Novel anesthetics and other treatment strategies for refractory status epilepticus

Refractory status epilepticus (RSE)-that is, seizures resistant to at least two antiepileptic drugs (AEDs)-is generally managed with barbiturates, propofol, or midazolam, despite a low level of evidence (Rossetti, 2007). When this approach fails, the need for alternative pharmacologic and nonpharmacologic strategies emerges. These have been investigated even less systematically than the aforementioned compounds, and are often used, sometimes in succession, in cases of extreme refractoriness (Robakis & Hirsch, 2006). Several possibilities are reviewed here. In view of the marked heterogeneity of reported information, etiologies, ages, and comedications, it is extremely difficult to evaluate a given method, not to say to compare different strategies among them. Pharmacologic Approaches Isoflurane and desflurane may complete the armamentarium of anesthetics,' and should be employed in a ''close'' environment, in order to prevent intoxication of treating personnel. c-Aminobutyric acid (GABA)A receptor potentiation represents the putative mechanism of action. In an earlier report, isoflurane was used for up to 55 h in nine patients, controlling seizures in all; mortality was, however, 67% (Kofke et al., 1989). More recently, the use of these inhalational anesthetics was described in seven subjects with RSE, for up to 26 days, with an endtidal concentration of 1.2-5%. All patients required vasopressors, and paralytic ileus occurred in three; outcome was fatal in three patients (43%) (Mirsattari et al., 2004). Ketamine, known as an emergency anesthetic because of its favorable hemodynamic profile, is an N-methyl-daspartate (NMDA) antagonist; the interest for its use in RSE derives from animal works showing loss of GABAA efficacy and maintained NMDA sensitivity in prolonged status epilepticus (Mazarati & Wasterlain, 1999). However, to avoid possible neurotoxicity, it appears safer to combine ketamine with GABAergic compounds (Jevtovic-Todorovic et al., 2001; Ubogu et al., 2003), also because of a likely synergistic effect (Martin & Kapur, 2008). There are few reported cases in humans, describing progressive dosages up to 7.5 mg/kg/h for several days (Sheth & Gidal, 1998; Quigg et al., 2002; Pruss & Holtkamp, 2008), with moderate outcomes. Paraldehyde acts through a yet-unidentified mechanism, and appears to be relatively safe in terms of cardiovascular tolerability (Ramsay, 1989; Thulasimani & Ramaswamy, 2002), but because of the risk of crystal formation and its reactivity with plastic, it should be used only as fresh prepared solution in glass devices (Beyenburg et al., 2000). There are virtually no recent reports regarding its use in adults RSE, whereas rectal paraldehyde in children with status epilepticus resistant to benzodiazepines seems less efficacious than intravenous phenytoin (Chin et al., 2008). Etomidate is another anesthetic agent for which the exact mechanism of action is also unknown, which is also relatively favorable regarding cardiovascular side effects, and may be used for rapid sedation. Its use in RSE was reported in eight subjects (Yeoman et al., 1989). After a bolus of 0.3 mg/kg, a drip of up to 7.2 mg/kg/h for up to 12 days was administered, with hypotension occurring in five patients; two patients died. A reversible inhibition of cortisol synthesis represents an important concern, limiting its widespread use and implying a careful hormonal substitution during treatment (Beyenburg et al., 2000). Several nonsedating approaches have been reported. The use of lidocaine in RSE, a class Ib antiarrhythmic agent modulating sodium channels, was reviewed in 1997 (Walker & Slovis, 1997). Initial boluses up to 5 mg/kg and perfusions of up to 6 mg/kg/h have been mentioned; somewhat surprisingly, at times lidocaine seemed to be successful in controlling seizures in patients who were refractory to phenytoin. The aforementioned dosages should not be overshot, in order to keep lidocaine levels under 5 mg/L and avoid seizure induction (Hamano et al., 2006). A recent pediatric retrospective survey on 57 RSE episodes (37 patients) described a response in 36%, and no major adverse events; mortality was not given (Hamano et al., 2006 Verapamil, a calcium-channel blocker, also inhibits P-glycoprotein, a multidrug transporter that may diminish AED availability in the brain (Potschka et al., 2002). Few case reports on its use in humans are available; this medication nevertheless appears relatively safe (under cardiac monitoring) up to dosages of 360 mg/day (Iannetti et al., 2005). Magnesium, a widely used agent for seizures elicited by eclampsia, has also been anecdotally reported in RSE (Fisher et al., 1988; Robakis & Hirsch, 2006), but with scarce results even at serum levels of 14 mm. The rationale may be found in the physiologic blockage of NMDA channels by magnesium ions (Hope & Blumenfeld, 2005). Ketogenic diet has been prescribed for decades, mostly in children, to control refractory seizures. Its use in RSE as ''ultima ratio'' has been occasionally described: three of six children (Francois et al., 2003) and one adult (Bodenant et al., 2008) were responders. This approach displays its effect subacutely over several days to a few weeks. Because ''malignant RSE'' seems at times to be the consequence of immunologic processes (Holtkamp et al., 2005), a course of immunomodulatory treatment is often advocated in this setting, even in the absence of definite autoimmune etiologies (Robakis & Hirsch, 2006); steroids, adrenocorticotropic hormone (ACTH), plasma exchanges, or intravenous immunoglobulins may be used alone or in sequential combination. Nonpharmacologic Approaches These strategies are described somewhat less frequently than pharmacologic approaches. Acute implantation of vagus nerve stimulation (VNS) has been reported in RSE (Winston et al., 2001; Patwardhan et al., 2005; De Herdt et al., 2009). Stimulation was usually initiated in the operation room, and intensity progressively adapted over a few days up to 1.25 mA (with various regimens regarding the other parameters), allowing a subacute seizure control; one transitory episode of bradycardia/asystole has been described (De Herdt et al., 2009). Of course, pending identification of a definite seizure focus, resective surgery may also be considered in selected cases (Lhatoo & Alexopoulos, 2007). Low-frequency (0.5 Hz) transcranial magnetic stimulation (TMS) at 90% of the resting motor threshold has been reported to be successful for about 2 months in a patient with epilepsia partialis continua, but with a weaning effect afterward, implying the need for a repetitive use (Misawa et al., 2005). More recently, TMS was applied in a combination of a short ''priming'' high frequency (up to 100 Hz) and longer runs of low-frequency stimulations (1 Hz) at 90-100% of the motor threshold in seven other patients with simple-partial status, with mixed results (Rotenberg et al., 2009). Paradoxically at first glance, electroconvulsive treatment may be found in cases of extremely resistant RSE. A recent case report illustrates its use in an adult patient with convulsive status, with three sessions (three convulsions each) carried out over 3 days, resulting in a moderate recovery; the mechanism is believed to be related to modification of the synaptic release of neurotransmitters (Cline & Roos, 2007). Therapeutic hypothermia, which is increasingly used in postanoxic patients (Oddo et al., 2008), has been the object of a recent case series in RSE (Corry et al., 2008). Reduction of energy demand, excitatory neurotransmission, and neuroprotective effects may account for the putative mechanism of action. Four adult patients in RSE were cooled to 31_-34_C with an endovascular system for up to 90 h, and then passively rewarmed over 2-50 h. Seizures were controlled in two patients, one of whom died; also one of the other two patients in whom seizures continued subsequently deceased. Possible side effects are related to acid-base and electrolyte disturbances, and coagulation dysfunction including thrombosis, infectious risks, cardiac arrhythmia, and paralytic ileus (Corry et al., 2008; Cereda et al., 2009). Finally, anecdotic evidence suggests that cerebrospinal fluid (CSF)-air exchange may induce some transitory benefit in RSE (Kohrmann et al., 2006); although this approach was already in use in the middle of the twentieth century, the mechanism is unknown. Acknowledgment A wide spectrum of pharmacologic (sedating and nonsedating) and nonpharmacologic (surgical, or involving electrical stimulation) regimens might be applied to attempt RSE control. Their use should be considered only after refractoriness to AED or anesthetics displaying a higher level of evidence. Although it seems unlikely that these uncommon and scarcely studied strategies will influence the RSE outcome in a decisive way, some may be interesting in particular settings. However, because the main prognostic determinant in status epilepticus appears to be related to the underlying etiology rather than to the treatment approach (Rossetti et al., 2005, 2008), the safety issue should always represent a paramount concern for the prescribing physician. Conclusion The author confirms that he has read the Journal's position on issues involved in ethical publication and affirms that this paper is consistent with those guidelines.

Surgical treatment of temporoparietooccipital cortical dysplasia in infants: report of two cases.

PURPOSE: Extensive multilobar cortical dysplasia in infants commonly is first seen with catastrophic epilepsy and poses a therapeutic challenge with respect to control of epilepsy, brain development, and psychosocial outcome. Experience with surgical treatment of these lesions is limited, often not very encouraging, and holds a higher operative risk when compared with that in older children and adults. METHODS: Two infants were evaluated for surgical control of catastrophic epilepsy present since birth, along with a significant psychomotor developmental delay. Magnetic resonance imaging showed multilobar cortical dysplasia (temporoparietooccipital) with a good electroclinical correlation. They were treated with a temporal lobectomy and posterior (parietooccipital) disconnection. RESULTS: Both infants had excellent postoperative recovery and at follow-up (1.5 and 3.5 years) evaluation had total control of seizures with a definite "catch up" in their development, both motor and cognitive. No long-term complications have been detected to date. CONCLUSIONS: The incorporation of disconnective techniques in the surgery for extensive multilobar cortical dysplasia in infants has made it possible to achieve excellent seizure results by maximizing the extent of surgical treatment to include the entire epileptogenic zone. These techniques decrease perioperative morbidity, and we believe would decrease the potential for the development of long-term complications associated with large brain excisions.

Can postictal memory predict postoperative memory in patients with temporal lobe epilepsy?

We investigated the contribution of postictal memory testing for lateralizing the epileptic focus and predicting memory outcome after surgery for temporal lobe epilepsy (TLE). Forty-five patients with TLE underwent interictal, postictal, and postoperative assessment of verbal and nonverbal memory. Surgery consisted of anterior temporal lobectomy (36), selective isolated amygdalohippocampectomy (6), or amygdalohippocampectomy coupled to lesionectomy (3). Postictal and postoperative but not interictal memory were significantly lower in left TLE than in right TLE. Nonverbal memory showed no significant difference in left TLE versus right TLE in all conditions. Postictal memory was significantly correlated with postoperative memory, but the effect disappeared when the lateralization of the focus was considered. Postictal verbal memory is a useful bedside tool that can help lateralize the epileptic focus. Larger studies are needed to further estimate its predictive value of the postoperative outcome.

O uso de escalas de avaliação de ambientes na educação infantil

Embora a ECERS tenha sido amplamente utilizada para orientar a melhoria de programas de educação infantil, relativamente pouco tem sido relatado sobre sua aplicação prática. Este artigo explora as qualidades que tornaram a ECERS útil em programas que atendem crianças de diferentes culturas e origem socioeconômica nos Estados Unidos e em outros países. A ECERS inclui indicadores para avaliar as três necessidades básicas comuns a todas as crianças: proteção da saúde e segurança, apoio e orientação para desenvolvimento social/emocional e estímulos de linguagem e desenvolvimento cognitivo. A escala é usada em diferentes países, culturas e idiomas, utilizando diferentes currículos, com apenas pequenos ajustes. A fim de assegurar a comparabilidade estão disponíveis materiais de treinamento, protocolos para prática de campo e requisitos para traduções. São descritos o uso das escalas na Quality Rating and Improvement Systems nos Estados Unidos, assim como sua utilização internacional generalizada.

Recurrence of status epilepticus: Prognostic role and outcome predictors.

OBJECTIVE: Predictors of morbidity and mortality after status epilepticus (SE) have been studied extensively in hospital- and population-based cohorts. However, little attention has been directed toward SE recurrence after an incident episode. We investigated clinical and demographic characteristics of patients presenting SE recurrence and its specific prognostic role. METHODS: In this observational cohort study, we screened our prospective registry of consecutive adults with SE between April 2006 and February 2014. Demographic and clinical data were compared between incident and recurrent SE episodes; risk of SE recurrence was assessed through survival analysis, and the prognostic role of SE recurrence with multivariable logistic regressions. RESULTS: Of the incident cohort (509 patients), 68 (13%) experienced recurrent SE. The cumulative recurrence rate over 4 years was 32%. Recurrence risk was significantly reduced after an acute SE etiology (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.31-0.82; p = 0.005), and was borderline increased in women (HR 1.59, 95% CI 0.97-2.65; p = 0.06). Although recurrent SE episodes showed lower morbidity and mortality, prognosis was independently related to Status Epilepticus Severity Score (STESS) and potentially fatal etiology, but not to SE recurrence. SIGNIFICANCE: This study provides class III evidence that SE recurrence involves a significant proportion of patients, and that recurrence risk is independently associated with chronic etiology and to a lesser extent with female gender. However, contrary to underlying cause and SE severity, SE recurrence per se does not independently correlate with outcome. Early identification of patients at higher risk of SE recurrence may influence their management during follow-up.

Sobre Internet y psicología

El crecimiento de Internet durante los últimos años ha sido exponencial. En sus orígenes, Internet era una comunidad con estructuras informales de reconocimiento de los méritos personales, y su funcionamiento estaba regulado por muy pocas normas. En la actualidad se han trasladado a la red las prácticas económicas habituales de la sociedad. La anarquia y autoorganización van cediendo paso al control. Internet esta transformando todos 10s ámbitos de la actividad humana: laboral, personal, familiar. La utilización generalizada de hipertextos e hipermedias incide también sobre la forma en que se estructura el conocimiento. La manera en que todo ello se va desnrrollando es objeto de estudio de gran interés para la psicologíg, e incide también en cambios que afectan a la forma de trabajar de los psicólogos.

A Lei de Lotka na bibliometria brasileira

Usando os dados reportados em artigos publicados em revistas brasileiras e trabalhos apresentados em congressos nacionais, replicaram-se as aplicações da Lei de Lotka à literatura brasileira em 10 campos diferentes. Utilizou-se o modelo do poder inverso pelos métodos do mínimo quadrado e probabilidade máxima. Das 10 literaturas nacionais analisadas, somente a literatura de medicina, siderurgia, jaca e biblioteconomia ajustaram-se ao modelo do poder inverso generalizado pelo método dos mínimos quadrados. No entanto, só duas literaturas (veterinária e cartas do Arquivo Privado de Getúlio Vargas) não se ajustaram ao modelo quando se usou o método da máxima probabilidade. Para ambas literaturas, tentaram-se modelos diferentes. A literatura de veterinária ajustou-se à distribuição binomial negativa, e as cartas do Arquivo Privado de Getúlio Vargas ajustaram-se melhor à distribuição Gauss-Poisson Inversa Generalizada.

Sintesis biostratigrafica de la fosa de la Cerdanya (Pirineos orientales).

En el presente trabajo se describen las principales características estratigráficas y sedimentológicas del relleno de la fosa de la Cerdanya. A partir de éstas se han diferenciado dos unidades: la Unidad Neógena Inferior y la Unidad Neógena Superior que reflejan dos situaciones tectónicas diferentes. La Unidad Inferior corresponde al período de formación y posterior evolución de la fosa bajo el movimiento direccional de la falla NE-SW de la Tet, mientras que la Unidad Superior refleja una situación extensional generalizada. La revisión de los numerosos yacimientos de Mamíferos fósiles de la Unidad Neógena Inferior, expuesta en esta nota, permiten concluir que esta se sedimentó en el Vallesiense. Por contra, el hallazgo del nuevo yacimiento de Can Vilella, indican que la sedimentación de la Unidad Superior se inició en el Turoliense superior (MN 13)

Sign language in Landau-Kleffner syndrome.

This article reviews the history of sign language (SL) and the rationale for its use in children with profound auditory agnosia due to Landau-Kleffner syndrome (LKS), illustrated by studies of children and adults followed for many years and rare cases from the literature. The reasons that SL was successful and brought some children out of isolation while it could not be implemented in others are discussed. The nowadays earlier recognition and treatment of LKS and better awareness of the crucial need to maintain communication have certainly improved the outcome of affected children. Alternatives to oral language, even for less severe cases, are increasingly accepted. SL can be learned at different ages with a clear benefit, but the ambivalence of the patients and their families with the world and culture of the deaf may sometimes explain its refusal or limited acceptance. There are no data to support the fear that SL learning may delay or prevent oral language recovery in children with LKS. On the contrary, SL may even facilitate this recovery by stimulating functionally connected core language networks and by helping speech therapy and auditory training.

A produtividade dos autores sobre a Lei de Lotka

Estuda a produção estratificada dos autores produtores da literatura sobre a Lei de Lotka de 1922 a 2003 e analisa essa produtividade através dos modelos Poisson lognormal e Gauss Poisson inversa generalizada. Para tanto, faz uso dos três tipos de contagem da literatura produzida: contagem direta, contagem completa e contagem fracionada. Os dados da pesquisa são avaliados usando o teste qui-quadrado ao 0.05 nível de significância. Ambos os modelos ajustam-se muito bem à distribuição da literatura produzida, porém a distribuição Poisson Gauss inversa generalizada produz um chi-quadrado menor e prediz melhor o total de autores do que a distribuição Poisson Lognormal.

La productividad de los autores en la ciencia de la información colombiana

Este trabajo analiza la productividad científica de los autores que han publicado documentos en cuatro revistas de ciencia de la información editadas en Colombia desde 1978 a 2009. Se encontraron 555 autores, de los cuales 422 (76%) publicaron un único artículo y 78 (24%) publicaron 2 o más artículos. También se identificaron 11 autores como los más productivos con 21 y 7 artículos cada uno. El número de autores observados fueron estinados con los modelos del poder inverso generalizado, Gauss Poisson inversa generalizada y Poisson lognormal por el método de la máxima probabilidad. Las pruebas de ajuste estadístico chi-cuadrado y K-S mostraron que los tres modelos se ajustan a los datos observados en este trabajo.

Tratamiento de la hiperhidrosis plantar con toxina butolínica tipo A

El problema de hiperhidrosis afecta al 0,5% de la población, y puede causar considerable estrés emocional, dificultando en ocasiones la vida personal, laboral y social del paciente, llevándole, por ejemplo, a evitar un acto como dar la mano o quitarse los zapatos en público. Por otra parte, el excesivo sudor puede ocasionar maceración cutánea, acrocianosis, queratoderma e incluso deshidratación. La forma más frecuente de hiperhidrosis es la idiopática y en el 60% de los casos afecta a palmas y plantas de los pies. En este artículo presentamos la aplicación del tratamiento con la toxina butolínica tipo A.

Identificação de duplicidades de acessos de feijão por meio de técnicas multivariadas

Este trabalho objetivou testar as técnicas de análise multivariada e da medida de divergência genética representada pela distância generalizada de Mahalanobis na seleção de descritores e na identificação de duplicidades de acessos de feijão (Phaseolus vulgaris L.). Cinqüenta acessos do Banco Ativo de Germoplasma (BAG-Feijão), da Embrapa - Centro Nacional de Pesquisa de Arroz e Feijão (CNPAF), foram avaliados em junho de 1993, utilizando-se delineamento experimental em blocos casualizados, com duas repetições. Dez descritores com características quantitativas e fenológicas foram analisados por meio de variáveis canônicas e distância de Mahalanobis. Todos os caracteres foram importantes na descrição do germoplasma. A técnica de agrupamento pela distância generalizada de Mahalanobis mostrou-se viável e eficaz na identificação de duplicidades do feijoeiro, podendo ser utilizada rotineiramente no Banco de Germoplasma.

Deficiência de macronutrientes em estévia: sintomas visuais e efeitos no crescimento, composição química e produção de esteviosídeo

Conduziu-se experimento objetivando descrever sintomas visuais de deficiências de macronutrientes em estévia (Stevia rebaudiana) e avaliar seus efeitos no crescimento, composição química e produção de esteviosídeo. Os sintomas foram: clorose generalizada, com -N; folhas verde-escuras, com -P; folhas com clorose, bronzeamento e necrose, com -K; necrose de ápices, com -Ca; clorose e necrose foliar, em "V" invertido, com -Mg e folhas verde-pálidas e menores, com -S. As deficiências de N, K e Mg reduziram o crescimento das folhas e a parte comercializável da planta, enquanto que a deficiência de Mg promoveu acentuada redução no desenvolvimento do sistema radicular. As deficiências de N, P, K e S diminuíram a relação entre matéria seca da parte aérea e das raízes, enquanto a deficiência de Mg aumentou-a. Todas as deficiências causaram a diminuição na absorção de macronutrientes, exceto a de Ca, que reduziu somente a absorção de Ca, e a de K, que não alterou as absorções de Mg e S. A composição química dos cinco últimos pares de folhas totalmente expandidas representou bem o estado nutricional da planta. As deficiências de K, Ca e S reduziram somente o teor de esteviosídeo, enquanto todas as deficiências, exceto a de P, diminuíram o conteúdo de esteviosídeo.

La cresta alveolar atrófica en implantología oral

Los implantes dentales endoóseos constituyen una alternativa terapéutica ideal en pacienfes parcial o totalmente edéntulos; sin embargo, en ocasiones, la atrofia ósea generalizada o localizada contraindica el tratamiento, siendo necesario realizar un aumento de cresta alveolar que permita, bien simultáneamente o deforma diferida, la adecuada rehabilitación implantológica. En el presente trabajo, hacemos una revisión de las distintas técnicas y materiales utilizados actualmente en implantología, para mejorar las condiciones de recepción de los implantes, en presencia de defectos óseos.