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Biomedical subjects

B Engelsen

Publications and source records attributed to B Engelsen.

13 recordsLinked to original sources

EFNS guideline on the management of status epilepticus.

The objective of the current paper was to review the literature and discuss the degree of evidence for various treatment strategies for status epilepticus (SE) in adults. We searched MEDLINE and EMBASE for relevant literature from 1966 to January 2005. Furthermore, the Cochrane Central Register of Controlled Trials (CENTRAL) was sought. Recommendations are based on this literature and on our judgement of the relevance of the references to the subject. Recommendations were reached by informative consensus approach. Where there was a lack of evidence but consensus was clear we have stated our opinion as good practice points. The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is intravenous (i.v.) administration of 4 mg of lorazepam or 10 mg of diazepam directly followed by 15-18 mg/kg of phenytoin or equivalent fosphenytoin. If seizures continue for more than 10 min after first injection another 4 mg of lorazepam or 10 mg of diazepam is recommended. Refractory GCSE is treated by anaesthetic doses of midazolam, propofol or barbiturates; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. The initial therapy of non-convulsive SE depends on the type and the cause. In most cases of absence SE, a small i.v. dose of lorazepam or diazepam will terminate the attack. Complex partial SE is initially treated such as GCSE, however, when refractory further non-anaesthetising substances should be given instead of anaesthetics. In subtle SE i.v. anaesthesia is required.

Anticonvulsants↗

Different brain areas activated during imagery of painful and non-painful 'finger movements' in a subject with an amputated arm.

The purpose of the present study was to investigate differences in brain activation with functional magnetic resonance imaging (fMRI) during imagery of painful and non-painful 'finger movements' and 'hand positioning' in a subject with an amputated arm. The subject was a right-handed man in his mid-thirties who lost his right arm just above the elbow in a car-train accident. MRI was performed with a 1.5 T Siemens Vision Plus scanner. The basic design involved four conditions: imagining 'painful finger movements', 'non-painful finger movements', 'painful hand positioning', 'non-painful hand positioning'. Imagery of finger movements uniquely activated the contralateral primary motor cortex which contains the classic 'hand area'. The lateral part of the anterior cerebellar lobe was also activated during imagery of finger movements. Imagery of pain uniquely activated the somatosensory area, and areas in the left insula and bilaterally in the ventral posterior lateral nucleus of the thalamus. It is suggested that the insula and thalamus may involve neuronal pathways that are critical for mental processing of pain-related experiences, which may relate to a better understanding of the neurobiology of phantom limb pain.

Adult↗

[Non-convulsive status epilepticus--confusion and cognitive failure during seizures].

BACKGROUND: Non-convulsive status epilepticus is characterized by confusion and impaired consciousness, lasting at least half an hour. Seizure activity in the EEG confirms the diagnosis, but ictal discharges can be heterogeneous and difficult to classify. There is controversy regarding evidence of morbidity in humans. MATERIAL AND METHODS: We report three patients with non-convulsive status epilepticus. RESULTS: In two patients, the clinical findings during seizures were subtle cognitive impairment. One patient was confused during seizures. Localisation of seizure activity in the EEG was mainly frontal in two patients, and generalised with focal predominance in one. There were no sign of neurologic sequelae after the seizures were terminated. INTERPRETATION: Complex partial status epilepticus of frontal origin is common, but differentiation between complex partial and generalised non-convulsive status can be difficult. The clinical symptoms may overlap, and generalised EEG seizure activity does not exclude initial focal ictal discharges. Presumably the reported sequelae after this condition are in most cases a consequence of underlying cerebral illness. Treatment response to diazepam can be variable, with high recurrence risk. Effective prophylactic treatment is most important.

Adult↗

Unilateral frontal decortication changes cerebral blood flow distribution during hyperbaric oxygen exposure in rats.

Distribution of rCBF was measured with 10.7 +/- 0.5 microns differently radiolabelled microspheres (MS) during control at 1 bar air, and after 5 and 35 min at 5 bar (0.5 MPa) 95% O2 on awake, habituated rats 10 d after right-sided frontal decortication. A decreased tolerance to hyperbaric O2 was found compared to normal rats of the same strain. The systolic arterial pressure increased during O2 exposure (11%, p < 0.05), the mean arterial pressure remained unchanged, but the cardiac output and heart rate fell by 29 and 14% (p < 0.01), respectively. The arterial acid-base balance remained normal during O2 exposure, although a small reduction of CO2 (24%) and HCO3 (11%) was observed (p < 0.01 and p < 0.05), possibly due to increased alveolar ventilation caused by an elevated respiratory rate of 24% (p < 0.05). The arterial O2 content at 5 bar increased by about 30% (p < 0.01). During control, blood flow in 16 regions of each hemisphere was found to be lower, more scattered, and differently distributed on the lesioned side. After 5 min at 5 bar, the blood flow fell in nearly all regions of the brain (up to 40%), similarly in the two brain halves. During the 35 min exposure, the blood flow increased, so that 60% of the examined areas on the lesioned side had blood flow levels of control or above, in contrast to the undisturbed side where blood flow remained below control values. The O2 supply to different regions varied similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

High ambient pressure of 41 bar increases the cerebral toxicity of penicillins.

Sodium benzylpenicillin, cloxacillin, and azlocillin were infused intravenously in awake rats at 1 and 41 bar until they convulsed. The doses necessary to elicit convulsions were significantly lower at 41 than at 1 bar, i.e., with a 24% (P less than 0.0005) lower dose of benzylpenicillin and a 23% lower dose of azlocillin (P less than 0.005). The convulsion threshold of cloxacillin was also lower (13%), but not statistically significant. The results show that high pressure reduces the convulsion threshold for some penicillins. Hippocampal amino acid concentrations were also measured in animals exposed to 1 and 41 bar with and without benzylpenicillin treatment. Infusion of benzylpenicillin at 1 bar led to a decrease of 15% in the glutamate level (P less than 0.05), whereas at 41 bar it decreased the level of glutamate by 17% (P less than 0.05) as well as that of glutamine by 19% (P less than 0.05). The results suggest that treatment with penicillin at high ambient pressure may increase the turnover of transmitter glutamate in the rat hippocampus and thus increase the excitability. These effects should be considered when high doses of penicillins are administered to man at high ambient pressure.

Amino Acids↗

2-Amino-7-phosphonoheptanoic acid inhibits insulin-induced convulsions and striatal aspartate accumulation in rats with frontal cortical ablation.

Pretreatment of rats with the excitatory amino acid antagonist 2-amino-7-phosphonoheptanoic acid (2-APH; 0.5 mmol/kg, i.p.) protected against insulin-induced clonic seizures. Complete protection was observed in 38% of the rats and partial protection in an additional 50%. Lesioning of the corticostriatal pathway by frontal cortical ablation caused decreases in the striatal levels of aspartate (-28%) and glutamate (-18%), an increase in striatal glutamine level (45%), and decreased high-affinity uptake of D-[3H]aspartate (-27%) in the lesioned dorsal neostriatum. Insulin-induced hypoglycemia caused a predicted sharp increase in aspartate level (165%) and decreased glutamate (-20%) and glutamine (-38%) levels in the intact striatum. Pretreatment of rats with 2-APH significantly reversed the insulin-induced changes in striatal aspartate, glutamate, and glutamine levels, especially in the intact hemisphere. In normoglycemic control rats, the "metabolic," i.e., concentration in the lesioned hemisphere, aspartate pool constituted 72% and the "synaptic," i.e., the concentration difference between the intact and lesioned hemispheres, 28% of the total striatal aspartate pool. 2-APH had no effect on the level of "metabolic" aspartate in the striata of normoglycemic rats but caused an almost complete suppression of "synaptic" aspartate. Following insulin-induced hypoglycemia, the "metabolic" aspartate pool doubled, whereas the "synaptic" aspartate pool increased 3.5-fold in the absence of 2-APH. The insulin-induced rise in "synaptic" aspartate level was almost completely blocked by 2-APH (a 5% rise instead of a 3.5-fold rise).(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

Effect of insulin-induced hypoglycemia on the concentrations of glutamate and related amino acids and energy metabolites in the intact and decorticated rat neostriatum.

The glutamate (Glu) terminals in rat neostriatum were removed by a unilateral frontal decortication. One to two weeks later the effects of insulin-induced hypoglycemia on the steady-state levels of amino acids [Glu, glutamine (Gln), aspartate (Asp), gamma-aminobutyric acid (GABA), taurine] and energy metabolites (glucose, glycogen, alpha-ketoglutarate, pyruvate, lactate, ATP, ADP, AMP, phosphocreatine) were examined in the intact and decorticated neostriatum from brains frozen in situ. The changes in the metabolite levels were examined during normoglycemia, hypoglycemia with burst-suppression (BS) EEG, after 5 and 30 min of hypoglycemic coma with isoelectric EEG, and 1 h of recovery following 30 min of isoelectric EEG. In normoglycemia Glu decreased and Gln and glycogen increased significantly on the decorticated side. During the BS period no significant differences in the measured compounds were noted between the two sides. After 5 min of isoelectric EEG Glu, Gln, GABA, and ATP levels were significantly lower and Asp higher on the intact than on the decorticated side. No differences between the two sides were found after 30 min of isoelectric EEG. After 1 h of recovery from 30 min of isoelectric EEG Glu, Gln, and glycogen had not reached their control levels. Glu was significantly lower, and Gln and glycogen higher on the decorticated side. The Asp and GABA levels were not significantly different from control levels. The results indicate that the turnover of Glu is higher in the intact than in decorticated neostriatum during profound hypoglycemia.

Amino Acids↗

Neurotransmitter glutamate: its clinical importance.

Excitatory amino acid glutamate has several important functions in the mammalian central nervous system (CNS). This review focuses on the transmitter role of glutamate and discusses anatomical and pharmacological data of clinical neurological relevance. Experimental and clinical conditions which have been associated with altered content, uptake, membrane binding or release of glutamate in the CNS are discussed. Such conditions include, epilepsy, disorders of the basal ganglia, cerebral ischemia, hypoxia, hypoglycemia, metabolic encephalopathies, olivopontocerebellar atrophy and cerebellar ataxias, amino acidopathies, mental and other neurological disorders. With the exception of a few fibre systems, it is very difficult to differentiate between glutamate and aspartate as CNS transmitters. The term glutamate is, thus, used in the sense glutamate and/or aspartate unless specifically stated.

Animals↗

The effect of methioninesulfoximine, an inhibitor of glutamine synthetase, on the levels of amino acids in the intact and decorticated rat neostriatum.

The glutamate terminals in rat rostral neostriatum were removed on one side by ipsilateral frontal cortical ablation. Intraperitoneal administration of L-methioninesulfoximine (MSO), an inhibitor of glutamine synthetase, induced different changes in amino acid concentration in the rostral neostriatum on the intact and decorticated sides. Glutamine was more reduced on the decorticated side than on the intact side. Glutamate changed less, but decreased more on the intact than on the lesioned side. There seems to be a correlation between the decrease in glutamine and the increase in alanine on both sides. GABA and taurine did not change significantly. The results indicate that the formation of glutamine probably formed from released glutamate is lower on the decorticated side than on the intact side.

Alanine↗

Lesions of the glutamatergic cortico-striatal projections in the rat ameliorate hypoglycemic brain damage in the striatum.

Unilateral ablations of the motor cortex were performed on rats. One to two weeks following the ablation they were subjected to 30 min of reversible insulin-induced hypoglycemic coma. The levels of glutamate, aspartate, gamma-aminobutyric acid (GABA), taurine, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and phosphocreatine (PCr) were determined in frozen tissue sections from the superior half of the caudate nucleus. The lesions induced a specific reduction in the levels of glutamate by approx. 10% in the dorsal caudate nucleus ipsilateral to the lesion, while no significant differences in the levels of aspartate, GABA, taurine, ATP, ADP, AMP or PCr were noted. Neuronal necrosis in the caudate nucleus in animals subjected to 30 min of insulin-induced hypoglycemic coma and one week recovery was assessed by light microscopy. Contralateral to the lesion, extensive neuronal necrosis, mainly affecting small and medium-sized neurons, was observed in the dorsal and lateral caudate nucleus. In the caudate ipsilateral to the lesion a complete amelioration of necrosis was noted in areas subjacent to the lesion. The data suggest that hypoglycemic brain damage is induced by excitotoxins such as glutamate or related compounds.

Animals↗

Increased concentrations of aspartic acid in the cerebrospinal fluid of patients with epilepsy and trigeminal neuralgia: an effect of medication?

The concentrations of free amino acids in the cerebrospinal fluid (CSF) were quantitated in 14 patients with epilepsy, 7 patients with trigeminal neuralgia, 10 patients with various neurological diseases and in 30 apparently healthy individuals. In the CSF of patients with epilepsy, the mean concentrations of aspartic acid (Asp), glutamine (Gln), histidine and phosphoserine were significantly higher than in the healthy individuals. The mean concentration of aspartic acid was higher in the patients on antiepileptic drug (AED) therapy than in the patients without AED therapy. The patients with trigeminal neuralgia had significantly increased CSF-concentrations of aspartic acid, glutamine and phosphoserine as compared to healthy individuals. Some patients receiving AED showed increased concentration of gamma-amino-butyric-acid (GABA).

Adolescent↗

Effects of hypoglycemia on the transmitter pool and the metabolic pool of glutamate in rat brain.

The glutamate terminals in rat neostriatum were removed by unilateral frontal decortication. Insulin-induced hypoglycemia was accompanied by different changes in amino acids in rostral neostriatum on the intact and lesion side. Thus the glutamate/aspartate ratio, glutamate concentration and glutamine concentration were significantly more reduced and the aspartate concentration more elevated on the non-operated than on the operated side. The results show a higher turnover of glutamate in the non-operated side indicating a higher turnover of the transmitter pool than of the metabolic pool of glutamate. The combination of brain lesions with drugs inhibiting the metabolism points to a new method to investigate the compartmentation of glutamate in the mammalian brain.

Animals↗