Metabolic responses to status epilepticus in the rat, cat, and mouse

1979 ◽  
Vol 57 (2) ◽  
pp. 205-212 ◽  
Author(s):  
D. C. N. Howse
Keyword(s):  
Status Epilepticus ◽  
Seizure Activity ◽  
Muscular Contraction ◽  
Metabolic Responses ◽  
Arterial Oxygen ◽  
Cortical Tissue ◽  
Similar Dose ◽  
Lactic Acidemia ◽  
Control Seizure

Prolonged sustained seizure activity (status epilepticus) was created in rats and cats using paralysis and ventilation to prevent muscular contraction and its secondary systemic effects. Under physiologic control, seizure activity was maintained for 30, 60, and 120 min. At this time the brains were frozen using the in situ technique and the cortical tissue was analyzed for energy-related metabolites. The alteration of metabolites found at these times was similar to that previously described in the first 10 min of seizure activity. No evidence was found of any significant or progressive derangement of oxidative metabolism. A progressive lactic acidemia developed in spite of adequate arterial oxygen tensions.In contrast, when mice received a similar dose of the convulsant and were allowed to convulse freely in an oxygen-enriched environment, major derangements of energy metabolism were found which were progressive and persisted following recovery for at least 18 h.

scholarly journals Metabolic Alterations Underlying the Development of Hypermetabolic Necrosis in the Substantia Nigra in Status Epilepticus

1987 ◽  
Vol 7 (1) ◽  
pp. 103-108 ◽  
Author(s):  
Martin Ingvar ◽  
Jaroslava Folbegrova ◽  
Bo K. Siesjö
Keyword(s):  
Status Epilepticus ◽  
Substantia Nigra ◽  
Seizure Activity ◽  
Energy Charge ◽  
Tissue Necrosis ◽  
Neuronal Necrosis ◽  
Energy Metabolites ◽  
Adenylate Pool ◽  
Marked Accumulation

The substantia nigra pars reticulata (SNPR) has previously been shown to undergo tissue necrosis following status epilepticus induced by flurothyl in the rat. Even if the rat is ventilated, the SNPR develops necrosis if the epileptic period lasts more than 30 min. Rat brains were frozen in situ after 20 and 60 min of seizure activity and after 60 min of seizure activity followed by 60 min recovery. Labile energy metabolites were then analyzed in the SNPR and in the periaqueductal grey matter (PAG, control region). In the PAG, the metabolite changes during status epilepticus were similar to those reported for cerebral cortex and hippocampus. Measurements showed an unchanged ATP content and energy charge (97% and 98% of control, respectively) and an accumulation of lactate to 9.2 ± 0.6 μmol/g in the 60-min group. In the PAG, all metabolites measured had returned to control values after 60 min of recovery. In the SNPR, the perturbation of the energy metabolites was much more pronounced during status epilepticus. The concentration of ATP decreased to 75 ± 3%, the energy charge to 91% ± 12% and the adenylate pool to 86.7 ± 5.7% of control. Lactate accumulated to concentrations of 16.1 ± 1.8 μmol/g and 24.9 ± 2.3 μmol/g in the 20-min and 60-min groups, respectively. The concentration of lactate was still increased above control after 60 min recovery, whereas the concentration of ATP and the energy charge were lower than control. The findings demonstrate that sustained and intense neuronal activation can cause metabolic disturbance and thereby lead to necrosis. The very marked accumulation of lactic acid, likely due to mitochondrial failure, yields a very low intracellular pH, possibly explaining why a tissue necrosis, rather than selective neuronal necrosis, develops in the SNPR during status epilepticus.

scholarly journals CDDO-Me Distinctly Regulates Regional Specific Astroglial Responses to Status Epilepticus via ERK1/2-Nrf2, PTEN-PI3K-AKT and NFκB Signaling Pathways

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1026
Author(s):  
Ji-Eun Kim ◽  
Hana Park ◽  
Tae-Cheon Kang
Keyword(s):  
Status Epilepticus ◽  
Signaling Pathways ◽  
Seizure Activity ◽  
Molecular Layer ◽  
Antioxidant Properties ◽  
Acid Methyl Ester ◽  
Related Factor ◽  
Nuclear Factor ◽  
Reactive Astrogliosis ◽  
Nrf2 Expression

2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid. CDDO-Me shows anti-inflammatory and neuroprotective effects. Furthermore, CDDO-Me has antioxidant properties, since it activates nuclear factor-erythroid 2-related factor 2 (Nrf2), which is a key player of redox homeostasis. In the present study, we evaluated whether CDDO-Me affects astroglial responses to status epilepticus (SE, a prolonged seizure activity) in the rat hippocampus in order to understand the underlying mechanisms of reactive astrogliosis and astroglial apoptosis. Under physiological conditions, CDDO-Me increased Nrf2 expression in the hippocampus without altering activities (phosphorylations) of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphatidylinositol-3-kinase (PI3K), and AKT. CDDO-Me did not affect seizure activity in response to pilocarpine. However, CDDO-Me ameliorated reduced astroglial Nrf2 expression in the CA1 region and the molecular layer of the dentate gyrus (ML), and attenuated reactive astrogliosis and ML astroglial apoptosis following SE. In CA1 astrocytes, CDDO-Me inhibited the PI3K/AKT pathway by activating PTEN. In contrast, CDDO-ME resulted in extracellular signal-related kinases 1/2 (ERK1/2)-mediated Nrf2 upregulation in ML astrocytes. Furthermore, CDDO-Me decreased nuclear factor-κB (NFκB) phosphorylation in both CA1 and ML astrocytes. Therefore, our findings suggest that CDDO-Me may attenuate SE-induced reactive astrogliosis and astroglial apoptosis via regulation of ERK1/2-Nrf2, PTEN-PI3K-AKT, and NFκB signaling pathways.

scholarly journals Sudden altered mental state in the elderly: nonconvulsive status epilepticus and the role of the Emergency Department

2011 ◽  
Vol 5 (1) ◽  
pp. 15-25
Author(s):  
Rocco Galimi
Keyword(s):  
Status Epilepticus ◽  
Seizure Activity ◽  
The Elderly ◽  
Altered Mental Status ◽  
Nonconvulsive Status Epilepticus ◽  
Recurrent Seizure ◽  
Memory Problems ◽  
Altered Mental State ◽  
New Onset

In the elderly, new onset of epilepsy is often associated with vague complaints such as confusion, altered mental status, or memory problems. The absence of clinically apparent convulsions in association with an electroencephalogram showing continuous or recurrent seizure activity has been called nonconvulsive status epilepticus (NCSE). The purpose of this article is to describe the clinical and electroencephalographic features of NCSE in older adults. NCSE is an important, under-recognised and reversible cause of acute prolonged confusion. Although attempts have been made to define and classify this disorder, there is no universally accepted definition or classification yet that encompasses all subtypes or electroclinical scenarios. A urgent electroencephalogram is considered as the method of choice in the diagnostic evaluation of NCSE. Further researches are needed to better define NCSE.

Consultation with the Specialist

1995 ◽  
Vol 16 (10) ◽  
pp. 386-389
Author(s):  
Margaret C. McBride
Keyword(s):  
Status Epilepticus ◽  
Primary Care Physicians ◽  
Seizure Activity ◽  
Medical Emergency ◽  
Partial Status Epilepticus ◽  
Primary Generalized Epilepsy ◽  
Generalized Epilepsy ◽  
Static Encephalopathy ◽  
Prolonged Absence ◽  
Partial Status

Status epilepticus has been defined as continuous seizure activity or intermittent seizure activity without recovery of consciousness between seizures that lasts for more than 30 minutes. However, if a seizure has continued unabated for 5 minutes, status epilepticus should be presumed and therapy initiated. Status epilepticus is a medical emergency, and all primary care physicians should know how to initiate its treatment. Usually status epilepticus consists of generalized or asymmetric clonic activity with unconsciousness. However, prolonged absence or partial seizures comprise 10% of episodes. Absence status epilepticus usually occurs in children who have severe primary generalized epilepsy or Lennox-Gastaut syndrome. Partial status epilepticus occurs in children who have focal brain pathology. The initial treatment of both is like that for generalized status epilepticus, with only slightly less urgency. The remainder of this review concerns generalized status epilepticus. Etiology It is important to obtain both remote and recent histories from the child's family or attendant as soon as possible so that an appropriate differential diagnosis may be developed. In 25% of cases, status is idiopathic. In another 25% it is provoked only by fever (febrile status). In the 20% of children who have a static encephalopathy, the condition is termed remote symptomatic status epilepticus. In another 20%, status is termed acute symptomatic and is an expression of an acute encephalopathy or brain injury.

Noncompliance Contributing to Apparent Drug Failure in Status Epilepticus

PEDIATRICS ◽  
1974 ◽  
Vol 53 (6) ◽  
pp. 938-940
Author(s):  
John T. Wilson
Keyword(s):  
Status Epilepticus ◽  
Plasma Levels ◽  
Seizure Activity ◽  
Drug Level ◽  
Continuous Control ◽  
Drug Plasma ◽  
Intravenous Diazepam ◽  
Grand Mal ◽  
History Of ◽  
Drug Plasma Levels

The case to be described illustrates apparent drug failure because of noncompliance in the drug delivery system, and the sequelae of this mishap. In connection with investigation of this case further occurrences of noncompliance were found. This incident also brings into focus the importance of plasma drug level determinations for effective application of therapy. CASE REPORT A 7-year-old, 26-kg, black girl was admitted with a 16-month history of nonprogressive neurologic disease accompanied by clinical and EEG evidence of petit mal and grand mal epilepsy which responded to diphenylhydantoin (DPH), phenobarbital or ethosuximide (Zarontin) treatment. Generalized convulsions had been infrequent for four months, but, before the present admission, a marked increase in grand mal seizures was noted. On the day of admission (day 1), recurrent generalized seizure activity progressed to status epilepticus within six hours. Intravenous diazepam (Valium [0.18/mg/kg]) controlled the seizures. Primidone (Mysoline), 250 mg tid, and ethosuximide, 500 mg tid were prescribed as maintenance anticonvulsants in an attempt to allay further progression to status epilepticus. For the next several days her seizures could be controlled only with paraldehyde (0.36 mg/kg intravenously), although administration of other drugs was continued. Assays of drug plasma levels did not become available until day 6. They disclosed that plasma levels of diazepam and demethyldiazepam were high (289 and 50 ng/ml, respectively) one hour after dosing with 0.18 mg/kg. This indicated that diazepam was not effective for continuous control of seizures, but this information was not acted upon immediately. The most striking finding was that primidone was not detected in plasma, although the prescibed dosage was 250 mg tid.

Temporal lobectomy for refractory status epilepticus in a case of limbic encephalitis

2008 ◽  
Vol 109 (4) ◽  
pp. 742-745 ◽  
Author(s):  
Tracy Weimer ◽  
Warren Boling ◽  
David Pryputniewicz ◽  
Adriana Palade
Keyword(s):  
Status Epilepticus ◽  
Limbic Encephalitis ◽  
Seizure Activity ◽  
Refractory Status Epilepticus ◽  
Temporal Lobectomy ◽  
Bronchial Biopsy ◽  
High Dose ◽  
Refractory Status ◽  
The Right ◽  
The Brain

The authors report a case of status epilepticus secondary to limbic encephalitis that was successfully treated with temporal lobectomy. A 45-year-old woman presented in status epilepticus refractory to high-dose suppressive medical therapy. Magnetic resonance imaging of the brain showed T2- and FLAIR-weighted hyperintensities in the right temporal lobe, left and right frontal lobes, and pons. A lumbar puncture revealed normal findings. Continuous electroencephalography monitoring showed continued right temporal seizure activity. A paraneoplastic panel was positive for N-type voltage-gated calcium channels. Subsequent bronchial biopsy revealed small cell carcinoma of the lung. A right temporal lobectomy was performed due to refractory status, resulting in resolution of seizure activity and recovery of good neurological function. The authors describe their case and review the literature on surgical therapy for refractory status epilepticus and limbic encephalitis.

Metabolic and contractile responses of rat fast-twitch muscle to 10-Hz stimulation

1991 ◽  
Vol 260 (4) ◽  
pp. C832-C840 ◽  
Author(s):  
D. A. Hood ◽  
G. Parent
Keyword(s):  
Metabolic Stress ◽  
Metabolic Responses ◽  
Contractile Responses ◽  
Atp Level ◽  
Phenotypic Changes ◽  
Muscle Ph ◽  
Fast Twitch Muscle ◽  
Fast Twitch ◽  
Twitch And Tetanic Tensions

Contractile and metabolic responses of rat fast-twitch gastrocnemius-plantaris muscles were studied. Acute in situ 10-Hz stimulation (STIM) for two 60-min periods, separated by 60 min of recovery (REC), was used. Muscles were removed at 1, 3, 15, 60, 75, 120, 123, or 180 min for metabolite measurements. Twitch and tetanic tensions were reduced to 36 and 28% of initial during the first 60 min of STIM. During REC, these tensions returned only to 56-58% of initial by 120 min. These contractile responses did not parallel changes in metabolites in mixed muscle. pH was reduced from 7.0 to 6.4 by 1 min, but by 15 min of STIM had returned to resting levels. Free ADP and AMP increased 3- and 15-fold during STIM, then decreased to resting levels by 3 min of REC. The most sensitive indicator of metabolic stress during STIM and REC was the phosphorylation potential, which varied up to 40-fold. After initial phases of depletion, ATP and phosphocreatine levels were partially restored despite ongoing STIM. Approximately 75% of the change in ATP level could be accounted for by IMP. In red gastrocnemius [fast-twitch red (FTR)] muscle, IMP was increased by 3 min of STIM but returned to control values by 60 min. Thus reamination of IMP occurred during contractions of FTR muscle. Metabolic and contractile responses during the second STIM period (120-180 min) were similar to the first. This cycle of metabolic and contractile responses occurs in fast-twitch muscle which, with chronically repeated STIM and REC periods, undergoes large phenotypic changes as a result of use.

Prehospital Administration of Rectal Diazepam in Pediatric Status Epilepticus

1990 ◽  
Vol 5 (2) ◽  
pp. 155-158
Author(s):  
Rodney E. Drawbaugh ◽  
Christopher G. Deibler ◽  
David R. Eitel
Keyword(s):  
Status Epilepticus ◽  
Seizure Activity ◽  
Neuronal Damage ◽  
Rectal Administration ◽  
The United States ◽  
Morbidity Rate ◽  
Drug Of Choice ◽  
Rectal Diazepam ◽  
Intravenous Diazepam ◽  
Alternate Routes

Seizures are a common pediatric problem encountered by prehospital personnel. Status epilepticus is defined as seizure activity lasting longer than 15 minutes, or recurrent seizures that occur close together without a period of consciousness between ictal periods. It is estimated that 60,000 to 160,000 cases of status epilepticus occur each year within the United States. Prior to 1960, status epilepticus carried a 50% morbidity rate. However, improved anticonvulsive medications, aggressive airway management, and the spread of EMS Systems throughout the nation have reduced the morbidity rate to a range of 8% to 12%.Prompt and vigorous treatment is paramount in the successful management of status epilepticus because delays can result in neuronal damage and death. Although intravenous diazepam currently is the drug of choice to terminate seizure activity, it may be difficult to rapidly establish a patent intravenous (IV) line during status epilepticus in young children with vigorous motor activity. Alternate routes, such as intramuscular injections, are unreliable due to unpredictable absorption. Rectal administration of diazepam may provide an useful alternate route for delivery of the drug during status epilepticus when IV attempts fail.In this review, the authors discuss a case of status epilepticus wherein intravenous access could not be established rapidly and the patient was given diazepam rectally with favorable results.

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