Efficacy of Nimodipine Combined with Latanoprost in Treating Open-Angle Glaucoma and Its Influence on Ocular Hemodynamics and Visual Field Defects.

Background: Open-angle glaucoma is a common ophthalmic disease, which has a great impact on the vision of middle-aged and elderly people. Medication plays an important role in the treatment of glaucoma, so finding effective drug treatment is of great significance to improve the quality of life of glaucoma patients. Objective: To explore the curative effect of nimodipine combined with latanoprost in the treatment of open-angle glaucoma and its effect on ocular hemodynamics and visual field defects. Methods: This study retrospectively analyzed the clinical data of 87 patients with open-angle glaucoma who came to the Shanxi Province Fenyang Hospital and The First Affiliated Hospital of Shanxi Datong University for treatment from January 2019 to January 2021. According to different treatment plans, the patients were divided into two groups: an observation group (n = 46) treated with nimodipine combined with latanoprost, and a control group (n = 41) treated by latanoprost monotherapy. Treatment efficacy, hemodynamics, visual field defects, 24-hour peak intraocular pressure, binocular optic disc parameters, adverse reactions and quality of life were recorded and compared between two groups of patients. Results: The overall therapeutic effect of the observation group was significantly better than that in the control group. After treatment, ocular hemodynamics, visual field defects, 24-hour peak intraocular pressure, binocular optic disc parameters and life quality of both groups were obviously improved compared to those before treatment, with more significant improvements in the observation group. In addition, there was no significant difference in the incidence of adverse reactions between the two groups. Conclusion: Nimodipine combined with latanoprost eye drops is effective in the treatment of primary open-angle glaucoma, which could effectively improve the ocular hemodynamics and visual field defects of patients with fewer adverse reactions and higher safety. Therefore, it can be further promoted and used in clinical practice.

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

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.

Efficacy and Safety of the Association of Nimodipine and Choline Alphoscerate in the Treatment of Cognitive Impairment in Patients with Cerebral Small Vessel Disease. The CONIVaD Trial.

BACKGROUND: No approved treatment is available for patients with vascular cognitive impairment (VCI) due to cerebral small vessel disease (SVD). OBJECTIVE: The CONIVaD (Choline Alphoscerate and Nimodipine in Vascular Dementia) study aimed to investigate the feasibility, efficacy, and safety of a combined treatment with choline alphoscerate and nimodipine in patients with SVD and mild-to-moderate cognitive impairment. METHODS: Within this pilot, single-center (university hospital), double-blinded, randomized clinical trial, patients were randomized to two arms: 1-year treatment with nimodipine 30 mg three times a day (TID) plus choline alphoscerate 600 mg twice a day (BID) (arm 1) or nimodipine 30 mg TID plus placebo BID (arm 2). Patients underwent an evaluation at baseline and after 12 months. Cognitive decline, defined as a ≥ 2-point loss on the Montreal Cognitive Assessment, was the primary endpoint. Functional, quality of life, other cognitive measures, and safety were secondary endpoints. Treatment adherence was measured by the count of medicine bottles returned by patients. RESULTS: Sixty-two patients were randomized (31 each arm). Fourteen patients (22%) dropped out for reasons including consent withdrawal (n = 9), adverse reactions (n = 4), and stroke (n = 1). Forty-eight patients (mean ± SD age 75.1 ± 6.8 years), well balanced between arms, completed the study. Regarding adherence, of the prescribed total drug dose, > 75% was taken by 96% of patients for choline alphoscerate, 87.5% for placebo, and 15% for nimodipine. No statistically significant differences were found between the treatment groups for the primary cognitive outcome, nor for the secondary outcomes. Eight patients had non-serious adverse reactions; five presented adverse events. CONCLUSION: Patients' adherence to treatment was low. With this limitation, the combined choline alphoscerate-nimodipine treatment showed no significant effect in our cohort of VCI patients with SVD. The safety profile was good overall. TRIAL REGISTRATION: Clinical Trial NCT03228498. Registered 25 July 2017.

Therapeutic effect of piracetam with nimodipine on vascular dementia after cerebral infarction.

This article investigated the clinical effects of piracetam with nimodipine in the treatment of vascular dementia (VD) after cerebral infarction. 98 patients with vascular dementia after cerebral infarction were selected and divided into the control group and the study group according to the treatment method. The control group was treated with nimodipine alone. The study group was treated with piracetam on the basis of this observation, and we test the ADL (life ability score), MoCA(montreal cognitive assessment scale), ADAS-Cog(alzheimer's scale-cognition), MMSE(mental status examination) scores and quality of life scores before and after treatment in the two groups. Before treatment, there were no significant differences in ADL, MoCA, and ADAS-Cog scores between the two groups (P>0.05). After treatment, the ADL, MoCA, and ADAS-Cog scores of the study group were superior to the control group. The difference was statistically significant (P<0.05). There was no significant difference in MMSE scores between the two groups before treatment and 1 month after treatment (P>0.05). The MMSE scores of the study group were better than the control group after 3 months of treatment and half a year after treatment. The difference was statistically significant (P <0.05). Before treatment, there was no significant difference in the quality of life scores between the two groups (P>0.05). After treatment, the quality of life scores was significantly higher than the control group, and the difference was statistically significant (P<0.05). For patients with vascular dementia after cerebral infarction, piracetam combined with nimodipine can improve the cognitive function, improve the quality of life, and have a significant clinical effect.

Does Nimodipine Interruption due to High Catecholamine Doses Lead to a Greater Incidence of Delayed Cerebral Ischemia in the Setting of Aneurysmal Subarachnoid Hemorrhage?

BACKGROUND: Current guidelines recommend the administration of nimodipine for the prevention of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, nimodipine can lead to significant drops in mean arterial pressure and cerebral perfusion pressure. Catecholamines are then used to maintain them while nimodipine is reduced and/or held. There is no evidence that nimodipine retains its neuroprotective effect at lower doses. We aimed to investigate the role of nimodipine interruption in the setting of aSAH and its possible impact on the incidence of DCI. METHODS: We performed a retrospective analysis in patients with aSAH admitted to our center from January 2012 to October 2015. Nimodipine prophylaxis duration and dosage and the incidence of DCI were recorded. Bivariate correlation with Spearman's rho (ρ) and ordinal regression analyses were performed. RESULTS: A total of 170 patients were included in the study. Of these, 165 (97.1%) received nimodipine prophylaxis starting on day 0. Nimodipine was interrupted in 85 of 165 (51.5%), whereas dose was reduced in 47 of 165 (28.5%); full dose was received by only 33 of 165 (20%). DCI was observed in 85 of 170 (50%). Nimodipine interruption correlated in a statistically significant way with a greater incidence of DCI (ρ = 0.431, P < 0.001); receiving full doses of nimodipine showed a statistically significant inverse correlation to DCI (ρ = -0.273, P < 0.001). Ordinal regression analysis revealed nimodipine interruption as a statistically significant independent predictor of DCI (odds ratio 0.194; 95% confidence interval 0.079-0.474, P < 0.001). CONCLUSIONS: Our analysis reveals a greater incidence of DCI in patients with aSAH when nimodipine is interrupted.

Calcium antagonists for acute ischemic stroke.

BACKGROUND: The sudden loss of blood supply in ischemic stroke is associated with an increase of calcium ions within neurons. Inhibiting this increase could protect neurons and might reduce neurological impairment, disability, and handicap after stroke. OBJECTIVES: To assess the effects of calcium antagonists for reducing the risk of death or dependency after acute ischemic stroke. We investigated the influence of different drugs, dosages, routes of administration, time intervals after stroke, and trial design on the outcomes. SEARCH METHODS: The evidence is current to 6 February 2018. We searched the Cochrane Stroke Group Trials Register (6 February 2018), Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), MEDLINE Ovid (1950 to 6 February 2018), Embase Ovid (1980 to 6 February 2018), and four Chinese databases (6 February 2018): Chinese Biological Medicine Database (CBM-disc), China National Knowledge Infrastructure (CNKI), Chinese Scientific Periodical Database of VIP information, and Wanfang Data. We also searched the following trials registers: ClinicalTrials.gov, EU Clinical Trials Register, Stroke Trials Registry, ISRCTN registry, WHO International Clinical Trials Registry Platform, and Chinese Clinical Trial Registry, and we contacted trialists and researchers. SELECTION CRITERIA: Randomized controlled trials comparing a calcium antagonist versus control in people with acute ischemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the quality of the evidence. We used death or dependency at the end of long-term follow-up (at least three months) in activities of daily living as the primary outcome. We used standard Cochrane methodological procedures. MAIN RESULTS: We included 34 trials involving 7731 participants. All the participants were in the acute stage of ischemic stroke, and their age ranged from 18 to 85 years, with the average age ranging from 52.3 to 74.6 years across different trials. There were more men than women in most trials. Twenty-six trials tested nimodipine, and three trials assessed flunarizine. One trial each used isradipine, nicardipine, PY108-608, fasudil, and lifarizine. More than half of these trials followed participants for at least three months. Calcium antagonists showed no effects on the primary outcome (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.98 to 1.13; 22 trials; 22 studies; 6684 participants; moderate-quality evidence) or on death at the end of follow-up (RR 1.07, 95% CI 0.98 to 1.17; 31 trials; 7483 participants; moderate-quality evidence). Thirteen trials reported adverse events, finding no significant differences between groups. Most trials did not report the allocation process or how they managed missing data, so we considered these at high risk of selection and attrition bias. Most trials reported double-blind methods but did not state who was blinded, and none of the trial protocols were available. AUTHORS' CONCLUSIONS: We found no evidence to support the use of calcium antagonists in people with acute ischemic stroke.

Impact of Early Versus Late Intravenous Followed by Oral Nimodipine Treatment on the Occurrence of Delayed Cerebral Ischemia Among Patients With Aneurysm Subarachnoid Hemorrhage.

BACKGROUND: Guidelines for aneurysm subarachnoid hemorrhage (aSAH) management recommend treatment with nimodipine to all patients to reduce delayed cerebral ischemia (DCI) and poor clinical outcome. However, it did not give the most beneficial time to start therapy and route of administration. OBJECTIVES: To compare the DCI occurrence and clinical outcome among aSAH patients who received nimodipine treatment at different times. METHODS: A retrospective cohort study was conducted by collecting data from medical chart reviews between August 30, 2010, and October 31, 2015, at Prasart Neurological Institute, Thailand. Patients were classified into 2 groups by time to receive nimodipine: early group and late group (<96 and >96 hours, respectively). All patients received intravenous (IV) followed by oral nimodipine to complete treatment course. Clinical outcome was graded using the Glasgow Outcome Scale at 21 days. The factors related to DCI were analyzed using multivariate logistic regression. RESULTS: A total of 149 patients were recruited: early (n = 97) and late (n = 52). No difference in baseline characteristics between groups was observed. The occurrence of DCI was not statistically significantly different between groups (early group, 18.60%, vs late group, 20.80%; P = 0.74). The World Federation of Neurosurgical Societies IV to V was associated with DCI occurrence. The proportion of patients with good outcome, poor outcome, or death did not show any difference between groups. CONCLUSIONS AND RELEVANCE: Receiving IV nimodipine 3 to 7 days following oral therapy after bleeding can be the alternative regimen in patients who did not start nimodipine within 96 hours.

Combining nanoscale magnetic nimodipine liposomes with magnetic resonance image for Parkinson's disease targeting therapy.

AIM: To enhance drug targeting and blood-brain barrier penetration for Parkinson's disease (PD), a novel nanoscale magnetic nimodipine (NMD) delivery system was designed and prepared. MATERIALS & METHODS: The PD rats were established and treated with free NMD or Fe3O4-modified NMD liposomes (Fe3O4-NMD-lips). Then, factional anisotropy values were measured by MRI to evaluate therapy efficacy. RESULTS: Fe3O4-NMD-lips showed the best neuroprotective effect, and the NMD concentration of lesions was 2.5-fold higher in Fe3O4-NMD-lips group than that of free NMD group. CONCLUSION: These results demonstrated that the magnetic drug system had a great potential to cross the blood-brain barrier and provided a noninvasive and effective therapeutic strategy for PD.

Efficacy and safety assessment of acupuncture and nimodipine to treat mild cognitive impairment after cerebral infarction: a randomized controlled trial.

BACKGROUND: Cerebral infarction frequently leads to mild cognitive impairment (MCI). Prompt management of MCI can prevent vascular dementia and improve patient outcome. This single center randomized controlled trial aims to investigate the efficacy and safety of acupuncture and nimodipine to treat post-cerebral infarction MCI. METHODS: A total of 126 Chinese patients with post-cerebral infarction MCI recruited from the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine between April 2013 and June 2014 were randomized at 1:1: 1 ratio into nimodipine alone (30 mg/time and 3 times daily), acupuncture alone (30 min/time, 6 times/week), and nimodipine + acupuncture groups. The treatments were 3 months. Cognitive function was evaluated using Montreal Cognitive Assessment (MoCA) scale at enrollment interview, at the end of 3-month therapy, and at the post-treatment 3-month follow-up. RESULTS: The per-protocol set included 39, 40, and 40 patients from nimodipine alone, acupuncture alone, and the combination group, respectively, was analyzed. Intra-group comparison revealed that MoCA score at the follow-up improved significantly by 15.8 ± 10.9, 20.9 ± 13.8 %, and 30.2 ± 19.7 % compared with the baseline MoCA for nimodipine alone, acupuncture alone, and the combination group, respectively. Inter-group comparison demonstrated that the combination therapy improved MoCA score (5.5 ± 2.2) at significantly higher extent than nimodipine alone (3.1 ± 1.8) and acupuncture alone (4.3 ± 2.3) at the follow-up (All P < 0.05), and significantly higher proportion of patients in acupuncture alone group (80 %) and the combination therapy group (90 %) than in nimodipine alone group (56.4 %) showed ≥12 % MoCA score improvement compared with the baseline MoCA (All P < 0.05). No adverse event was reported during the study. CONCLUSION: Acupuncture may be used as an additional therapy to conventional pharmacological treatment to further improve the clinical outcomes of patients with post-cerebral infarction MCI. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ , Unique Identifier: ChiCTR-IOR-15007366 ). The date of registration is November 4, 2015.

Nimodipine Dose Reductions in the Treatment of Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The incidence of cerebral infarction and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH) is reduced by oral nimodipine but acute effects of the drug may include a significant decrease in mean arterial blood pressure (MAP). A dose reduction or discontinuation of the drug is recommended if recurrent MAP drops occur. The aim of our study was to evaluate the frequency and clinical significance of nimodipine dose modifications in patients suffering from aSAH. METHODS: 270 patients were included in our retrospective analysis of consecutively collected data of patients suffering from aSAH. The local treatment protocol was in accordance to national and international guidelines. Nimodipine was intended to be applied orally with a dosage of 60 mg every 4 h. RESULTS: Only 43.6 % of patients eligible for vasospasm prophylaxis with nimodipine received the full daily dose of 60 mg every 4 h. In 28.6 %, the dose had to be reduced by 50 % due to a significant reduction in blood pressure after administration and/or high dose of catecholamines. In 27.7 % of patients, oral administration of the drug was discontinued for the same reason. Dose reduction and discontinuation occurred with a significantly higher frequency in patients in poor clinical condition. Application of the full nimodipine dosage decreased the risk of unfavorable clinical outcome in multivariate analysis (OR 0.895, p = 0.029). CONCLUSIONS: Our results show that dose reduction or discontinuation of nimodipine due to changes in MAP occur frequently in clinical routine and may be associated with unfavorable clinical outcome.

Timing of nimodipine therapy for the treatment of vocal fold paralysis.

OBJECTIVES/HYPOTHESIS: To retrospectively determine optimal timing for initiation of nimodipine within a cohort of patients with acute vocal fold paralysis (VFP). STUDY DESIGN: Retrospective patient review. METHODS: Subjects were divided into three groups: initiation within 15 days postinjury (n = 19), between 15 and 30 days postinjury (n = 23), or greater than 30 days postinjury (n = 11). RESULTS: Fifty-one patients (53 paralyzed vocal folds [VFs]) met entrance criteria and were offered and started off-label nimodipine treatment. Thirty-six of 53 VFs recovered purposeful motion (67.9%). There was no significant difference in the rate of VF recovery among patients who began nimodipine within 15 days (68.4%), patients who started nimodipine between 15 and 30 days (73.9%) of nerve injury (P = .1405), and patients who initiated nimodipine after 30 days postinjury (54.5%). CONCLUSIONS: Nimodipine treatment for acute VFP yielded equal VF motion recovery rates regardless of when the medication was initiated. Time to recovery of motion was not different between groups studied.

Prospective investigation of nimodipine for acute vocal fold paralysis.

INTRODUCTION: Nimodipine has been shown to be beneficial for recovery from acute vocal fold paralysis (AVFP) in an animal model. METHODS: prospective, open-label trial of patients with AVFP was performed using nimodipine. Consecutive patients were evaluated and offered nimodipine therapy. RESULTS: Fifty-three patients were considered for treatment with nimodipine. Thirteen did not qualify for inclusion, 5 were lost to follow-up, and 7 had side effects requiring cessation of treatment. Thus 28 patients (30 paralyzed vocal folds) were analyzed. Eighteen of the paralyzed vocal folds experienced recovery of purposeful motion (60%). Historical controls and laryngeal electromyography meta-analysis suggest no more than a 20% recovery rate from AVFP. CONCLUSIONS: This open label study using nimodipine for treatment of AVFP demonstrates tripling of the recovery rate of vocal fold motion compared with historical controls. Further study in a randomized, controlled manner is warranted.

Rationale and design of a double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of nimodipine in preventing cognitive impairment in ischemic cerebrovascular events (NICE).

BACKGROUND: Stroke is the second most common cause of mortality and the leading cause of neurological disability, cognitive impairment and dementia worldwide. Nimodipine is a dihydropyridinic calcium antagonist with a role in neuroprotection, making it a promising therapy for vascular cognitive impairment and dementia. METHODS/DESIGN: The NICE study is a multicenter, randomized, double-blind, placebo-controlled study being carried out in 23 centers in China. The study population includes patients aged 30-80 who have suffered an ischemic stroke (≤7 days). Participants are randomly allocated to nimodipine (90 mg/d) or placebo (90 mg/d). The primary efficacy is to evaluate the level of mild cognitive impairment following treatment of an ischemic stroke with nimodipine or placebo for 6 months. Safety is being assessed by observing side effects of nimodipine. Assuming a relative risk reduction of 22%, at least 656 patients are required in this study to obtain statistical power of 90%. The first patient was recruited in November 2010. DISCUSSION: Previous studies suggested that nimodipine could improve cognitive function in vascular dementia and Alzheimer's disease dementia. It is unclear that at which time-point intervention with nimodipine should occur. Therefore, the NICE study is designed to evaluate the benefits and safety of nimodipine, which was adminstered within seven days, in preventing/treating mild cognitive impairment following ischemic stroke.

Endovascular treatment: balloon angioplasty versus nimodipine intra-arterial for medically refractory cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm (CV) accounts significant morbimortality after aneurysmal subarachnoid hemorrhage. The objective of this study was to compare the clinical outcome of patients with CV treated by 2 endovascular procedures: intra-arterial nimodipine angioplasty (IANA) and balloon angioplasty (BA). Between 2008 and June 2011, we performed 22 IANA and 8 BA in 30 patients. The mean age was 44 years and 60% was female. In 17 patients, the treatment was clipping, whereas 13 underwent coil treatment. The CV was severe in 63%, moderate in 30%, and mild in 7%. Good outcome between 2 groups was similar (P = .36). The clinical outcome according to the subgroups of CV severity and modality treatment was equivalent (P = .22). Mortality at 3 months was 16% and 20% at 1 year. We did not find differences in the clinical outcome despite the fact that both techniques produce adequate angiographic resolution of CV.

Continuous selective intraarterial infusion of nimodipine for therapy of refractory cerebral vasospasm.

BACKGROUND: For endovascular treatment of vasospasm after aneurysmal subarachnoid hemorrhage (aSAH), an intraarterial treatment course with the calcium channel antagonist nimodipine infused for 30 min is proposed. As some patients still show ongoing vasospasm thereafter, we report on our experience with an extended time period of selective intraarterial nimodipine administration. METHODS: In nine patients with aSAH and refractory cerebral vasospasm, we left the catheter in place within the internal carotid artery after angiography. On the neurosurgical ICU, a continuous infusion of intraarterial nimodipine was commenced, combined with intraarterial heparin anticoagulation. Therapy was controlled with extended neuromonitoring techniques. RESULTS: Three patients died from refractory vasospasm and a fourth suffered lethal sepsis. Three patients survived in a good clinical condition, two of them without apparent neurologic deficit. The efficacy of intraarterial nimodipine was best verified with regional CBF monitoring. TCD failed to detect vasospasm in two patients and missed improvement in four. Brain tissue oxygenation increased in all patients, but was not indicative of vasospasm in one. CT perfusion reflected the treatment course adequately in the qualitative scans. CONCLUSION: Selective continuous intraarterial nimodipine treatment for refractory cerebral vasospasm after aSAH seems feasible and may add to the endovascular therapeutic options. Appropriate monitoring technology is essential for further investigation of this novel technique.

Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies.

Nimodipine is a 1,4-dihydropyridine-derivative Ca(2+)-channel blocker developed approximately 30 years ago. It is highly lipophilic, crosses the blood-brain barrier, and reaches brain and cerebrospinal fluid. Early treatment with nimodipine reduces the severity of neurological deficits resulting from vasospasm in subarachnoid haemorrhage (SAH) patients. In SAH, nimodipine reduced spasm-related deficits of all severities, but no spasm-unrelated deficits. This paper has reviewed preclinical studies on the influence of nimodipine in various animal models of cerebral ischemia, with particular attention toward investigations published in the last 10 years. These studies further support the main indication of nimodipine, by clarifying some mechanisms of the anti-ischemic activity of the compound. Papers reporting a possible role of nimodipine in epileptogenesis were also examined. Clinical studies on nimodipine were grouped into subarachnoid hemorrhage, acute ischemic stroke, cerebral ischemia without stroke, dementia disorders, and migraine. Clinical investigations have shown that the drug improves neurological outcome by reducing the incidence and severity of ischemic deficits in patients with SAH from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition. No relevant effects of treatment with nimodipine were reported for acute ischemic stroke, cerebral ischemia without stroke, and migraine, except than for cluster headache. The less pronounced cardiovascular effects of nimodipine compared to other dihydropyridine-type Ca(2+)-channel blockers probably accounts for its use out of label for treating patients affected by chronic cerebral ischemia and vascular cognitive impairment. However, the blood pressure-lowering effects of nimodipine should not be minimized, as clinical studies have documented lowering blood pressure in small groups of patients, including cases of withdrawn due to pronounced hypotension induced by nimodipine administration. In the area of vascular cognitive impairment, short-term benefits of nimodipine do not justify its use as a long-term anti-dementia drug, and benefits obtained in elderly patients affected by subcortical vascular dementia require to be confirmed by other groups and in larger scale trials. In conclusion, nimodipine is a safe drug with an important place in pharmacotherapy and with the main documentation for reduction in the severity of neurological deficits resulting from vasospasm in SAH patients.

Feasibility and safety of intrathecal nimodipine on posthaemorrhagic cerebral vasospasm refractory to medical and endovascular therapy.

OBJECTIVE: The effectiveness of balloon angioplasty and intra-arterial infusion of vasodilating agents for patients suffering from severe vasospasm following aneurysmal subarachnoid haemorrhage (SAH) is often unsatisfying and there is still demand for further last resort treatment strategies. In the current prospective study, we attempted the intrathecal lavage administration of nimodipine in cases of severe cerebral vasospasm that were refractory to medical and endovascular therapy. METHODS: Eight of 146 patients with aneurysmal SAH were included in the prospective study, which had been approved by the local ethics committee. Treatment was instituted by intraventricular nimodipine bolus (0.4 mg), followed by a continuous lumbar intrathecal infusion (0.4 mg/h). Effectiveness was monitored angiographically, with transcranial Doppler (TCD), perfusion CT (pCT), and by neurological examination during treatment course and follow-up. RESULTS: The neurological condition improved directly in three patients and remained unchanged in four patients. Seventeen (70.8%) CT perfusion analyses revealed improved perfusion. A reduction of vasospasm was seen angiographically by digital subtraction angiography (DSA) in seven (66.6%) investigations. Additional ischaemic infarction after onset of the intrathecal therapy was documented in two (25%) patients. There were no serious adverse effects observed. CONCLUSION: The present study has for the first time demonstrated the feasibility and safety of intrathecal nimodipine lavage in patients with severe vasospasm resistant to the established medical and endovascular treatment strategies. The results of the study are therefore encouraging, and further experimental and clinical trials should be carried out so as to investigate the efficacy of intrathecal nimodipine lavage in vasospasm therapy.

Nimodipine: test your drug IQ.

Find out how this calcium channel blocker treats cerebral vasospasm after subarachnoid hemorrhage.

Different responses to rivastigmine in subcortical vascular dementia and multi-infarct dementia.

Vascular dementia (VaD) is associated with a large amount of heterogeneity, as it groups together a broad category of patients in whom various manifestations of cognitive decline are attributed to cerebrovascular or cardiovascular disease. Thus, a study was designed to determine the effects of rivastigmine on cognitive function, global daily living performance, and behavioral disorders in VaD patients versus an active control (nimodipine), stratifying patients according to the type of VaD, subcortical vascular dementia (sVAD), and multi-infarct dementia (MID). The trial was a prospective study. This study shows that long-term treatment with rivastigmine, at dosages approved for therapeutic use in Alzheimer's disease, produces significant improvement in all behavioral symptoms in 2 forms of VaD, MID and sVaD, except delusions. It also suggests that rivastigmine may enable a reduction in concomitant neuroleptics and benzodiazepines in VaD, especially in MID. The results are discussed with an overview of the literature.