RESUMEN
BACKGROUND AND OBJECTIVE: Cerebral small vessel disease (CSVD) often coexists with cognitive dysfunction in patients, leading to significant challenges in treatment and management. This study aimed to examine the efficacy of combined application of donepezil and nimodipine on patients with comorbid CSVD and cognitive dysfunction and the effects on patients' albumin and prealbumin levels. METHODS: The records of 112 patients with comorbid CSVD and cognitive dysfunction treated at the People's Hospital of Suzhou New District from January 2019 to December 2022 were analysed retrospectively. A total of 50 patients receiving donepezil were allocated to the control group, and 62 patients receiving both nimodipine and donepezil to the study group. Outcomes compared between the two groups included serum homocysteine (Hcy), high sensitivity C-reactive protein (hs-CRP), albumin, and prealbumin before and after therapy, efficacy, and adverse reactions. Additionally, logistic regression was performed to analyze the risk factors impacting patient prognosis. RESULTS: Prior to therapy, the two groups did not differ significantly in Hcy and hs-CRP levels (p > 0.05), whereas after therapy, the levels in both groups dropped significantly (p < 0.01), with more obvious lower levels in the study group (p < 0.05). After treatment, the study group presented significantly higher albumin and prealbumin levels than the control group (p < 0.001). An obvious higher overall response rate was observed in the study group compared to the control group (p = 0.012). No significant inter-group discrepancy was found regarding the total incidence of adverse reactions (p = 0.752). Univariate analysis identified age, course of disease, heart rate (HR), Montreal Cognitive Assessment (MoCA) score, diastolic blood pressure (DBP), systolic blood pressure (SBP), drinking history, as well as medication regimen as risk factors impacting patient prognosis. Multivariate logistic regression analysis identified SBP, DBP, and medication regimen as the independent risk factors. CONCLUSION: Combined application of donepezil and nimodipine can effectively treat patients with comorbid CSVD and cognitive dysfunction. It can significantly lower the Hcy and hs-CRP levels and improve the nutritional status without increasing the frequency of adverse reactions. In addition, for CSVD patients with cognitive dysfunction, age, course of disease, MoCA score, HR, SBP, DBP, drinking history, and medication regimen are risk factors impacting patient prognosis, while SBP, DBP, and medication regimen are independent risk factors.
Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Disfunción Cognitiva , Donepezilo , Quimioterapia Combinada , Nimodipina , Estado Nutricional , Humanos , Femenino , Masculino , Donepezilo/administración & dosificación , Donepezilo/uso terapéutico , Enfermedades de los Pequeños Vasos Cerebrales/tratamiento farmacológico , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Disfunción Cognitiva/tratamiento farmacológico , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Nimodipina/administración & dosificación , Nimodipina/uso terapéutico , Resultado del Tratamiento , Nootrópicos/administración & dosificación , Nootrópicos/uso terapéutico , Nootrópicos/efectos adversos , Homocisteína/sangreRESUMEN
This study aims to explore the value of nimodipine combined with Ginkgo biloba extract in improving cognitive function and daily living abilities in patients with Parkinson's disease. Clinical data from 551 patients with Parkinson's disease admitted to the Neurology Department of the Affiliated Hospital of Beihua University from January 2022 to December 2022 were retrospectively collected. Cognitive function and daily living abilities were assessed in patients before treatment, and a reevaluation was conducted after 12 weeks of medication. Patients treated solely with nimodipine were categorized into the monotherapy group, while patients treated with nimodipine combined with Ginkgo biloba extract were included in the combination group. After 1:1 propensity score matching, a total of 83 pairs of patients were matched, and differences in relevant indicators between the 2 groups were compared. The total effective rate of treatment in the combination group was 90.36%, which was higher than the control group at 72.29% (Pâ <â .05). However, after treatment, the observation group showed higher Mini-Mental State Examination and activities of daily living scores compared to the control group (Pâ <â .05). The combined treatment of nimodipine and Ginkgo biloba extract in patients with Parkinson's disease has a significant effect and can effectively improve cognitive function and enhance daily living abilities.
Asunto(s)
Actividades Cotidianas , Cognición , Quimioterapia Combinada , Ginkgo biloba , Nimodipina , Enfermedad de Parkinson , Extractos Vegetales , Humanos , Nimodipina/uso terapéutico , Nimodipina/administración & dosificación , Masculino , Extractos Vegetales/uso terapéutico , Femenino , Estudios Retrospectivos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/psicología , Anciano , Cognición/efectos de los fármacos , Persona de Mediana Edad , Resultado del Tratamiento , Extracto de GinkgoRESUMEN
Nimodipine, an L-type cerebroselective calcium channel antagonist, is the only drug approved by the US Food and Drug Administration for the neuroprotection of patients with aneurysmal subarachnoid hemorrhage (aSAH). Four randomized, placebo-controlled trials of nimodipine demonstrated clinical improvement over placebo; however, these occurred before precision medicine with pharmacogenomics was readily available. The standard enteral dose of nimodipine recommended after aSAH is 60 mg every 4 h. However, up to 78% of patients with aSAH develop systemic arterial hypotension after taking the drug at the recommended dose, which could theoretically limit its neuroprotective role and worsen cerebral perfusion pressure and cerebral blood flow, particularly when concomitant vasospasm is present. We investigated the association between nimodipine dose changes and clinical outcomes in a consecutive series of 150 patients (mean age, 56 years; 70.7% women) with acute aSAH. We describe the pharmacogenomic relationship of nimodipine dose reduction with clinical outcomes. These results have major implications for future individualized dosing of nimodipine in the era of precision medicine.
Asunto(s)
Bloqueadores de los Canales de Calcio , Nimodipina , Farmacogenética , Hemorragia Subaracnoidea , Humanos , Nimodipina/administración & dosificación , Nimodipina/efectos adversos , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/genética , Hemorragia Subaracnoidea/complicaciones , Persona de Mediana Edad , Femenino , Masculino , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/uso terapéutico , Anciano , Farmacogenética/métodos , Resultado del Tratamiento , Relación Dosis-Respuesta a Droga , Adulto , Medicina de Precisión/métodos , Vasoespasmo Intracraneal/tratamiento farmacológicoRESUMEN
BACKGROUND: The prophylactic use of nimodipine following subarachnoid hemorrhage is a practice established four decades ago when clinical management differed from current and the concept of Delayed Cerebral Ischemia (DCI) was not established. The applicability of the original studies is limited by the fact of not reflecting current practice; by utilising a dichotomised outcome measure such as good neurological outcome versus death and vegetative state; by applying variable dosing regimens and including all causes of poor neurological outcome different than DCI. This study aims to review the available evidence to discuss the ongoing role of nimodipine in contemporaneous clinical practice. METHODS: PRISMA guidelines based review, evaluated the evidence on the prophylactic use of nimodipine. The following search engines: Medline, Embase, Cochrane, Web of Science and PubMed, identified Randomized Control Trials (RCTs) with neurological benefit as outcome measure and the impact of fixed versus weight-based nimodipine dosing regimens. RESULTS: Eight RCT were selected. Three of those trials with a total of 349 patients, showed a reduction on death and vegetative state (pooled RR: 0.62; 95 % confidence interval-CI: 0.45, 0.86) related to DCI. Amongst all studies, all cause death (pooled RR = 0.73, [95 % CI: 0.56, 0.97]) favoured a fixed-dose regimen (pooled RR: 0.60; [95 % CI: 0.43, 0.85]). CONCLUSION: Available evidence demonstrates that nimodipine only reduces the risk for DCI-related death or vegetative state and that fixed-dose regimens favour all cause infarct and death independent of DCI. Contemporaneous studies assessing the benefit of nimodipine beyond death or vegetative states and applying individualized dosing are warranted.
Asunto(s)
Nimodipina , Hemorragia Subaracnoidea , Nimodipina/administración & dosificación , Nimodipina/uso terapéutico , Humanos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/uso terapéutico , Vasodilatadores/administración & dosificación , Vasodilatadores/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Sleep disorders are one of the most common acute reactions on the plateau, which can cause serious complications. However, there is no effective and safe treatment currently available. Nimodipine (NMD) is a dihydropyridine calcium channel blocker with neuroprotective and vasodilating activity, mainly used for the treatment of ischemic brain injury. Commercial oral or injectable NMD formulations are not a good option for central neuron diseases due to their poor brain delivery. In this study, nimodipine dissolving microneedles (NDMNs) were prepared for the prevention of sleep disorders caused by hypoxia. NDMNs were composed of NMD and polyvinyl pyrrolidone (PVP) K90 with a conical morphology and high rigidity. After administration of NDMNs on the back neck of mice, the concentration of NMD in the brain was significantly higher than that of oral medication as was confirmed by the fluorescent imaging on mouse models. NDMNs enhanced cognitive function, alleviated oxidative stress, and improved the sleep quality of mice with high-altitude sleep disorders. The blockage of calcium ion overloading may be an important modulation mechanism. NDMNs are a promising and user-friendly formulation for the prevention of high-altitude sleep disorders.
Asunto(s)
Bloqueadores de los Canales de Calcio , Nimodipina , Trastornos del Sueño-Vigilia , Animales , Ratones , Nimodipina/administración & dosificación , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Trastornos del Sueño-Vigilia/prevención & control , Masculino , Bloqueadores de los Canales de Calcio/administración & dosificación , Altitud , Agujas , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Estrés Oxidativo/efectos de los fármacos , Povidona/química , Ratones Endogámicos C57BLRESUMEN
Dysregulation of calcium homeostasis has been hypothesized to play a role in Alzheimer's disease (AD) pathogenesis. Increased calcium levels can impair axonal transport, disrupt synaptic transmission, and ultimately lead to cell death. Given the potential role of calcium dyshomeostasis in AD, there is interest in testing the ability of already approved drugs targeting various calcium channels to affect amyloid pathology and other aspects of disease. The objective of this study was to test the effects of FDA-approved L-type calcium channel antagonist nimodipine on amyloid accumulation and dystrophic neurite formation in 5XFAD mice, a mouse model of amyloid pathology. 5XFAD transgenic mice and non-transgenic littermates were treated with vehicle or nimodipine-containing chow from two to eight months of age, then brains were harvested and amyloid pathology assessed by immunoblot and immunofluorescence microscopy analyses. Nimodipine was well tolerated and crossed the blood brain barrier, as expected, but there was no effect on Aß accumulation or on the relative amount of neuritic dystrophy, as assessed by either immunoblot, dot blot or immunofluorescence imaging of Aß42 and dystrophic neurite marker LAMP1. While we conclude that nimodipine treatment is not likely to improve amyloid pathology or decrease neuritic dystrophy in AD, it is worth noting that nimodipine did not worsen the phenotype suggesting its use is safe in AD patients.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Modelos Animales de Enfermedad , Neuritas/efectos de los fármacos , Distrofias Neuroaxonales/tratamiento farmacológico , Nimodipina/administración & dosificación , Placa Amiloide/tratamiento farmacológico , Administración Oral , Enfermedad de Alzheimer/patología , Animales , Bloqueadores de los Canales de Calcio/administración & dosificación , Femenino , Humanos , Masculino , Ratones , Ratones Transgénicos , Neuritas/patología , Distrofias Neuroaxonales/patología , Placa Amiloide/patologíaRESUMEN
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.
Asunto(s)
Glicoproteínas/uso terapéutico , Nimodipina/uso terapéutico , Hemorragia Subaracnoidea/complicaciones , Inhibidores de Tripsina/uso terapéutico , Vasodilatadores/uso terapéutico , Vasoespasmo Intracraneal/tratamiento farmacológico , Adulto , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Arterias Cerebrales/efectos de los fármacos , Arterias Cerebrales/fisiopatología , Quimioterapia Combinada , Femenino , Glicoproteínas/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Nimodipina/administración & dosificación , Hemorragia Subaracnoidea/fisiopatología , Resultado del Tratamiento , Inhibidores de Tripsina/administración & dosificación , Vasodilatadores/administración & dosificación , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/fisiopatologíaRESUMEN
PURPOSE: This study aimed to investigate the effect of nimodipine on peripapillary and macular capillary vessel density (VD) in patients with normal-tension glaucoma (NTG) using optical coherence tomography angiography (OCTA). METHODS: Sixty mg nimodipine was administered to 20 enrolled NTG patients for 3 months. Patients were treated with glaucoma medication simultaneously. The macular and peripapillary VD were measured automatically by OCTA at baseline, 1.5 h after administering nimodipine, and after 3 months of administering the drug. The retinal nerve fibre layer (RNFL), ganglion cell complex thickness, visual field (VF) testing, intraocular pressure (IOP), blood pressure and pulse rate in each subject were assessed during each follow-up. RESULTS: Compared with the baseline, the parafovea VD was higher (50.89 ± 4.26 versus 46.80 ± 5.40, P = .044) 1.5 h after administration of nimodipine. After administration of nimodipine for 3 months, the parafovea VD was obviously increased (51.14 ± 5.68 versus 46.80 ± 5.40, P = .039), while IOP, systolic blood pressure, mean arterial pressure and mean ocular perfusion pressure were decreased compared to baseline (all P < .05). No significant differences were found between the radial peripapillary capillary and disc VD. The parafovea VD was positively correlated with the administration of nimodipine (ß = 0.39, P = .004), RNFL thickness (ß = 0.49, P = .022), and VF mean deviation (ß = 0.4, P = .040) in the multivariate analysis. CONCLUSIONS: Nimodipine effectively increased superficial macular capillary VD, but did not affect peripapillary capillary VD in patients with NTG. This finding indicates that patients with NTG may benefit from the administration of nimodipine.
Asunto(s)
Angiografía con Fluoresceína/métodos , Glaucoma de Baja Tensión/tratamiento farmacológico , Mácula Lútea/irrigación sanguínea , Densidad Microvascular , Nimodipina/administración & dosificación , Vasos Retinianos/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Administración Oral , Adulto , Anciano , Capilares/efectos de los fármacos , Capilares/fisiopatología , Femenino , Estudios de Seguimiento , Fondo de Ojo , Humanos , Glaucoma de Baja Tensión/fisiopatología , Masculino , Persona de Mediana Edad , Disco Óptico/irrigación sanguínea , Estudios Retrospectivos , Vasodilatadores/administración & dosificación , Campos VisualesRESUMEN
Diabetics have a higher risk of developing cerebral vasospasms (CVSP) after subarachnoid hemorrhagic stroke than non-diabetics. Serotonin (5-HT) is one of the key vasoconstrictors released in the hemorrhagic blood and an important contributor to the etiology of CVSP. The combination of the ryanodine receptor blocker dantrolene and the Ca2+ channel blocker nimodipine significantly reduces phenylephrine (PHE)-induced vascular contraction in both diabetic and nondiabetic rats, but the effectiveness of this drug combination in reducing 5-HT-induced contraction is unknown. Dose-response curves for the 5-HT-induced contraction (from 0.1 nM to 100 µM) were performed on aortic rings from diabetic and non-diabetic rats after a 30-min incubation period with dantrolene, nimodipine, and both drugs in combination. In diabetic rats, 10 µM of dantrolene alone failed to reduce 5-HT-induced maximal contraction (Emax), but 50 µM reduced this parameter by 34% (n = 7, p < 0.05). In non-diabetic rats, by contrast, dantrolene did not modify the vascular response to 5-HT. 50 nM of nimodipine alone, however, reduced this parameter by 57% in diabetic rats (n = 10, p < 0.05), and by 34% in non-diabetic rats (n = 10, p < 0.05). In addition, concomitant administration of dantrolene and nimodipine reduced vascular reactivity to a similar extent in both diabetic (~ 60% reduction, n = 10, p < 0.05) and non-diabetic rats (~ 70% reduction, n = 10, p < 0.05). Moreover, the combination of nimodipine with the higher concentration of dantrolene significantly increased the EC50 values for the 5-HT-induced contraction curves in both diabetics (from 10.31 ± 1.17 µM to 19.26 ± 2.82; n = 10, p < 0.05) and non-diabetic rats (5.93 ± 0.54 µM to 15.80 ± 3.24; n = 10, p < 0.05). These results suggest that simultaneous administration of dantrolene and nimodipine has a synergistic effect in reducing 5-HT-induced vascular contraction under both diabetic and non-diabetic conditions. If our findings with rats are applicable to humans, concomitant administration of these drugs may represent a promising alternative for the management of CVSP in both diabetics and non-diabetics.
Asunto(s)
Dantroleno/administración & dosificación , Diabetes Mellitus Experimental/complicaciones , Nimodipina/administración & dosificación , Vasoespasmo Intracraneal/tratamiento farmacológico , Animales , Bloqueadores de los Canales de Calcio/administración & dosificación , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Quimioterapia Combinada , Humanos , Masculino , Contracción Muscular/efectos de los fármacos , Relajantes Musculares Centrales/administración & dosificación , Músculo Liso Vascular/efectos de los fármacos , Ratas , Serotonina/metabolismo , Estreptozocina/administración & dosificación , Estreptozocina/toxicidad , Hemorragia Subaracnoidea/etiología , Hemorragia Subaracnoidea/prevención & control , Vasoespasmo Intracraneal/etiologíaRESUMEN
The aim of this study was to build up a novel chiral mesoporous silica called PEIs@TA-CMS through a facile biomimetic strategy and to explore its potential to serve as a drug carrier for improving the delivery efficiency of poorly water-soluble drug. PEIs@TA-CMS was synthesized by using a chiral crystalline complex associated of tartaric acid and polyethyleneimine (PEIs) as templates, scaffolds and catalysts. The structural features including morphology, size, pore structure and texture properties were systematacially studied. The results showed that PEIs@TA-CMS was monodispersed spherical nanoparticles in a uniformed diameter of 120-130 nm with well-developed pore structure (SBET: 1009.94 m2/g, pore size <2.21 nm). Then PEIs@TA-CMS was employed as nimodipine (NMP) carrier and compared with the drug carry ability of MCM41. After drug loading, NMP was effectively transformed from the crystalline state to an amorphous state due to the space confinement in mesopores. As expected, PEIs@TA-CMS had superiority in both drug loading and drug release compared to MCM41. It could incorporate NMP with high efficiency, and the dissolution-promoting effect of PEIs@TA-CMS was more obvious because of the unique interconnected curved pore channels. Meanwhile, PEIs@TA-CMS could significantly improve the oral adsorption of NMP to a satisfactory level, which showed approximately 3.26-fold higher in bioavailability, and could effectively prolong the survival time of mice on cerebral anoxia from 10.98 to 17.33 min.
Asunto(s)
Nanopartículas/química , Nimodipina/farmacocinética , Polietileneimina/química , Dióxido de Silicio/química , Tartratos/química , Administración Oral , Animales , Química Farmacéutica , Portadores de Fármacos/química , Liberación de Fármacos , Masculino , Nimodipina/administración & dosificación , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Solubilidad , Propiedades de SuperficieRESUMEN
Neuronal activity in the brain reflects an excitation-inhibition balance that is regulated predominantly by glutamatergic and GABAergic neurotransmission, and often disturbed in neuropsychiatric disorders. Here, we tested the effects of a single oral dose of two anti-glutamatergic drugs (dextromethorphan, an NMDA receptor antagonist; perampanel, an AMPA receptor antagonist) and an L-type voltage-gated calcium channel blocker (nimodipine) on transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) potentials (TEPs) and TMS-induced oscillations (TIOs) in 16 healthy adults in a pseudorandomized, double-blinded, placebo-controlled crossover design. Single-pulse TMS was delivered to the hand area of left primary motor cortex. Dextromethorphan increased the amplitude of the N45 TEP, while it had no effect on TIOs. Perampanel reduced the amplitude of the P60 TEP in the non-stimulated hemisphere, and increased TIOs in the beta-frequency band in the stimulated sensorimotor cortex, and in the alpha-frequency band in midline parietal channels. Nimodipine and placebo had no effect on TEPs and TIOs. The TEP results extend previous pharmaco-TMS-EEG studies by demonstrating that the N45 is regulated by a balance of GABAAergic inhibition and NMDA receptor-mediated glutamatergic excitation. In contrast, AMPA receptor-mediated glutamatergic neurotransmission contributes to propagated activity reflected in the P60 potential and midline parietal induced oscillations. This pharmacological characterization of TMS-EEG responses will be informative for interpreting TMS-EEG abnormalities in neuropsychiatric disorders with pathological excitation-inhibition balance.
Asunto(s)
Dextrometorfano/administración & dosificación , Corteza Motora/fisiología , Nimodipina/administración & dosificación , Nitrilos/administración & dosificación , Piridonas/administración & dosificación , Estimulación Magnética Transcraneal/métodos , Adulto , Estudios Cruzados , Método Doble Ciego , Electroencefalografía , Electromiografía , Potenciales Evocados Motores , Voluntarios Sanos , Humanos , Masculino , Transmisión Sináptica , Adulto JovenRESUMEN
BACKGROUND: Peripheral nerve damage is a frequent problem, with an estimated 2.8%-5.0% of trauma admissions involving peripheral nerve injury. End-to-end, tension-free microsurgical repair (neurorrhaphy) is the current gold standard treatment for complete transection (neurotmesis). While neurorrhaphy reapproximates the nerve, it does not address the complex molecular regenerative process. Evidence suggests that botulinum toxin A (BTX) and nimodipine (NDP) may improve functional recovery, but mechanisms of action remain unknown. METHODS: This research investigates BTX and NDP for their novel capacity to improve neural regeneration in the setting of neurorrhaphy using a Lewis rat tibial nerve neurotmesis model. In a triple-masked, placebo-controlled, randomized study design, we compared functional (rotarod, horizontal ladder walk), electrophysiological (conduction velocity, duration), and stereological (axon count, density) outcomes of rats treated with: NDP+saline injection, BTX+NDP, Saline+placebo, and BTX+placebo. Additional controls included sham surgery +/- BTX. RESULTS: NDP+saline outperformed other treatment groups in the ladder walk. This group had the fewest deep slips (15.07% versus 30.77% in BTX+NDP, P = 0.122), and the most correct steps (70.53% versus 55.58% in BTX+NDP, P = 0.149) in functional testing. NDP+saline also had the fastest nerve conduction velocity (0.811m/s versus 0.598m/s in BTX+NDP, P = 0.126) among treatment groups. BTX+NDP had the highest axon count (10,012.36 versus 7,738.18 in NDP+Saline, P = 0.009). CONCLUSION: This study is the first to test NDP with BTX in a multimodal assessment of nerve recovery following neurotmesis and neurorrhaphy. NDP outperformed BTX+NDP functionally. Future work will focus on nimodipine in an effort to improve nerve recovery in trauma patients.
Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Regeneración Nerviosa/efectos de los fármacos , Procedimientos Neuroquirúrgicos , Nimodipina/administración & dosificación , Traumatismos de los Nervios Periféricos/terapia , Animales , Terapia Combinada , Modelos Animales de Enfermedad , Humanos , Masculino , Proyectos Piloto , Ratas , Recuperación de la Función , Nervio Tibial/efectos de los fármacos , Nervio Tibial/lesiones , Nervio Tibial/cirugíaRESUMEN
OBJECTIVE: To investigate the clinical efficacy of combination of mouse nerve growth factor (NGF) and nimodipine in the treatment of neonatal intracranial hemorrhage (NICH) and its effect on plasma platelet-activating factor (PAF), C-type natriuretic peptide (CNP), matrix metalloproteinase-2 (MMP-2), and neurological function. PATIENTS AND METHODS: A total of 90 infants with severe ICH admitted to our hospital from December 2016 to December 2018 were enrolled for retrospective study. According to different treatment schemes, they were assigned into 2 groups: group A (n=40) treated with mouse NGF plus nimodipine; group B (n=50) treated with nimodipine. The recovery time, serum indexes (PAF, MMP-2, CNP), neurological function (neonatal behavioral neurological assessment (NBNA) score), complications, and total effective rate of patients were recorded, and the satisfaction degree of family members was statistically analyzed. RESULTS: Patients in group A showed shorter recovery time, down-regulated PAF and MMP-2, evidently up-regulated CNP, and significantly increased NBNA score after one/two weeks of treatment, as well as fewer complications, higher total effective rate and higher satisfaction of family members. CONCLUSIONS: To sum up, the combination of mouse NGF and nimodipine achieves good clinical efficacy in NICH, which down-regulates plasma PAF and MMP-2, up-regulates CNP, and improves neurological function. Therefore, it is suitable for clinical promotion.
Asunto(s)
Enfermedades del Recién Nacido/tratamiento farmacológico , Hemorragias Intracraneales/tratamiento farmacológico , Factor de Crecimiento Nervioso/farmacología , Nimodipina/farmacología , Animales , Humanos , Recién Nacido , Enfermedades del Recién Nacido/sangre , Inyecciones Intramusculares , Hemorragias Intracraneales/sangre , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Péptido Natriurético Tipo-C/sangre , Péptido Natriurético Tipo-C/metabolismo , Factor de Crecimiento Nervioso/administración & dosificación , Nimodipina/administración & dosificación , Factor de Activación Plaquetaria/metabolismo , Estudios RetrospectivosRESUMEN
BACKGROUND: Randomized-controlled trials and meta-analyses showed nimodipine use after aneurysmal subarachnoid hemorrhage (aSAH) leads to reduction in incidence of cerebral infarction, persistent neurological deficits, and poor outcomes. Trials administered it for 21 days; however, we assessed whether a shorter duration might be reasonable for a subset of patients. METHODS: We performed a retrospective single-center study to compare outcomes between patients who received ≤14 days, 15-20 days or ≥21 days of nimodipine. Primary outcome was defined as rate of good functional outcome at final follow-up, assessed using dichotomized modified Rankin Score (mRS). Secondary outcomes included median mRS at follow-up, discharge disposition, and readmission for stroke or vasospasm. RESULTS: 195 patients were included: 101 patients received nimodipine for ≤14 days, 72 patients for 15-20 days, and 22 patients for ≥21 days. There were differences in baseline characteristics of the groups. The shorter duration groups had higher admission GCS score (GCS 15 for ≤14 days, GCS 13 for 15-20 days, GCS 8 for ≥21 days, pâ¯=â¯0.003) and lower Hunt-Hess grade (2 for ≤14 days, 3 for 15-20 days, 4 for ≥21 days, pâ¯=â¯0.001). Of the group of patients that received ≤14 days of nimodipine, 3 patients (3%) were readmitted for concerns for possible stroke or vasospasm, but they did not experience worsening of their functional status related to this. CONCLUSION: Our data suggests a more limited 14-day course of nimodipine therapy after aSAH may be reasonable and efficacious in patients with higher GCS and lower Hunt-Hess grade on presentation.
Asunto(s)
Nimodipina/administración & dosificación , Alta del Paciente/tendencias , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/tratamiento farmacológico , Vasodilatadores/administración & dosificación , Adulto , Anciano , Esquema de Medicación , Femenino , Estudios de Seguimiento , Hospitalización/tendencias , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Hemorragia Subaracnoidea/cirugía , Factores de TiempoRESUMEN
A 2016 published randomized multicenter phase III trial of prophylactic nimodipine treatment in vestibular schwannoma surgery showed only a tendency for higher hearing preservation rates in the treatment group. Gender was not included in statistical analysis at that time. A retrospective analysis of the trial considering gender, preoperative hearing, and nimodipine treatment was performed. The treatment group received parenteral nimodipine from the day before surgery until the seventh postoperative day. The control group was not treated prophylactically. Cochlear nerve function was determined by pure-tone audiometry with speech discrimination preoperatively, during in-patient care, and 1 year after surgery and classified according to the Gardner-Robertson grading scale (GR). Logistic regression analysis showed a statistically significant effect for higher hearing preservation rates (pre- and postoperative GR 1-4) in 40 men comparing the treatment (n = 21) and the control (n = 19) groups (p = 0.028), but not in 54 women comparing 27 women in both groups (p = 0.077). The results were also statistically significant for preservation of postoperative hearing with pre- and postoperative GR 1-3 (p = 0.024). There were no differences in tumor sizes between the treatment and the control groups in men, whereas statistically significant larger tumors were observed in the female treatment group compared with the female control group. Prophylactic nimodipine is safe, and an effect for hearing preservation in 40 men with preoperative hearing ability of GR 1-4 was shown in this retrospective investigation. The imbalance in tumor size with larger tumors in females of the treatment group may falsely suggest a gender-related effect. Further investigations are recommended to clarify whether gender has impact on nimodipine's efficacy.
Asunto(s)
Audición/efectos de los fármacos , Neuroma Acústico/tratamiento farmacológico , Neuroma Acústico/cirugía , Nimodipina/administración & dosificación , Profilaxis Pre-Exposición/tendencias , Adulto , Anciano , Femenino , Audición/fisiología , Pruebas Auditivas/tendencias , Humanos , Masculino , Persona de Mediana Edad , Neuroma Acústico/diagnóstico , Estudios Prospectivos , Radiocirugia/métodos , Estudios Retrospectivos , Método Simple Ciego , Resultado del TratamientoRESUMEN
RATIONALE: Reversible splenial lesion syndrome (RESLES) is a recently identified clinico-radiological syndrome, the etiology is miscellaneous. Atrial septal defect (ASD) as an underlying etiology for RESLES has not been reported. We first report a rare case of RESLES associated with ASD. The clinical, radiological, and ultrasonic profiles were presented and the pathophysiological mechanism was analyzed. PATIENT CONCERNS: A 23-year-old man presented with headache, drowsiness, occasional paraphasia, and paroxysmal dry cough. Brain magnetic resonance imaging (MRI) on admission showed an ovoid isolated lesion in the splenium of corpus callosum, which exhibited hyperintensity on diffusion-weighted imaging and hypointensity on apparent diffusion coefficient, and completely disappeared on the follow-up MRI 14 days later. ASD was found by transthoracic echocardiography, Right-to-left shunts were detected on color Doppler of transesophageal echocardiography, and microemboli were captured by transcranial Doppler ultrasound. DIAGNOSES: According to his clinical history and imaging results, we confirmed the diagnosis of RESLES associated with ASD. INTERVENTIONS: The patient was treated by oral aspirin and lopidogrel sulfate to inhibit platelet aggregation. In addition, oral nimodipine to suppress vasoconstriction. OUTCOMES: After 14 days treatment, all the symptoms presenting on admission resolved completely. Subsequently, a repair surgery of ASD under thoracoscopy was successfully performed. LESSONS: To our knowledge, this is the first reported case of ASD may be an underlying etiology for RESLES and need require an etiotropic treatment.
Asunto(s)
Encefalopatías/etiología , Cuerpo Calloso/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Defectos del Tabique Interatrial/complicaciones , Administración Oral , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Encefalopatías/diagnóstico por imagen , Encefalopatías/patología , Cuerpo Calloso/patología , Combinación de Medicamentos , Quimioterapia Combinada , Ecocardiografía/métodos , Estudios de Seguimiento , Cefalea/etiología , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/tratamiento farmacológico , Defectos del Tabique Interatrial/cirugía , Humanos , Lopinavir/administración & dosificación , Lopinavir/uso terapéutico , Masculino , Nimodipina/administración & dosificación , Nimodipina/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ritonavir/administración & dosificación , Ritonavir/uso terapéutico , Síndrome , Resultado del Tratamiento , Ultrasonografía Doppler Transcraneal/métodos , Adulto JovenAsunto(s)
Isquemia Encefálica/tratamiento farmacológico , Nimodipina/farmacología , Hemorragia Subaracnoidea , Vasodilatadores/farmacología , Vasoespasmo Intracraneal , Angiografía de Substracción Digital , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiología , Angiografía Cerebral , Fosa Craneal Posterior/patología , Humanos , Recién Nacido , Enfermedades del Recién Nacido , Imagen por Resonancia Magnética , Masculino , Nimodipina/administración & dosificación , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico , Ultrasonografía Doppler Transcraneal , Vasodilatadores/administración & dosificación , Vasoespasmo Intracraneal/complicaciones , Vasoespasmo Intracraneal/diagnóstico , Vasoespasmo Intracraneal/etiologíaRESUMEN
BACKGROUND: A sustained release microparticle formulation of nimodipine (EG-1962) was developed for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To assess safety, tolerability, and pharmacokinetics of intracisternal EG-1962 in an open-label, randomized, phase 2 study of up to 12 subjects. METHODS: Subjects were World Federation of Neurological Surgeons grades 1 to 2, modified Fisher grades 2 to 4, and underwent aneurysm clipping within 48 h of aSAH. EG-1962, containing 600 mg nimodipine, was administered into the basal cisterns. Outcome on the extended Glasgow Outcome Scale (eGOS), pharmacokinetics, delayed cerebral ischemia and infarction, rescue therapy, and safety were evaluated. RESULTS: The study was halted when a phase 3 study of intraventricular EG-1962 stopped because that study was unlikely to meet its primary endpoint. Six subjects were randomized (5 EG-1962 and 1 oral nimodipine). After 90-d follow-up, favorable outcome on the eGOS occurred in 1 of 5 EG-1962 and in the single oral nimodipine patient. Four EG-1962 and the oral nimodipine subject had angiographic vasospasm. One EG-1962 subject had delayed cerebral ischemia, and all subjects with angiographic vasospasm received rescue therapy except 1 EG-1962 patient. One subject treated with EG-1962 developed right internal carotid and middle cerebral artery narrowing 5 mo after placement of EG-1962, leading to occlusion and cerebral infarction. Pharmacokinetics showed similar plasma concentrations of nimodipine in both groups. CONCLUSION: Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of EG-1962. Internal carotid artery narrowing and occlusion after placement of EG-1962 in the basal cisterns has not been reported.
Asunto(s)
Antihipertensivos/administración & dosificación , Nimodipina/administración & dosificación , Hemorragia Subaracnoidea/tratamiento farmacológico , Adulto , Antihipertensivos/efectos adversos , Antihipertensivos/farmacocinética , Preparaciones de Acción Retardada/administración & dosificación , Femenino , Humanos , Ácido Hialurónico , Inyecciones Intraventriculares/métodos , Persona de Mediana Edad , Nimodipina/efectos adversos , Nimodipina/farmacocinética , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Resultado del TratamientoAsunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Hemiplejía/tratamiento farmacológico , Migraña con Aura/tratamiento farmacológico , Nimodipina/farmacología , ATPasa Intercambiadora de Sodio-Potasio/genética , Administración Intravenosa , Adolescente , Bloqueadores de los Canales de Calcio/administración & dosificación , Femenino , Hemiplejía/etiología , Hemiplejía/genética , Humanos , Migraña con Aura/complicaciones , Migraña con Aura/genética , Nimodipina/administración & dosificaciónRESUMEN
We investigated the pharmacokinetics of nimodipine (NMD) in rats plasma and tissues following intraocular (io), intragastric (ig), and intravenous (iv) administration at doses of 5.0 mg/kg io and iv and 10.0 mg/kg ig. After a single dose of NMD, plasma, heart, liver, spleen, lung, kidney, and brain samples were collected at the scheduled time points. The concentration of NMD in rat plasma and tissues was determined by high-performance liquid chromatography, and the main pharmacokinetic parameters were calculated and compared. NMD was rapidly absorbed and reached the maximum plasma concentration in approximately 5 min after io administration. The absolute bioavailability after io administration was higher than that after ig administration (40.05% vs. 5.67%). There were significant differences in the tissue distribution of NMD with different administration routes. After io administration, NMD was distributed more in the lung, spleen, and brain tissues, and less in the kidney. The maximum drug concentration after io administration in the heart, liver, spleen, lung, kidney, and brain was 1.00, 0.47, 2.02, 1.47, 0.22, and 5.79 times higher than that after via ig administration, and the area under the curve value was 0.59, 0.78, 1.71, 1.84, 0.25, and 4.59 times greater, respectively. Nimodipine appears to achieve systemic effects via io administration. Compared with ig, io administration could significantly increase NMD distribution in the brain tissue, indicating that NMD could be delivered to the brain via io administration.