Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamate is the major excitatory neurotransmitter of the central nervous system. Besides its importance in many physiological processes, increased glutamate release and subsequent excessive stimulation of the various glutamate receptors are thought to play critical roles in the pathophysiological mechanisms underlying many neurologic diseases. Experimental data suggest that blockade of glutamate receptors or inhibition of glutamate release has positive effects in many disease models. Glutamate antagonists are already in clinical use for the treatment of Parkinson's disease, epilepsy, spasticity, and neuropathic pain. Overall, glutamate antagonists have not been found clinically effective for neuroprotective treatment of cerebral ischemia or chronic neurodegenerative diseases, with one exception. Side effects of glutamate antagonists can be mainly attributed to central mechanisms and include psychosis, agitation, and disorientation. It is to be hoped that further development of new glutamate antagonists that block disease-relevant subtypes of glutamate receptors will lead to more effective drugs with fewer side effects.
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PMID:[Glutamate antagonists in neurology]. 1143 98

23% of all septic patients develop septic encephalopathy which is associated with an increased mortality rate. Symptoms such as agitation, confusion and disorientation ranging from stupor to coma often develop in early sepsis. Severe hypotension is significantly associated with the development of septic encephalopathy. Several other factors which may play a role are also discussed: effects of inflammatory mediators on the brain, inadequate cerebral perfusion pressure, blood-brain barrier derangements, disturbances of the cerebral microcirculation, cerebral ischemia e.g. due to hypocapnia,metabolic changes, altered amino acid levels, transmitter imbalances, liver insufficiency, multiple organ failure and infections of the CNS, respectively. Compared to patients with an isolated infection,patients in septic shock have increased levels of aromatic amino acids such as phenylalanine and tryptophan in the plasma and brain as well as decreased levels of branched chain amino acids. Patients who died had higher levels of aromatic amino acids than the survivors. The correlation between aromatic amino acids and the APACHE II score was significant. The tryptophan metabolite quinolinic acid which can be synthesized in activated macrophages could act as an excitatory transmitter on the N-methyl-D-aspartate (NMDA) -receptor. Observations from experimental models indicate that activated NMDA receptors activate the neuronal isoform of the NO-synthase and other calcium dependent enzymes. This releases free radicals which may damage the DNA and activate the nuclear enzyme Poly-ADP-ribose-synthetase (PARS), resulting in energy depletion and cell death. Sepsis is the main cause of metabolic encephalopathies in critically ill patients. The differential diagnoses include hepatic, renal,hypoxic-ischemic or cardiovascular encephalopathies as well as encephalopathies,metabolic disorders and organ dysfunctions of other origin. Therapeutic interventions are numerous,however, so far only investigated in few controlled studies. The primary therapeutic goal is to maintain an adequate perfusion pressure and to prevent hypoxia and hypocapnia. Although the infusion of branched chain amino acids is controversial, experimental investigations demonstrated improvements improvements in an animal model with septic encephalopathy. Further investigations with respect to glutamate receptor antagonists, new radical scavengers, NO- and PARS-inhibitors may show whether these substances are suitable for the prophylaxis or early therapy of septic encephalopathy.
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PMID:[Septic encephalopathy. Diagnosis und therapy]. 1275 14

A 38-year old male patient with no history of psychiatric illness developed a progressive psychotic disorder after bilateral (predominantly left) mesencephalo-thalamic cerebral ischaemia. The reason of the emergency hospitalization was the sudden onset of a confusional state, culminating in a fluctuating comatose status. The neurological examination found mild right hemiparesia, praxic disorders and reactive left mydriasis with paresia of the downward vertical stare, leading to the hospitalisation in the neurology department for suspicion of a cerebral vascular ischaemic accident. The psychiatric symptoms started with acoustic-verbal hallucinations, poorly structured paranoid delusions, progressively developed over two weeks, followed by behavioural disorders with psychomotor agitation and heteroaggressivity. The patient was transferred to the psychiatric department, because of the heteroaggressive risk and lack of morbid consciousness, in spite of recovering from the confusional status. An intensive psychiatric management was proposed, combining a psychotherapeutic approach with 4 mg of risperidone and adjustable doses of benzodiazepine according to the psychomotor agitation. During the next days, there was a net recovery of the behavioural disorders, in spite of the persistence of the ideas of persecution. All the neurological symptoms also decreased. An anomaly of the polygon of Willis was found on a cerebral arteriography (the posterior cerebral arteries had a foetal origin, dependent on carotidal axes and not on the vertebro-basilar system). The main emboligen risk factor was the presence of a permeable foramen ovale, discovered during a transoesophageal echography. The patient underwent a surgical correction of the permeable foramen ovale. The psychiatric hospitalization for three months was continued by ambulatory follow-up. The initial positive symptoms (delusions, acoustic-verbal hallucinations) progressively diminished while negative symptoms became predominant after few months. One year after the first hospitalization the patient presented a second psychotic decompensation, with delusions of persecution, jealousy and behavioural disorders with heteroaggressivity, that required an emergency psychiatric hospitalization. The wife of the patient decided to divorce, because she was "frightened by the threats of death" from her husband. A neurological assessment during the second hospitalization in psychiatry did not find new ischaemic lesions after the cardiac surgery for the permeable foramen ovale, nor relevant changes in cerebral perfusion. The final diagnosis after the psychiatric follow-up of 14 months was: psychotic disorder with delusional ideas, due to cerebral ischaemia (DSM IV). There are relatively few data in the literature regarding persistent psychotic disorders in the context of ischaemic mesencephalo-thalamic lesions. However, several authors support the hypothesis of a possible disconnection of the thalamic nuclei, the frontal lobes and limbic system as a risk factor or a triggering factor for psychotic disorders in cerebral ischaemia. Observations concerning the occurrence of psychotic disorders following cerebral--especially localised--ischaemia may help to better understand the neuro-physiological mechanisms triggering or accompanying the psychiatric symptomatology. The role of functional cerebral imagery in the detection of possible structural lesions related to clinical observations must be emphasised. The slow progression (over a year) to psychotic disorder with predominantly negative symptoms emphasized the importance for long-term prospective studies. Isolated clinical observations arouse the interest for a specific scale for psychotic disorders occurring after cerebral ischaemia, similar to existing specific scale for post-ischaemic depressive disorders. The necessity of systematic psychiatric examination and re-evaluations in thalamic cerebral ischaemia is to be highlighted, both for the differential diagnosis and for the early psychiatric care.
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PMID:[Persistent psychotic disorder following bilateral mesencephalo-thalamic ischaemia: case report]. 1553 16

Ischemic preconditioning (IP) uses transient ischemia to render tissues tolerant to subsequent, prolonged ischemia. This study sought to evaluate factors that contributed to the development of cerebral ischemia during PercuSurge balloon (Medtronic, Santa Rosa, CA) occlusion in patients undergoing carotid angioplasty and stenting (CAS). The PercuSurge occlusion balloon was used in 43 of 165 patients treated with CAS for high-grade stenosis; 20% were symptomatic. Symptoms of cerebral hypoperfusion during temporary occlusion of the internal carotid artery occurred in 10 of 43 patients and included dysarthria, agitation, decreased level of consciousness, and focal hemispheric deficit. The development of neurologic symptoms after initial PercuSurge balloon inflation and occluded internal carotid artery flow was associated with a decrease in the mean Glasgow Coma Scale (GCS) from 15 to 10 (range 9-14); the GCS returned to normal after occlusion balloon deflation. The mean time to spontaneous recovery of full neurologic function was 8 minutes (range 4-15 minutes). The mean subsequent procedure duration was 11.9 minutes (range 6-21 minutes). No recurrence of neurologic symptoms occurred when the occlusion balloon was reinflated. All 10 patients underwent successful CAS without occlusion, dissection, cerebrovascular accident, or death. Ischemic preconditioning can be used to enable CAS with embolic protection in patients who cannot tolerate initial interruption of antegrade cerebral perfusion by PercuSurge occlusion.
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PMID:Ischemic preconditioning during the use of the PercuSurge occlusion balloon for carotid angioplasty and stenting. 1825 56

A simple and solvent-minimized sample preparation technique based on two-phase hollow fiber liquid phase microextraction has been developed and used to quantify the osthole in cerebral ischemia reperfusion rat plasma following oral administration. The analysis was performed by reversed phase high performance liquid chromatography with fluorescence detection. Extraction conditions such as solvent identity, agitation rate, salt concentration, extraction time, and length of the hollow fiber were optimized. Under the optimized conditions, the linear range of osthole in rat plasma was 5-500 ng mL(-1) (r(2) = 0.9997). The limit of detection (LOD) was 2 ng mL(-1) (S/N = 3) with limit of quantification (LOQ) being 5 ng mL(-1). The validated method has been successfully applied for pharmacokinetic studies of osthole from cerebral ischemia reperfusion rat plasma after oral administration.
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PMID:Application of hollow fiber liquid phase microextraction coupled with high-performance liquid chromatography for the study of the osthole pharmacokinetics in cerebral ischemia hypoperfusion rat plasma. 2173 62

Delayed cerebral ischemia (DCI) is the most common and disabling complication among patients admitted to the hospital for subarachnoid hemorrhage (SAH). Clinical and radiographic methods often fail to detect DCI early enough to avert irreversible injury. We assessed the clinical feasibility of implementing a continuous EEG (cEEG) ischemia monitoring service for early DCI detection as part of an institutional guideline. An institutional neuromonitoring guideline was designed by an interdisciplinary team of neurocritical care, clinical neurophysiology, and neurosurgery physicians and nursing staff and cEEG technologists. The interdisciplinary team focused on (1) selection criteria of high-risk patients, (2) minimization of safety concerns related to prolonged monitoring, (3) technical selection of quantitative and qualitative neurophysiologic parameters based on expert consensus and review of the literature, (4) a structured interpretation and reporting methodology, prompting direct patient evaluation and iterative neurocritical care, and (5) a two-layered quality assurance process including structured clinician interviews assessing events of neurologic worsening and an adjudicated consensus review of neuroimaging and medical records. The resulting guideline's clinical feasibility was then prospectively evaluated. The institutional SAH monitoring guideline used transcranial Doppler ultrasound and cEEG monitoring for vasospasm and ischemia monitoring in patients with either Fisher group 3 or Hunt-Hess grade IV or V SAH. Safety criteria focused on prevention of skin breakdown and agitation. Technical components included monitoring of transcranial Doppler ultrasound velocities and cEEG features, including quantitative alpha:delta ratio and percent alpha variability, qualitative evidence of new focal slowing, late-onset epileptiform activity, or overall worsening of background. Structured cEEG reports were introduced including verbal communication for findings concerning neurologic decline. The guideline was successfully implemented over 27 months, during which neurocritical care physicians referred 71 SAH patients for combined transcranial Doppler ultrasound and cEEG monitoring. The quality assurance process determined a DCI rate of 48% among the monitored population, more than 90% of which occurred during the duration of cEEG monitoring (mean 6.9 days) beginning 2.7 days after symptom onset. An institutional guideline implementing cEEG for SAH ischemia monitoring and reporting is feasible to implement and efficiently identify patients at high baseline risk of DCI during the period of monitoring.
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PMID:Clinical Development and Implementation of an Institutional Guideline for Prospective EEG Monitoring and Reporting of Delayed Cerebral Ischemia. 2725 45