Antibody response and avidity of respiratory syncytial virus-specific total IgG, IgG1, and IgG3 in young children.

Respiratory syncytial virus (RSV) is a major cause of acute respiratory disease in infants and young children. Considering that several aspects of the humoral immune response to RSV infection remain unclear, this study aimed to investigate the occurrence, levels, and avidity of total IgG, IgG1, and IgG3 antibodies against RSV in serum samples from children ≤5 years old. In addition, a possible association between antibody avidity and severity of illness was examined. The occurrence and levels of RSV-specific IgG depended on age, with infants <3 months old displaying high levels of antibodies, which were probably acquired from the mother. Children ≥24 months old also showed frequent occurrence and high levels of IgG, which was produced actively during infection. In addition, the avidity assay showed that the avidity of RSV-specific total IgG and IgG1 was lower in infants <3 months old who had acute respiratory disease than in age-matched controls. The avidity of RSV-specific IgG detected in children ≥24 months old with lower respiratory infection was lower than that in children with upper respiratory infection. These results indicate that the presence of high avidity RSV-specific IgG antibodies may lead to better protection against RSV infection in children <3 months old, who may have a lower probability of developing disease of increased severity. In addition, children ≥24 months old with RSV-specific IgG antibodies of low avidity tended to develop more severe RSV illness. These findings may be helpful in establishing vaccination schedules when a vaccine becomes available.

Prevalence and clinical aspects of respiratory syncytial virus A and B groups in children seen at Hospital de Clínicas of Uberlândia, MG, Brazil.

Respiratory syncytial virus (RSV) is well recognized as the most important pathogen causing acute respiratory disease in infants and young children, mainly in the form of bronchiolitis and pneumonia. Two major antigenic groups, A and B, have been identified; however, there is disagreement about the severity of the diseases caused by these two types. This study investigated a possible association between RSV groups and severity of disease. Reverse transcription-polymerase chain reaction was used to characterize 128 RSV nasopharyngeal specimens from children less than five years old experiencing acute respiratory disease. A total of 82 of 128 samples (64.1%) could be typed, and, of these, 78% were group A, and 22% were group B. Severity was measured by clinical evaluation associated with demographic factors: for RSV A-infected patients, 53.1% were hospitalized, whereas for RSV B patients, 27.8% were hospitalized (p = 0.07). Around 35.0% of the patients presented risk factors for severity (e.g., prematurity). For those without risk factors, the hospitalization occurred in 47.6% of patients infected with RSV A and in 18.2% infected with RSV B. There was a trend for RSV B infections to be milder than those of RSV A. Even though RSV A-infected patients, including cases without underlying condition and prematurity, were more likely to require hospitalization than those infected by RSV B, the disease severity could not to be attributed to the RSV groups.

Prevalence and clinical aspects of respiratory syncytial virus A and B groups in children seen at Hospital de Clínicas of Uberlândia, MG, Brazil

Respiratory syncytial virus (RSV) is well recognized as the most important pathogen causing acute respiratory disease in infants and young children, mainly in the form of bronchiolitis and pneumonia. Two major antigenic groups, A and B, have been identified; however, there is disagreement about the severity of the diseases caused by these two types. This study investigated a possible association between RSV groups and severity of disease. Reverse transcription-polymerase chain reaction was used to characterize 128 RSV nasopharyngeal specimens from children less than five years old experiencing acute respiratory disease. A total of 82 of 128 samples (64.1 percent) could be typed, and, of these, 78 percent were group A, and 22 percent were group B. Severity was measured by clinical evaluation associated with demographic factors: for RSV A-infected patients, 53.1 percent were hospitalized, whereas for RSV B patients, 27.8 percent were hospitalized (p = 0.07). Around 35.0 percent of the patients presented risk factors for severity (e.g., prematurity). For those without risk factors, the hospitalization occurred in 47.6 percent of patients infected with RSV A and in 18.2 percent infected with RSV B. There was a trend for RSV B infections to be milder than those of RSV A. Even though RSV A-infected patients, including cases without underlying condition and prematurity, were more likely to require hospitalization than those infected by RSV B, the disease severity could not to be attributed to the RSV groups.

Prevention of deep venous thrombosis and pulmonary embolism following stroke: a systematic review of published articles.

We performed a systematic review of the literature on venous thromboembolism (VTE) prophylaxis following cerebral infarct (CI) and haemorrhagic stroke. MEDLINE, Cochrane, LILACS and SciELO databases were scanned, and the Abstracts from Brazilian, American and European Neurology and Stroke Congresses were scrutinized for clinical trials. Moreover, the reference lists of articles and reviews were searched. A pooled analysis of two large studies with aspirin was made. Both unfractionated heparin and low molecular weight heparins/heparinoids (LMWH) are partially effective for VTE prophylaxis after CI, and should be routinely used in patients with motor deficit and reduced mobility and no contraindications. Reduction of deep venous thrombosis is better established than the effect over pulmonary embolism or mortality. Some evidence points to a greater efficacy of LMWH. The available evidence does not support the use of mechanical methods or dextran. Aspirin may have a mild protective effect. Low-dose Warfarin might be useful in the rehabilitation setting. Strict recommendations cannot be made in patients with haemorrhagic stroke but intermittent pneumatic compression merits further study. There are important limitations of current VTE preventive strategies following stroke. Additional studies on the combination of methods after CI and of low doses of anticoagulants following cerebral haemorrhage are urgently needed.

Sensitivity of transcranial Doppler for confirming brain death: a prospective study of 270 cases.

OBJECTIVE: The reported sensitivity of transcranial Doppler ultrasonography (TCD) for confirming brain death (BD) ranges from 91% to 100%. We assessed the frequency and causes of false-negative results in TCD examination in a series of patients with BD and in the literature. METHODS: We carried out a prospective TCD examination of consecutive patients with the clinical diagnosis of BD. RESULTS: In 204 (75.5%) of 270 patients, TCD showed a pattern compatible with BD. The causes of the false-negative results were persistent flow in the intracranial arteries in 47 (17.4%) patients and a lack of signal in 19 (7%). Absence of sympathomimetic drug use [odds ratio (OR) 5.4, 95% confidence interval (CI) 1.8-16.0, P = 0.003) and female gender (OR 3.7, 95% CI 1.1-12.5, P = 0.03) were associated with false-negative results. A review of 16 studies showed a sensitivity of 88% and a specificity of 98% of TCD for confirming BD. CONCLUSIONS: The sensitivity of TCD for confirming BD may be lower than previously reported, but is probably similar to that of other non-invasive methods. The specificity of TCD is close to 100%. Uniform criteria are needed for the routine use of TCD as a confirmatory test for BD.

Regulation and function of neurogenesis in the adult vertebrate brain

Most adult tissues retain a reservoir of self-renewing, multipotent stem cells that can generate differentiated tissue components. Until recently, the brain was thought to be an exception to this rule and for many years the pervasive dogma of neurobiology relegated neurogenesis to the embryonic and earlier postnatal stages of development. The discovery of constant neuronal replacement in the adult brain has changed the way we think about neurological diseases and about the exploration of new strategies for brain repair. In this review we will explore the potential of adult neural stem cells and we will present some of our own work on this subject. We will also discuss the possibility that adult neurogenesis and neuronal replacement may also play a role in therapies aimed at restoring impaired brain function. A better understanding of the various aspects of spontaneous neuronal replacement may also be used to increase the success of procedures with cell therapies.

Regulation and function of neurogenesis in the adult vertebrate brain.

Most adult tissues retain a reservoir of self-renewing, multipotent stem cells that can generate differentiated tissue components. Until recently, the brain was thought to be an exception to this rule and for many years the pervasive dogma of neurobiology relegated neurogenesis to the embryonic and earlier postnatal stages of development. The discovery of constant neuronal replacement in the adult brain has changed the way we think about neurological diseases and about the exploration of new strategies for brain repair. In this review we will explore the potential of adult neural stem cells and we will present some of our own work on this subject. We will also discuss the possibility that adult neurogenesis and neuronal replacement may also play a role in therapies aimed at restoring impaired brain function. A better understanding of the various aspects of spontaneous neuronal replacement may also be used to increase the success of procedures with cell therapies.

Different perceived foreign accents in one patient after prerolandic hematoma.

Foreign accent syndrome (FAS), a rare disorder characterized by the emergence of a new accent perceived as foreign by listeners, is usually reported with left brain damage. We here report the case of a 28-year-old native Brazilian who appeared, to the examiner, to show a North American accent during recovery from Broca's aphasia. The lesion was due to a frontal hematoma. Without referring specifically to speech, we asked 10 independent observers to comment on a videotape of the patient's interview. Seven reported that the patient had a foreign accent, while 3 simply noted a 'strange' accent. The observers did not agree on the origin of the accent, 5 identifying it as Spanish, 1 as German, and 1 as south Brazilian. These findings suggest that FAS is not due to the acquisition of a specific foreign accent, but to impairment of the suprasegmental linguistic abilities (tone, accent, pauses, rhythm, and vocal stress) that make it possible to distinguish native language.

Complex spinal reflexes during transcranial Doppler ultrasound examination for the confirmation of brain death.

OBJECTIVE: Complex sets of movements of the extremities can be seen in patients with brain death (BD), and are typically observed during apnea testing or removal of ventilatory support (also called the Lazarus sign). We here describe brain-dead patients who had not shown previous movements, even during apnea testing, but presented complex spinal reflexes during transcranial Doppler (TCD) examination elicited by neck flexion. METHODS: We performed a prospective TCD study of patients with the clinical diagnosis of BD. RESULTS: Four (2.5%) of 161 brain-dead patients presented complex spinal reflexes exclusively during TCD examination. TCD showed vertebro-basilar circulatory arrest in all four. Their systolic blood pressure was significantly lower than that of brain-dead patients not presenting movements during TCD examination. CONCLUSIONS: Hypotension and mechanical stimulation play a role in the pathophysiology of complex spinal reflexes present in BD, which are not exclusively seen in terminal hypoxia. Intensive care personnel and neurologists who perform TCD to confirm BD should be aware of these movements.

Persistence of isolated flow in the internal carotid artery in brain death.

The criteria for the confirmation of brain death (BD) using transcranial Doppler ultrasonography (TCD) state that flow should not be observed in the internal carotid artery (ICA). In 94 brain-dead patients examined by TCD, 19 (20%) had flow in the ICA despite cerebral circulatory arrest. There was no difference in the clinical characteristics of patients with or without isolated flow in the ICA. Shunting of blood from the ICA into the external carotid system or the arrest of blood flow at a higher level than the carotid siphon may explain our findings. Our results show that the current TCD criteria can result in a high rate of false negatives. We suggest that the TCD criteria for the diagnosis of brain death should be reviewed.

A CADASIL case with normal skin biopsy and without mutations in exons 3 and 4 of the Notch3 gene.

The diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is usually confirmed by genetic testing or skin biopsy. We here report the case of a 69-year-old woman with recurrent transient ischemic attacks (TIAs) and strokes, seizures, and dementia without any mutations in exons 3 and 4 of the Notch3 gene and with a normal skin biopsy, but who showed characteristic CADASIL abnormalities on brain pathological examination. Our findings suggest that negative results in these two tests do not exclude the disease and a leptomeningeal biopsy or a second skin biopsy should be considered in such cases.

Primary stroke prevention.

Stroke is one of the leading causes of death and disability worldwide. Although important advances in therapeutic approaches have been made, treatment is still far from satisfactory. Thus, major efforts should be made on stroke prevention. We present evidence-based recommendations for primary stroke prevention. Changes to modifiable risk factors, the role of drugs and surgery are discussed. New markers may help identification of subjects at high risk.

Stroke with internal carotid artery stenosis.

BACKGROUND: Stroke patterns in patients with different degrees of carotid stenosis have not been systematically studied. OBJECTIVE: To determine first-ever stroke subtypes in nonselected patients with extracranial internal carotid artery (ICA) stenosis, based on a primary care hospital stroke registry. METHODS: One hundred seventy-three patients who experienced their first-ever stroke and who had 50% or greater (North American Symptomatic Carotid Endarterectomy Trial method) ipsilateral extracranial ICA stenosis, corresponding to 6.5% of 2649 patients with anterior circulation stroke included in the Lausanne Stroke Registry, were studied. All these patients underwent Doppler ultrasonography, carotid angiography (conventional or magnetic resonance angiography), neuroimaging (computed tomography or magnetic resonance imaging), and other investigations from the standard protocol of the Lausanne Stroke Registry. RESULTS: We found the following types of infarct in the middle cerebral artery territory: anterior pial in 54 (31%) of the patients; subcortical, 34 (20%); posterior pial, 32 (19%); large hemispheral, 20 (12%); and border zone, 17 (10%). There were multiple pial in 14 (8%) and multiple deep infarcts in 2 (1%) of the patients. Moderate (50%-69%) ICA stenosis was significantly associated with large hemispheral infarcts and a normal contralateral ICA (P =.04 and P =.02, respectively). Seventy percent to 89% of ICA stenosis was associated with prior transient ischemic attacks (P =.02). After adjusting for cardioembolism, border zone infarcts showed a strong trend to appear mostly in patients with 90% to 99% ICA stenosis (P =.06). CONCLUSIONS: The association of a large hemispheral infarct with moderate ICA stenosis suggests a large embolism and/or an inadequate collateral supply. While an embolism may also contribute, the association of border zone infarcts with 90% to 99% ICA stenosis emphasizes the significance of hemodynamic disturbance in the pathogenesis of these types of infarct.

Massive haemorrhagic transformation in cardioembolic stroke: the role of arterial wall trauma and dissection.

The pathogenesis of massive haemorrhagic transformation is not well established. Fatal haemorrhagic transformation associated with in situ dissection after acute middle cerebral artery (MCA) occlusion in a patient with atrial fibrillation is reported. An 80 year old woman with atrial fibrillation developed mild hemiparesis and aphasia. Brain CT and MRI at 4 and 5 hours, respectively, of symptom onset showed proximal MCA trunk occlusion with developing striatocapsular infarct and hypoperfusion in the superficial MCA territory. A few hours later, she developed massive bleeding into the ischaemic area and died. Pathological examination showed MCA trunk dissection, surrounded by a subarachnoid clot which communicated with the cerebral haematoma. It is suggested that direct arterial wall trauma as a result of cardioembolic MCA occlusion caused bleeding into the infarct. Secondary in situ dissection may be an overlooked mechanism of haemorrhagic transformation.

Do transient ischemic attacks have a neuroprotective effect?

OBJECTIVE: To determine whether TIAs have a neuroprotective effect. BACKGROUND: Ischemic tolerance or preconditioning, which protects the brain against stroke, has been demonstrated in animal models of cerebral ischemia. Because TIA may represent a clinical model of ischemic tolerance, patients with TIA before cerebral infarction (CI) may therefore have a better outcome than patients without TIA before CI. METHODS: A total of 2,490 patients admitted consecutively to a primary care center for first-ever CI in the anterior circulation were divided into two groups on the basis of the presence or absence of prior ipsilateral TIAs. Duration of TIA was classified into three groups (<10 minutes, 10 to 20 minutes, and >20 minutes). The severity of the neurologic picture on admission and functional disability after stroke were compared between patients with and without TIAs. RESULTS: A total of 293 (12%) of the 2,490 patients had prior ipsilateral TIAs before CI. Risk factors did not differ between patients with or without TIAs, whereas the topography and etiology of ischemic stroke did differ (p < 0.001). Patients without prior TIAs had a more severe clinical picture on admission, with a greater reduction of consciousness (p = 0.009). Patients with previous TIAs had a more favorable outcome than those without TIAs (67% versus 58%, p = 0.004). After adjustment for confounding variables, TIAs lasting 10 to 20 minutes were still associated with a favorable outcome (odds ratio, 1.98; 95% confidence interval, 1.27 to 3.08; p = 0.002). The interval between TIA and CI influenced the outcome (p = 0.007). CONCLUSIONS: This study suggests that ischemic tolerance may play a role in patients with ipsilateral TIAs before CI, allowing better recovery from a subsequent ischemic stroke.

Better outcome after stroke with higher serum cholesterol levels.

OBJECTIVE: To examine whether serum cholesterol levels have any prognostic value in the first month following acute ischemic stroke. BACKGROUND: Although the association between serum cholesterol levels and cerebrovascular disorders has been extensively studied, the relationship between cholesterol levels and outcome following ischemic stroke has not been investigated. METHODS: Using data from 3,273 consecutive patients with first-ever ischemic stroke, the authors compared poor functional outcome (severe disability or death) at 1 month in patients with high cholesterol (total serum cholesterol greater than 6.5 mmol/L or 250 mg/dL) and normal cholesterol (level equal to or less than 6.5 mmol/L or 250 mg/dL). Data were analyzed by univariate and multivariate analysis. RESULTS: In comparison with patients with normal cholesterol levels, patients with high cholesterol levels had a 2.2-fold lower risk of death (p = 0.002) and a 2.1-fold lower risk of poor functional outcome at 1 month (p < 0.001). After adjustment for known confounding variables, multivariate analysis showed that higher cholesterol levels remained an independent predictor of better functional outcome (OR 0.48, CI 0. 34 to 0.69, p < 0.001). CONCLUSIONS: The authors' findings suggest that higher levels of cholesterol are associated with a better outcome in the early phase after ischemic stroke.

Motor strokes sparing the leg: different lesions and causes.

BACKGROUND: A considerable number of patients develop stroke without involvement of the lower limb. However, there are few reports about the motor syndrome when the leg is spared. OBJECTIVE: To study clinical findings, causative factors, and lesion topography in stroke patients with a motor deficit sparing the leg. PATIENTS AND METHODS: We studied 895 patients with paresis sparing the leg from the 3,901 patients enrolled in the Lausanne Stroke Registry. They were compared with 1,644 stroke patients with paresis involving the leg, by means of univariate and multivariate analysis. RESULTS: Eight hundred forty-four infarcts (94.3%) and 51 hemorrhages (5.7%) led to weakness sparing the leg. Different sites of lesion were found, but the majority were caused by superficial infarcts. Almost half of the lesions were confined to superficial branches of the middle cerebral artery territory, with 276 (30.8%) in the anterior (superior) and 138 (15.4%) in the posterior (inferior) middle cerebral artery. More than half of the infarcts had a presumed embolic source from large-artery disease or from the heart. In comparison with patients with paresis involving the leg, patients without leg involvement had a lower prevalence of small-artery disease (P<.001), but a higher prevalence of migraine (P<.001), transient ischemic attack (P = .001), atherosclerosis without stenosis (P = .005), large-artery disease (P<.001), and left hemispheric strokes (P<.001). They also had a lower frequency of hemorrhagic stroke. CONCLUSIONS: Patients without leg involvement had different stroke lesions and causes and were characterized by more superficial infarcts mainly caused by emboli from large-artery disease and atherosclerosis without stenosis.

Seizures in Chédiak-Higashi syndrome. Case report.

Chédiak-Higashi syndrome is a rare hematological disease characterized by increased fusion of cytoplasmatic granules. Neurological symptoms occur in approximately half of the patients. We describe the clinical, eletrophysiological, hematological and radiological findings in a girl who had Chédiak-Higashi syndrome and seizures.