Marina Diomedi

Cerebral hemodynamic changes in sleep apnea syndrome and effect of continuous positive airway pressure treatment

Background and Objective: A clear association among snoring, sleep apnea, and increased risk of stroke has been shown by previous studies. However, the possible role played by sleep apnea in the pathogenesis of cerebrovascular disease is subject to debate. To evaluate the influence of hemodynamic changes caused by obstructive sleep apnea syndrome (OSAS), we investigated cerebrovascular reactivity to hypercapnia in patients with OSAS. Methods: The study was performed at baseline and after 1 night and 1 month of nasal continuous positive airway pressure (n-CPAP) therapy, with patients in the waking state (8:00 to 8:30 AM and 5:30 to 6:00 PM) with transcranial Doppler ultrasonography. Cerebrovascular reactivity was calculated with the breath-holding index (BHI). Results: In the baseline condition, compared with normal subjects, patients with OSAS showed significantly lower BHI values in both the morning (0.57 versus 1.40, p < 0.0001) and the afternoon (1.0 versus 1.51, p < 0.0001). Cerebrovascular reactivity was significantly higher in the afternoon than it was in the morning in both patients (p < 0.0001) and controls (p < 0.05). In patients, the BHI returned to normal values, comparable with those of control subjects, after both 1 night and 1 month of n-CPAP therapy. Conclusions: These findings suggest an association between OSAS and diminished cerebral vasodilator reserve. This condition may be related to the increased susceptibility to cerebral ischemia in patients with OSAS, particularly evident in the early morning.

Carotid Artery Wall Thickness in Patients With Obstructive Sleep Apnea Syndrome

Background and Purpose— Epidemiological studies have suggested a pathophysiological link between sleep apnea syndrome and cerebrovascular diseases. The mechanism by which sleep disturbance can affect the predisposition to developing stroke is not clear. The aim of this study was to investigate whether patients with obstructive sleep apnea syndrome have an increase in atherosclerosis indicators at the carotid artery level. Methods— We included 23 male patients with severe obstructive sleep apnea syndrome (respiratory disturbance index >30). Intima-media thickness and the presence of steno-occlusive lesions in the common carotid arteries were investigated with B-mode high-resolution ultrasonography. Results of the ultrasonographic examination were compared with those of a group of 23 subjects without obstructive sleep apnea syndrome who were matched for age and comorbid factors. Results— The intima-media thickness of the common carotid arteries of patients with obstructive sleep apnea syndrome was significantly higher (P <0.0001) than that of control subjects (1.429±0.34 versus 0.976±0.17 mm). Conclusions— Results of the present study show that carotid wall thickness is increased in patients with severe sleep apnea syndrome. There is strong evidence that an increase in the thickness of the carotid artery wall is a valid marker of the risk of stroke. For this reason, our finding seems to further strengthen the hypothesis that patients with obstructive sleep apnea syndrome are at risk of developing cerebrovascular diseases regardless of the association with other vascular risk factors.

Sleep abnormalities in mentally retarded autistic subjects: Down's syndrome with mental retardation and normal subjects

We compared sleep parameters in mentally retarded infantile autism (MRIA) and mentally retarded Downs syndrome (MRDS) by means of polysomnography, evaluating traditional analysis with particular attention to the phasic components in each disorder. Data were compared with those obtained in normal subjects matched for age and sex. Mental age, Intellectual Quotient and the Childhood Autism Rating Scale were performed to obtain an estimation of the neuropsychological deficit. Abnormalities of phasic components of sleep and the presence of REM sleep components into non-REM sleep were observed in both MRIA and MRDS even if in different ways. In fact, MRDS subjects presented a reduction of REM sleep percentage and R index (number of high frequency REMs against number of low frequency REMs) and this was positively correlated to a low IQ. Unlike MRDS subjects, MRIA subjects did not show any parallelism between intellectual abilities and REM sleep deficit. In addition, the presence of undifferentiated sleep in autistic subjects implies a maturational deficit that is still present in adulthood. Finally, a high R index in MRIA was observed. This finding, which is not present in MRDS, could represent an estimation of the disorganized arrival of information caused by a dyscontrol or a reduction of inhibitor pathway. With reference to sleep mechanisms, our results suggest that the cognitive deficit in MRIA may differ from that of MRDS subjects. A maturational deficit of CNS with a dysfunction of brainstem monoaminergic neurons could represent the underlying mechanism.

Cytotoxin-Associated Gene-A–Positive Helicobacter pylori Strains Are Associated With Atherosclerotic Stroke

Background—It is uncertain whether Helicobacter pylori is associated with ischemic syndromes and whether this association is mediated by the induction of atherosclerosis. In this study, we tested the hypothesis that atherosclerotic stroke shows a selective association with virulent H pylori strains. Methods and Results—The seroprevalence of infection by H pylori and by strains bearing the cytotoxin-associated gene-A (CagA), a strong virulence factor, was assessed by ELISA in 138 patients with large-vessel stroke (group A), in 61 patients with cardioembolic stroke (group B), and in 151 healthy control subjects. The 3 groups had a similar socioeconomic status. Serum levels of C-reactive protein were also measured by ELISA. The prevalence of infection was 71% in group A, 63.9% in group B, and 70.2% in the control group (P =NS), whereas the prevalence of CagA-positive strains was higher in group A than in group B (42.8% versus 19.7%, respectively; odds ratio 3.04, 95% CI 1.43 to 6.49;P <0.001) and higher in group A than in the control group (42.8% versus 17.9%, respectively; odds ratio 4.3, 95% CI 2.12 to 8.64;P <0.001), after adjusting for main cardiovascular risk factors and social class. A trend toward a difference in C-reactive protein was observed between CagA-positive (2.00±3.43 [mean±SD] mg/dL) and CagA-negative (1.31±1.72 [mean±SD] mg/dL) patients (P =0.072, Mann-Whitney U test). Conclusions—The association between H pylori and acute cerebrovascular disease seems to be due to a higher prevalence of more virulent H pylori strains in patients with atherosclerotic stroke.

Nocturnal sleep and daytime somnolence in untreated patients with temporal lobe epilepsy: changes after treatment with controlled-release carbamazepine

Summary: Purpose: To define sleep disturbances in patients with temporal lobe epilepsy (TLE) and explore the association between carbamazepine (CBZ) therapy, sleep, and daytime somnolence.

Distinguishing forms of generalized epilepsy using magnetic brain stimulation

In this study, we have used paired transcranial stimulation of the motor cortex to test the hypothesis that cortical inhibition is decreased in juvenile myoclonic epilepsy (JME). The double shock technique was adopted here because it offers a means for highlighting abnormal inhibitory mechanisms. From previous experiments performed on healthy subjects, it is known that a magnetic conditioning stimulus, of subthreshold intensity, suppresses the MEP in response to a subsequent suprathreshold stimulus delivered after 1-4 msec. JME patients were selected as a potential contrast with other forms of idiopathic generalized epilepsy, because they complain of myoclonic jerks without loss of consciousness, indicating with certainty a dysfunction of the motor cortex. Two patients with sporadic grand mal and one non-epileptic patient were also investigated. Paired stimulation was produced by a Bi-stim (Magstim) stimulator, with a figure-of-8 coil placed over the hand area of the motor cortex, and a set of interstimulus intervals (ISIs) ranging from 1 to 6 msec was analyzed. In JME patients there were two indications of abnormality with respect to normal subjects and to the other epileptic patients: (1) the absence of MEP suppression to paired stimulation; (2) a progressive amplitude increase of MEPs to the test stimulus alone. In the two patients with the other form of epilepsy the pattern of inhibition was broadly preserved, even though there was some difference from the normal profile. The results suggest that the loss of MEP inhibition can be regarded as a marker of JME.

CagA-positive Helicobacter pylori strains may influence the natural history of atherosclerotic stroke.

Objective: To test the hypothesis that infection with virulent cytotoxin-associated gene-A (CagA)-bearing Helicobacter pylori strains influences the atherosclerotic process and the clinical course in atherosclerotic stroke patients. Methods: ELISA was used to assess the seroprevalence of infection by H. pylori and CagA-positive strains in 185 patients. Intima-media thickness (IMT) was determined by Doppler ultrasound. Baseline, 1-week, and 1-month NIH Stroke Scale (NIHSS) scores were used to evaluate the short-term clinical course. Results: H. pylori infection was found in 79% of patients; 58% of these tested positive for CagA. IMT was higher among CagA-positive patients than among CagA-negative ones (1.13 ± 0.26 mm vs 0.97 ± 0.15 mm; univariate analysis, p = 0.0001; multivariate analysis, odds ratio [OR], 2.36; 95% CI, 1.57 to 3.54; p = 0.0001) or H. pylori-negative ones (1.01 ± 0.17 mm; univariate analysis, p = 0.007; multivariate analysis, OR, 1.90; 95% CI, 1.22 to 2.97; p = 0.005). CagA-positive patients had poorer initial outcomes based on serial measurements of the NIHSS score (repeated measures analysis of variance, p < 0.0001). No significant difference in IMT and NIHSS score was found between H. pylori-positive and H. pylori-negative patients. Conclusions: Infection with cytotoxin-associated gene-A-positive Helicobacter pylori strains in atherosclerotic stroke patients is associated with greater intima-media thickness and poorer short-term outcome compared with cytotoxin-associated gene-A-negative patients.

Cytotoxin-associated Gene-A-positive Helicobacter pylori strains infection increases the risk of recurrent atherosclerotic stroke.

Background: CagA‐positive Helicobacter pylori infection has been found to be associated with a first‐ever atherosclerotic stroke. The aim of this study was to investigate whether these strains represent an independent risk factor for recurrent atherosclerotic stroke.

Sildenafil increases cerebrovascular reactivity: A transcranial Doppler study

The authors performed a double-blind, placebo-controlled study in 28 patients to evaluate the effects of sildenafil on cerebral hemodynamics. A significant improvement of cerebrovascular reactivity, without any modification of other variables, was recorded 1 hour after the administration of 50 mg sildenafil. Further investigations are needed to evaluate whether cerebrovascular reactivity improvement could contribute to triggering sildenafil-induced migraine.

Lack of potentiation of anticonvulsant effect by fluoxetine in drug-resistant epilepsy

To test the hypothesis that fluoxetine may be a useful adjunct to antiepileptic therapy, we treated with fluoxetine (20-40 mg/day) nine patients suffering from medically intractable epilepsy with daily seizures. Five patients remained unchanged and four worsened. Worsening was more evident at 40 mg/day. One patient improved when receiving the lower dose (20 mg/day) and worsened with the higher dose (40 mg/day). These data suggest: (1) that fluoxetine is not effective as add-on antiepileptic treatment; (2) that caution should be exerted when using fluoxetine as an antidepressive treatment in epileptic patients.