Mitochondrial transplantation ameliorates hippocampal damage following status epilepticus

Background:Hippocampal damage caused by status epilepticus(SE)can bring about cognitive decline and emotional disorders,which are common clinical comorbidities in patients with epilepsy.It is therefore imperative to develop a novel therapeutic strat-egy for protecting hippocampal damage after SE.Mitochondrial dysfunction is one of contributing factors in epilepsy.Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria,we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE.Methods:Pilocarpine was used to induced SE in mice.SE-generated cognitive de-cline and emotional disorders were determined using novel object recognition,the tail suspension test,and the open field test.SE-induced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes.The metabolites underlying mitochondrial transplantation were determined using metabonomics.Results:The results showed that peripheral administration of isolated mitochon-dria could improve cognitive deficits and depressive and anxiety-like behaviors.Exogenous mitochondria blunted the production of reactive oxygen species,pro-liferation of microglia and astrocytes,and loss of neurons in the hippocampus.The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism.Among potential affected metabolites,mitochondrial transplantation decreased levels of sphingolipid(d18:1/18:0)and methylmalonic acid,and elevated levels of D-fructose-1,6-bisphosphate.Conclusion:To the best of our knowledge,these findings provide the first direct ex-perimental evidence that artificial mitochondrial transplantation is capable of amelio-rating hippocampal damage following SE.These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy-associated psychiat-ric and cognitive disorders.

Activation of metabotropic glutamate receptor 1 regulates hippocampal CA1 region excitability in rats with status epilepticus by suppressing the HCN1 channel

Dysregulation of hyperpolarization-activated cyclic nucleotide-gated cation(HCN)channels alters neuronal excitability.However,the role of HCN channels in status epilepticus is not fully understood.In this study,we established rat models of pentylenetetrazole-induced status epilepticus.We performed western blot assays and immunofluorescence staining.Our results showed that HCN1 channel protein expression,particularly HCN1 surface protein,was significantly decreased in the hippocampal CA1 region,whereas the expression of HCN2 channel protein was unchanged.Moreover,metabolic glutamate receptor 1(mGluR1)protein expression was increased after status epilepticus.The mGluR1 agonist(RS)-3,5-dihydroxyphenylglycine injected intracerebroventricularly increased the sensitivity and severity of pentylenetetrazole-induced status epilepticus,whereas application of the mGluR1 antagonist(+)-2-methyl-4-carboxyphenylglycine(LY367385)alleviated the severity of pentylenetetrazole-induced status epilepticus.The results from double immunofluorescence labeling revealed that mGluR1 and HCN1 were co-localized in the CA1 region.Subsequently,a protein kinase A inhibitor(H89)administered intraperitoneally successfully reversed HCN1 channel inhibition,thereby suppressing the severity and prolonging the latency of pentylenetetrazole-induced status epilepticus.Furthermore,H89 reduced the level of mGluR1,downregulated cyclic adenosine monophosphate(cAMP)/protein kinase A expression,significantly increased tetratricopeptide repeat-containing Rab8b-interacting protein(TRIP8b)(1a-4)expression,and restored TRIP8b(1b-2)levels.TRIP8b(1a-4)and TRIP8b(1b-2)are subunits of Rab8b interacting protein that regulate HCN1 surface protein.

Ocimum sanctum extract preserves neuronal echotexture and controls seizure in lithium-pilocarpine induced status epilepticus rats

Objective:To investigate the effect of Ocimum sanctum hydroalcoholic extract(OSHE)on seizure control and neuronal injury in rats with lithium-pilocarpine-induced status epilepticus(SE).Methods:SE was induced by administering lithium chloride followed by pilocarpine 24 h later.OSHE was administered either alone or in combination with valproate(VPA)3 days before SE induction until 14 days post-SE induction.Seizure parameters were recorded on day 1(0-3 h),day 1-3 and day 4-14 post-SE.On day 14 post-SE,neurobehavioural tests(elevated plus maze and passive avoidance)were done followed by total antioxidant capacity,neuron-specific enolase,immunohistochemistry,and electron microscopic assessment in the hippocampus and cortex tissue.Results:OSHE+VPA provided more significant seizure protection(75%)than VPA(62.5%),OSHE(62.5%),or SE control(12.5%)(overall P=0.003).The latency to stage-3/4 seizures was increased and the number of stage-3/4 seizures was reduced in all treatment groups compared to the SE control group(P=0.002 and<0.001,respectively).The OSHE+VPA group also had better memory retention than other treatment groups(P<0.001)in the passive avoidance test.Total antioxidant capacity level was significantly higher and neuron-specific enolase was lower in the OSHE and OSHE+VPA groups compared to the SE control group.Electron microscopic study showed significant myelin sheath damage(67.5%,P<0.05)and axonal degeneration(51.8%,P<0.001)in the hippocampus of the SE control group,which were alleviated by OSHE or OSHE+VPA treatment.In immunohistochemical analysis,the OSHE,OSHE+VPA,and VPA groups had a significantly higher number of viable neurons and less neuronal loss compared to the SE control in the hippocampus(P<0.001).Conclusions:OSHE either alone or in combination with VPA shows better seizure control by preservation of neuronal echotexture and reducing oxidative stress in the hippocampus.

Hippocampus protection from apoptosis by Baicalin in a LiClpilocarpine-induced rat status epilepticus model through autophagy activation

BACKGROUND Autophagy is associated with hippocampal injury following status epilepticus(SE)and is considered a potential therapeutic mechanism.Baicalin,an emerging multitherapeutic drug,has shown neuroprotective effects in patients with nervous system diseases due to its antioxidant properties.AIM To investigate the potential role of autophagy in LiCl-pilocarpine-induced SE.METHODS The drugs were administered 30 min before SE.Nissl staining showed that Baicalin attenuated hippocampal injury and reduced neuronal death in the hippocampus.Western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling assay confirmed that Baicalin reversed the expression intensity of cleaved caspase-3 and apoptosis in hippocampal CA1 following SE.Furthermore,western blotting and immunofluorescence staining were used to measure the expression of autophagy markers(p62/SQSTM1,Beclin 1,and LC3)and apoptotic pathway markers(cleaved caspase-3 and Bcl-2).RESULTS Baicalin significantly upregulated autophagic activity and downregulated mitochondrial apoptotic pathway markers.Conversely,3-methyladenine,a commonly used autophagy inhibitor,was simultaneously administered to inhibit the Baicalin-induced autophagy,abrogating the protective effect of Baicalin on the mitochondrial apoptotic level.CONCLUSION We illustrated that Baicalin-induced activation of autophagy alleviates apoptotic death and protects the hippocampus of SE rats.

Non Convulsive Status Epilepticus: An Elusive Diagnosis

Absence status is the most common form of non-convulsive status epilepticus and is characterized by confusion with varying degrees of memory loss and cognitive impairment. Patients and Method: Three children were sent to neurological consultation due to behavioral alterations and a prolonged confused state;they were hospitalized and treated with sodium diphenylhydantoinate (DPH) IV at a dose of 10 mg/Kg. Results: The duration of symptoms varied from 6 months to 10 days. All three patients presented with global mental alterations, showing slowness in response and action. The electroencephalogram showed a pattern of slow, generalized stem and poly-stem-wavelengths of 3 - 4 Hz, which were registered for one hour. After the DPH bolus, the attack spontaneously ended in the 3 patients and upon examination all three presented with amnesia of the events occurring during the attack. In the follow-up, two of the patients did not experience further episodes and they showed normal scholastic achievement. The third patient however, after suffering a 6-month status epilepticus, failed the school year and finished his elementary education until the age of 15, experiencing similar difficulties with his secondary education. Discussion: Non-convulsive status epilepticus is more difficult to diagnose mainly because the manifestations are predominantly psychiatric and can be confused with other diseases or with an overdose of anti- convulsive drugs. A prolonged state of mental confusion, with no other explanation, should alert the attending physician to take an electroencephalogram in order to confirm the diagnosis. In our patients, DPH immediately controlled paroxysmal activity. We can therefore conclude that the problem is not in the treatment, but rather in making the correct diagnosis.

Propofol pump controls nonconvulsive status epilepticus in a hepatic encephalopathy patient: A case report

BACKGROUND Status epilepticus is an emergent and critical condition which needs management without hesitation. Nonconvulsive status epilepticus (NCSE) tends to be less recognized, and its diagnosis is delayed in comparison with overt status epilepticus because of the absence of specific clinical signs. It is often difficult to make a diagnosis, particularly in patients with hepatic encephalopathy. CASE SUMMARY A 38-year-old man with a history of alcoholic liver cirrhosis presented with altered mental status;the initial diagnosis was hepatic encephalopathy. Although optimal treatment for hepatic encephalopathy was administered, the patient's mental status did not improve. A final diagnosis of NCSE was made by continuous electroencephalogram (EEG) monitoring. Treatment with levetiracetam and propofol pump was immediately started. The patient’s consciousness gradually improved after discontinuation of propofol therapy, and no further epileptic discharge was observed by EEG monitoring. After 1 wk, the patient returned to full consciousness, and he was able to walk in the hospital ward without assistance. He was discharged with minimal sequela of bilateral conjunctivitis. CONCLUSION In cases of persistent altered mental status without reasonable diagnosis, NCSE should be considered in hepatic encephalopathy patients with persistently altered levels of consciousness, and EEG monitoring is very important. We also recommend propofol as a safe and efficient therapy for NCSE in liver cirrhosis patients.

Propofol effectively inhibits lithium-pilocarpine-induced status epilepticus in rats via downregulation of N-methyl-D-aspartate receptor 2B subunit expression

Status epilepticus was induced via intraperitoneal injection of lithium-pilocarpine.The inhibitory effects of propofol on status epilepticus in rats were judged based on observation of behavior,electroencephalography and 24-hour survival rate.Propofol（12.5-100 mg/kg） improved status epilepticus in a dose-dependent manner,and significantly reduced the number of deaths within 24 hours of lithium-pilocarpine injection.Western blot results showed that,24 hours after induction of status epilepticus,the levels of N-methyl-D-aspartate receptor 2A and 2B subunits were significantly increased in rat cerebral cortex and hippocampus.Propofol at 50 mg/kg significantly suppressed the increase in N-methyl-D-aspartate receptor 2B subunit levels,but not the increase in N-methyl-D-aspartate receptor 2A subunit levels.The results suggest that propofol can effectively inhibit status epilepticus induced by lithium-pilocarpine.This effect may be associated with downregulation of N-methyl-D-aspartate receptor 2B subunit expression after seizures.

Nonconvulsive status epilepticus disguising as hepatic encephalopathy

Nonconvulsive status epilepticus has become an important issue in modern neurology and epileptology.This is based on difficulty in definitively elucidating thecondition and its various clinical phenomena and on our inadequate insight into the intrinsic pathophysiological processes.Despite nonconvulsive status epilepticus being a situation that requires immediate treatment,this disorder may not be appreciated as the cause of mental status impairment.Although the pathophysiology of nonconvulsive status epilepticus remains unknown,this disorder is thought to lead to neuronal damage,so its identification and treatment are important.Nonconvulsive status epilepticus should be considered in the differential diagnosis of patients with liver cirrhosis presenting an altered mental status.We report a case of a 52-year-old male with liver cirrhosis presenting an altered mental status.He was initially diagnosed with hepatic encephalopathy but ultimately diagnosed with nonconvulsive status epilepticus by electroencephalogram.

Effects of ethanol extracts of scorpion on hippocampal apoptosis and caspase-3 expression in lithium chloride-pilocarpine-induced status epilepticus rats

BACKGROUND： Previous studies have demonstrated that scorpion venom in the scorpion can inhibit epilepsy and apoptosis. However, it remains unclear whether ethanol extracts of scorpion （EES） exhibit similar effects. OBJECTIVE： To investigate the effects of EES on hippocampal apoptosis and caspase-3 expression, and to compare the effects on sodium valproate （positive control drug） in a rat model of status epilepticus induced by lithium chloride-pilocarpine. DESIGN, TIME AND SETTING： This randomized, controlled study was conducted at the Drug Research and Development Center, Kanghong Pharmaceuticals Group, and the Department of Pathology, Sichuan Academy of Medical Sciences ＆ Sichuan Provincial People＇s Hospital, China from May 2007 to April 2008. MATERIALS： EES were prepared by Huashen Pharmaceutical, China. Sodium valproate （Hunan Xiangzhong Pharmaceutical, China） and lithium chloride-pilocarpine （Sigma, USA） were also used in the present study. METHODS： From a total of 156 rats, six served as normal controls. The remaining rats were intraperitoneally injected with lithium chloride-pilocarpine to establish status epileptlcus models, and then assigned to five groups （n = 30, respectively）. Animals in each group were administered drugs at 15 minutes after epileptic seizure by gavage, i.e. in the normal control and model groups, rats were treated with 1 mL/0.1 kg saline. The sodium valproate group was administered 120 mg/kg/d sodium valproate. The low-, moderate-, and high-dose EES groups received treatments of 290, 580 and 1 160 mg/kg/d EES. The dispensed concentration was 1 mL/0.1 kg. Rat seizure behavior was observed. If status epilepticus did not terminated after 1 hour, the rats were intraperitoneally administered atropine （1 mg/kg） and diazepam （10 mg/kg） to terminate seizure. These rats were continuously observed for 6 hours to ensure seizure termination. Then rats were treated with the above-mentioned drugs at 8：00 am each day until sacrifice, which took place 4 hours after drug administration. MAIN OUTCOME MEASURES： Terminal dUTP nick end labeling （TUNEL）-positive cells and caspase-3 expression were, respectively, determined by TUNEL and immunohistochemistry at 6, 24 48, and 72 hours, as well as 7 days, after status epilepticus. Behavioral changes were also measured. RESULTS： A few caspase-3-positive cells were observed. TUNEL- and caspase-3-positive ceils were mainly visible in the hippocampal CA1 and CA3 regions 6 hours following status epilepticus in the model and drug intervention groups. The number of TUNEL-positive cells reached a peak at 48 hours following status epilepticus in the sodium valproate group, as well as the moderate- and high-dose EES groups, and number of TUNEL-positive cells reached a peak at 72 hours in the model and low-dose EES groups. The number of caspase-3-positive cells reached a peak at 48 hours in each group. Following treatment of sodium valproate and EES, the number of TUNEL- and caspase-3-positive cells significantly decreased compared with the model group at various time points （P 〈 0.05）. The number of TUNEL- and caspase-3-positive cells was greatest in the low-dose EES group, followed by the moderate- and high-dose EES groups. The number of TUNEL- and caspase-3-positive cells was similar between the sodium valproate and high-dose EES groups. Epileptic seizure was significantly improved in the sodium valproate group, as well as the moderate- and high-dose EES groups, compared with the model group （P〈 0.05 or P〈 0.01）. Treatment with sodium valproate and high-dose EES resulted in the best outcome, although the results were similar （P 〉 0.05）. CONCLUSION： A dose of 1 160 mg/kg/d EES significantly inhibited status epilepticus. This outcome corresponded to a decreased number of apoptotlc cells and caspase-3-positive cells, which was similar to sodium valproate. These results suggest that it is not necessary to extract a component from the scorpion for the treatment of epilepsy. The high dose of EES significantly inhibited epilepsy, which correlated with decreased hippocampal caspase-3 expression.

Mitochondrial and nuclear changes in hippocampal neurons in a lithium-pilocarpine-induced status epilepticus rat model

BACKGROUND： Mitochondrial damage plays a key role in neuronal damage. OBJECTIVE： To observe ultrastructural damage to mitochondria and nuclei, as well as caspase-3 expression, in hippocampal CA3 neurons of lithium-pilocarpine-induced status epilepticus rats. DESIGN, TIME AND SETTING： The neuropathological, randomized, controlled study was performed at the Animal Experimental Center, Shandong University, China in May 2008. MATERIALS： A total of 75 healthy, adult, male, Wistar rats were randomly assigned into model （n = 45） and control （n = 30） groups. Lithium-pilocarpine （Sigma, USA） was used in this study. METHODS： Rats in the model group were intraperitoneally injected with lithium chloride （3 mEq/kg）, and 24 hours later with pilocarpine （45 mg/kg）, to induce seizures for 2 hours. Rats in the control group were intraperitoneally infused with the same volume of saline. Rat hippocampal CA3 tissue was obtained at 3, 12, and 24 hours following status epilepticus. MAIN OUTCOME MEASURES： Neuronal changes were observed under an optical microscope. Ultrastructural changes in mitochondria and nuclei were observed using an electron microscope. caspase-3 mRNA levels were quantified by semiquantitative RT-PCR. RESULTS： After 3 hours of status epilepticus, mitochondria with swollen cristae and ruptured membranes were observed by electron microscopy. Nuclei with marginated chromatin were observed after 24 hours status epilepticus. RT-PCR results demonstrated increased caspase-3 expression at 12 hours, and significantly increased expression at 24 hours following termination of status epilepticus. This was in accordance with acidophilia occurrence, as indicated by hematoxylin-eosin staining, and time of ultrastructural damage to nuclei. CONCLUSION： In lithium-pilocarpine-induced status epilepticus rat models, ultrastructural damage to mitochondria in hippocampal neurons occurred during early stages, followed by increased caspase-3 expression and nuclear changes. These results suggested that mitochondrial damage plays a key role in neuronal damage following status epilepticus.

Sodium valproate suppresses abnormal neurogenesis induced by convulsive status epilepticus

Status epilepticus has been shown to activate the proliferation of neural stem cells in the hippocampus of the brain, while also causing a large amount of neuronal death, especially in the subgranular zone of the dentate gyrus and the subventricular zone. Simultaneously, proliferating stem cells tend to migrate to areas with obvious damage. Our previous studies have clearly confirmed the effect of sodium valproate on cognitive function in rats with convulsive status epilepticus. However, whether neurogenesis can play a role in the antiepileptic effect of sodium valproate remains unknown. A model of convulsive status epilepticus was established in Wistar rats by intraperitoneal injection of 3 mEq/kg lithium chloride, and intraperitoneal injection of pilocarpine 40 mg/kg after 18–20 hours. Sodium valproate(100, 200, 300, 400, 500, or 600 mg/kg) was intragastrically administered six times every day(4-hour intervals) for 5 days. To determine the best dosage, sodium valproate concentration was measured from the plasma. The effective concentration of sodium valproate in the plasma of the rats that received the 300-mg/kg intervention was 82.26 ± 11.23 μg/mL. Thus, 300 mg/kg was subsequently used as the intervention concentration of sodium valproate. The following changes were seen: Recording excitatory postsynaptic potentials in the CA1 region revealed high-frequency stimulation-induced long-term potentiation. Immunohistochemical staining for BrdU-positive cells in the brain revealed that sodium valproate intervention markedly increased the success rate and the duration of induced long-term potentiation in rats with convulsive status epilepticus. The intervention also reduced the number of newborn neurons in the subgranular area of the hippocampus and subventricular zone and inhibited the migration of newborn neurons to the dentate gyrus. These results indicate that sodium valproate can effectively inhibit the abnormal proliferation and migration of neural stem cells and newborn neurons after convulsive status epilepticus, and improve learning and memory ability.

Dynamic expression of P-glycoprotein in the CA1,CA3 and dentate gyrus of the rat hippocampus following lithium-pilocarpine-induced status epilepticus

Epileptic seizures induce overexpression of P-glycoprotein in the blood-brain barrier. However, it is unclear whether hippocampal neurons also overexpress P-glycoprotein following seizure. This study confirmed that the clinical manifestation, pathological characteristics and electroencephalography in the rat model of lithium-pilocarpine-induced mesial temporal lobe epilepsy were consistent with clinical reports of mesial temporal lobe epilepsy in humans.Immunohistochemistry staining demonstrated that P-glycoprotein positive staining was found in neurons in the pyramidal layer of the hippocampus. Westem blot assay and real-time polymerase chain reaction revealed that P-glycoprotein overexpression was exhibited in the CA1, CA3, and dentate gyrus of the hippocampus at 24 and 60 days following model induction, but no significant dffierence was detected in the same region at various time points. These results indicate that seizures led to overexpression of P-glycoprotein in neurons of the hippocampus, but no evidence was found for a positive association between P-glycoprotein expression and seizure frequency.

Status epilepticus as a complication after COVID-19 mRNA-1273 vaccine:A case report

BACKGROUND We present a rare case of status epilepticus in a 56-year-old man which arose as a complication after vaccination with the coronavirus disease 2019(COVID-19)mRNA-1273 vaccine.The patient's history included well-compensated secondary epilepsy.The root cause of the situation was a fever which had developed as a side effect of the vaccination.CASE SUMMARY A 56-year-old man received the first dose of mRNA-1273 vaccine against the severe acute respiratory syndrome-coronavirus-2.The vaccine was administered intramuscularly(100 mg,0.5 mL).The next morning the man was found to be suffering from fever and headaches while at the same time experiencing general weakness.He lost consciousness suddenly and experienced generalized clonic seizures which turned into status epilepticus.When the Emergency Medical Service arrived the patient was unconscious with spontaneous breathing and generalized clonic seizures.It was necessary to administer diazepam repeatedly.It was also necessary to administer high doses of levetiracetam and temporary propofol.The status epilepticus was brought under control approximately 90 min after the patient’s transport to the Emergency Department.A follow-up electroencephalogram no longer revealed abnormal indications of epileptic fit.The patient was temporarily hospitalized in the Intensive Care Unit and after seven days care was discharged without any further apparent effects.CONCLUSION There is currently no specific treatment against COVID-19.Therefore,the benefits of COVID-19 vaccine protection outweigh the risks.

Status epilepticus as an initial manifestation of hepatic encephalopathy:A case report

BACKGROUND Status epilepticus in patients with hepatic encephalopathy (HE) is a rare butserious condition that is refractory to antiepileptic drugs, and current treatmentplans are vague. Diagnosis may be difficult without a clear history of cirrhosis.Liver transplantation (LT) is effective to alleviate symptoms, however, there arefew reports about LT in the treatment of status epilepticus with HE. To ourknowledge, this is the first report of status epilepticus present as initialmanifestation of HE.CASE SUMMARY A 59-year-old woman with a 20-year history of heavy drinking was hospitalizedfor generalized tonic-clonic seizures. She reported no history of episodes of HE,stroke, spontaneous bacterial peritonitis, ascites or gastrointestinal bleeding.Neurological examination revealed a comatose patient, without papilledema.Laboratory examination suggested liver cirrhosis. Plasma ammonia levels uponadmission were five times normal. Brain computed tomography (CT) was normal,while abdominal CT and ultrasound revealed mild ascites, liver cirrhosis andsplenomegaly. Electroencephalography (EEG)showed diffuse slow waves rhythm,consistent with HE, and sharp waves during ictal EEG corresponding to clinicalsemiology of focal tonic seizures. The symptoms were reversed by continuousantiepileptic treatment and lactulose. She was given oral levetiracetam, and focalaware seizures occasionally affected her 10 mo after LT.CONCLUSION Status epilepticus could be an initial manifestation of HE. Antiepileptic drugs combined with lactulose are essential for treatment of status epilepticus with HE,and LT is effective to prevent the relapse.

Status epilepticus increases mature granule cells in the molecular layer of the dentate gyrus in rats

Enhanced neurogenesis in the dentate gyrus of the hippocampus following seizure activity, especially status epilepticus, is associated with ectopic residence and aberrant integration of newborn granule cells. Hilar ectopic granule cells may be detrimental to the stability of dentate circuitry by means of their electrophysiological properties and synaptic connectivity. We hypothesized that status epilepticus also increases ectopic granule cells in the molecular layer. Status epilepticus was induced in male Sprague-Dawley rats by intraperitoneal injection of pilocarpine. Immunostaining showed that many doublecortin-positive cells were present in the molecular layer and the hilus 7 days after the induction of status epilepticus. At least 10 weeks after status epilepticus, the estimated number of cells positive for both prospero homeobox protein 1 and neuron-specific nuclear protein in the hilus was significantly increased. A similar trend was also found in the molecular layer. These findings indicate that status epilepticus can increase the numbers of mature and ectopic newborn granule cells in the molecular layer.

Status epilepticus and acute promyelocytic leukemia

Neurological manifestations are rare as initial presentation in acute promyelocytic leukemia (APL). This case illustrates status epilepticus as initial presentation in this disease. Atypical cells on peripheral smear led to the diagnosis of leukemia.

Alterative application of five anticonvulsants according to the half life for the treatment of status epilepticus in children with severe viral encephalitis

BACKGROUND： Traditional subhibernation therapy may easily cause complications, such as respiratory depression and hyportension because of application of chlorpromazine hydrochloride and promethazine in a large dosage. OBJECTIVE： To observe therapeutic effect of modified subhibernation therapy （alterative application of five anticonvulsants according to the half life） on status epilepticus in children with severe viral encephalitis （VE）. DESIGN： Contrast observation. SETTING： Department of Pediatrics, the First Hospital of Jilin University. PARTICIPANTS： The participants in present study were 96 patients with severe viral encephalitis including 52 boys and 44 girls who received treatment in the Department of Pediatrics, the First Hospital of Jilin University from February 2000 to March 2006. All children met the diagnostic criteria of Zhufutong Practice Pediatrics （the seventh edition）. Two weeks ago, they ever got upper respiratory infection or enteronitis and so on before the onset, spirit abnormal, behavior disorder, limbs act disorder, vomit, headache, convulsion, nervous system masculine signs such as limbs act disord, autonomic nerve damage manifestation, brain nerve palsy, dysreflexia, meningeal irritation sign, cerebrospinal fluid and electroencephalography （EEG） abnormity. All parents provided the confirmed consent. The patients were randomly divided into control group （n =40） and experimental group （n =56）. METHODS： Patients in the control group received anticonvulsion, ice compress and routine treatment. The convulsion was treated with five drugs： 0.5 mg/kg wintermin and phenergan, respectively, 100 g/L chlorpromazine hydrochloride （0.5 mL/kg）, 5 mg/kg luminal, 0.3 mg/kg ansiolin. When convulsion attacked, those five drugs were given alternatively; however, those were not given if the convulsion did not attack. Children in the experimental group were treated with improved subhibernation therapy based on routine treatment. The dosages of anticonvulsants were as the same as those in the control group. Based on the half life, every drug was alternated every 4-6 hours. In addition, anticonvulsants administrated for 2 successive days whether tic attacked or not. Then the hypnotic was removed gradually. MAIN OUTCOME MEASURES： Therapeutic efficacy, time of disappeared clinical symptoms and physical sign, and security of administration. RESULTS： All the 96 patients were involved in the final analysis. ① Total effective rate and reliability： Total effective rate was higher in the treatment groups than the control group （χ2=5.871 7, P 〈 0.05）. All patients did not have respiratory depression and side effects. ② Time of disappeared clinical symptoms and physical sign： Recovery time of convulsion, fever, headache and vomit was shorter in the treatment group than that in the control group, and there was significant difference （t =17.612 1-34.330 7, P 〈 0.05）; in addition, symptoms of status epilepticus were relieved obviously. Meanwhile, recovery time of paralysis, coma and anepia was shorter in the treatment group than that in the control group, and there was significant difference （t =10.660 8-24.700 8, P 〈 0.05）. CONCLUSION： Therapeutic effect of improved subhibernation therapy on status epilepticus induced by severe viral encephalitis is positively and safer.

癫痫持续状态(Status epilepticus)的治疗

治疗原则1.控制抽搐发作。2.防止并发症的发生并根据病情变化,作适宜的对症处理。3.查出病因,尽早施行病因治疗。

Status Epilepticus in Children: A Study of 54 Cases

Objectives: To review the clinical character, the management and outcome of status epilepticus in children. Methodology: We conducted a retrospective review of 54 cases treated between 1996 and 1997 at the Royal Alexandra Hospital for Children, Sydney, Australia. Among the variables collected for analysis in this study were age, sex, etiology of status epilepticus, median length of Paediatric Intensive Care Unit (PICU) stay and days of mechanical ventilation, and mortality of status epilepticus. Results: Of the patients with status epilepticus, 61% were male and 39% female, with an age range of 3 months to 15 years (mean 5.3 years). The etiology of status epilepticus is largely age related, with acute causes common in 1 - 3 year and 4 - 7 year ages, 44 cases (81.5%). The etiology of status epilepticus included febrile (35.18%), acute symptomatic (27.58%) and idiopathic (16.6%), total was 44 cases (81.4%). Median length of PICU stay and days of mechanical ventilation were 3.02 ± 1.6 days and 1.24 ± 0.5 days respectively. Mortality was 5.3%. Most patients were treated with diazepam and phenytoin. The total number of the patients with a favorable outcome was 41 (75.89%). Conclusions: One of the most common neurologic emergencies in children of status epilepticus remains a major problem in morbidity and mortality. There are multiple causes of status epilepticus that include the categories of idiopathic, febrile, acute symptomatic and remote symptomatic. Intravenously administered phenytoin and diazepam remains the first-line therapy for status epilepticus. Most of the patients will respond to this treatment. The etiology of status epilepticus included febrile (35.18%), acute symptomatic (27.58%), idiopathic (16.6%) and total was 44 (81.4%).

A Descriptive Analysis of Prognostic Indicators in Patients with Non-Convulsive Status Epilepticus in a Tertiary Hospital Population

Background: Non-convulsive status epilepticus (NCSE) is defined as a change in mental state of at least 30 minutes associated with continuous or nearly continuous epileptiform discharges. Identification of prognostic indicators can guide decision making surrounding the use of poorly established treatment interventions in this heterogeneous population. Methods: We identified 66 consecutive inpatients with NCSE. Data surrounding clinical, electrographic, and treatment factors were collected via a retrospective systematic review of medical records and electronic EEGs, and were correlated with discharge outcome (return to baseline, new disability, or death). Results: Of all subjects, 21% returned to baseline, 26% acquired new disability, and 53% died, of whom half had anoxic encephalopathy. On univariate analysis, seventeen variables correlated significantly with death, although multivariate logistic regression analysis subsequently identified only comatose state and number of life threatening comorbidities as independent predictors of mortality. Of survivors, comatose state, critical care environment, length of hospital stay, and acute symptomatic seizures predicted new disability, with the latter two showing independent significance. Following exclusion of cases with anoxic encephalopathy, the use of an anaesthetic infusion was also an independent predictor of mortality. Conclusions: NCSE is associated with variable morbidity and mortality. While one fifth of our NCSE patients returned to baseline, those comatose with acute structural/metabolic seizures, anaesthetic infusions, and life threatening comorbidities were unlikely to survive without disability at discharge.