RESUMO
In the wake of acquired brain insults such as status epilepticus (SE), time-dependent neuronal network alterations may occur resulting in cortical hyperexcitability and enhanced synchrony merging into chronic epilepsy. To better understand the underlying processes, we performed electrophysiological and optical imaging studies on combined hippocampal-entorhinal cortex slices. These were prepared from rats 1, 4 and 8 weeks after electrically-induced SE. Non-invasive imaging using intrinsic optical signal changes allowed detailed analysis of onset and spread patterns of seizure-like events (SLE) since coverage of the entire preparation is possible. The latency to occurrence of first SLEs after omission of Mg(2+) from the artificial cerebrospinal fluid was significantly reduced at 4 and 8 weeks after SE compared with all other groups indicating increased brain excitability. Optical imaging displayed multiregional onset and discontiguous propagation of SLEs 8 weeks after SE. Such patterns indicate neuronal hypersynchrony and are not encountered in naïve rodents in which SLEs commonly begin in the entorhinal cortex and display contiguous spread to invade adjacent regions. The electrophysiological and optical findings of the current study indicate evolving fundamental brain plasticity changes after the detrimental event predisposing to chronic epilepsy. The current results should be incorporated in any strategies aiming at prevention of chronic epilepsy.
Assuntos
Potenciais de Ação/fisiologia , Sincronização Cortical/fisiologia , Hipocampo/fisiopatologia , Vias Neurais/fisiopatologia , Estado Epiléptico/patologia , Animais , Doença Crônica , Modelos Animais de Doenças , Estimulação Elétrica/efeitos adversos , Hipocampo/patologia , Masculino , Vias Neurais/patologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Estado Epiléptico/fisiopatologia , Estado Epiléptico/prevenção & controle , Imagens com Corantes Sensíveis à Voltagem/métodosRESUMO
The objective of the current article 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 and in the current updated version all pertinent publications from January 2005 to January 2009. 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 4-8 mg lorazepam or 10 mg diazepam directly followed by 18 mg/kg phenytoin. If seizures continue more than 10 min after first injection, another 4 mg lorazepam or 10 mg diazepam is recommended. Refractory GCSE is treated by anaesthetic doses of barbiturates, midazolam or propofol; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. The initial therapy of non-convulsive SE depends on type and cause. Complex partial SE is initially treated in the same manner as GCSE. However, if it turns out to be refractory, further non-anaesthetising i.v. substances such levetiracetam, phenobarbital or valproic acid should be given instead of anaesthetics. In subtle SE, in most patients, i.v. anaesthesia is required.
Assuntos
Estado Epiléptico/tratamento farmacológico , Adulto , Anestésicos/administração & dosagem , Anestésicos/uso terapêutico , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Quimioterapia Combinada , Humanos , Estado Epiléptico/epidemiologiaRESUMO
Twenty-six Austrian, Dutch, German, and Swiss epilepsy centers were asked to report on use of the Wada test (intracarotid amobarbital procedure, IAP) from 2000 to 2005 and to give their opinion regarding its role in the presurgical diagnosis of epilepsy. Sixteen of the 23 centers providing information had performed 1421 Wada tests, predominantly the classic bilateral procedure (73%). A slight nonsignificant decrease over time in Wada test frequency, despite slightly increasing numbers of resective procedures, could be observed. Complication rates were relatively low (1.09%; 0.36% with permanent deficit). Test protocols were similar even though no universal standard protocol exists. Clinicians rated the Wada test as having good reliability and validity for language determination, whereas they questioned its reliability and validity for memory lateralization. Several noninvasive functional imaging techniques are already in use. However, clinicians currently do not want to rely solely on noninvasive functional imaging in all patients.
Assuntos
Epilepsia/fisiopatologia , Idioma , Memória/fisiologia , Testes Neuropsicológicos/estatística & dados numéricos , Áustria , Alemanha , Humanos , Estudos Multicêntricos como Assunto , Países Baixos , SuíçaRESUMO
Old age is the most common time for patients to develop epileptic seizures, and due to their frequent unusual clinical presentation the diagnosis of epilepsy is often delayed in the elderly. It is as yet unknown if pronounced alterations in the plastic properties of aging nervous tissue contribute to these phenomena. We employed a non-lesional in vitro epilepsy model to study seizure susceptibility, spread pattern, and propagation velocities in combined hippocampal-entorhinal cortex slices of aged rats and controls using electrophysiological methods and imaging of intrinsic optical signals. In aged animals we saw a less extensive spread of seizure-like events into areas adjacent to the region of onset of activity and a decreased spread velocity in various anatomical regions. In addition, both the activity-dependent shrinkage of the extracellular space (ECS)-volume and the extracellular K(+) concentration were significantly reduced compared to controls. The results of this study are consistent with the clinical observation that epileptic seizures in the elderly have a reduced tendency to spread. In addition, our data suggest that in the absence of structural lesions seizure susceptibility in the aging brain is not increased.
Assuntos
Envelhecimento/fisiologia , Epilepsia/fisiopatologia , Microscopia/métodos , Animais , Eletrofisiologia , Córtex Entorrinal/fisiopatologia , Epilepsia/induzido quimicamente , Espaço Extracelular/fisiologia , Hipocampo/fisiopatologia , Técnicas In Vitro , Magnésio/farmacologia , Masculino , Óptica e Fotônica , Potássio/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Wistar , Tetraetilamônio/farmacologiaRESUMO
The acute effects of partial (focal) epileptic seizures on serum prolactin levels were studied in two groups of patients: (1) 10 with temporal lobe seizures and (2) 11 with seizures that arose from the frontal lobes, recorded on cable video-electroencephalographic telemetry. Six of the eight complex partial seizures of temporal lobe origin were associated with a marked rise in prolactin levels at 10 minutes after onset (rise in levels, from a mean of 279 to 534 mU/L), compared with a rise in only one of the eight frontal lobe complex partial seizures. None of the five simple partial seizures (two of temporal and three of frontal lobe origin) was associated with a marked rise in prolactin levels. This difference in prolactin response following complex partial seizures of frontal and temporal lobe origin may help in the clinical differentiation of these seizures. A failure of prolactin levels to rise does not, however, exclude a diagnosis of complex partial seizures; thus, this measurement will not help in the clinical differentiation of frontal lobe complex partial seizures from psychogenic attacks.
Assuntos
Epilepsia do Lobo Temporal/sangue , Lobo Frontal/fisiopatologia , Lobo Temporal/fisiopatologia , Adolescente , Adulto , Eletroencefalografia , Epilepsia Parcial Complexa/sangue , Epilepsia Parcial Complexa/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Convulsões/sangue , Convulsões/fisiopatologiaRESUMO
BACKGROUND: The familial spastic paraplegias (FSPs) are hereditary neurodegenerative disorders with an unknown pathogenesis. Pure and complicated forms are currently differentiated on clinical grounds. To date, no linkage studies in complicated FSP have been reported, and candidate genes have not been suggested. Three different gene loci responsible for pure autosomal dominant FSP and 1 for pure autosomal recessive FSP recently have been found. This raises the question of whether the complicated forms may also be linked to any of these loci. OBJECTIVE: To investigate whether complicated autosomal dominant FSP is allelic to any of the pure forms with defined loci. DESIGN: Clinical characterization of a large kindred that included 4 generations and multipoint linkage analyses. SETTING: Universitätsklinikum Charité, Humboldt-Universität Berlin, Neurologische Klinik und Poliklinik, Berlin, Germany. PATIENTS: Twenty-six family members, 13 of whom were affected. RESULTS: Thirteen members of a large family of 4 generations experienced a slowly progressive syndrome of spastic paraplegia. Hypomimia, bradykinesia, axial and limb rigidity, supranuclear gaze palsy, dysarthria, bladder and sphincter disturbances, cerebellar signs, and epilepsy were noted as additional features in some of the affected individuals. The mean age at onset was 20 years (range, 5-30 years), and the pattern of transmission was compatible with an autosomal dominant mode of inheritance. The CAG-repeat expansions in the spinocerebellar ataxia type 1 and Machado-Joseph disease genes were not found. Linkage analysis with the use of a panel of (AC)n dinucleotide repeat markers from the Généthon map demonstrated exclusion of all 4 FSP loci recently mapped by linkage to pure forms of FSP on chromosomes 14q, 2p, 15q, and 8. CONCLUSIONS: Complicated FSP in this family is not linked to any of the known pure FSP loci, including the recessive one. Therefore, the clinical differentiation of both forms still is of major relevance.ACKG
Assuntos
Paraplegia Espástica Hereditária/genética , Idoso , Feminino , Genes Dominantes , Genes Recessivos , Ligação Genética , Humanos , Repetições de TrinucleotídeosRESUMO
A total of 110 patients underwent diagnostic evaluation for attacks of uncertain origin by means of video-EEG telemetry and had a diagnosis of pseudoseizures confirmed. Eighty-six patients (78%) were female, mean age of onset 25 years, and mean duration of attacks was 3 years. Many of the patients had erroneously been thought to be suffering from epilepsy. The attacks could be divided into two broad categories: attacks of collapse (one-third) and attacks with prominent motor activity (two-thirds). In some patients, the attacks were associated with incontinence and injury. The differential diagnosis and clinical features of the attacks are described. Additional psychiatric features were present in 52 (47%) patients. Follow-up (for a median 5 years; range, 1 to 14 years) showed that 40% of these patients stopped having pseudoseizures. This favorable outcome was associated with being female, leading an independent life, a formal psychological approach to therapy and counseling, and the absence of coexisting epilepsy, but not with the duration of pseudoepilepsy, prior episodes of pseudostatus, the coexistence of overt psychiatric disease, or the clinical features of the attacks.
Assuntos
Eletroencefalografia , Convulsões/diagnóstico , Adulto , Eletroencefalografia/métodos , Epilepsia/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Telemetria , Gravação de VideoteipeRESUMO
Anticonvulsant properties of furosemide have been suggested to reduce neuronal synchronization via its inhibitory effect on the Na+/K+/2Cl- co-transport system. We have studied effects of furosemide on spontaneous epileptiform activity and analysed effects of furosemide on amplitudes of stimulus-induced population-spikes, on stimulus-induced K+ changes, on extracellular pH changes at rest and during stimulation, and on changes in the extracellular space-volume. We used three different in vitro models of epilepsy in the combined hippocampal-entorhinal cortex slice preparation. Furosemide reversibly suppressed low Ca2+-induced epileptiform activity in hippocampus proper and blocked or significantly reduced different types of epileptiform discharges in the low Mg2+ model and the 4-aminopyridine model. Amplitudes of evoked field potentials underwent an initial slight increase followed by a significant reduction after prolonged treatment with furosemide. Stimulus-induced increases in extracellular potassium were also significantly reduced. Furosemide caused an alkaline shift at rest. Stimulus-induced pH transients changed from a biphasic alkalotic-acidotic sequence to a monophasic alkalotic shift. Stimulation-induced shrinkage of extracellular space-volume was reduced by furosemide, whereas no effect on baseline extracellular space-volume was seen. We conclude, that furosemide possesses strong anticonvulsive effects in various in vitro models of epilepsy. The anticonvulsive properties of furosemide cannot be explained by its effects on extracellular pH changes but appear in part to be mediated via a reduced excitability with consequent reduction of activity-induced potassium rises. Finally, partial inhibition of activity-induced extracellular space shrinkage may contribute to its anticonvulsant properties.
Assuntos
Anticonvulsivantes/farmacologia , Córtex Entorrinal/fisiopatologia , Epilepsia/fisiopatologia , Furosemida/farmacologia , Hipocampo/fisiopatologia , 4-Aminopiridina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Cálcio/administração & dosagem , Cálcio/farmacologia , Estimulação Elétrica , Feminino , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Magnésio/administração & dosagem , Magnésio/farmacologia , Masculino , Concentração Osmolar , Potássio/metabolismo , Ratos , Ratos Wistar , Tetraetilamônio/metabolismoRESUMO
1. Lowering of the extracellular Mg(2+)-concentration induces various patterns of epileptiform activity in combined rat entorhinal cortex-hippocampal brain slices. After a prolonged period of exposure to Mg(2+)-free medium seizure-like events in the entorhinal cortex change to a state of late recurrent discharges which cannot be blocked by clinically available antiepileptic drugs. This late epileptiform activity thus represents a useful model to test the effects of new anticonvulsant substances. 2. A mechanism possibly underlying the development of sustained seizure-like activity is the loss of synaptically released gamma-aminobutyric acid (GABA). Drugs which increase the amount of GABA available in presynaptic endings might thus be useful in the treatment of these therapeutically complicated forms of epilepsy. 3. Therefore, we studied the effects of various substances increasing GABA-mediated inhibition on early and late forms of epileptiform activity. GABA and the GABAA receptor agonist muscimol blocked both the pharmacosensitive discharges in the hippocampus and entorhinal cortex as well as the late recurrent discharges in the medial entorhinal cortex. The GABAB receptor agonist baclofen blocked the recurrent short discharges very potently, but did not consistently block seizure-like events and late recurrent discharges in the entorhinal cortex. 4. GABA uptake blockers showed a differential potency to block the various discharge patterns. Whereas nipecotic acid and beta-alanine suppressed all forms of epileptiform activity albeit at high concentrations (1-5 mM), tiagabine was much more potent in blocking the hippocampal recurrent short discharges and the seizure-like events in the medial entorhinal cortex, but could not block the late recurrent discharges. 5. Our data support the idea that prolonged neuronal overactivity might result in a loss of synaptically available GABA. Selective block of uptake into glia cells or substitution of the transmitter may therefore be an efficient strategy for the treatment of severe prolonged epileptic discharges whereas block of neuronal GABA uptake fails to counteract synchronized discharges in this situation.
Assuntos
Córtex Entorrinal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Prolina/análogos & derivados , Ácido gama-Aminobutírico/farmacologia , Animais , Baclofeno/farmacologia , Relação Dose-Resposta a Droga , Córtex Entorrinal/fisiologia , Córtex Entorrinal/fisiopatologia , Epilepsia/tratamento farmacológico , Feminino , Agonistas GABAérgicos/farmacologia , Hipocampo/fisiologia , Hipocampo/fisiopatologia , Técnicas In Vitro , Magnésio/farmacologia , Masculino , Potenciais da Membrana/fisiologia , Muscimol/farmacologia , Neurônios/fisiologia , Inibidores da Captação de Neurotransmissores , Ácidos Nipecóticos/farmacologia , Ratos , Ratos Wistar , TiagabinaRESUMO
A reproducible increase in transmission of infrared light was observed during spontaneous seizure-like events (SLEs) induced by low Mg2+ solutions in combined rat entorhinal cortex-hippocampal slices. Comparison of half maxima of transmission change in different regions indicated propagation of SLEs from the medial entorhinal cortex towards the temporal cortex suggesting spread along existing anatomical pathways. Thus, optical imaging of spontaneous epileptiform activity is possible and may improve the assessment of spread patterns. The optical signal outlasted both SLEs and associated K+ signals. In contrast, the tetraethylammonium signal, indicating changes of the extracellular space (ECS) volume, had a longer time course than the transmission changes. ECS volume changes are widely held to be responsible for transmission change. Our data suggest that other mechanisms may also contribute to increased light transmission during epileptiform activity.
Assuntos
Córtex Entorrinal/patologia , Epilepsia/patologia , Deficiência de Magnésio/patologia , Animais , Eletrofisiologia , Espaço Extracelular/fisiologia , Citometria por Imagem , Processamento de Imagem Assistida por Computador , Técnicas In Vitro , Raios Infravermelhos , Cinética , Potássio/fisiologia , Ratos , Ratos WistarRESUMO
Application of 4-aminopyridine (4AP) has previously been reported to produce different patterns of epileptiform discharges in entorhinal cortex-hippocampal-slices. Here we describe that 4-AP induced epileptiform activity in the EC becomes insensitive to anticonvulsant drugs (phenytoin, carbamazepine, valproic acid, phenobarbital) when GABAergic transmission is blocked by bicuculline. We propose that the activities induced by 4-aminopyridine and bicuculline may provide an in vitro model for the development of new drugs against difficult-to-treat focal epilepsy.
Assuntos
4-Aminopiridina , Anticonvulsivantes/farmacologia , Bicuculina , Convulsivantes , Epilepsia/tratamento farmacológico , Potenciais Evocados/efeitos dos fármacos , Animais , Córtex Entorrinal/efeitos dos fármacos , Córtex Entorrinal/fisiologia , Epilepsia/induzido quimicamente , Epilepsia/fisiopatologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , RatosRESUMO
Results regarding the anticonvulsant potency of bromide have been questioned, and the mechanisms of its action are unclear. Using combined rat hippocampus-entorhinal cortex slices we analyzed the effects of NaBr on four types of epileptiform discharges in two different models of epilepsy, the low-Ca2+ and the low-Mg2+ model. NaBr concentration-dependently reduced the frequency and finally blocked the low Ca2+-induced discharges. Low Mg2+-induced short recurrent discharges were also reduced in a concentration-dependent manner. In the entorhinal cortex the frequency of seizure-like events was reduced by 3 and 5 mM and the discharges were blocked by 7 mM NaBr. Also, the late recurrent discharges in the entorhinal cortex which do not respond to most clinically employed anticonvulsants were reduced by concentrations of 10 and 15 mM and completely blocked by 30 mM NaBr. Using pH-sensitive microelectrodes different effects of NaBr were seen than those of acetazolamide on extracellular pH under control conditions and after stimulation. Acetazolamide at 1 mM caused a reversible acidification of delta pH: 0.2+/-0.14 at rest whereas no change on extracellular pH was seen with 5 mM NaBr. Acetazolamide increased the transient alkalosis induced by repetitive stimulation of the stratum radiatum in area CA1 and reduced the subsequent acidosis. NaBr also increased the alkalosis but had no effect on the subsequent acidosis. A significant increase in paired-pulse inhibition was seen in a paired-pulse stimulation protocol used to monitor the efficacy of GABAergic inhibition at concentrations of 5 mM NaBr. This finding was confirmed in whole-cell patch clamp recordings from cultured hippocampal neurons showing an increase in inhibitory postsynaptic current amplitude. In summary, our results suggest a broad-spectrum anticonvulsant activity which is likely to be caused by its effects on membrane excitability, by an increase in GABAergic inhibition and is less likely caused by its effects on extracellular pH.
Assuntos
Anticonvulsivantes/farmacologia , Brometos/farmacologia , Epilepsia/fisiopatologia , Espaço Extracelular/metabolismo , Compostos de Sódio/farmacologia , Ácido gama-Aminobutírico/fisiologia , Acetazolamida/farmacologia , Algoritmos , Animais , Cálcio/fisiologia , Inibidores da Anidrase Carbônica/farmacologia , Estimulação Elétrica , Eletrofisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Espaço Extracelular/efeitos dos fármacos , Feminino , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Magnésio/fisiologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Microeletrodos , Técnicas de Patch-Clamp , Ratos , Ratos Wistar , Fatores de TempoAssuntos
Lobo Parietal/patologia , Pseudoartrose/complicações , Pseudoartrose/patologia , Idoso , Estimulação Elétrica/métodos , Potenciais Somatossensoriais Evocados/fisiologia , Dedos/inervação , Dedos/efeitos da radiação , Humanos , Imageamento por Ressonância Magnética , Masculino , Distúrbios Somatossensoriais/etiologiaRESUMO
Pharmacological concepts tailored to status epilepticus, to epileptogenesis following acquired brain insults, and to ictogenesis in established epilepsy vary considerably and should ideally be directed at those pathophysiological mechanisms that presumably underly these conditions. Currently known important molecular targets include voltage-gated sodium and calcium channels, the gamma-aminobutyric acid (GABA) system and ionotropic glutamate receptors. Metabotropic glutamate receptors, potassium channels, and neurotransmitters such as acetylcholine, glycine, and monoamines are beyond the scope of this review. In status epilepticus, immediate failure of GABAergic inhibition occurs, and administration of benzodiazepines and barbiturates displays the pharmacostrategic mainstay. In epileptogenesis within limbic structures, the most important underlying pathophysiological mechanisms currently discussed are transient loss of inhibition and aberrant mossy fiber sprouting. Both processes may be facilitated by N-methy-D: -aspartat (NMDA) receptor regulation. NMDA antagonists may exhibit antiepileptogenic properties in experimental animals, but reliable data in humans are lacking. In established epilepsy, voltage-gated ion channels and impairment of GABAergic functions contribute to mechanisms facilitating ictogenesis. Blockade of sodium and calcium channels and enhancement of GABAergic inhibition are currently the most important tools to prevent the occurrence of seizures.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Animais , Canais de Cálcio/efeitos dos fármacos , Epilepsia/etiologia , Epilepsia/fisiopatologia , Humanos , Receptores de GABA/efeitos dos fármacos , Receptores de Glutamato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/fisiologia , Canais de Sódio/efeitos dos fármacos , Estado Epiléptico/tratamento farmacológico , Ácido gama-Aminobutírico/fisiologiaRESUMO
Status epilepticus in patients often does not respond to first-line anticonvulsants, and subsequent treatment escalation with continuous intravenous anesthetics may be associated with significant side-effects. Therefore, alternative treatment regimens are urgently needed. Hypothermia has been shown to reduce excitatory transmission and may thus serve as an interesting adjunct in the management of status epilepticus. In the current experiments, three treatment groups were compared. Animals with self-sustaining status epilepticus were treated with external cooling for 3 h, with low-dose diazepam, or with a combination of both. The effect of these regimens on epileptic activity was compared with untreated controls. Animals that underwent cooling were rewarmed, and all animals were monitored for 5 h to assess occurrence and severity of motor seizures and frequency and amplitude of spontaneous epileptic discharges. Cooling alone significantly reduced number and severity of motor seizures but did not alter epileptic discharges. Cooling in addition to low-dose diazepam significantly diminished amplitudes and frequencies of epileptic discharges, while diazepam alone had only a minor reducing effect on discharge amplitudes. However, at later stages of status epilepticus, diazepam significantly reduced motor seizures. Following rewarming, the discharge frequency tended to increase again, suggesting partial reversibility. The current experiments show that in status epilepticus hypothermia exhibits anticonvulsant effects which are most pronounced if co-administered with low-dose diazepam. The results still require confirmation in other animal models and also clinical studies are urgently needed. However, our data indicate that cooling could well become a future adjunct in the treatment of status epilepticus in patients.
Assuntos
Temperatura Corporal/fisiologia , Encéfalo/fisiopatologia , Epilepsia/terapia , Hipotermia Induzida/métodos , Convulsões/terapia , Estado Epiléptico/terapia , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Temperatura Baixa , Giro Denteado/efeitos dos fármacos , Giro Denteado/fisiopatologia , Diazepam/farmacologia , Diazepam/uso terapêutico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Epilepsia/fisiopatologia , Epilepsia/prevenção & controle , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipotermia Induzida/normas , Hipotermia Induzida/tendências , Masculino , Ratos , Ratos Wistar , Convulsões/fisiopatologia , Convulsões/prevenção & controle , Estado Epiléptico/fisiopatologia , Estado Epiléptico/prevenção & controle , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologiaRESUMO
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.
Assuntos
Estado Epiléptico/terapia , Anticonvulsivantes/uso terapêutico , Europa (Continente) , Humanos , Incidência , Garantia da Qualidade dos Cuidados de Saúde , Estado Epiléptico/classificação , Estado Epiléptico/epidemiologiaRESUMO
OBJECTIVE: To assess risk factors and prognosis in patients with refractory status epilepticus (RSE). METHODS: We retrospectively analysed all episodes of status epilepticus (SE) treated between 1993 and 2002 on the neurological intensive care unit (NICU) of the Charite-Universitatsmedizin Berlin. The predictive and prognostic features of RSE were compared with non-RSE (NRSE). All patients with "de novo" SE were followed up to identify the possible development of post-SE symptomatic epilepsy. RESULTS: A total of 83 episodes fulfilled our criteria of SE. Of these 43% were refractory to first line anticonvulsants. The mean age of patients with SE was 53.3 (SD 19) years, with only two patients younger than 18 years. Encephalitis was significantly more often the primary cause in RSE (p<0.05), whereas low levels of antiepileptic drugs were significantly more often associated with NRSE (p<0.001). Hyponatraemia within the first 24 hours after onset of status activity was significantly more often associated with RSE (p<0.05). In RSE, compared with NRSE, significantly longer duration of seizure activity (p<0.001), more frequent recurrence of epileptic activity within the first 24 hours after the end of seizure activity (p<0.001), longer stay in the NICU and in hospital (p<0.001 and p<0.01, respectively), and more frequent development of symptomatic epilepsy (p<0.05) were seen. CONCLUSIONS: SE treated in the NICU is frequently refractory to first line anticonvulsant drugs. Encephalitis is a predictor for RSE, which is associated with markedly poor outcome, in particular, the development of post-SE symptomatic epilepsy. Thus prevention of this most severe form of SE should be the primary target of treatment of SE.
Assuntos
Anticonvulsivantes/uso terapêutico , Unidades de Terapia Intensiva , Neurologia/métodos , Período Refratário Eletrofisiológico/fisiologia , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/reabilitação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Criança , Feminino , Hospitalização , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Estado Epiléptico/etiologia , Resultado do TratamentoRESUMO
The pathophysiological mechanisms that cause spontaneous seizures following status epilepticus are largely unknown. Erosion of inhibition is regarded as an important pathophysiological hallmark of ongoing status epilepticus. Therefore, we investigated if loss of inhibitory functions also plays an important role in the development of spontaneous seizures after status epilepticus. Furthermore, we analyzed possible changes in excitation that might contribute to epileptogenesis. Finally, neuronal cell loss in the dentate gyrus granule cell layer was analyzed. In rats, inhibition and excitation in the dentate gyrus were monitored 1, 4, and 8 weeks after electrically induced self-sustaining status epilepticus (SSSE). Control animals had electrodes implanted either without subsequent stimulation or with stimulation but under barbiturate anesthesia, neither of which resulted in subsequent spontaneous seizures or impairment of inhibition. Following SSSE 80% of animals developed seizures after 8 weeks. A pronounced impairment of inhibition 1 week after SSSE was followed by gradual recovery over 8 weeks. In the dentate gyrus, cell damage was highly variable most likely explaining the heterogeneity of changes in excitatory parameters. Loss of GABAergic inhibition in the dentate gyrus may facilitate initiation of epileptogenesis but impaired inhibition is not required for the process of epileptogenesis to be maintained.
Assuntos
Inibição Neural/fisiologia , Convulsões/fisiopatologia , Estado Epiléptico/fisiopatologia , Animais , Contagem de Células/métodos , Giro Denteado/patologia , Giro Denteado/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Masculino , Ratos , Ratos Wistar , Convulsões/patologia , Estado Epiléptico/patologia , Fatores de TempoRESUMO
The general and ictal clinical features, including EEG findings, of 20 consecutive patients with frontal lobe epilepsy are presented. Diagnosis in all cases was based on video-EEG telemetry using strict criteria. Among the ictal motor phenomena, turning movements, dystonic, choreic and ballistic features prevailed. Ten patients vocalised during their seizures but loss of consciousness was rare, even if there was pronounced motor involvement. The duration of attacks generally was short, not exceeding 60 seconds in 18 patients, in whom sudden onset and cessation of seizures was noted. Ten patients showed inter-ictal epileptiform EEG activity and 19 had ictal abnormalities. The short duration and ictal clinical course may be helpful in differentiating frontal seizures from pseudoseizures.