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Role of platelet function in symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

To evaluate the role of platelet function in the pathogenesis of cerebral vasospasm, we compared sequential changes of platelet aggregability and beta-thromboglobulin and thromboxane B2 concentrations in blood samples from the internal jugular and peripheral vein of 13 patients with aneurysmal subarachnoid hemorrhage. Platelet function in blood from the internal jugular vein tended to be enhanced during days 0-1 but recovered to the normal range during days 2-4. After day 5, platelet function showed various patterns depending on the presence of symptomatic vasospasm. In patients without symptomatic vasospasm, sequential changes were relatively minor, with normal or slightly high values. Patients with symptomatic vasospasm already showed high platelet aggregability during the early stage of vasospasm. The concentration of beta-thromboglobulin increased several days after the onset of vasospasm, reaching 80 ng/ml or more in patients with a poor prognosis. Two of the five patients with symptomatic vasospasm showed markedly high concentrations of thromboxane B2 after day 8. These results suggest that vasospasm activates platelets and promotes aggregability and that the resulting increased tendency for thrombus formation may affect the patient's prognosis during the advanced stage.

Adult↗

Is Marfan syndrome associated with symptomatic intracranial aneurysms?

BACKGROUND AND PURPOSE: Marfan syndrome is a heritable disorder of connective tissue caused by a deficiency of the glycoprotein fibrillin. In several publications and neurological textbooks, a relationship between Marfan syndrome and intracranial aneurysms has been assumed. METHODS: The records of 135 patients classified as having Marfan syndrome who visited the Amsterdam Marfan clinic or were admitted to the departments of neurology and neurosurgery and the records of all patients with a subarachnoid hemorrhage or intracranial aneurysm who visited or were admitted to the departments of neurology and neurosurgery between January 1, 1982, and January 1, 1994, were retrieved. The literature was reviewed regarding Marfan syndrome and intracranial aneurysms. RESULTS: No patient visiting the Marfan clinic had a symptomatic intracranial aneurysm. No patient with Marfan syndrome had been admitted with a ruptured intracranial aneurysm at the departments of neurology or neurosurgery in this period, while during that period 826 patients with symptomatic intracranial aneurysms had been admitted. During follow-up of 129 of the 135 patients with Marfan syndrome (2850 retrospective patient observation years and 581 prospective patient observation years), none presented a symptomatic intracranial aneurysm. The suggested relationship between Marfan syndrome and intracranial aneurysms is based mainly on 10 case reports. However, the diagnosis of Marfan syndrome is doubtful in several of these reports. Several large studies of patients with Marfan syndrome did not mention a ruptured intracranial aneurysm as a clinical manifestation. CONCLUSIONS: We conclude that there is insufficient evidence to presume a relationship between symptomatic intracranial aneurysms and Marfan syndrome on the basis of currently available data.

Adolescent↗

Misdiagnosis of symptomatic cerebral aneurysm. Prevalence and correlation with outcome at four institutions.

BACKGROUND AND PURPOSE: It is not known what fraction of patients with symptomatic cerebral aneurysms are misdiagnosed at initial medical presentation. It is also not clear whether misdiagnosed patients more frequently deteriorate before definitive aneurysm diagnosis and therapy or achieve a poorer outcome than correctly diagnosed patients. METHODS: We reviewed records of consecutive patients with symptomatic cerebral aneurysms managed by four tertiary-care neurosurgical services during a recent 19-month period. Clinical course and outcome were analyzed according to misdiagnosis or correct diagnosis at initial medical evaluation. RESULTS: Fifty-four of 217 patients (25%) were misdiagnosed at initial medical evaluation, including 46 of 121 patients (38%) initially in good clinical condition (clinical grade 1 or 2). Forty-six of 54 patients (85%) in the misdiagnosis group were initially grade 1 or 2 compared with 75 of 163 patients (46%) with correct initial diagnosis (P < .01). Twenty-six of 54 misdiagnosed patients (48%) deteriorated or rebled before definitive aneurysm treatment compared with 4 of 165 correctly diagnosed patients (2%) (P < .001). Among patients initially presenting as clinical grade 1 or 2, overall good or excellent outcome was achieved in 91% of those with correct initial diagnosis and 53% of patients with initial misdiagnosis (P < .001). Deterioration before correct diagnosis accounted for 16 of 67 patients (24%) with poor or worse final outcome in this series. CONCLUSIONS: Patients in good clinical condition with symptomatic cerebral aneurysms were commonly misdiagnosed. Misdiagnosed patients were more likely than correctly diagnosed patients to deteriorate clinically and had a worse overall outcome. Misdiagnosed cases accounted for a significant fraction of overall poor outcomes among consecutive cases of symptomatic aneurysms.

Adult↗

Stent angioplasty for cervical carotid artery stenosis in high-risk symptomatic NASCET-ineligible patients.

BACKGROUND AND PURPOSE: Although the North American Symptomatic Carotid Endarterectomy Trial (NASCET) has shown carotid endarterectomy (CEA) to be protective compared with medical therapy alone, its stringent eligibility criteria excluded patients with severe medical, angiographic, and neurological risk factors. We sought to determine the safety and efficacy of stent angioplasty in this high-risk subset for whom the perioperative morbidity and mortality of surgery are elevated. METHODS: Twenty-eight consecutive symptomatic NASCET-ineligible patients (10 female; median age, 72.2 years) underwent microcatheter-based carotid stent angioplasty. Half of the patients had sustained a previous stroke. Classification of surgical risk by Sundt criteria yielded no patients in grade 1, 3 patients in grade 2 (10.7%), 8 in grade 3 (28.6%), and 17 (60.7%) in grade 4. Stratification of stroke risk for medical therapy according to the European Carotid Surgery Trial (ECST) 5-point score showed 8 patients with a score of 3 (28.6%), 12 with 4 (42.8%), and 8 with 5 (28.6%). Follow-up was obtained in all patients at a median of 14 months. RESULTS: The procedure was technically successful in all cases (100%), with immediate stenosis reduction from a mean of 80.3% to 2.7%. There were no periprocedural deaths, 1 major stroke (3.6%), no minor strokes, and 3 transient ischemic attacks (10.7%). In-hospital complications included 2 nonfatal myocardial infarctions, 1 case of acute renal failure, and 1 groin hematoma requiring transfusion. There were 5 deaths during the follow-up period, all beyond 30 days after the procedure: 3 from cardiac causes, 1 from lung cancer, and 1 following unrelated surgery. The patient with major stroke died at 7.8 months during rehabilitation. No surviving patients had further strokes, and all except 1 (95.5%) remained asymptomatic. Anatomic follow-up in 20 patients showed occlusion in 2 (10%) (1 symptomatic, 1 asymptomatic) and intimal hyperplasia in 3 asymptomatic patients (15%). CONCLUSIONS: The clinical results and sustained freedom from symptoms and stroke during the short available follow-up period suggest that stent angioplasty may be useful in the treatment of symptomatic cervical carotid stenosis in high-risk patients despite a notable incidence of restenosis.

Aged↗

Systematic comparison of the early outcome of angioplasty and endarterectomy for symptomatic carotid artery disease.

BACKGROUND AND PURPOSE: Endoluminal treatment is being increasingly used for carotid artery disease. The aim of this study was to compare the stroke and death risk within 30 days of endovascular treatment or endarterectomy for symptomatic carotid artery disease. METHODS: systematic comparison of the 30-day outcome of angioplasty with or without stenting and endarterectomy for symptomatic carotid artery disease reported in single-center studies, published since 1990, was performed. RESULTS: Thirty-three studies (13 angioplasty and 20 carotid endarterectomy) were included in this analysis. Carotid stents were deployed in 44% of angioplasty patients. Mortality within 30 days of angioplasty was 0.8% compared with 1.2% after endarterectomy (OR 0.68, 95% CI 0.43 to 1.05; P=0.6). The stroke rate was 7.1% for angioplasty and 3.3% for endarterectomy (OR 2.22, CI 1.62 to 3.04; P<0.001), while the risk of fatal or disabling stroke was 3.2% and 1.6%, respectively (OR 2.09, CI 1.3 to 3.33; P<0.01). The risk of stroke or death was 7.8% for angioplasty and 4% for endarterectomy (OR 2.02, CI 1.49 to 2.75; P<0.001), while disabling stroke or death was 3.9% after angioplasty and 2.2% after endarterectomy (OR 1.86, CI 1.22 to 2.84; P<0.01). CONCLUSIONS: In the treatment of symptomatic carotid artery disease, the risk of stroke is significantly greater with angioplasty than carotid endarterectomy. At present, carotid angioplasty is not recommended for the majority of patients with symptomatic carotid artery disease.

Angioplasty, Balloon↗

A longitudinal study of collateral flow patterns in the circle of Willis and the ophthalmic artery in patients with a symptomatic internal carotid artery occlusion.

BACKGROUND AND PURPOSE: The purpose of the present study was to assess whether the direction of flow via the circle of Willis and the ophthalmic artery (OphA) changed over time in patients with a symptomatic occlusion of the internal carotid artery (ICA) who did not experience recurrent cerebral ischemic symptoms. METHODS: Sixty-two patients with a symptomatic ICA occlusion were investigated within 6 months after symptoms occurred. The investigations were repeated after 6 and 12 months. The directions of flow in the A1 segment and the posterior communicating artery (PCoA), both on the side of the symptomatic ICA occlusion, were assessed with the use of magnetic resonance angiography. The pattern of collateral flow via the circle of Willis was categorized as via the A1 segment only, via the PCoA only, via the A1 segment plus the PCoA, or no collateral flow via the circle of Willis. The direction of flow in the OphA was investigated with transcranial Doppler sonography. CO(2) reactivity was determined with transcranial Doppler sonography to investigate whether changes in flow patterns were accompanied by changes in cerebrovascular reactivity. RESULTS: There were no statistically significant changes over time in the direction of blood flow in the A1 segment and the PCoA or in the pattern of collateral flow via the circle of Willis. On average, 72% of patients with a unilateral ICA occlusion (n=41) had willisian collateral flow compared with 37% of patients with a bilateral ICA occlusion (n=21; P<0.05). Patients with a unilateral ICA occlusion tended to a lower prevalence of reversed flow via the OphA over time. CO(2) reactivity did not change significantly in any patient group. In patients with a unilateral ICA occlusion, decreased CO(2) reactivity was associated with a higher prevalence of absent willisian collateral flow and a lower prevalence of collateral flow via the A1 segment plus the PCoA. CONCLUSIONS: The absence of recurrent cerebral ischemic symptoms in patients with a symptomatic ICA occlusion is not associated with an improvement in collateral flow via the circle of Willis or the OphA during 1.5-year follow-up.

Blood Gas Analysis↗

Endovascular treatment of symptomatic carotid stenosis using stent placement: long-term follow-up of patients with a balanced surgical risk/benefit ratio.

BACKGROUND AND PURPOSE: Carotid endarterectomy (CEA) is not necessarily beneficial in all patients with symptomatic high-grade (>/=70%) internal carotid artery (ICA) stenosis. Independent risk factors modulate both the individual stroke risk under medical treatment and the combined stroke and death risk after CEA. Endovascular stenting of symptomatic ICA stenosis may be an alternative to CEA in patients with a balanced surgical risk/benefit ratio. METHODS: We included 43 patients (71% men; median age, 67 years) with a recently symptomatic ICA stenosis with >/=70% luminal narrowing in whom the individual sum of medical and surgical risk factors suggested a balanced surgical risk/benefit ratio (risk-modeling appraisal derived from the European Carotid Surgery Trial). After stenting of the stenosed ICA with distal balloon protection, the mean+/-SD follow-up, including clinical and ultrasonographic examinations, was 20+/-11.8 months, with a median number of examinations of 5 per patient. RESULTS: Recanalization of ICA stenoses was technically successful in 40 of 43 procedures (93%). Within the 30-day postinterventional period 1 death occurred (2.5%), and the combined stroke and death rate within follow-up was 5%. Except for 1 asymptomatic ICA occlusion, no restenosis >/=70% occurred during follow-up. CONCLUSIONS: ICA stenting in symptomatic patients with a balanced surgical risk/benefit ratio is technically feasible, with a low periprocedural risk of stroke or death. Furthermore, the risk of future stroke and rate of significant restenosis during long-term follow-up appears to be low, suggesting that ICA stenting may be useful in carotid revascularization and stroke prevention.

Aged↗

Ultrasound measurement of the fibrous cap in symptomatic and asymptomatic atheromatous carotid plaques.

BACKGROUND: Fibrous cap thickness (FCT) is an important determinant of atheroma stability. We evaluated the feasibility and potential clinical implications of measuring the FCT of internal carotid artery plaques with a new ultrasound system based on boundary detection by dynamic programming. METHODS AND RESULTS: We assessed agreement between ultrasound-obtained FCT values and those measured histologically in 20 patients (symptomatic [S]=9, asymptomatic [AS]=11) who underwent carotid endarterectomy for stenosing (>70%) carotid atheromas. We subsequently measured in vivo the FCT of 58 stenosing internal carotid artery plaques (S=22, AS=36) in 54 patients. The accuracy in discriminating symptomatic from asymptomatic plaques was assessed by receiver operating characteristic curves for the minimal, mean, and maximal FCT. Decision FCT thresholds that provided the best correct classification rates were identified. Agreement between ultrasound and histology was excellent, and interobserver variability was small. Ultrasound showed that symptomatic atheromas had thinner fibrous caps (S versus AS, median [95% CI]: minimal FCT=0.42 [0.34 to 0.48] versus 0.50 [0.44 to 0.53] mm, P=0.024; mean FCT=0.58 [0.52 to 0.63] versus 0.79 [0.69 to 0.85] mm, P<0.0001; maximal FCT=0.73 [0.66 to 0.92] versus 1.04 [0.94 to 1.20] mm, P<0.0001). Mean FCT measurement demonstrated the best discriminatory accuracy (area under the curve [95% CI]: minimal 0.74 [0.61 to 0.87]; mean 0.88 [0.79 to 0.97]; maximal 0.82 [0.71 to 0.93]). The decision threshold of 0.65 mm (mean FTC) demonstrated the best correct classification rate (82.8%; positive predictive value 75%, negative predictive value 88.2%). CONCLUSIONS: FCT measurement of carotid atheroma with ultrasound is feasible. Discrimination of symptomatic from asymptomatic plaques with mean FCT values is good. Prospective studies should determine whether this ultrasound marker is reliable.

Aged↗

Progression and clinical recurrence of symptomatic middle cerebral artery stenosis: a long-term follow-up transcranial Doppler ultrasound study.

BACKGROUND AND PURPOSE: Patients with symptomatic intracranial atherosclerotic stenosis have a high rate of recurrence. We conducted a prospective study to determine which factors are associated with the progression of symptomatic middle cerebral artery (MCA) stenosis and to evaluate the relationship between progression and clinical recurrence. METHODS: Between January 1996 and February 2000, of a total of 2564 consecutive first-ever transient ischemic attack (TIA) or stroke patients admitted to our cerebrovascular unit, 145 showed an MCA stenosis signal on transcranial Doppler (TCD) on admission, and 40 fulfilled all criteria to enter this study, including angiographic confirmation. Patients were prescribed antiplatelet or anticoagulant agents following the criteria of the neurologist in charge. TCD recordings and clinical interviews were performed regularly during follow-up. Progression of MCA stenosis was defined as an increase >30 cm/s in TCD-recorded maximum mean flow velocity. Logistic regression analyses were used to identify predictors of progression and clinical recurrence. RESULTS: With a median follow-up of 26.55 months, 13 (32.5%) MCA stenoses progressed, 3 (7.5%) regressed, and 24 (60%) remained stable. Absence of significant extracranial internal carotid artery (ICA) stenosis (P=0.049) and the use of oral anticoagulants (P=0.045) were significantly associated with a lower progression rate in univariate analysis, and anticoagulation remained an independent predictor when a logistic regression model was applied (OR 7.25, CI 1.1 to 48.1, P=0.019). A new ischemic event during follow-up in the territory supplied by the stenosed MCA occurred in 8 cases (20%), and 13 patients had a major vascular event. Progression of the MCA stenosis detected by TCD was independently associated with a new ipsilateral ischemic event (OR 2.89, CI 1.09 to 7.71, P=0.031) and with the occurrence of any major vascular event (OR 7.03, CI 1.6 to 30.9, P=0.0071). CONCLUSIONS: Progression of symptomatic MCA stenosis detected by means of TCD predicts clinical recurrence. Anticoagulation is independently associated with a lower progression rate of symptomatic MCA stenosis.

Administration, Oral↗

Protocol of a prospective cohort study of the effect of different methods of drainage of neuropathic bladder on occurrence of symptomatic urinary infection, and adverse events related to the urinary drainage system in spinal cord injury patients.

BACKGROUND: To present a protocol of a prospective, cohort study in which four groups of spinal cord injury (SCI) patients will participate. (Patients with indwelling urethral catheter; patients who perform intermittent catheterisation without wearing a penile sheath; patients who perform intermittent catheterisation and wear penile sheath as well; and patients with penile sheath drainage). OBJECTIVES: (1) What is the incidence of symptomatic urinary infection in men with spinal cord injury who use different types of bladder drainage? (2) Which are predisposing factors for the occurrence of symptomatic urinary infection in men with spinal cord injury who practise different methods of bladder drainage? (3) What is the incidence of catheter and urinary drainage system-related adverse events in the four groups of SCI patients? PATIENTS: The criteria for inclusion are as follow: (1) Male patients with neuropathic bladder due to spinal cord injury, who are registered with the Regional Spinal Injuries Centre, Southport, England. (2) Age: 18 years or above. (3) Patients who are willing to give informed consent for participation in the study. (4) Patients willing to be contacted every two weeks by a staff of the spinal unit for 36 months. (5) Patients who are willing to maintain an accurate record of adverse events related to urinary catheter and urinary drainage system and predisposing factors for the occurrence of symptomatic urinary infection. (6) Patients, who are stabilised in a particular method of bladder drainage, and therefore, unlikely to make a permanent change in the method of bladder drainage (e.g. from penile sheath drainage to the use of long-term indwelling catheter) during a foreseeable future. METHODS: The participants will be observed for a period of 36 months. A staff of the spinal injuries unit will contact the participants by telephone every two weeks on a mutually agreed day and time. The information obtained during this standardised telephonic interview conducted once in two weeks will be entered in a database. When a participant develops symptom(s) suggestive of urinary infection, he will undergo urine and blood tests, and imaging studies of the urinary tract. CONCLUSION: This study will provide information regarding the occurrence of symptomatic urinary infection, predisposing factors for development of urinary infection, and adverse events related to urinary catheter and urinary drainage system in SCI patients using different methods of bladder drainage.

Adult↗

Dual-transcriptomic analysis of human nasal transcriptome and microbiome reveals host-bacteria associations in symptomatic respiratory infection.

BACKGROUND: The human nasopharynx is colonized by a diverse community of commensal microbiota linked to many respiratory diseases, yet their associations with the host remain unclear. RESULTS: In this study, we introduced a dual-transcriptomics analysis strategy, which can characterize the host transcriptome and microbiome from nasal samples simultaneously. We applied this workflow to a local SARS-CoV-2 cohort with 76 asymptomatic infected patients, among whom 52 (68.42%) developed symptomatic infection during a 1-week follow-up period. Nasal swabs were collected from all 76 patients at enrollment and from 73 patients at one-week later follow-up. We detected a median of 8.94% reads that did not map to the human genome across all 149 samples, among which around half (median 49.68%) were successfully mapped to microbiome genome. Meta-transcriptomic analysis detected significantly higher SARS-related coronavirus loads in samples from the symptomatic group at enrollment (P&#x2009;=&#x2009;0.004), and both groups showed decreased loads one week later (symptomatic, P&#x2009;=&#x2009;0.001; asymptomatic, P&#x2009;=&#x2009;0.035). Compared with benchmarking 16&#xa0;S rRNA sequencing on 53 samples, our computational strategy showed high correlation of relative abundance in all top 20 genera (median Rho&#x2009;=&#x2009;0.90, Pmax < 0.001). A total of 670 bacteria species were identified to show a relative abundance&#x2009;&#x2265;&#x2009;0.01% in at least 10% samples. Differential abundance analysis identified 76 species (DASs) from six phyla with significantly decreased abundance in samples from the symptomatic group (log2(fold change or FC) < -1 and adjusted P&#x2009;<&#x2009;0.05) compared to the asymptomatic group at enrollment. Integrating these symptom-associated DASs with host's gene expression using an expression quantitative trait bacteria (eQTB) model, we found 45 symptom-associated DASs identified at enrollment were significantly associated with one to 14 genes (adjusted P&#x2009;<&#x2009;0.05). GSEA showed a series of symptom-associated DASs were significantly correlated with pathways related to olfactory function, keratinocyte differentiation, and DNA methylation. CONCLUSIONS: In summary, our dual-transcriptomic analysis strategy effectively characterized host-microbiome associations, offering insights into microbial contributions to respiratory diseases.

Humans↗

Symptomatic medication use in multiple sclerosis.

Multiple sclerosis (MS) is one of the most studied neurological diseases, although scarce attention has been placed on symptomatic therapy. The aim of the study was to evaluate the frequency of medication prescription for the major symptoms related to MS in order to better understand the needs of patients. The study was conducted during an epidemiological survey in the province of Genoa, Italy. Out of 856 patients with MS in the study area, 665 agreed to participate in a structured interview. Two hundred and forty-nine (37%) subjects, with a mean age of 53 years and a mean Expanded Disability Status Scale (EDSS) score of 5.2, were taking at least one symptomatic medication. Four hundred and sixteen (63%) subjects, with a mean age of 49 years and a mean EDSS score of 4.5, were not using symptomatic therapy. The most commonly treated symptoms were pain (28%), spasticity (27%) and mood disorder (16%), while bladder dysfunction (8%) and fatigue (3%) were less frequently treated with medication. Seventy-seven patients (12%) were taking medications for reasons not directly related to MS. This cross-sectional study underlines the frequency of medication prescription for symptoms such as spasticity and pain, while other common symptoms, such as bladder dysfunction and fatigue, may perhaps be undertreated. The present findings also underline the need for clinical trials on symptomatic therapies.

Adult↗

Extended enoxaparin monotherapy for acute symptomatic pulmonary embolism.

We investigated the efficacy and safety of extended enoxaparin monotherapy in symptomatic patients with acute pulmonary embolism (PE). We randomized 40 patients in a 1:1 allocation to enoxaparin monotherapy (1 mg/kg twice daily for 10-18 days, and then 1.5mg/kg once daily until day 90) (n = 20) or to enoxaparin 1.0 mg/kg twice daily as a bridge to warfarin with a target international normalized ratio of 2.0-3.0 for 90 days (at least 10 doses of enoxaparin overlapping with warfarin for at least 4 days) (n = 20). All patients underwent echocardiography, cardiac troponin I (TnI), and brain natriuretic peptide testing to identify patients with an increased likelihood of adverse clinical outcomes. The end-points were newly diagnosed deep venous thrombosis (DVT) or PE and bleeding events through day 90. In 15 patients on extended enoxaparin therapy, we used repeated measure analysis of variance (ANOVA) to investigate differences in anti-Xa levels obtained at 2, 4, 8 and 12 weeks. The patients' mean age was 52 +/- 17 years; the most common comorbidities were obesity (58%), hypertension (30%), concomitant DVT (30%) and cancer (15%). Twelve (30%) patients had elevated cardiac Tnl >0.1 mg/l and 11 (28%) had moderate or severe right ventricular dysfunction on echocardiography. Ten (25%) patients received thrombolysis with a continuous infusion of 100 mg alteplase prior to randomization. During a 90-day follow-up, one patient from the enoxaparin monotherapy group suffered symptomatic distal DVT; one from the warfarin group had recurrent symptomatic PE (p = 1.0). None of the study patients had major hemorrhage; two warfarin group patients had minor bleeding compared with none in the enoxaparin monotherapy group (p = 0.49). Repeated measure ANOVA did not reveal significant differences in anti-Xa levels over time (p = 0.217). In patients with acute symptomatic PE, extended enoxaparin monotherapy is feasible and warrants further investigation in a large clinical trial.

Acute Disease↗

Perceived stress as a predictor of the self-reported new diagnosis of symptomatic CHD in older women.

This article describes one aspect of a prospective cohort study of 10,432 women aged between 70 and 75 years. After a 3-year period, 503 women self-reported a new diagnosis by a doctor of angina or myocardial infarction (symptomatic coronary heart disease [CHD]). Time one psychosocial variables (Duke Social Support Index, time pressure, Perceived Stress Scale, Mental Health Index, having a partner, educational attainment, and location of residence) were analyzed using univariate binary logistic regression for their ability to predict subsequent symptomatic CHD. Of these variables, the Duke Social Support Index, Perceived Stress Scale and the Mental Health Index were found to be significant predictors of symptomatic CHD diagnosis. Only the Perceived Stress Scale, however, proved to be a significant independent predictor. After controlling for time one nonpsychosocial variables, as well as the frequency of family doctor visits, perceived stress remained a significant predictor of the new diagnosis of symptomatic CHD in this cohort of older women over a 3-year period.

Aged↗

Metformin does not adversely affect hormonal and symptomatic responses to recurrent hypoglycemia.

Body weight gain and severe hypoglycemia are the major adverse effects of insulin therapy in type 2 diabetic patients. Metformin has been shown to prevent insulin therapy-induced body weight gain when used in combination with insulin. However, the effects of metformin on hormonal and symptomatic responses to hypoglycemia mediating hypoglycemia awareness have not been assessed to date. Fifteen young healthy men were treated with 850 mg metformin and placebo twice daily for a 16-d period in a double blind, cross-over design. On the last 2 d of the treatment period, the subjects underwent three hypoglycemic clamp experiments, with the first and the last performed with identical patterns of plasma glucose decrease. Differences between the effects of metformin and placebo (effect of metformin) as well as between first and last hypoglycemic clamps (effect of antecedent hypoglycemia) were assessed. Antecedent hypoglycemia significantly reduced epinephrine, ACTH, cortisol, glucagon, GH, and symptomatic responses to hypoglycemia (P < 0.05 for all variables). There was no detectable effect of metformin on epinephrine, norepinephrine, ACTH, cortisol, glucagon, or autonomic symptomatic response to hypoglycemia (P > 0.05 for all comparisons), except that metformin slightly increased the response of GH to hypoglycemia (P = 0.039). The latter finding may be due to an IGF-I-reducing effect of metformin, as after 14 d of metformin treatment baseline levels of IGF-I were significantly lower than in the placebo condition (236.9 +/- 13.9 vs. 263.2 +/- 14.4 microg/liter; P = 0.015). The data indicate that metformin does not adversely affect hormonal and symptomatic responses to hypoglycemia. This finding appears to be relevant with regard to the safety of the combination of metformin with insulin therapy.

Adult↗

Stroke recurrences in patients with symptomatic vs asymptomatic middle cerebral artery disease.

BACKGROUND: Although the natural history of extracranial carotid artery disease has been investigated systematically, limited data are available on the course of middle cerebral artery (MCA) disease. METHODS: The authors observed 102 consecutive patients (67 men, 35 women; mean age 61.9 years) with significant MCA stenosis or occlusion as demonstrated by transcranial Doppler and transcranial color-coded duplex ultrasonography. Forty-six patients entered the study after TIA (n = 17) or stroke (n = 29); 56 patients were asymptomatic. Neurologic and ultrasound investigations were performed at regular intervals with a mean follow-up of 31 (range 6 to 117) months. Patients were continuously treated with either platelet inhibitors (n = 75) or anticoagulation (n = 27). RESULTS: Nineteen cerebral ischemic events (11 strokes, 8 TIAs) occurred during follow-up, resulting in an overall annual rate of 7.3%. Thirteen events (8 strokes, 5 TIAs) were attributable to the vascular territory ipsilateral to MCA disease. Patients with symptomatic MCA disease at study entry had an overall stroke risk of 12.5% per year (ipsilateral: 9.1%), whereas the annual incidence in primarily asymptomatic MCA disease was only 2.8% (ipsilateral: 1.4%; p < 0.01). Symptomatic MCA disease was an independent predictor for overall (hazard ratio [HR] 7.91, 95% CI 2.03 to 30.79; p < 0.01) and ipsilateral (HR 9.66, 95% CI 1.5 to 62.25; p = 0.02) cerebrovascular events. CONCLUSIONS: Compared with asymptomatic middle cerebral artery disease, there was a high and continuous recurrence rate of ischemic events in symptomatic patients, which was even higher than in patients with symptomatic extracranial carotid artery disease.

Aged↗

Intrathecal humoral immunologic response in neurologically symptomatic and asymptomatic patients with human immunodeficiency virus infection.

We analyzed the intrathecal humoral immunologic response in 42 human immunodeficiency virus (HIV)-infected patients. Eighteen patients had clinical neurologic abnormalities, while the remaining 24 patients were neurologically symptom-free. Nine of the neurologically symptomatic patients at early infection had slight neurologic dysfunction; in nine other subjects at late infection, the neurologic impairment was moderate or severe. When compared with symptom-free patients, neurologically symptomatic patients had increased intra-blood-brain barrier (BBB) HIV-specific IgG (p less than 0.001) and total IgG synthesis (p less than 0.01) with oligoclonal bands (OCBs) in the CSF and/or serum (11/18 versus 3/24). At early stages of the infection, neurologically symptomatic patients showed increased total intrathecal IgG synthesis (9/9) coincident with OCBs in the CSF and serum (7/9) and slight mononuclear pleocytosis (7/9), but less frequent HIV-specific IgG production within the CNS (6/9). In advanced infection, the number of neurologically symptomatic patients with intrathecal HIV-specific IgG synthesis (8/9) was higher, while the number of those with increased total intra-BBB IgG synthesis (5/9; p less than 0.01), OCBs (4/9), and increased CSF leukocyte count (1/9; p less than 0.001) was lower than at early infection. Our data suggest humoral intra-BBB immunoactivation at early stages of HIV infection followed by declining B cell response within the CNS at advanced infection.

Acquired Immunodeficiency Syndrome↗

Infantile spasms: outcome and prognostic factors of cryptogenic and symptomatic groups.

We reviewed the outcome (developmental, neurologic, and seizure) and prognostic factors of 57 cases of infantile spasms (17 cryptogenic, 40 symptomatic). The mean developmental score of the cryptogenic group (71.2 +/- 24.2) was significantly higher than that of the symptomatic group (48.4 +/- 24.5), as assessed by the Griffith Mental Developmental Scale. A resultant neurologic deficit was present in 23.5% of the cryptogenic group and 75.0% of the symptomatic group. Coexistence of other forms of seizures was observed in 35.3% of the cryptogenic group and 57.5% of the symptomatic group. Outcome was affected by the coexistence of other seizures, presence of neurologic deficit, time lag in initiation of treatment (cognitive outcome only), poor response to ACTH treatment, and persistent EEG abnormality. Character of spasms and time lag in initiation of treatment (seizure outcome only) did not have any significant effect on outcome.

Adrenocorticotropic Hormone↗