Dexamethasone Addition Impairs the Therapeutic Effects of Nimodipine for Subarachnoid Hemorrhage: An Experimental Animal Study.

AIM: To evaluate the effects of the combination of nimodipine and dexamethasone in subarachnoid hemorrhage (SAH). MATERIAL AND METHODS: In this study, 35 female adult Wistar Albino rats were randomly assigned to four groups: Sham (n=8), SAH with no treatment (n=9), SAH with nimodipine (n=9, oral gavage, 12 mg/kg, BID) treatment, and SAH with combined therapy with nimodipine and dexamethasone (n=9, intraperitoneally, 1mg/kg, BID). The "cisterna magna double injection of autologous blood" model was used. The animals were euthanized 5 days after the first injection. RESULTS: Of the total, five rats died before euthanasia. The SAH+Nontreatment group showed the worst score in neurological examinations, and the most severe histopathological findings were noted in terms of vasospasm. The SAH+Nimodipine group showed the best neurological score and the closest histopathological results to those of the Sham group, whereas adding dexamethasone to nimodipine treatment (the SAH+Nimodipine+Dexamethasone group) worsened the neurological and histopathological outcomes. CONCLUSION: We thus concluded that the therapeutic effects of nimodipine were impaired when combined with dexamethasone. We thus hypothesized that dexamethasone possibly induces the CYP3A4-enzyme that metabolizes nimodipine. However, it should be noted that our results are based on laboratory findings obtained on a small sample, therefore further studies with drug-drug interaction on a larger sample size through CYP3A4-enzyme and clinical confirmation are warranted.

Evaluation of DeGIR registry data on endovascular treatment of cerebral vasospasm in Germany 2018-2021: an overview of the current care situation. / Auswertung der DeGIR-Registerdaten zur endovaskulären Therapie von zerebralen Vasospasmen in Deutschland 2018­2021: Ein Überblick über die aktuelle Versorgungssituation.

BACKGROUND: Evaluation of endovascular therapies for cerebral vasospasm (CVS) documented in the DeGIR registry from 2018-2021 to analyse the current clinical care situation in Germany. METHODS: Retrospective analysis of the clinical and procedural data on endovascular spasm therapies (EST) documented anonymously in the DeGIR registry. We analysed: pre-interventional findings of CTP and consciousness; radiation dose applied, interventional-technical parameters (local medication, devices, angiographic result), post-interventional symptoms, complications and mortality. RESULTS: 3584 patients received a total of 7628 EST (median age/patient: 53 [range: 13-100, IQR: 44-60], 68.2 % women) in 91 (2018), 92 (2019), 100 (2020) and 98 (2021) centres; 5388 (70.6 %) anterior circulation and 378 (5 %) posterior circulation (both involved in 1862 cases [24.4 %]). EST was performed once in 2125 cases (27.9 %), with a mean of 2.1 EST/patient. In 7476 times, purely medicated EST were carried out (nimodipine: 6835, papaverine: 401, nitroglycerin: 62, other drug not specified: 239; combinations: 90). Microcatheter infusions were documented in 1132 times (14.8 %). Balloon angioplasty (BA) (additional) was performed in 756 EST (9.9 %), other mechanical recanalisations in 154 cases (2 %) and stenting in 176 of the EST (2.3 %). The median dose area product during ET was 4069 cGycm² (drug: 4002/[+]BA: 8003 [p < 0.001]). At least 1 complication occurred in 95 of all procedures (1.2 %) (drug: 1.1 %/[+]BA: 4.2 % [p < 0.001]). Mortality associated with EST was 0.2 % (n = 18). After EST, overall improvement or elimination of CVS was found in 94.2 % of cases (drug: 93.8 %/[+]BA: 98.1 % [p < 0.001]). In a comparison of the locally applied drugs, papaverine eliminated CVS more frequently than nimodipine (p = 0.001). CONCLUSION: EST have a moderate radiation exposure and can be performed with few complications. Purely medicated EST are predominantly performed, especially with nimodipine. With (additional) BA, radiation exposure, complication rates and angiographic results are higher or better. When considering drug EST alone, there is evidence for an advantage of papaverine over nimodipine, but a different group size has to be taken into account. In the analysis of EST, the DeGIR registry data are suitable for answering more specific questions, especially due to the large number of cases; for this purpose, further subgroupings should be sought in the data documentation. KEY POINTS: · In Germany, there are currently no guidelines for the endovascular treatment of cerebral vasospasm following spontaneous subarachnoid hemorrhage.. · In addition to oral nimodipine administration endovascular therapy is used to treat cerebral vasospasm in most hospitals.. · This is the first systematic evaluation of nationwide registry data on endovascular treatment of cerebral vasopasm in Germany.. · This real-world data shows that endovascular treatment for cerebral vasospasm has a moderate radiation exposure and can be performed with few complications overall. With (additional) balloon angioplasty, radiation exposure, complication rates and angiographic therapy results are higher or better.. CITATION FORMAT: · Neumann A, Weber W, Küchler J et al. Evaluation of DeGIR registry data on endovascular treatment of cerebral vasospasm in Germany 2018-2021: an overview of the current care situation. Fortschr Röntgenstr 2023; 195: 1018 - 1026.

Analysis of Angiographic Treatment Response to Intra-Arterial Nimodipine Bolus Injection in Patients with Medically Refractory Cerebral Vasospasm After Spontaneous Subarachnoid Hemorrhage.

BACKGROUND: Intra-arterial nimodipine (IAN) injections are performed in refractory delayed cerebral ischemia (DCI) related to cerebral vasospasm (CVS) after spontaneous subarachnoid hemorrhage (sSAH), but the clinical benefits are inconclusive and angiographic treatment failure is observed. We analyzed angiographic IAN response in a detailed vessel-specific manner and examined the impact of poor angiographic response on the further clinical course. METHODS: Clinical data were retrospectively assessed in patients with spontaneous subarachnoid hemorrhage with symptomatic CVS receiving IAN bolus treatment. Clinical and angiographic predictors for poor angiographic response, DCI-related infarction, and unfavorable outcome were analyzed. RESULTS: Eighty-nine patients were included and 356 treated vessel segments, mainly located in the anterior circulation (93%), were analyzed. Angiographic response was good in 77% of the treated segments. Older age, poor World Federation of Neurosurgical Societies (WFNS) grade 4-5 and early onset of CVS were independently associated with poor angiographic response. The factors short-segment, distal, and bilateral CVS as well as treatment of multiple vessel segments, WFNS grade 4-5, and early onset of CVS were significantly associated with an increased risk of DCI-related infarction. Clinical outcome was significantly influenced by poor WFNS grade and early onset of CVS, whereas poor angiographic response was not related to DCI-related infarction or unfavorable outcome. CONCLUSIONS: The risk of angiographic treatment failure is significantly increased in older patients and those with poor WFNS grade as in cases of early-onset CVS. Although the extent of angiographic CVS significantly affected the development of DCI-related infarction, poor angiographic response had no impact on cerebral infarction and clinical outcome.

Therapeutic Approaches for Cerebrovascular Dysfunction After Aneurysmal Subarachnoid Hemorrhage: An Update and Future Perspectives.

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe subtype of stroke occurring at a relatively young age with a significant socioeconomic impact. Treatment of aSAH includes early aneurysm exclusion, intensive care management, and prevention of complications. Once the aneurysm rupture occurs, blood spreading within the subarachnoid space triggers several molecular pathways causing early brain injury and delayed cerebral ischemia. Pathophysiologic mechanisms underlying brain injury after aSAH are not entirely characterized, reflecting the difficulties in identifying effective therapeutic targets for patients with aSAH. Although the improvements of the last decades in perioperative management, early diagnosis, aneurysm exclusion techniques, and medical treatments have increased survival, vasospasm and delayed cerebral infarction are associated with high mortality and morbidity. Clinical practice can rely on a few specific therapeutic agents, such as nimodipine, a calcium-channel blocker proved to reduce severe neurologic deficits in these patients. Therefore, new pharmacologic approaches are needed to improve the outcome of this life-threatening condition, as well as a tailored rehabilitation plan to maintain the quality of life in aSAH survivors. Several clinical trials are investigating the efficacy and safety of emerging drugs, such as magnesium, clazosentan, cilostazol, interleukin 1 receptor antagonists, deferoxamine, erythropoietin, and nicardipine, and continuous lumbar drainage in the setting of aSAH. This narrative review focuses on the most promising therapeutic interventions after aSAH.

Hemodynamic response and clinical outcome following intravenous milrinone plus norepinephrine-based hyperdynamic hypertensive therapy in patients suffering secondary cerebral ischemia after aneurysmal subarachnoid hemorrhage.

PURPOSE: Intravenous and intra-arterial milrinone as a rescue measure for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been adopted by several groups, but so far, evidence for the clinical benefit is unclear and effect on brain perfusion is unknown. The aim of the actual analysis was to define cerebral hemodynamic effects and outcome of intravenous milrinone plus norepinephrine supplemented by intra-arterial nimodipine as a rescue strategy for DCI following aneurysmal SAH. METHODS: Of 176 patients with aneurysmal SAH treated at our neurosurgical department between April 2016 and March 2021, 98 suffered from DCI and were submitted to rescue therapy. For the current analysis, characteristics of these patients and clinical response to rescue therapy were correlated with hemodynamic parameters, as assessed by CT angiography (CTA) and perfusion CT. Time to peak (TTP) delay in the ischemic focus and the volume with a TTP delay of more than 4 s (T4 volume) were used as hemodynamic parameters. RESULTS: The median delay to neurological deterioration following SAH was 5 days. Perfusion CT at that time showed median T4 volumes of 40 cc and mean focal TTP delays of 2.5 ± 2.1 s in these patients. Following rescue therapy, median T4 volume decreased to 10 cc and mean focal TTP delay to 1.7 ± 1.9 s. Seventeen patients (17% of patients with DCI) underwent additional intra-arterial spasmolysis using nimodipine. Visible resolution of macroscopic vasospasm on CTA was observed in 43% patients with DCI and verified vasospasm on CTA, including those managed with additional intra-arterial spasmolysis. Initial WFNS grade, occurrence of secondary infarction, ischemic volumes and TTP delays at the time of decline, the time to clinical decline, and the necessity for additional intra-arterial spasmolysis were identified as the most important features determining neurological outcome at 6 months. CONCLUSION: The current analysis shows that cerebral perfusion in the setting of secondary cerebral ischemia following SAH is measurably improved by milrinone and norepinephrine-based hyperdynamic therapy. A long-term clinical benefit by the addition of milrinone appears likely. Separation of the direct effect of milrinone from the effect of induced hypertension is not possible based on the present dataset.

Continuous intra-arterial nimodipine infusion as rescue treatment of severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

Severe refractory cerebral vasospasm (CV) is a major cause of disability and death in patients with aneurysmal subarachnoid hemorrhage (SAH). One rescue therapy in selected patients is intra-arterial nimodipine, either given as a single shot or as continuous infusion. To evaluate treatment efficacy, we analyzed outcome factors such as the incidence of craniectomy, ventriculo-peritonial (VP) shunting, and tracheotomy after intra-arterial nimodipine infusion. We retrospectively analyzed the rates of cerebral infarction, decompressive craniectomy, VP shunting, and tracheotomy in patients with severe CV after SAH. Three different patient groups were compared: group 1 had only been treated with oral nimodipine and hypervolemic hypertensive therapy (HHT) (2006-2010), group 2 with a single shot of intra-arterial nimodipine (SSN) in addition to oral conservative treatment (2006-2010), and group 3 with continuous intra-arterial nimodipine (CIAN) (2011-2017). The incidence of cerebral infarction was significantly lower in CIAN group (p = 0.005) than in conservative and SSN group. The indication for consecutive decompressive craniectomy was significantly lower in CIAN group in comparison with the conservative group (p = 0.018). The rates of VP shunting and tracheotomy were significantly higher in the CIAN group than in the conservative group (p = 0.028 for VP, and p = 0.003 for tracheotomy). The significantly lower rate of craniectomy in the CIAN group was most probably attributable to the significantly lower rate of CV-induced infarction. The higher rate of tracheotomy reflects more extensive sedation and the need of longer stays on the intensive care unit. Thus, the effect on long-term neurological outcome and quality of life has to be evaluated separately.

Radiation exposure in the intra-arterial nimodipine therapy of subarachnoid hemorrhage related cerebral vasospasm.

The selective intra-arterial nimodipine application for the treatment of cerebral vasospasm (CVS) in patients after spontaneous subarachnoid hemorrhage (sSAH) is widely employed. The purpose of this study is to examine the radiation exposure and to determine local diagnostic reference levels (DRLs) of intra-arterial nimodipine therapy. In a retrospective study design, DRLs and achievable dose (AD) were assessed for all patients undergoing (I) selective intra-arterial nimodipine application or (II) additional mechanical angioplasty for CVS treatment. Interventional procedures were differentiated according to the type of procedure and the number of probed vessels. Altogether 494 neurointerventional procedures of 121 patients with CVS due to sSAH could be included. The radiation exposure indices were distributed as follows: (I) DRL 74.3 Gy·cm2, AD 59.8 Gy·cm2; (II) DRL 128.3 Gy·cm2, AD 94.5 Gy·cm2. Kruskal-Wallis test confirmed significant dose difference considering the number of probed vessels (p< 0.001). The mean cumulative dose per patient was 254.9 Gy·cm2(interquartile range 88.6-315.6 Gy·cm2). The DRLs of intra-arterial nimodipine therapy are substantially lower compared with DRLs proposed for other therapeutic interventions, such as thrombectomy or aneurysm coiling. However, repeated therapy sessions are often required, bearing the potential risk of a cumulatively higher radiation exposure.

Influence of nimodipine combined with ulinastatin on neurological function and inflammatory reaction in patients with cerebral vasospasm after subarachnoid hemorrhage.

OBJECTIVE: This study aimed to discuss the influence of nimodipine+ulinastatin on the neurological function and inflammatory reaction in patients with cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). METHODS: Overall, 90 patients with CVS after SAH who were admitted to our hospital were enrolled in this study and randomly divided into research and control groups (n = 45 for both groups). On the basis of conventional therapy, patients in the control group were injected with ulinastatin and those in the research group were injected with ulinastatin+nimodipine through an intravenous drip for 7 days with the others the same as those of the control group. RESULTS: Blood flow velocity in all cerebral arteries was lower in the research group than in the control group after treatment (P < 0.05). Calcitonin gene-related peptide and nitric oxide levels were higher in the research group than in the control group after treatment (P < 0.05). Endothelin levels were lower in the research group than in the control group (P < 0.05). The total effective rate was higher in the research group than in the control group (P < 0.05). Glasgow Coma Scale scores were higher in the research group than in the control group (P < 0.05). CONCLUSION: The drug combination of nimodipine and ulinastatin improved blood flow and neurological function in patients with CVS after SAH and enhanced the therapeutic efficacy; the underlying mechanism may be associated with the regulation of vascular endothelial dilatation function and the inhibition of relevant inflammatory factors' expression.

COVID-19 Associated Reversible Cerebral Vasoconstriction Syndrome Successfully Treated with Nimodipine and Aspirin.

There have been limited cases linking SARS-CoV-2 infection with the development of reversible cerebral vasoconstriction syndrome (RCVS). We hereby report a rare case of RCVS in the setting of mild SARS-CoV-2 respiratory infection successfully treated with nimodipine and aspirin. SARS-CoV-2 attacks the ACE2-receptors, which are expressed in various body organs including the lungs, kidneys, and blood vessels. Vasoconstriction can result from down-regulation of the ACE2-receptors that can lead to sympathetic hypertonia of the cerebral blood vessel walls and/or over-activation of the renin-angiotensin axis.

Vasorelaxing cell permeant phosphopeptide mimetics for subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) due to rupture of an intracranial aneurysm leads to vasospasm resulting in delayed cerebral ischemia. Therapeutic options are currently limited to hemodynamic optimization and nimodipine, which have marginal clinical efficacy. Nitric oxide (NO) modulates cerebral blood flow through activation of the cGMP-Protein Kinase G (PKG) pathway. Our hypothesis is that SAH results in downregulation of signaling components in the NO-PKG pathway which could explain why treatments for vasospasm targeting this pathway lack efficacy and that treatment with a cell permeant phosphopeptide mimetic of downstream effector prevents delayed vasospasm after SAH. Using a rat endovascular perforation model, reduced levels of NO-PKG pathway molecules were confirmed. Additionally, it was determined that expression and phosphorylation of a PKG substrate: Vasodilator-stimulated phosphoprotein (VASP) was downregulated. A family of cell permeant phosphomimetic of VASP (VP) was wasdesigned and shown to have vasorelaxing property that is synergistic with nimodipine in intact vascular tissuesex vivo. Hence, treatment targeting the downstream effector of the NO signaling pathway, VASP, may bypass receptors and signaling elements leading to vasorelaxation and that treatment with VP can be explored as a therapeutic strategy for SAH induced vasospasm and ameliorate neurological deficits.

Reversible cerebral vasoconstriction syndrome (RCVS) caused by over-the-counter calcium supplement ingestion.

A 59-year-old woman was found unresponsive at home. Initial neurologic examination revealed aphasia and right-sided weakness. Laboratory results demonstrated a serum calcium level of 17.3 mg/dL (corrected serum calcium for albumin concentration was 16.8 mg/dL). Extensive workup for intrinsic aetiology of hypercalcemia was unrevealing. Further discussion with family members and investigation of the patient's home for over-the-counter medications and herbal supplements revealed chronic ingestion of calcium carbonate tablets. CT angiogram of the brain revealed multifocal intracranial vascular segmental narrowing, which resolved on a follow-up cerebral angiogram done 2 days later. These findings were consistent with reversible cerebral vasoconstriction syndrome.Appropriate blood pressure control with parenteral agents, calcium channel blockade with nimodipine and supportive care therapies resulted in significant improvement in neurologic status. By discharge, patient had near-complete resolution of neurologic symptoms.

Non-steroidal anti-inflammatory drugs in the pathophysiology of vasospasms and delayed cerebral ischemia following subarachnoid hemorrhage: a critical review.

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition associated with the development of early brain injury (EBI) and delayed cerebral ischemia (DCI). Pharmacological treatment of vasospasm following aSAH currently mainly comprises nimodipine administration. In the past few years, many drugs that can potentially benefit cases of subarachnoid hemorrhage have become available. The objective of this review is to critically assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) following aSAH. A systematic literature review was conducted following PRISMA guidelines. The search was aimed at studies addressing aSAH and NSAIDs during the 2010 to 2019 period, and it yielded 13 articles. Following the application of search criteria, they were divided into two groups, one containing 6 clinical articles and the other containing 7 experimental articles on animal models of aSAH. Inflammatory cerebral changes after aneurysm rupture contribute to the development of EBI, DCI and cerebral vasospasm. It appears that NSAIDs (especially coxibs) are even more effective in reducing vasospasm than nimodipine. Other beneficial effects of NSAIDs include reduction in mortality, improved functional outcome and increased hypoaggregability. However, despite these positive effects, there is only one randomized, double-blind, placebo-controlled trial showing a tendency towards a better outcome with lower incidence of vasospasm or mortality in patients following aSAH.

Herbal medicines for the prevention and treatment of cerebral vasospasm after subarachnoid hemorrhage: A protocol for systematic review and meta-analysis.

BACKGROUND: Despite the rapid advances in medical technology, including endovascular interventions and medications, cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is still one of the major threats to the lives of patients with SAH. In East Asian countries, various types of herbal medicines have been used to treat cerebrovascular diseases, including SAH. In this review, we aim to evaluate the efficacy and safety of herbal medicines for the prevention and treatment of CVS after SAH. METHODS AND ANALYSIS: Seven databases will be searched for relevant studies from inception to the present date "June 2020". Only randomized controlled trials (RCTs) that assess the effect and safety of herbal medicines for the prevention and treatment of CVS after SAH will be included. The methodological quality will be evaluated using the Cochrane risk of bias assessment tool. After selecting the appropriate studies, a meta-analysis of the RCTs will be performed. RESULTS: This study will provide a high-quality synthesis of current evidence of herbal medicines for CVS after SAH. CONCLUSION: Our systematic review will provide evidence to judge whether herbal medicines are effective interventions for patients with CVS after SAH. ETHICS AND DISSEMINATION: Ethical approval is not required, as this study is based on a review of published research. This review will be published in a peer-reviewed journal and disseminated electronically and in print. TRIAL REGISTRATION NUMBER: Research registry reviewregistry923.

Effects of nimodipine combined with betahistine on CRP and other inflammatory cytokines and vascular endothelial function in patients with hypertensive cerebral vasospasm.

OBJECTIVE: This study aims to investigate the effect of nimodipine combined with betahistine on the levels of CRP and other inflammatory cytokines, as well as vascular endothelial function in patients with hypertensive cerebral vasospasm. METHODS: A total of 80 patients with hypertensive cerebral vasospasm from March 2016 to September 2018 were enrolled and randomly equally divided into two groups. At 1 week before enrollment, the application of all antihypertensive drugs was stopped. Then amlodipine tablets were used in control group, based on which nimodipine tablets were applied in observation group. All the patients included were followed up for 1 month. The changes in the cerebral vasospasm index in the course of treatment as well as inflammatory cytokines and indicators related to vascular endothelial function at 1 month after treatment were measured and compared between the two groups. The correlations of the cerebral vasospasm index with the changes in inflammatory cytokines and vascular endothelial function-related factors in the body were analyzed. Finally, the effective rates of blood pressure regulation and cerebral vasospasm treatment were compared, while the adverse reactions and the overall clinical treatment effect of the two groups were evaluated. RESULTS: The cerebral vasospasm indexes in observation group were significantly lower than those in control group at 3 d, 1 week and 1 month after treatment (p < 0.05). At 1 month after treatment, the levels of inflammatory cytokines such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in observation group were significantly reduced compared to those in control group (p < 0.05). As for vascular endothelial function-related indicators, the endothelin-1 (ET-1) level in observation group was markedly lower than that in control group, whereas the level of nitric oxide (NO) was statistically higher than that in control group (p < 0.05). The cerebral vasospasm index was statistically positively correlated with changes in hs-CRP, IL-6, TNF-α and ET-1 (p < 0.05), but negatively correlated with changes in NO (p < 0.05). Besides, the effective rates of blood pressure regulation and cerebral vasospasm treatment in observation group were significantly higher than those in control group (p < 0.05). The overall treatment effective rate in observation group was markedly higher than that in control group (p < 0.05), and there were no significant differences of adverse reactions between the two groups (p > 0.05). CONCLUSION: For the treatment of hypertensive cerebral vasospasm, combined application of betahistine on the basis of nimodipine can effectively reduce the body's aseptic inflammatory responses, improve vascular endothelial function and increase the cerebral circulation blood flow, which offers a favorable strategy for clinical therapy.

Pharmacologic Management of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is responsible for 5% to 10% of all strokes in the United States annually and is a neurologic emergency with considerable morbidity and mortality. A common complication of aSAH is cerebral vasospasm (CVS) or narrowing of the cerebral arteries. While nearly 70% of aSAH patients will develop CVS, approximately 30% of those patients will go on to develop delayed cerebral ischemia, defined as symptomatic vasospasm or cerebral infarction demonstrated on imaging. While the pathophysiology of CVS is unclear, the prevention and treatment of this complication are a focus of ongoing research. Despite continued efforts, only one medication, nimodipine, is Food and Drug Administration approved for the improvement of neurologic outcomes by reducing the incidence and severity of ischemic deficits in patients with CVS during aSAH. This review provides nurse practitioners and the bedside nursing staff with a summary of the available literature on the pharmacologic management of CVS. It focuses on oral, intravenous, intra-arterial, and intraventricular medications available in the United States that may be utilized in the management of CVS.

Reversible cerebral vasoconstriction with thunderclap headache: A case report.

RATIONALE: Reversible cerebral vasoconstriction syndrome (RCVS) is often accompanied by thunderclap headaches. Although symptoms usually resolve spontaneously within 2 months, it can cause fatal complications, such as cerebral hemorrhage, and is difficult to differentiate from a migraine and other headaches on the basis of symptoms and Imaging study. In this case report, we explore clinical findings and appropriate treatment methods for RCVS through the case study of a female patient who experienced severe headache upon defecation PATIENT CONCERNS:: A 42-year-old female patient complained of a severe throbbing headache with a Numeric Rating Scale (NRS) score of 10 after defecation. The pain subsided temporarily after treatment with diclofenac 75 mg and Tridol 50 mg propacetamol 1 g, but the headache returned upon defecation; soon after, the patient complained again of regular headaches at 4 to 6-hour intervals irrespective of defecation. DIAGNOSIS: Brain computed tomography (CT) and head and neck magnetic resonance angiography, performed during a headache episode, revealed no specific neurological findings. Blood analysis was also normal. Head and neck CT angiography, performed one month after the start of the headaches, revealed RCVS. INTERVENTIONS: Treatment commenced with pregabalin (150 mg), oxycodone HCl/naloxone (10/5 mg), Alpram (0.5 mg), milnacipran (25 mg), and frovatriptan 25 mg, but there was no improvement in the headaches. The patient received bilateral trigger point injections (TPI) in the temporal muscles on four occasions at the pain clinic. OUTCOMES: Medication showed no effect, but after the patient received four sessions of bilateral TPI in the temporal muscles her NRS score eventually decreased from 10 to 2. The patient is currently continuing medication while still experiencing headaches at reduced intensities. LESSONS: RCVS is difficult to diagnose; moreover, it is difficult differentiate RCVS from other headaches. However, as it can cause fatal complications, it should not be overlooked. It is essential to consider diagnostic treatment for all types of headaches because RCVS can be accompanied by headaches originating from other causes.

The dual-functional memantine nitrate MN-08 alleviates cerebral vasospasm and brain injury in experimental subarachnoid haemorrhage models.

BACKGROUND AND PURPOSE: Cerebral vasospasm and neuronal apoptosis after subarachnoid haemorrhage (SAH) is the major cause of morbidity and mortality in SAH patients. So far, single-target agents have not prevented its occurrence. Memantine, a non-competitive NMDA re3ceptor antagonist, is known to alleviate brain injury and vasospasm in experimental models of SAH. Impairment of NO availability also contributes to vasospasm. Recently, we designed and synthesized a memantine nitrate MN-08, which has potent dual functions: neuroprotection and vasodilation. Here, we have tested the therapeutic effects of MN-08 in animal models of SAH. EXPERIMENTAL APPROACH: Binding to NMDA receptors (expressed in HEK293 cells), NO release and vasodilator effects of MN-08 were assessed in vitro. Therapeutic effects of MN-08 were investigated in vivo, using rat and rabbit SAH models. KEY RESULTS: MN-08 bound to the NMDA receptor, slowly releasing NO in vitro and in vivo. Consequently, MN-08 relaxed the pre-contracted middle cerebral artery ex vivo and increased blood flow velocity in small vessels of the mouse cerebral cortex. It did not, however, lower systemic blood pressure. In an endovascular perforation rat model of SAH, MN-08 improved the neurological scores and ameliorated cerebral vasospasm. Moreover, MN-08 also alleviated cerebral vasospasm in a cisterna magna single-injection model in rabbits. MN-08 attenuated neural cell apoptosis in both rat and rabbit models of SAH. Importantly, the therapeutic benefit of MN-08 was greater than that of memantine. CONCLUSION AND IMPLICATIONS: MN-08 has neuroprotective potential and can ameliorate vasospasm in experimental SAH models.

A novel rescue therapy for cerebral vasospasm: Cisternal Nimodipine application via stereotactic catheter ventriculocisternostomy.

Delayed Cerebral Infarction (DCI) due to Cerebral Vasospasm (CVS) is an important contributor to poor outcome after aneurysmal subarachnoid haemorrhage (aSAH). Despite established risk factors CVS and DCI are unpredictable at the individual patient level. Efficient treatments are lacking. We report a novel rescue therapy for DCI: Access to the basal cisterns by stereotactic catheter ventriculocisternostomy (STX-VCS) and direct cisternal application of the spasmolytic agent Nimodipine. On the basis of individual treatment decisions three aSAH patients who developed CVS underwent STX-VCS. Continuous lavage with Nimodipine was performed. CVS was assessed by daily transcranial doppler ultrasonography. Neurological outcome at 3 months was assessed by modified Rankin scale. STX-VCS was performed without complications in all patients. CVS rapidly resolved upon cisternal application of Nimodipine. CVS recurred in two patients upon interruption of Nimodpine application and resolved upon restart of Nimodipine. DCI did not occur in all three cases. STX-VCS and cisternal Nimodipine application is a novel rescue therapy for CVS treatment and DCI-prevention in patients with aSAH.