five couples with habitual abortion were studied: 43 were primary aborters (i.e., had no advanced pregnancy beyond 20 weeks gestation), and 42 were secondary aborters. The only significant finding in primary female aborters was a reduction in the incidence of B35. In contrast, in secondary female aborters there was a reduction in the incidence of DR3 and A1/B8/DR3 and an increase in the degree of homozygosity of HLA B. In the male partners of primary aborters, there was a reduced incidence of DR3 and A1/B8/DR3. In addition, in male partners of both primary and secondary aborters, there was increased HLA-B homozygosity and increased frequency of DR4-5 phenotype. Increased sharing of HLA antigens between partners was not found to be significantly different from the control population. These findings emphasize that primary and secondary female aborters form distinct populations, which could explain differences in immunological responses to various antigens, including fetal-related antigens. The closely related findings in female secondary aborters and male partners of primary aborters are intriguing but cannot be explained. Whether or not these genetic markers bear any relationship to reproductive success remains to be determined.