Levetiracetam dosing for seizure prophylaxis in neurocritical care patients

Hedges, Ashley; Findlay, Matthew C.; Davis, George K.; Wolfe, Brianne M; Hawryluk, Gregory; Menacho, Sarah T.; Ansari, Safdar

doi:10.1080/02699052.2023.2184495

Cited by 4 publications

(2 citation statements)

References 33 publications

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“…Treatment of acute TBI includes the prophylactic use of antiseizure drugs to prevent TBI-related early (≤7 d) seizures [ 36 , 37 , 38 ]. Although prophylactic use of LEV has not shown superiority in its antiseizure efficacy for the treatment of human post-TBI seizures compared with other antiseizure drugs, its pharmacokinetic profile, ease of use, safety, and lack of interactions with other ongoing treatments promotes its use over other antiseizure medications in both civilian and combat situations [ 36 , 39 , 40 , 41 ]. Also, in rat models of induced seizures and SE, LEV demonstrates good antiseizure efficacy at the doses used in the present study, particularly the higher dose of 150 mg/kg [ 42 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Treatment of Status Epilepticus after Traumatic Brain Injury Using an Antiseizure Drug Combined with a Tissue Recovery Enhancer Revealed by Systems Biology

Kajevu,

Lipponen,

Andrade

et al. 2023

IJMS

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We tested a hypothesis that in silico-discovered compounds targeting traumatic brain injury (TBI)-induced transcriptomics dysregulations will mitigate TBI-induced molecular pathology and augment the effect of co-administered antiseizure treatment, thereby alleviating functional impairment. In silico bioinformatic analysis revealed five compounds substantially affecting TBI-induced transcriptomics regulation, including calpain inhibitor, chlorpromazine, geldanamycin, tranylcypromine, and trichostatin A (TSA). In vitro exposure of neuronal-BV2-microglial co-cultures to compounds revealed that TSA had the best overall neuroprotective, antioxidative, and anti-inflammatory effects. In vivo assessment in a rat TBI model revealed that TSA as a monotherapy (1 mg/kg/d) or in combination with the antiseizure drug levetiracetam (LEV 150 mg/kg/d) mildly mitigated the increase in plasma levels of the neurofilament subunit pNF-H and cortical lesion area. The percentage of rats with seizures during 0–72 h post-injury was reduced in the following order: TBI-vehicle 80%, TBI-TSA (1 mg/kg) 86%, TBI-LEV (54 mg/kg) 50%, TBI-LEV (150 mg/kg) 40% (p < 0.05 vs. TBI-vehicle), and TBI-LEV (150 mg/kg) combined with TSA (1 mg/kg) 30% (p < 0.05). Cumulative seizure duration was reduced in the following order: TBI-vehicle 727 ± 688 s, TBI-TSA 898 ± 937 s, TBI-LEV (54 mg/kg) 358 ± 715 s, TBI-LEV (150 mg/kg) 42 ± 64 (p < 0.05 vs. TBI-vehicle), and TBI-LEV (150 mg/kg) combined with TSA (1 mg/kg) 109 ± 282 s (p < 0.05). This first preclinical intervention study on post-TBI acute seizures shows that a combination therapy with the tissue recovery enhancer TSA and LEV was safe but exhibited no clear benefit over LEV monotherapy on antiseizure efficacy. A longer follow-up is needed to confirm the possible beneficial effects of LEV monotherapy and combination therapy with TSA on chronic post-TBI structural and functional outcomes, including epileptogenesis.

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Section: Discussionmentioning

confidence: 99%

Treatment of Status Epilepticus after Traumatic Brain Injury Using an Antiseizure Drug Combined with a Tissue Recovery Enhancer Revealed by Systems Biology

Kajevu,

Lipponen,

Andrade

et al. 2023

IJMS

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“…Although there have been advancements, the FDA has yet to approve specific TBI therapies, and few drugs have been clinically adopted. Repurposing drugs like levetiracetam, which reduces post-traumatic seizures in TBI patients [111,112], is a quick treatment option. Yet, its role in overall brain damage reduction is limited, as it does not prevent cortical damage associated with seizures.…”

Section: Multifaceted Approaches To Traumatic Brain Injury (Tbi) Trea...mentioning

confidence: 99%

Innovative Insights into Traumatic Brain Injuries: Biomarkers and New Pharmacological Targets

Silvestro,

Raffaele,

Quartarone

et al. 2024

IJMS

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A traumatic brain injury (TBI) is a major health issue affecting many people across the world, causing significant morbidity and mortality. TBIs often have long-lasting effects, disrupting daily life and functionality. They cause two types of damage to the brain: primary and secondary. Secondary damage is particularly critical as it involves complex processes unfolding after the initial injury. These processes can lead to cell damage and death in the brain. Understanding how these processes damage the brain is crucial for finding new treatments. This review examines a wide range of literature from 2021 to 2023, focusing on biomarkers and molecular mechanisms in TBIs to pinpoint therapeutic advancements. Baseline levels of biomarkers, including neurofilament light chain (NF-L), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), Tau, and glial fibrillary acidic protein (GFAP) in TBI, have demonstrated prognostic value for cognitive outcomes, laying the groundwork for personalized treatment strategies. In terms of pharmacological progress, the most promising approaches currently target neuroinflammation, oxidative stress, and apoptotic mechanisms. Agents that can modulate these pathways offer the potential to reduce a TBI’s impact and aid in neurological rehabilitation. Future research is poised to refine these therapeutic approaches, potentially revolutionizing TBI treatment.

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Levetiracetam

2023

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Levetiracetam dosing for seizure prophylaxis in neurocritical care patients

Cited by 4 publications

References 33 publications

Treatment of Status Epilepticus after Traumatic Brain Injury Using an Antiseizure Drug Combined with a Tissue Recovery Enhancer Revealed by Systems Biology

Treatment of Status Epilepticus after Traumatic Brain Injury Using an Antiseizure Drug Combined with a Tissue Recovery Enhancer Revealed by Systems Biology

Innovative Insights into Traumatic Brain Injuries: Biomarkers and New Pharmacological Targets

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