Neuroprotective Efficacy of Prophylactic Enteral and Parenteral Nimodipine Treatment in Vestibular Schwannoma Surgery: A Comparative Study

Scheller, Christian; Wienke, Andreas; Wurm, Franziska; Simmermacher, Sebastian; Rampp, Stefan; Prell, Julian; Rachinger, Jens; Scheller, Konstanze; Koman, Gershom; Strauß, Christian; Herzfeld, Eva

doi:10.1055/s-0033-1355164

Cited by 9 publications

(3 citation statements)

References 43 publications

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“…Significance shows that this is not due to chance. The concentration-dependent potency of nimodipine was also seen in clinical trials, where detectibly higher nimodipine concentrations in the blood serum of patients correlated with better clinical outcomes [28]. …”

Section: Discussionmentioning

confidence: 99%

Investigation of the Neuroprotective Impact of Nimodipine on Neuro2a Cells by Means of a Surgery-Like Stress Model

Herzfeld

Strauß

Simmermacher

et al. 2014

IJMS

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Nimodipine is well characterized for the management of SAH (subarachnoid hemorrhage) and has been shown to promote a better outcome and less DIND (delayed ischemic neurological deficits). In rat experiments, enhanced axonal sprouting and higher survival of motoneurons was demonstrated after cutting or crushing the facial nerve by nimodipine. These results were confirmed in clinical trials following vestibular Schwannoma surgery. The mechanism of the protective competence of nimodipine is unknown. Therefore, in this study, we established an in vitro model to examine the survival of Neuro2a cells after different stress stimuli occurring during surgery with or without nimodipine. Nimodipine significantly decreased ethanol-induced cell death of cells up to approximately 9% in all tested concentrations. Heat-induced cell death was diminished by approximately 2.5% by nimodipine. Cell death induced by mechanical treatment was reduced up to 15% by nimodipine. Our findings indicate that nimodipine rescues Neuro2a cells faintly, but significantly, from ethanol-, heat- and mechanically-induced cell death to different extents in a dosage-dependent manner. This model seems suitable for further investigation of the molecular mechanisms involved in the neuroprotective signal pathways influenced by nimodipine.

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Section: Discussionmentioning

confidence: 99%

Investigation of the Neuroprotective Impact of Nimodipine on Neuro2a Cells by Means of a Surgery-Like Stress Model

Herzfeld

Strauß

Simmermacher

et al. 2014

IJMS

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“…Dies wird möglicherweise durch die perioperative Gabe von Nimodipin begünstigt. Es gibt Hinweise, dass Nimodipin neuroprotektive Eigenschaften besitzt und einen positiven Einfluss auf die Myelinisierung zu haben scheint [6,8].…”

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Makroskopische und mikroskopische Veränderungen des N. vestibulocochlearis nach Gamma-Knife-Therapie

Scheer

Scheller

Prell

et al. 2021

HNO

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ZusammenfassungWir berichten über einen Fall, bei dem makroskopische und mikroskopische Veränderungen des Verstibularnervs nach radiochirurgischer Behandlung eines intrameatalen Vestibularisschwannoms beobachtet wurden. Der Fallbericht zeigt das erste Mal ein morphologisches Korrelat der unerwünschten Effekte der Gamma-Knife-Therapie von Vestibularisschwannomen und unterstreicht, dass trotz eines deutlichen Abstands zum bestehenden Tumor degenerative Veränderungen der neuralen Strukturen erwartet werden können.

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“…Herzfeld et al demonstrated a reduction of apoptosis in nimodipine-treated neuro2a cells via surgery-like stress models [4,5]. Several monocenter, retro-and prospective clinical trials pointed to a beneficial effect of nimodipine on the long-term outcome of cranial nerve functions following VS surgery [7][8][9][10][11][12][13][14]. A monocentric pilot study on 30 subjects showed a superiority of its prophylactic administration compared to an intraoperative start or no treatment [9].…”

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Prophylactic nimodipine treatment for hearing preservation after vestibular schwannoma surgery: study protocol of a randomized multi-center phase III trial—AkniPro 2

Scheller

Strauß

Leisz

et al. 2021

Trials

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Background A previously performed phase III trial on 112 subjects investigating prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery showed no clear beneficial effects on preservation of facial and cochlear nerve functions, though it should be considered that protection of facial nerve function was the primary outcome. However, the risk for postoperative hearing loss was halved in the nimodipine group compared to the control group (OR 0.49; 95% CI 0.18–1.30; p = 0.15). Accordingly, this phase III extension trial investigates the efficacy and safety of prophylactic nimodipine for hearing preservation in VS surgery. Methods This is a randomized, multi-center, two-armed, open-label phase III trial with blinded expert review and two-stage with interim analysis. Three hundred thirty-six adults with the indication for microsurgical removal of VS (Koos I–IV) and serviceable preoperative hearing (Gardner-Robertson scale (GR) 1–3) are assigned to either the therapy (intravenous nimodipine 1–2 mg/h from the day before surgery until the fifth postoperative day and standard of care) or the control group (surgery only and standard of care). The primary endpoint of the trial is postoperative cochlear nerve function measured before discharge according to GR 1–3 versus GR 4–5 (binary). Hearing function will be determined by pre- and postoperative audiometry with speech discrimination, which will be evaluated by a blinded expert reviewer. Furthermore, patient-reported outcomes using standardized questionnaires will be analyzed. Discussion Prophylactic parenteral nimodipine treatment may have a positive effect on hearing preservation in VS surgery and would improve patient’s quality of life. Further secondary analyses are planned. Except for dose-depending hypotension, nimodipine is known as a safe drug. In the future, prophylactic nimodipine treatment may be recommended as a routine medication in VS surgery. VS can be considered as an ideal model for clinical evaluation of neuroprotection, since hearing outcome can be classified by well-recognized criteria. The beneficial effect of nimodipine may be transferable to other surgical procedures with nerves at risk and may have impact on basic research. Trial registration EudraCT 2019-002317-19, DRKS00019107. 8th May 2020.

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Neuroprotective Efficacy of Prophylactic Enteral and Parenteral Nimodipine Treatment in Vestibular Schwannoma Surgery: A Comparative Study

Abstract: These results support a dependency of nimodipine's neuroprotective efficacy on its serum levels. Parenteral nimodipine treatment produces higher serum levels and has a higher neuroprotective potency in vestibular schwannoma surgery compared with enteral treatment.

Cited by 9 publications

References 43 publications

Investigation of the Neuroprotective Impact of Nimodipine on Neuro2a Cells by Means of a Surgery-Like Stress Model

Investigation of the Neuroprotective Impact of Nimodipine on Neuro2a Cells by Means of a Surgery-Like Stress Model

Makroskopische und mikroskopische Veränderungen des N. vestibulocochlearis nach Gamma-Knife-Therapie

Prophylactic nimodipine treatment for hearing preservation after vestibular schwannoma surgery: study protocol of a randomized multi-center phase III trial—AkniPro 2

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