Comparing the Effect of Memantine and Placebo on Clinical Outcome of Intracranial Hemorrhage: A Randomized Double Blind Clinical Trial

Babak, Bakhshayesh Eghbali; Mohadese, Hajinnori; Mohammad, Seyed Saadat Seyed; Nazanin, Seyed Saadat Seyed; Ehsan, Kazemnezhad Leili; Melina, Rouhi Rad

doi:10.18869/acadpub.cjns.1.3.11

Cited by 7 publications

(6 citation statements)

References 24 publications

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“…The effect of this combination on PHE was better than the use of single agent (104). A single-centered RCT of 64 ICH patients confirmed the beneficial effect of memantine with better modified Rankin score and Barthel index at 90 days (105). With supportive data from animal studies and a single-centered RCT in humans, there is enough preliminary data to support a large multicenter RCT to confirm these findings.…”

Section: Perihemorrhagic Edemamentioning

confidence: 92%

“…Another rat study with a combination therapy with memantine and celecoxib showed a reduction in cerebral inflammation, apoptosis, hematoma volume, and better functional recovery (104). A single-centered RCT of 64 ICH patients confirmed the beneficial effect to memantine in humans on outcomes, but they did not study its effect on HE (105). The effect of memantine on HE and clinical outcomes in animals would need further evidence in humans to achieve clinical utility.…”

Section: Hematoma Expansionmentioning

confidence: 99%

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Intracerebral Hemorrhage: Perihemorrhagic Edema and Secondary Hematoma Expansion: From Bench Work to Ongoing Controversies

Mittal

LacKamp

2016

Front. Neurol.

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Intracerebral hemorrhage (ICH) is a medical emergency, which often leads to severe disability and death. ICH-related poor outcomes are due to primary injury causing structural damage and mass effect and secondary injury in the perihemorrhagic region over several days to weeks. Secondary injury after ICH can be due to hematoma expansion (HE) or a consequence of repair pathway along the continuum of neuroinflammation, neuronal death, and perihemorrhagic edema (PHE). This review article is focused on PHE and HE and will cover the animal studies, related human studies, and clinical trials relating to these mechanisms of secondary brain injury in ICH patients.

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Section: Perihemorrhagic Edemamentioning

confidence: 92%

Section: Hematoma Expansionmentioning

confidence: 99%

Intracerebral Hemorrhage: Perihemorrhagic Edema and Secondary Hematoma Expansion: From Bench Work to Ongoing Controversies

Mittal

LacKamp

2016

Front. Neurol.

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“…Results showed a significant increase of the mean in the BI and a decrease in the mRs in the memantine-treated group compared to placebo; these results were measured from admission time until the 3 months ( P = <0.05). No significant differences were demonstrated when analyzing mortality rate, GCS, or NIHSS score ( P = >0.05) ( Bakhshayesh-Eghbali et al, 2015 ). This further increases the potential therapeutic landscape suggesting that the benefits of memantine may also extend to other etiological types of stroke; however, further research needs to be done before any conclusions can be drawn.…”

Section: Memantine’s Clinical Use In Stroke?mentioning

confidence: 99%

Memantine as a neuroprotective agent in ischemic stroke: Preclinical and clinical analysis

Pichardo-Rojas

Cornejo-Bravo

et al. 2023

Front. Neurosci.

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The primary mechanism for neuron death after an ischemic stroke is excitotoxic injury. Excessive depolarization leads to NMDA-mediated calcium entry to the neuron and, subsequently, cellular death. Therefore, the inhibition of the NMDA channel has been proposed as a neuroprotective measure in ischemic stroke. The high morbimortality associated with stroke warrants new therapies that can improve the functional prognosis of patients. Memantine is a non-competitive NMDA receptor antagonist which has gained attention as a potential drug for ischemic stroke. Here we analyze the available preclinical and clinical evidence concerning the use of memantine following an ischemic stroke. Preclinical evidence shows inhibition of the excitotoxic cascade, as well as improved outcomes in terms of motor and sensory function with the use of memantine. The available clinical trials of high-dose memantine in patients poststroke have found that it can improve patients’ NIHSS and Barthel index and help patients with poststroke aphasia and intracranial hemorrhage. These results suggest that memantine has a clinically relevant neuroprotective effect; however, small sample sizes and other study shortcomings limit the impact of these findings. Even so, current studies show promising results that should serve as a basis to promote future research to conclusively determine if memantine does improve the outcomes of patients’ post-ischemic stroke. We anticipate that future trials will fill current gaps in knowledge, and these latter results will broaden the therapeutic arsenal for clinicians looking to improve the prognosis of patients poststroke.

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“…One preclinical trial of memantine reported an approximate 50% reduction in ICH volume coupled with the inhibition of MMP-9 following treatment for 14 days (Lee et al, 2006). In another study, 64 patients were allocated to either memantine (10 mg daily for a month and then increased to 20 mg daily for 2 months) or placebo within 24 h of ictus (Bakshayesh-Ebhbali and Hajinnori, 2015). At 3 months, patients treated with memantine reported better motor function compared to those receiving the placebo (Bakshayesh-Ebhbali and Hajinnori, 2015).…”

Section: Putative Neuroprotectantsmentioning

confidence: 99%

“…In another study, 64 patients were allocated to either memantine (10 mg daily for a month and then increased to 20 mg daily for 2 months) or placebo within 24 h of ictus (Bakshayesh-Ebhbali and Hajinnori, 2015). At 3 months, patients treated with memantine reported better motor function compared to those receiving the placebo (Bakshayesh-Ebhbali and Hajinnori, 2015). Data also suggest that memantine may improve cognition and aphasia (Berthier et al, 2009), but this needs to be tested further.…”

Section: Putative Neuroprotectantsmentioning

confidence: 99%

Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history, and potential treatments from translation to clinical trials

Krishnan,

Campos,

Nguyen

et al. 2023

Front. Stroke

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Acute intracerebral hemorrhage is the most devastating stroke subtype and is associated with significant morbidity and mortality. Poor prognosis is associated with primary brain injury from the presenting hematoma, and despite advances in clinical trials of evacuation or reducing expansion, management is largely limited to supportive care and secondary prevention. Recent research has led to a better understanding of the pathophysiology of the cerebral edema surrounding the hematoma (perihematomal edema) and the identification of treatment targets and potential interventions. Some therapies have progressed to testing in phase 2 and 3 clinical trials, while novel agents are in development. This review focuses on the pathogenesis of perihematomal edema and its natural history and summarizes the results of potential interventions including preclinical and clinical studies. This review also lists the gaps in the current knowledge and suggests directions for future trials of perihematomal edema that could potentially change clinical practice.

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Comparing the Effect of Memantine and Placebo on Clinical Outcome of Intracranial Hemorrhage: A Randomized Double Blind Clinical Trial

Cited by 7 publications

References 24 publications

Intracerebral Hemorrhage: Perihemorrhagic Edema and Secondary Hematoma Expansion: From Bench Work to Ongoing Controversies

Intracerebral Hemorrhage: Perihemorrhagic Edema and Secondary Hematoma Expansion: From Bench Work to Ongoing Controversies

Memantine as a neuroprotective agent in ischemic stroke: Preclinical and clinical analysis

Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history, and potential treatments from translation to clinical trials

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