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Trauma of the Brain and Spinal Cord
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
Fernando D. Goldenberg, Ali Mansour
It is fundamental to avoid, and correct, hypoxia (PaO2 < 60 mmHg, O2 sat < 90%), hypotension (systolic blood pressure [SBP] < 90 mmHg), hyperglycemia, and hyperthermia. Injury to visceral organs, or long bone fractures, may contribute to blood loss, hypovolemia, hypotension, and increased morbidity. In the traumatized patient, other diagnoses such as intoxication, anoxic insult, metabolic encephalopathy, postictal state, or status epilepticus may be present. Nonconvulsive status epilepticus may present with decreased level of consciousness. The diagnosis of this condition may require prolonged electroencephalographic monitoring.
Brand-Name Antiepileptic Drugs Versus Generics
Published in Stanley R. Resor, Henn Kutt, The Medical Treatment of Epilepsy, 2020
Many patients with epilepsy do equally well or badly in spite of shifts in AED preparation. However, in patients where loss of seizure control or deterioration of seizure control will impose a high social or professional cost, such as loss of driver’s license or limited vocational options, the substitution of generic AEDs that are not of established bioequivalance carries with it a substantial risk for a small financial gain. The same can be said for those infrequent patients with bouts of status epilepticus, each of which is potentially life threatening. If financial factors are an important consideration in the choice of medications, a generic medication of a known manufacturer should be chosen and adjusted in the usual manner using patient response and AED serum levels. The patient should seek a pharmacist or mail order house who will cooperate in dispensing the product of a designated manufacturer, and large quantities of medication should be purchased at one time if possible. Only physicians should be permitted to change medication formulation. Until bioequivalance standards are established, no generic AED should be prescribed without identifying its manufacturer.
Benzodiazepines: Anticonvulsant and other clinical uses
Published in Adam Doble, Ian L Martin, David Nutt, Calming the Brain: Benzodiazepines and related drugs from laboratory to clinic, 2020
Adam Doble, Ian L Martin, David Nutt
Status epilepticus is a life-threatening condition in which the brain is in a state of continuous seizure activity. During ‘status’ respiration is frequently impaired and the main danger is hypoxic brain damage which is common after periods of status lasting for more than 15–20 minutes. This in turn can lead to brain scarring and more epilepsy. For these reasons, status epilepticus is a medical emergency that requires quick and effective intervention. An intravenous administration of a benzodiazepine is the first-line treatment and can abort the episode almost immediately. Alternative routes of administration are also effective and have the benefit of being more amenable for non-professionals such as parents and carers. As intramuscular benzodiazepines are poorly and slowly absorbed the only alternative route, until recently, was to use diazepam rectally, where fast absorption led to a good onset of anticonvulsant effect. However, there are difficulties and sensitivities about rectal administration and lately an alternative, midazolam given nasally, has been tried (O’Regan et al, 1996). It has the advantage of extremely easy access and high patient acceptability although the current availability of the spray formulations is relatively limited.
Clinical findings, etiological factors, and prognosis markers in status epilepticus: a university hospital experience
Published in Neurological Research, 2022
Mehmet Fatih Göl, Füsun Ferda Erdoğan, Mehmet Fatih Yetkin, Ömer Faruk Bolattürk
Non-convulsive status epilepticus is a clinical manifestation in which consciousness is usually affected at various levels [27]. Convulsive status epilepticus, in which significant motor symptoms are at the forefront, can be more easily identified by the patient’s relatives, nurses and people around the patient. NCSE is often overlooked due to the nature of the manifestation. The diagnosis of NCSE is extremely difficult and impossible to diagnose without an EEG [28,29]. The prevalence of NCSE is approximately 8% in comatose patients who do not have clinical seizures in the ICU [30]. In the literature, the mortality rate in NCSE cases was found to be 6.3–18% [31,32]. In our study, the rate of NCSE in SE patients was 16.7%, and 6.1% of the patients monitored in the ICU with SE had NCSE. Mortality in NCSE was higher than in the literature. This can be explained by the difficulty of NCSE diagnosis and the higher number of NCSE patients evaluated in the literature compared to our study.
Epilepsy: expert opinion on emerging drugs in phase 2/3 clinical trials
Published in Expert Opinion on Emerging Drugs, 2022
Amanda W Pong, Jonathan Ross, Ivana Tyrlikova, Alexander J Giermek, Maya P Kohli, Yousef A Khan, Roger D Salgado, Pavel Klein
Status epilepticus (SE) is defined as a seizure with 5 min or more of continuous clinical and/or electrographic seizure activity or recurrent seizure activity without recovery between seizures [80]. Refractory status epilepticus (RSE) is defined as SE that is refractory to benzodiazepines and one anti-epileptic drug, lasting > 1 hour [81]. Under normal conditions, there is recycling of the synaptic GABA-A receptors from the synapse to the cytosol and back. In seizures lasting 30–45 min or longer, the recycling starts to fail. GABA-A receptors are cycled from the synapse to the cytosol, but are not replaced. This results in decreased number of GABA-A receptors at the synapse, with resulting decreased GABA-ergic post-synaptic inhibition and loss of efficacy of GABA-ergic ASMs such as benzodiazepines, the standard treatment of SE [82]. As noted above, ganaxolone activates not only the synaptic but also the parasynaptic GABA-A receptors which are not reduced in RSE. Thus, it may continue to be effective in RSE where benzodiazepines and the GABA-ergic medications lose efficacy [82].
Ganaxolone treatment for epilepsy patients: from pharmacology to place in therapy
Published in Expert Review of Neurotherapeutics, 2021
Simona Lattanzi, Antonella Riva, Pasquale Striano
Scientific and clinical communities welcome the evaluation of new strategies throughout the SE continuum that may lead to favorable discharge settings and reduce mortality, morbidity, and post-hospital costs. Prolonged seizure activity can result in permanent neuronal damage. Status epilepticus becomes more refractory to treatment as it progresses, and the severity of SE is associated with clinical outcomes and health care utilization [121]. The Phase 2 study of GNX in RSE demonstrated the rapid onset of action of the drug and met the primary endpoint of no escalation to intravenous anesthesia within 24 hours from GNX initiation, providing the rationale for the ongoing Phase 3 trial. Of note, the first patient was enrolled in the trial in January 2021. The drug company is also planning a clinical trial of GNX in established SE in patients presenting to the emergency room, with a projected trial initiation in the second half of 2021 to expand clinical opportunities from RSE to a broader SE case mix.