Emergency neurological life support: status epilepticus.
ABSTRACT Patients with prolonged or rapidly recurring convulsions lasting more than 5 min are in status epilepticus (SE) and require immediate resuscitation. Although there are relatively few randomized clinical trials, available evidence and experience suggest that early and aggressive treatment of SE improves patient outcomes, for which reason it was chosen as an Emergency Neurologic Life Support protocol. The current approach to the emergency treatment of SE emphasizes rapid initiation of adequate doses of first line therapy, as well as accelerated second line anticonvulsant drugs and induced coma when these fail, coupled with admission to a unit capable of neurologic critical care and electroencephalography monitoring. This protocol not only will focus on the initial treatment of SE but also review subsequent steps in the protocol once the patient is hospitalized.
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ABSTRACT: Human rabies has traditionally been considered a uniformly fatal disease. However, recent decades have seen several instances in which individuals have developed clinical signs of rabies, but survived, usually with permanent neurologic sequelae. Most of these patients had received prophylactic rabies vaccine before the onset of illness. The best outcomes have been seen in patients infected with bat viruses, which appear to be less virulent for humans than strains associated with other rabies vectors. In 2003, an article by rabies experts suggested that survival might be improved through a combination of vaccine, anti-rabies immunoglobulin, antiviral drugs and the anesthetic ketamine, which had shown benefit in an animal model. One year later, a girl in Milwaukee who developed rabies after bat exposure was treated with some of these measures, plus a drug-induced (therapeutic) coma, and survived her illness with mild neurologic sequelae. Although the positive outcome in this case has been attributed to the treatment regimen, it more likely reflects the patient's own brisk immune response, as anti-rabies virus antibodies were detected at the time of hospital admission, even though she had not been vaccinated. This conclusion is supported by the failure of the "Milwaukee Protocol" to prevent death in numerous subsequent cases. Use of this protocol should therefore be discontinued. Future research should focus on the use of animal models to improve understanding of the pathogenesis of rabies and for the development of new therapeutic approaches.Antiviral research 01/2013; 99(1). DOI:10.1016/j.antiviral.2013.01.003 · 3.43 Impact Factor
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ABSTRACT: Minocyline is a tetracycline derivative with anti-inflammatory, anti-apoptotic, and anti-oxidant properties. Therapy has proved useful in some experimental models of both noninfectious and infectious neurological diseases and also in clinical trials in humans, including acute traumatic cervical spinal cord injury. In models of viral encephalitis, treatment has shown both beneficial and deleterious effects. In reovirus infection in mice, minocycline delayed the disease, but did not improve either the morbidity or mortality of the disease. In neuroadapted Sindbis virus infection of mice, minocycline prevented disease, but therapy needed to be given before clinical signs were present in most of the animals. In experimental rabies in neonatal mice minocycline aggravated the disease, likely related to anti-inflammatory effects. Minocycline has also been shown to aggravate disease in a mouse model of Huntington disease, in a monkey model of Parkinson disease, and in a mouse model of hypoxic-ischemic brain injury. Hence, there is experimental evidence of benefit of minocycline in both infectious and noninfectious neurological diseases, but there is a lack of benefit and harmful effects in other diseases. This may reflect multiple mechanisms of actions that cannot be predicted in a new disease or in an infection caused by a specific viral agent. Minocycline therapy is a double-edged sword and this drug should not be given empirically to patients with acute viral encephalitis for anticipated neuroprotective effects. Much more work needs to be done in experimental models in animals as well as in clinical trials. Because patient enrollment in clinical trials on acute viral encephalitis has proven to be difficult, funding will be a challenge.Antiviral research 06/2012; 95(3):242-4. DOI:10.1016/j.antiviral.2012.06.005 · 3.43 Impact Factor
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ABSTRACT: This study compares 2 treatment protocols allowing low vs high continuous IV midazolam (cIV-MDZ) doses. We compared adults with refractory status epilepticus treated with a protocol allowing for high-dose cIV-MDZ (n = 100; 2002-2011) with those treated with the previous lower-dose cIV-MDZ (n = 29; 1996-2000). We collected data on baseline characteristics, cIV-MDZ doses, seizure control, hospital course, and outcome. Median maximum cIV-MDZ dose was 0.4 mg/kg/h (interquartile range [IQR] 0.2, 1.0) for the high-dose group and 0.2 mg/kg/h (IQR 0.1, 0.3) for the low-dose group (p < 0.001) with similar duration of infusion. Median time from status epilepticus onset to cIV-MDZ start was 1 day (IQR 1, 3) for the high-dose group and 2 days (IQR 1, 5) for the low-dose group (p = 0.016). "Withdrawal seizures" (occurring within 48 hours of discontinuation of cIV-MDZ) were less frequent in the high-dose group (15% vs 64%, odds ratio 0.10, 95% confidence interval 0.03-0.27). "Ultimate cIV-MDZ failure" (patients requiring change to a different cIV antiepileptic medication) and hospital complications were not different between groups. Hypotension was more frequent with higher cIV-MDZ doses but was not associated with worse outcome. Discharge mortality was lower in the high-dose group (40% vs 62%, odds ratio 0.34, 95% confidence interval 0.13-0.92 in multivariate analysis). High-dose cIV-MDZ treatment of refractory status epilepticus can be performed safely, is associated with a lower seizure rate after cIV-MDZ discontinuation, and may be associated with lower mortality than traditional lower-dose protocols. This study provides Class III evidence that midazolam at higher infusion rates is associated with a reduction in seizure recurrence within 48 hours after discontinuation and may be associated with lower mortality.Neurology 12/2013; 82(4). DOI:10.1212/WNL.0000000000000054 · 8.30 Impact Factor