The Effectiveness of Antiepileptic Medications as Prophylaxis of Early Seizure in Patients with Traumatic Brain Injury Compared with Placebo or No Treatment: A Systematic Review and Meta-Analysis

Wat, Ricky; Mammi, Marco; Paredes, José María Rubio; Haines, J R; Alasmari, Mohammed; Liew, Aaron; Lu, Victor M.; Arnaout, Omar; Smith, Timothy R.; Gormley, William B.; Aglio, Linda S.; Mekary, Rania A.; Zaidi, Hasan A.

doi:10.1016/j.wneu.2018.11.076

Cited by 49 publications

(38 citation statements)

References 29 publications

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“…Post-traumatic seizures (PTS) can be seen early (after the first seven days of the trauma) and late (after the 7 th day after the trauma) after traumatic brain injury, and have the potential to induce secondary injury and post-traumatic epilepsy in the traumatic brain. Thus, the use of prophylactic antiepileptic drugs in patients with traumatic brain injury is recommended, albeit controversial [13,14] . This practice has been adopted by the appropriate clinics of our hospital, and antiepileptic treatment is routinely added to the treatment in cases where brain damage is predicted to occur.…”

Section: Discussionmentioning

confidence: 99%

Analysis Of The Adult Traumatic Brain Injury Patients, Experiences of Neurosurgery and Intensive Care Unit

Özgültekin¹

2020

Haydarpasa Numune Med J

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Introduction: Traumatic brain injuries and intracranial bleeding are the most severe forms of traumatic injuries with a high probability of devastating prognosis. Secondary injuries of the brain, following the primary injury, are preventable, and transportation to and in the hospital; the interventions in the emergency department, operational procedures and intensive care (ICU) stay are all crucial for the prevention of the secondary insult to the injured brain. In this retrospective cohort study, we analyzed the traumatic brain injuries that were followed by the neurosurgical and intensive care departments together in ICU for the last two years. Methods: With the written permission of the hospital administration, the data in the Hospital Information System were examined. Fifty-six patients admitted to the ICU with the diagnosis of traumatic intracranial bleeding over the age of 18 were analyzed. GCS scores on admission and discharge from ICU were regarded as ≥8 (Good outcome) and <8 (Bad outcome), and patients' clinical measures were examined according to these groups. Results: Pupillary reflexes showed a statistically significant difference between the ≥8 and <8 patients on admission. Blood glucose levels were clinically higher in the GCS<8 group. On the analysis of the 17 patients whose GCS scores <8 (Bad outcome) on discharge, it was seen that 8 of them had GCS scores below 8 on admission. These patients had severe head trauma, multiple intracranial pathologies and underwent decompressive surgery besides the polytrauma of the whole body. Discussion and Conclusion: We found that patients who had polytrauma with high intracranial pressure that could not be controlled with the first-line therapies and undergoing decompressive surgery, and also the patients who had high glucose levels on admission (>200mg/dl) showed worse prognosis. Hospitals should have an algorithmic approach and periodic analysis of the performances to prevent those delicate patients from having secondary insults to the brain during the emergency interventions and after.

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Section: Discussionmentioning

confidence: 99%

Analysis Of The Adult Traumatic Brain Injury Patients, Experiences of Neurosurgery and Intensive Care Unit

Özgültekin¹

2020

Haydarpasa Numune Med J

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“…significantly reduced the heightened cortical excitation in these mice. It is currently thought that antiepileptic medications have little therapeutic impact early after TBI (Wat et al, 2019) and there is even less evidence suggesting efficacy in later phases for reducing post-traumatic epilepsy (Temkin et al, 1990;Thompson et al, 2015). Because of urgent medical need (Temkin, 2009), the potential value of a dampener of TBI-induced cortical excitation in helping TBI patients should be considered.…”

Section: Discussionmentioning

confidence: 99%

“…Seizure probabilities and the development of epilepsy (post-traumatic epilepsy) are increased in cases of TBI. Early after trauma, the probability of seizures is relatively high, making anticonvulsant treatment a relatively standard procedure despite only small proven efficacy (Wat et al, 2019). Although seizure likelihood decreases after the first few weeks of injury, posttraumatic epilepsy develops later in TBI patients and is associated with affective, neurocognitive, and psychosocial disruption of life (Semple et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

The Positive Allosteric Modulator ofα2/3-Containing GABA_AReceptors, KRM-II-81, Is Active in Pharmaco-Resistant Models of Epilepsy and Reduces Hyperexcitability after Traumatic Brain Injury

Witkin

Golani

et al. 2019

J Pharmacol Exp Ther

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The imidizodiazepine, 5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f] imidazo [1,5-a][1,4]diazepin-3-yl)oxazole (KRM-II-81), is selective for a2/3-containing GABA A receptors. KRM-II-81 dampens seizure activity in rodent models with enhanced efficacy and reduced motor-impairment compared with diazepam. In the present study, KRM-II-81 was studied in assays designed to detect antiepileptics with improved chances of impacting pharmaco-resistant epilepsies. The potential for reducing neural hyperactivity weeks after traumatic brain injury was also studied. KRM-II-81 suppressed convulsions in corneal-kindled mice. Mice with kainate-induced mesial temporal lobe seizures exhibited spontaneous recurrent hippocampal paroxysmal discharges that were significantly reduced by KRM-II-81 (15 mg/kg, orally). KRM-II-81 also decreased convulsions in rats undergoing amygdala kindling in the presence of lamotrigine (lamotrigineinsensitive model) (ED 50 5 19 mg/kg, i.p.). KRM-II-81 reduced focal and generalized seizures in a kainate-induced chronic epilepsy model in rats (20 mg/kg, i.p., three times per day). In mice with damage to the left cerebral cortex by controlledcortical impact, enduring neuronal hyperactivity was dampened by KRM-II-81 (10 mg/kg, i.p.) as observed through in vivo two-photon imaging of layer II/III pyramidal neurons in GCaMP6-expressing transgenic mice. No notable side effects emerged up to doses of 300 mg/kg KRM-II-81. Molecular modeling studies were conducted: docking in the binding site of the a1b3g2L GABA A receptor showed that replacing the C8 chlorine atom of alprazolam with the acetylene of KRM-II-81 led to loss of the key interaction with a1His102, providing a structural rationale for its low affinity for a1-containing GABA A receptors compared with benzodiazepines such as alprazolam. Overall, these findings predict that KRM-II-81 has improved therapeutic potential for epilepsy and post-traumatic epilepsy. SIGNIFICANCE STATEMENTWe describe the effects of a relatively new orally bioavailable small molecule in rodent models of pharmaco-resistant epilepsy and traumatic brain injury. KRM-II-81 is more potent and generally more efficacious than standard-of-care antiepileptics. In silico docking experiments begin to describe the structural basis for the relative lack of motor impairment induced by KRM-II-81. KRM-II-81 has unique structural and anticonvulsant effects, predicting its potential as an improved antiepileptic drug and novel therapy for posttraumatic epilepsy.

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“…A child with a brief generalized seizure following mTBI within the first 24 hours who recovers rapidly and with no complications is low risk and does not need prophylaxis, but children with more severe presentations, structural abnormalities, and significant EEG abnormalities are treated for longer periods and should be individualized. [107][108][109]…”

Section: Posttraumatic Seizures and Epilepsymentioning

confidence: 99%

Assessment and Treatment of Concussion in the Pediatric Population

et al. 2021

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Traumatic brain injury (TBI) is common in children. The evaluation and management of children with TBI is based on the research performed in adults. There is a relative paucity of research in the literature involving children and many of the practice recommendations for this age are based on expert opinion in the absence of good research studies in both sports and non–sports-related injuries. The pediatric population is heterogeneous and the approach might be specific for infants, preschoolers, school age children, and adolescents. Children may also suffer from neurodevelopmental disabilities, making their evaluation even more challenging. Adult neurologists are often asked to see children due to increasing demands. This review will focus on specific issues related to TBI in children that might be useful to adult neurologists. Science, however, is evolving rapidly and physicians should make sure to remain up to date to offer evidence-based services to their patients.

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The Effectiveness of Antiepileptic Medications as Prophylaxis of Early Seizure in Patients with Traumatic Brain Injury Compared with Placebo or No Treatment: A Systematic Review and Meta-Analysis

Cited by 49 publications

References 29 publications

Analysis Of The Adult Traumatic Brain Injury Patients, Experiences of Neurosurgery and Intensive Care Unit

Analysis Of The Adult Traumatic Brain Injury Patients, Experiences of Neurosurgery and Intensive Care Unit

The Positive Allosteric Modulator ofα2/3-Containing GABA_AReceptors, KRM-II-81, Is Active in Pharmaco-Resistant Models of Epilepsy and Reduces Hyperexcitability after Traumatic Brain Injury

Assessment and Treatment of Concussion in the Pediatric Population

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The Effectiveness of Antiepileptic Medications as Prophylaxis of Early Seizure in Patients with Traumatic Brain Injury Compared with Placebo or No Treatment: A Systematic Review and Meta-Analysis

Cited by 49 publications

References 29 publications

Analysis Of The Adult Traumatic Brain Injury Patients, Experiences of Neurosurgery and Intensive Care Unit

Analysis Of The Adult Traumatic Brain Injury Patients, Experiences of Neurosurgery and Intensive Care Unit

The Positive Allosteric Modulator ofα2/3-Containing GABAAReceptors, KRM-II-81, Is Active in Pharmaco-Resistant Models of Epilepsy and Reduces Hyperexcitability after Traumatic Brain Injury

Assessment and Treatment of Concussion in the Pediatric Population

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Resources

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The Positive Allosteric Modulator ofα2/3-Containing GABA_AReceptors, KRM-II-81, Is Active in Pharmaco-Resistant Models of Epilepsy and Reduces Hyperexcitability after Traumatic Brain Injury