Short and Mid-Term Predictors of Response to OnabotulinumtoxinA: Real-Life Experience Observational Study.
对 onabotulinumoxina 反应的短期和中期预测因子: 真实生活经验观察性研究。
- 作者列表："Alpuente A","Gallardo VJ","Torres-Ferrús M","Álvarez-Sabin J","Pozo-Rosich P
OBJECTIVE:To identify clinical predictors of excellent response to OnabotulinumtoxinA in patients with chronic migraine (CM) at 6 and 12 months of follow-up. BACKGROUND:Clinical predictors of response to OnabotulinumtoxinA are scarce and have not been clearly reproduced and analyzed in detail. So far, predictors of response to OnabotulinumtoxinA assess response in general or good response, but not an excellent response. METHODS:Cohort study of patients attended in a specialized Headache Clinic in treatment with OnabotulinumtoxinA were classified according to their improvement in frequency: no-response (<25%) and excellent response (≥75%). A comparative analysis was carried out at 6 and 12 months identifying clinical predictors of excellent response to OnabotulinumtoxinA at each timepoint. RESULTS:Data were collected from 221 patients. After 6 and also 12 months, we observed a statistically significant mean reduction in frequency and analgesic intake. At month 6, independent variables associated with excellent response (OR[95%CI]) were daily headache frequency (0.32[0.14-0.74]; P = .005), medication overuse (MO) (2.28[1.19-4.37]; P = .013), and a higher ratio of migraine days/month (MDM) (1.20[1.10-1.45]; P = .018) at baseline. At month 12, independent predictors of excellent response were patients with less than 30 years of migraine evolution (0.43[0.23-0.82]; P = .011), presence of anxiety (0.44[0.23-0.85]; P = .018), and aura (0.48[0.25-0.92]; P = .037). Excellent responders showed a higher improvement rate in pain intensity at 6 and 12 months. CONCLUSIONS:Patients with daily frequency and MO show a clinical improvement in short-term. Patients with comorbidities who start treatment earlier in the course of the disease need a longer duration of treatment. The profile of response to treatment with OnabotulinumtoxinA determines its minimum treatment duration and the timepoint of a meaningful response.
目的: 在 6 个月和 12 个月的随访中，确定慢性偏头痛 (CM) 患者对 onabotulinumoxina 反应良好的临床预测因子。 背景: 临床上对甲氧丁胺反应的预测因子很少，尚未明确复制和详细分析。到目前为止，对 onabotulinumoxina 反应的预测因子评估一般反应或良好反应，但不是极好的反应。 方法: 队列研究的患者参加了在专门的头痛门诊治疗与 onabotumtoxina 根据其在频率的改善分类: 无反应 (
METHODS::Multiple sclerosis (MS) is a chronic neurodegenerative disorder with clinical symptoms of neuroinflammation and demyelination in the central nervous system. Recently, herbal medicines are clinically effective against MS as the current disease-modifying drugs have limited effectiveness. Hence, the present study evaluated the therapeutic potential of Ocimum basilicum essential oil (OB) in ethidium bromide (EB)-induced cognitive deficits in the male rats. Further, the effect of OB (50, 100 and 200 μL/kg) was evaluated on EB-induced neuroinflammation, astrogliosis and mitochondrial dysfunction in the pre-frontal cortex (PFC) of the animals. The EB was injected through bilateral intracerebroventricular route into hippocampus to induce MS-like manifestations in the rats. OB (100 and 200 μL/kg) and Ursolic acid (UA) significantly reduced the EB-induced cognitive deficits in Morris water maze and Y-maze test paradigms. OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced neuroinflammation in terms of increase in the levels of pro-inflammatory cytokines (TNF-alpha and IL-6) in the rat PFC. Further, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced astrogliosis in terms of increase in the levels of GFAP (Glial fibrillary acidic protein) and Iba-1 (Ionized calcium binding adaptor molecule-1) in the rat PFC. In addition, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced decrease in the mitochondrial function, integrity, respiratory control rate and ADP/O in the PFC of the rodents. Moreover, OB (100 and 200 μL/kg) and UA significantly reduced the EB-induced mitochondria-dependent apoptosis in the PFC of the rat. Hence, it can be presumed that OB could be a potential alternative drug candidate in the pharmacotherapy of MS.
METHODS::Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2-3 weeks post-fragmentation and were sacrificed 3-50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.
METHODS:BACKGROUND:Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a recently approved therapy for patients with drug-resistant epilepsy. To date, there is a poor understanding of the mechanism of action and lack of in vivo biomarkers. We propose a method for investigating the in vivo stimulation effects using blood-oxygen-level dependent (BOLD) MRI and present the brain activation pattern associated with ANT DBS. METHODS:Two patients undergoing ANT DBS for epilepsy underwent BOLD MRI using a block design after the DBS was programmed to alternate ON/OFF in 30 second blocks. The scanner was triggered utilizing surface electrophysiological recording to detect the DBS cycle. Nine total runs were obtained and were analyzed using a general linear model. RESULTS:Active ANT stimulation produced activation within several areas of the brain, including the thalamus, bilateral anterior cingulate and posterior cingulate cortex, precuneus, medial prefrontal cortex, amygdala, ventral tegmental area, hippocampus, striatum, and right angular gyrus. CONCLUSIONS:Utilizing block-design BOLD MRI, we were able to show widespread activation resulting from ANT DBS. Overlap with multiple areas of both the default mode and limbic networks was shown suggesting that these nodes may modulate the effect of seizure control with ANT DBS.