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PubMed1998

Mechanisms of alcohol-related strokes.

Epidemiological investigations have shown a linear positive correlation between the risk of haemorrhagic stroke and level of alcohol consumption. Ischaemic stroke shows a weaker relationship, which is J-shaped, suggesting that regular light-to-moderate alcohol consumption may carry a decreased risk. Case reports and case-control studies indicate that heavy recent drinking, but not heavy former drinking, increases the risk for both types of stroke. Larger amounts of alcohol are needed to trigger aneurysmal subarachnoid haemorrhage than spontaneous intracerebral haemorrhage. The increased risk caused by recent heavy drinking may be partly due to elevated systolic blood pressure, but alcohol may also provoke cerebral arterial vasospasm, as observed in animal experiments. Alcohol-induced fluctuation in haemostatic and fibrinolytic factors has not been proved to precipitate alcohol-related strokes, but may contribute to both an increase and a decrease of the risk. Subtypes of ischaemic stroke associate differently with alcohol consumption. A recent series of patients with ischaemic brain infarction showed that of the victims having a high and medium risk for cardiogenic embolism, 50% and 45% were intoxicated, respectively. This suggests that cardiogenic embolism is a significant mechanism leading to ischaemic stroke during heavy drinking of alcohol.

Adult↗
PubMed2005

HLA-DRB1 alleles in Hb SS patients with avascular necrosis of the femoral head.

Strong associations have been established between various HLA alleles and different complications of sickle cell disease (SCD). Recently, the HLA-DRB1*03 allele was shown to be associated with susceptibility to stroke while the HLA-DRB1*02 allele may be protective. While stroke and silent brain infarcts (SBI) are unusual in Kuwaiti children with SCD, avascular necrosis of the femoral head (AVNFH) is quite common. The modulatory association factors must still be elucidated. An investigation of HLA-DRB1 alleles was carried out in a group of 68 Kuwaiti SS patients, of age 7-44 years, of whom 20 (29.4%) had AVNFH, confirmed by magnetic resonance imaging. A group of 167 apparently healthy age- and sex-matched individuals served as controls. Comparison of the HLA alleles between the whole SS group and the controls showed a significant over-representation of DRB1*01 (P < 0.01) and DRB1*10 (P < 0.05) in the patient group. No significant differences in the allele frequencies in the SS patients with or without AVNFH were observed. It therefore appears that the HLA-DRB1 locus does not play a significant role in the pathogenesis of AVNFH Kuwaiti patients.

Adolescent↗
PubMed1994

Association of the apolipoprotein E epsilon 4 allele with clinical subtypes of autopsy-confirmed Alzheimer's disease.

Consistent with previous reports, we observed a significant association of the APOE epsilon 4 allele with Alzheimer's Disease (AD) in a series of 91 autopsy-confirmed cases. The epsilon 4 allele frequency was higher in cases with a family history of AD-like dementia (0.54 +/- 0.07), although the epsilon 4 allele frequency in the AD cases with a negative family history (0.38 +/- 0.05) remained significantly greater than that for the non-AD control group (0.13 +/- 0.03). A similar increase in epsilon 4 allele frequency (0.54 +/- 0.07) was observed in the AD cases with amyloid angiopathy, compared to those who did not have amyloid angiopathy (0.36 +/- 0.04). Contrary to previous reports, no effect of the dosage of the epsilon 4 allele was found on the age of onset of dementia among the AD cases and, contrary to reports suggesting an association of epsilon 4 and atherosclerosis, the epsilon 4 allele frequency was similar in cases with or without concurrent brain infarcts. Modest but consistent correlations were observed between the dosage of epsilon 4 alleles and the cortical density of senile plaques, but not neurofibrillary tangles. The last finding suggests that the pathogenic events mediated by the epsilon 4 allele may be more directly involved in the formation of senile plaques, the identifying lesions in AD, than neurofibrillary tangles. A robust association of both the presence of an epsilon 4 allele and a family history of AD-like dementia with concurrent amyloid angiopathy occurred within our sample of AD cases. This association arose from an interaction of the epsilon 4 allele with a separate familial factor for which a family history of dementia served as a surrogate. These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE epsilon 4 allele.

Aged↗
PubMed1989

Atherosclerosis: current concepts on pathogenesis and interventional therapies.

Atherosclerosis, the primary pathological condition accounting for most stroke syndromes, has been the intense focus of epidemiological, basic, and clinical investigations. Since these studies have direct bearing on the prevention of atherothrombotic brain infarction, this review emphasizes those advances in treatment resulting from their findings. The two most prominent theories on the pathogenesis of atherosclerosis relate to aberrations in lipoprotein metabolism and to enhanced proliferation of smooth muscle cells; likely, the theories are complementary. As a practical guideline for preventive therapy, the importance of using the total cholesterol level is stressed, although finer distinctions must rely on the low-density and high-density lipoprotein concentrations and their normalization. Since prevention of stroke may ultimately be its most effective therapy, consideration of cholesterol level, akin to strategies for preventing coronary heart disease, and efforts to avert platelet adhesion or aggregation and coagulation are warranted.

Arteriosclerosis↗
PubMed1993

Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS): clinical, radiological, pathological, and genetic observations.

We reviewed 10 patients (5 males, 5 females) with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The age of symptom onset ranged from 3 months to 12 years. All had lactic acidosis, multiple stroke-like events with secondary neurological deficits, radiological changes of progressive brain infarction, and muscle biopsy showing ragged-red fibers. In patients with earlier onset of symptoms (< 2 yr), involvement tended to be more diffuse, with failure to thrive and early onset of delayed development. Patients whose symptoms appeared later tended to have focal neurological deficits with migraine-like headache, and a rate of cognitive regression reflecting the rapidity of disease progression. Radiological changes included multiple areas of infarction with initial predilection for parietal occipital areas, progressing to generalized atrophy. Pathological findings in muscle biopsies included type 1 fiber predominance, ragged-red fibers, increased intermyofibrillar lipid deposition, and abnormal mitochondria. Four patients showed mitochondrial DNA tRNA mutation at position 3,243. No difference was noted in clinical, radiological, or pathological findings in patients with and without this mutation, suggesting that multiple sites of point mutation may give rise to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.

Base Sequence↗
PubMed1995

Interleukin-6 and interleukin-1 receptor antagonist in acute stroke.

Elevated plasma levels of interleukin-6 (IL-6), a key regulator of the acute phase response that includes increased fibrinogen synthesis, have recently been detected in patients with acute stroke. Nevertheless, the role of the acute phase response in stroke has been controversial, with some studies suggesting that preexisting infection accounts for most of the acute phase response. Increased IL-6 could signal the involvement of antiinflammatory activity, since IL-6 stimulates the production of endogenous antiinflammatory mediators such as interleukin-1 receptor antagonist (IL-1RA). To better understand the interaction of pro- and antiinflammatory acute phase processes in brain infarction, plasma levels of IL-1RA, IL-6, and acute phase proteins including fibrinogen and c-reactive protein (CRP) were measured within 4 +/- 2 days of onset in 50 patients with acute ischemic stroke and in 20 age-matched healthy controls. After excluding patients with evidence of infection, both IL-1RA and IL-6 were significantly elevated in stoke patients compared with controls (p < 0.0001). IL-1RA and IL-6 were both significantly correlated with levels of CRP, p < 0.05 and p < 0.001, respectively, but not with each other. Levels of IL-6 and IL-1RA, together with fibrinogen and CRP were higher in patients with infarcts of greater than 3 cm and lowest in patients with lacunar syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed2004

Carotid artery surgery vs. stent: a cardiovascular perspective.

Stroke is a major health catastrophe that is responsible for the third most common cause of death and the leading cause of disability. Carotid artery stenosis is an important cause of brain infarctions and the risk of stroke is directly related to the severity of carotid artery stenosis and to the presence of symptoms. Familiarity with different methods of measuring degrees of carotid artery stenosis is a key in understanding the role of revascularization of this disorder. Carotid endarterectomy (CEA), surgical removal of the carotid atherosclerotic plaque, is intended to prevent stroke in patients with carotid artery stenosis and currently the most commonly performed vascular procedure in the United States. Several randomized clinical trials had demonstrated the benefits of CEA in selected groups of patients with symptomatic and asymptomatic carotid artery stenosis. However, CEA can cause stroke, the very thing it intended to prevent, and is associated with significant perioperative complications such as those related to general anesthesia, cardiac or nerve injury. Moreover, several anatomical and medical conditions may limit candidates for CEA. Carotid artery stenting (CS) is an evolving and less invasive technique for carotid artery revascularization. Recent studies demonstrated that CS with embolic protection devices has become an alternative to CEA for high-surgical-risk patients and the procedure of choice for stenoses inaccessible by surgery. The role of CS in low risk patients awaits the completion of several ongoing studies.

Algorithms↗
PubMed2004

Transient focal ischemia in rat brain differentially regulates mRNA expression of protease-activated receptors 1 to 4.

Degeneration or survival of cerebral tissue after ischemic injury depends on the source, intensity, and duration of the insult. In the model of focal ischemia, reduced blood flow results in a cascade of pathophysiologic events, including inflammation, excitotoxicity, and platelet activation at the site of injury. One serine protease that is associated closely with and produced in response to central nervous system (CNS) injury is thrombin. Thrombin enters the injury cascade in brain either via a compromised blood-brain barrier or possibly from endogenous prothrombin. Thrombin mediates its action through the protease-activated receptor family (PAR-1, -3, and -4). PARs belong to the superfamily of G protein-coupled receptors with a 7-transmembrane domain structure and are activated by proteolytic cleavage of their N-terminus. We showed that thrombin can be neuroprotective or deleterious when present at different concentrations before and during oxygen-glucose deprivation, an in vitro model of ischemia. We examined the change in mRNA expression levels of PAR-1 to 4 as a result of transient focal ischemia in rat brain, induced by microinjection of endothelin near the middle cerebral artery. Using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis, after ischemic insult on the ipsilesional side, PAR-1 was found to be downregulated significantly, whereas PAR-2 mRNA levels decreased only moderately. PAR-3 was upregulated transiently and then downregulated, and PAR-4 mRNA levels showed the most striking (2.5-fold) increase 12 hr after ischemia, in the injured side. In the contralateral hemisphere, mRNA expression was also affected, where decreased mRNA levels were observed for PAR-1, -2, and -3, whereas PAR-4 levels were reduced only after 7 days. Taken together, these data suggest involvement of the thrombin receptors PAR-1, PAR-3, and PAR-4 in the pathophysiology of brain ischemia.

Animals↗
PubMed1998

Temporal and regional changes during focal ischemia in rat brain studied by proton spectroscopic imaging and quantitative diffusion NMR imaging.

The early development of focal ischemia after permanent occlusion of the right middle cerebral artery (MCA) was studied in six rats using interleaved measurements by diffusion-weighted NMR imaging (DWI) of water and two variants of proton spectroscopic imaging (SI), multiecho SI (TE: 136, 272, 408 ms) and short TE SI (TE: 20 ms). Measurements on a 4.7-T NMR imaging system were performed between the control phase and approximately 6 h postocclusion. In the center of the ischemic lesion of all rats, the apparent diffusion coefficient (ADC) decreased rapidly to 84.4 +/- 4.2% (mean +/- SD) of the control values approximately 2 min postocclusion. Approximately 6 h postocclusion, the ADC was reduced to 67.1 +/- 5.9%. In contrast, large differences between the animals were observed for the temporal increase of lactate (Lac) in the ipsilateral hemisphere. The maximum Lac signal was reached in four rats after 0.5-1.5 h, and in two rats was not reached even after 6 h postocclusion. Six h postocclusion, SI spectra measured at a TE of 136 ms revealed a decrease in the CH3 signal of N-acetylaspartate (NAA) to 67 +/- 13% of the control values. Differences were observed between the spatial regions of decreased NAA and increased Lac. In the lesions, a T2 relaxation time of Lac of 292 +/- 40 ms, considering a J-coupling constant of 6.9 Hz, was measured. Furthermore, a prolongation of the T2 of the CH3 signal of creatine/phosphocreatine (Cr/PCr) was observed in the lesion, from 163 +/- 22 ms during control to 211 +/- 41 ms approximately 6 h postocclusion. The experiments proved that DWI and proton SI are valuable tools to provide complementary information on processes associated with brain infarcts.

Animals↗
PubMed2007

Moyamoya syndrome following childhood acute lymphoblastic leukemia.

BACKGROUND: Long-term survivors of childhood acute lymphoblastic leukemia (ALL) sometimes suffer from adverse long-term sequelae. We analyzed the incidence, clinical course and prognosis of moyamoya syndrome (MoS) following childhood ALL. PROCEDURE: A total of 1,846 ALL patients were treated with four consecutive TCCSG ALL protocols (L84-11, L89-12, L92-13, and L95-14) between 1984 and 1999. We surveyed the MoS cases among these patients in the follow-up studies. RESULTS: Six patients with MoS were identified: four boys and two girls whose ages ranged from 2 years and 1 month (abbreviated as "2y1m") to 14y 1 m at diagnosis of ALL. None of the patients had central nervous system (CNS) leukemia. All six patients received prophylactic cranial irradiation with a dosage of 18 or 24 Gy. Although one patient died of brain infarction due to MoS, no leukemic relapse was observed in the group. The cumulative incidence of MoS in our series was 0.46 +/- 0.02% at 8 years. Among several clinical characteristics, use of cranial irradiation was the only factor that appeared to be significantly related to the development of MoS. CONCLUSIONS: MoS occurs with increased frequency in children treated for ALL, and might be associated with cranial irradiation. Prophylactic cranial irradiation should be used cautiously in ALL patients who can be cured by other CNS-directed therapies.

Adolescent↗
PubMed1994

Chloroquine treatment of interstitial lung disease in children.

Seven children aged 3 months to 11 years with histologically confirmed interstitial lung disease (ILD) [6 with desquamative interstitial pneumonitis (DIP) and 1 with chronic interstitial pneumonitis] were treated with chloroquine, 10 mg/kg/day. One patient, diagnosed late in the course of the disease, died after three weeks of treatment, despite the addition of systemic corticosteroids. Another patient responded to combined therapy with chloroquine and prednisone and had a normal lung biopsy after 6 months of treatment. He underwent surgical repair of mitral valve stenosis and died after extensive brain infarction. The other 5 patients responded well to chloroquine therapy with major improvement in oxygenation within a few weeks and in lung function over the next few months. They remained well clinically and physiologically, including a normal response to incremental exercise, during a mean follow-up period of 9.8 years (range 3.5 to 15.7 years). None of the patients has developed retinopathy or any other ocular complication. Bronchoalveolar lavage was a useful tool for evaluation of the activity of the disease (predominance of neutrophils) in 3 out of 4 patients. We suggest that chloroquine should be considered as an effective treatment in ILD in children. Incremental exercise test may be helpful for routine follow-up and evaluation of the efficacy of a specific treatment.

Child↗
PubMed2005

The effect of subarachnoid sodium nitroprusside on the prevention of vasospasm in subarachnoid haemorrhage.

OBJECTIVE: The aim of this study was to evaluate the effect of preventive and therapeutic use of subarachnoid sodium nitroprusside (SNP) administration in patients with non-traumatic subarachnoid haemorrhage (SAH). METHODS: All consecutive adult patients admitted in the period 2000-2003 with SAH, Hunt-Hess grade I-IV, indicated for neurosurgical intervention, were enrolled in the study. In the postoperative period they were treated with mechanical ventilation and triple H protocol with nimodipine. Subarachnoid preventive SNP was administred in initial dose of 1 mg by catheter inserted into basal cisterns during the neurosurgical procedure. The timing of following dosage was directed by the changes of respiratory parameters of brain tissue in the region of interest by multiparameter sensor (Codman Neurotrend) and findings of blood flow velocity on the level of circle of Willis were measured by transcranial doppler ultrasonography (TCD). RESULTS: 17 patients were enrolled to study. All patients survived. No brain infarction developed. The increase blood flow velocity was found in three patients. CONCLUSION: Preventive subarachnoid use of SNP in combination with multimodal monitoring might be a possible preventive strategy. Its efficacy has to be proved on a greater group of patients in the future. The therapeutical use of SNP requires an increase in application rate.

Adult↗
PubMed1988

Non-stationary spatial filtering and accelerated curve fitting for parametric imaging with dynamic PET.

A non-stationary spatial low pass filter was developed and implemented in combination with an accelerated non-linear curve fitting routine to create low noise-high contrast images of physiological parameters with dynamic positron emission tomography. The method was applied to 18F-2-fluoro-2-deoxyglucose (FDG) studies, and images of local blood volume, kinetic rate constants, precursor pool volume and glucose metabolism were generated. Noise reduction and contrast preservation was demonstrated in a simulated pie phantom and a study of a patient with a recent brain infarct. Considerably improvement in quantitative accuracy of pixel parameter values was observed in the phantom study in comparison with unprocessed or conventionally smoothed images.

Cerebral Infarction↗
PubMed1987

Carotid endarterectomy: factors influencing perioperative complications.

Early carotid surgery has been suggested to be an important cause of perioperative deterioration due to secondary haemorrhage into a recent brain infarction. It has also been suggested that the existence of preoperative neurological deficits may worsen the prognosis of surgical treatment in carotid disease. Neither of these observations could be confirmed; severe perioperative complications (5%) in this study of carotid endarterectomy were strongly related to the degree of carotid stenosis. This aspect of carotid surgery has not been previously studied. Even though technical difficulties may play an exaggerated role in a training hospital system, it is nevertheless necessary to assess the impact of surgical procedures of different extent when the "acceptable risk" for carotid surgery is calculated.

Adult↗
PubMed1988

Pure homonymous hemiachromatopsia. Findings with neuro-ophthalmologic examination and imaging procedures.

The study describes neuro-ophthalmologic findings in two patients with brain infarction who developed homonymous hemiachromatopsia with resolution to pure homonymous achromatopsia in an upper quadrant. All other visual parameters were normal; only color perimetry was capable of demonstrating the visual disorder. The results are presented with special emphasis on the macular region. Computed tomography studies and magnetic resonance imaging revealed lesions in the caudal and medial occipitotemporal gyri as well as in adjacent cortical regions. The lesions were secondary to disordered circulation in a proximal occipitotemporal branch of the posterior cerebral artery. The anatomical findings and functional relations of color vision in man are discussed in the light of animal findings.

Adult↗
PubMed1986

Psychoacoustic and electrophysiologic correlates of central hearing disorders in man.

Evaluation of central hearing disorders in neuropsychologic patients is handicapped by their insufficient ability to describe auditory deficits and by the lack of easily applicable audiological tests. A novel psychoacoustic discrimination test (PDT) was developed to determine ear asymmetries in the discrimination of changes in intensity, frequency, or temporal structure of regularly presented dichotic stimuli. In 19 of 21 patients with lesions of the auditory cortex or the acoustic radiation according to CT scan evaluation a higher error score was observed for target stimuli presented at the ear contralateral to the side of brain infarction (6 right, 15 left). In the remaining 2 and in 3 other patients with lesions sparing auditory structures no significant ear asymmetries were seen. This may indicate that auditory perception is reduced in patients with only one intact auditory cortex or one intact acoustic radiation, possibly because of a limitation in information processing capacity. Auditory evoked potential results are presented for a normal subject and two patients to illustrate electrophysiologic correlates of central hearing disorders. Using a transformation of scalp into dipole source activity (Scherg and von Cramon 1986), a unilateral loss of middle latency activity was found in case A, who had a lesion of the left acoustic radiation. The extended lesion of the right auditory cortex in case B resulted in a loss of both middle and late latency dipole source potentials of the right temporal lobe. In both cases a corresponding increase in the PDT error score on the contralateral ear was found.

Adult↗
PubMed1980

The lipopigments in human brain tissue necroses. I. Ceroid.

The ceroid pigment of macrophages were subdivided into four different types according to their own color and their ability to stain with luxol fast blue. With reference to this mode a series of more than 200 brain infarcts which had happened 1 day to 56 years before death, was examined systematically. According to the results the ceroid variants do not only succeed one another chronologically but they also represent histochemically successive phases of development which correspond to the progressive auto-oxidation of unsaturated lipids. The occurrence of the different stages is chronologically defined. During this development cortical and subcortical macrophages show different speeds in the ageing process of their pigments. There is no evidence for an essential participation of proteins in the maturation of the ceroid. Not during any phase of development is the reaction pattern identical with that of neuronal and glial lipofuscin.

Cerebral Infarction↗
PubMed1992

Abnormalities of cerebral blood flow in the acute phase of bacterial meningitis in adults.

The frequency, course and clinical significance of changes in regional cerebral blood flow (rCBF) during bacterial meningitis were investigated in 14 adult patients. The results of 99mTc-hexamethylpropylene amine oxime (HMPAO) single photon emission computed tomography (SPECT) were compared with the clinical signs and findings using cerebral angiography and conventional CT. HMPAO SPECT was performed 2-15 days (median 4.5 days) after the onset of neurological disease. Decreased HMPAO accumulation was detected in 13 patients. SPECT studies revealed focal hypoperfusion corresponding to the clinical symptoms in 6 patients suffering from hemiparesis or hemiataxia. Conventional cranial CT disclosed brain infarction in only 1 patient. Focal hypoperfusion was also found in 7 of 8 patients without clinical evidence of focal neurological deficits. In 6 patients, HMPAO SPECT findings were abnormal although cerebral angiography was normal. At follow-up examinations 3-45 weeks after the acute disease, abnormalities revealed by HMPAO SPECT had improved or had even disappeared in all patients studied. Our results indicate that reduced rCBF is a frequent finding in bacterial meningitis in the adult. In most patients it probably represents a functional and reversible disorder without structural lesion detectable on CT.

Acute Disease↗