Zonisamide has been used as an add-on treatment in order to overcome the deficiencies of the general therapies currently used to resolve the motor complications and non-motor symptoms of Parkinson disease. Various trials have been designed to investigate the mechanism of action and treatment effects of zonisamide in this condition. Most clinical trials of zonisamide in Parkinson disease were from Japan. The vast majority of studies used changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) scores and daily “OFF” time as primary endpoints. Based on adequate randomized controlled trials, zonisamide is considered a safe and efficacious add-on treatment in Parkinson disease. The most convincing proof is available for a dosage of 25–50 mg, which was shown to lead to a significant reduction in the UPDRS III score and daily “OFF” time, without increasing disabling dyskinesia. Furthermore, zonisamide may play a beneficial role in improving non-motor symptoms in PD, including impulsive–compulsive disorder, rapid eye movement sleep behavior disorder, and dementia. Among the various mechanisms reported, inhibition of monoamine oxidase-B, blocking of T-type calcium channels, modulation of the levodopa–dopamine metabolism, modulation of receptor expression, and neuroprotection are the most often cited. The mechanisms underlying neuroprotection, including modulation of dopamine turnover, induction of neurotrophic factor expression, inhibition of oxidative stress and apoptosis, inhibition of neuroinflammation, modulation of synaptic transmission, and modulation of gene expression, have been most extensively studied. This review focuses on structure, pharmacokinetics, mechanisms, therapeutic effectiveness, and safety and tolerability of zonisamide in patients with Parkinson disease.

Sleep–wake disruptions are among the most prevalent and burdensome non-motor symptoms of Parkinson’s disease (PD). Clinical studies have demonstrated that these disturbances can precede the onset of typical motor symptoms by years, indicating that they may play a primary function in the pathogenesis of PD. Animal studies suggest that sleep facilitates the removal of metabolic wastes through the glymphatic system via convective flow from the periarterial space to the perivenous space, upregulates antioxidative defenses, and promotes the maintenance of neuronal protein homeostasis. Therefore, disruptions to the sleep–wake cycle have been associated with inefficient metabolic clearance and increased oxidative stress in the central nervous system (CNS). This leads to excessive accumulation of alpha-synuclein and the induction of neuronal loss, both of which have been proposed to be contributing factors to the pathogenesis and progression of PD. Additionally, recent studies have suggested that PD-related pathophysiological alterations during the prodromal phase disrupt sleep and circadian rhythms. Taken together, these findings indicate potential mechanistic interactions between sleep–wake disorders and PD progression as proposed in this review. Further research into the hypothetical mechanisms underlying these interactions would be valuable, as positive findings may provide promising insights into novel therapeutic interventions for PD.

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Objective:Postoperative pain was a common symptom after spinal surgery. This meta-analysis aimed to assess whether intravenous glucocorticoids has a beneficial role in reducing pain in patients following spinal fusion.Methods:We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and Google databases, from inception to March 2, 2018. Randomized controlled trials (RCTs) that comparing intravenous glucocorticoids with control treatment for spinal fusion were included. A meta-analysis was performed to generate pooled risk ratio (RR) and weighted mean difference with corresponding 95% confidence interval (CI) for discontinuous outcomes (the occurrence of nausea and infection) and continuous outcomes (visual analog scale [VAS] at 12, 24, and 48 h; total morphine consumption; and the length of hospital stay), respectively.Results:Eight clinical trials involving 918 patients (glucocorticoid group = 449, control group = 469) were finally included in this meta-analysis. Compared with control, intravenous glucocorticoids had significantly reduced VAS at 12, 24, and 48 hours with statistically significance (P < .05). Intravenous glucocorticoids can decrease the occurrence of nausea (RR = 0.42, 95% CI 0.29–0.62, P = .000; I2 = 0.0%) and the length of hospital stay. No difference was noticed in the occurrence of infection between glucocorticoids intravenous and control (P > .05).Conclusion:Existing evidence indicated that intravenous glucocorticoids have a beneficial role in decreasing early pain and the occurrence of nausea after spinal fusion surgery. In consideration of the limitation in current meta-analysis, more high-quality RCTs were needed to identify the optimal dose of glucocorticoids in spinal fusion patients.