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Background: Although Idiopathic Parkinson's disease (IPD) develops in considerable patients with drug-induced Parkinsonism (DIP), the association hasn't been well defined. We aimed to evaluate the underlying association and risk factors of DIP and IPD., Methods: A retrospective cohort study using National Health Insurance Claims data in 2011-2016 was conducted. New-onset DIP patients in 2012 were selected and matched with active controls having diabetes mellitus at a 1:4 ratio by age, sex, and Charlson's Comorbidity Index score. Comorbidity, causative drugs, and prescription days were evaluated as covariates., Results: A total of 441 DIP were selected. During the 4-year follow up, 14 IPD events in the DM group but 62 events in the DIP group were observed (adjusted hazard ratio, HR: 18.88, 95% CI, 9.09-39.22, adjusting for comorbidities and causative drugs). IPD diagnosis in DIP was observed high in males compared to females (15.58/13.24%). The event was the most within the 1st year follow-up, mean days 453 (SD 413.36). Subgroup analysis in DIP showed calcium channel blocker (verapamil, diltiazem, and flunarizine) was significantly associated with increased IPD risk (HR: 2.24, 95% CI, 1.27-3.93)., Conclusion: Increased IPD in DIP patients might not be from the causal toxicity of antidopaminergic effects but from a trigger by the causative drugs on the DIP patients who already had subclinical IPD pathology. DIP can serve as a strong proxy for IPD incidence. Subjects who develop DIP should be monitored carefully for potential IPD incidence., Competing Interests: The authors declared that no competing interests exist.

Although proton magnetic resonance spectroscopy (1H-MRS) is a common method for the evaluation of intracranial meningiomas, controversy exists regarding which parameter of 1H-MRS best predicts the histopathological grade of an intracranial meningioma. In this study, we evaluated the results of pre-operative 1H-MRS to identify predictive factors for high-grade intracranial meningioma. Thirteen patients with World Health Organization (WHO) grade II-III meningioma (confirmed by pathology) were defined as high-grade; twenty-two patients with WHO grade I meningioma were defined as low-grade. All patients were evaluated by 1H-MRS before surgery. The relationships between the ratios of metabolites (N-acetylaspartate [NAA], creatine [Cr], and choline [Cho]) and the diagnosis of high-grade meningioma were analyzed. According to Mann-Whitney U test analysis, the Cho/NAA ratio in cases of high-grade meningioma was significantly higher than in cases of low-grade meningioma (6.34 ± 7.90 vs. 1.58 ± 0.77, p<0.05); however, there were no differences in age, Cho/Cr, or NAA/Cr. According to conditional inference tree analysis, the optimal cut-off point for the Cho/NAA ration between high-grade and low-grade meningioma was 2.409 (sensitivity = 61.54%; specificity = 86.36%). This analysis of pre-operative 1H-MRS metabolite ratio demonstrated that the Cho/NAA ratio may provide a simple and practical predictive value for high-grade intracranial meningiomas, and may aid neurosurgeons in efforts to design an appropriate surgical plan and treatment strategy before surgery., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We estimated the volume of vestibular schwannomas by an ice cream cone formula using thin-sliced magnetic resonance images (MRI) and compared the estimation accuracy among different estimating formulas and between different models., Methods: The study was approved by a local institutional review board. A total of 100 patients with vestibular schwannomas examined by MRI between January 2011 and November 2015 were enrolled retrospectively. Informed consent was waived. Volumes of vestibular schwannomas were estimated by cuboidal, ellipsoidal, and spherical formulas based on a one-component model, and cuboidal, ellipsoidal, Linskey's, and ice cream cone formulas based on a two-component model. The estimated volumes were compared to the volumes measured by planimetry. Intraobserver reproducibility and interobserver agreement was tested. Estimation error, including absolute percentage error (APE) and percentage error (PE), was calculated. Statistical analysis included intraclass correlation coefficient (ICC), linear regression analysis, one-way analysis of variance, and paired t-tests with P < 0.05 considered statistically significant., Results: Overall tumor size was 4.80 ± 6.8 mL (mean ±standard deviation). All ICCs were no less than 0.992, suggestive of high intraobserver reproducibility and high interobserver agreement. Cuboidal formulas significantly overestimated the tumor volume by a factor of 1.9 to 2.4 (P ≤ 0.001). The one-component ellipsoidal and spherical formulas overestimated the tumor volume with an APE of 20.3% and 29.2%, respectively. The two-component ice cream cone method, and ellipsoidal and Linskey's formulas significantly reduced the APE to 11.0%, 10.1%, and 12.5%, respectively (all P < 0.001)., Conclusion: The ice cream cone method and other two-component formulas including the ellipsoidal and Linskey's formulas allow for estimation of vestibular schwannoma volume more accurately than all one-component formulas.

Objectives: Generic and disease-specific health-related quality of life (HRQoL) instruments may reflect different aspects of lives in patients with Parkinson's disease (PD) and thus be associated with different determinants. We used the same cluster of predictors for the generic and disease-specific HRQoL instruments to examine and compare the determinants of HRQoL., Method: HRQoL was measured in 92 patients with PD by the 36-item Short-Form Health Survey (SF-36) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). The predictors included demographic and disease characteristics, and motor and non-motor symptoms. Multiple regression analyses were used to identify HRQoL determinants., Results: Depressive symptoms and motor difficulties of daily living were the first two significant determinants for both instruments. The other significant determinant for the SF-36 was fatigue and non-motor difficulties of daily living, and for the PDQ-39 was motor signs of PD., Conclusions: The results suggest the importance of the evaluation and intervention focused on depressive symptoms and motor difficulties of daily living in patients with PD. In addition, the SF-36 seems more related to non-motor symptoms, while the PDQ-39 appears more associated with motor symptoms. This information is important for understanding results from these two instruments and for choosing which to use.

Background: Most studies of smartphone-based assessments of motor symptoms in Parkinson's disease (PD) focused on gait, tremor or speech. Studies evaluating bradykinesia using wearable sensors are limited by a small cohort size and study design. We developed an application named smartphone tapper (SmT) to determine its applicability for clinical purposes and compared SmT parameters to current standard methods in a larger cohort., Methods: A total of 57 PD patients and 87 controls examined with motor UPDRS underwent timed tapping tests (TT) using SmT and mechanical tappers (MeT) according to CAPSIT-PD. Subjects were asked to alternately tap each side of two rectangles with an index finger at maximum speed for ten seconds. Kinematic measurements were compared between the two groups., Results: The mean number of correct tapping (MCoT), mean total distance of finger movement (T-Dist), mean inter-tap distance, and mean inter-tap dwelling time (IT-DwT) were significantly different between PD patients and controls. MCoT, as assessed using SmT, significantly correlated with motor UPDRS scores, bradykinesia subscores and MCoT using MeT. Multivariate analysis using the SmT parameters, such as T-Dist or IT-DwT, as predictive variables and age and gender as covariates demonstrated that PD patients were discriminated from controls. ROC curve analysis of a regression model demonstrated that the AUC for T-Dist was 0.92 (95% CI 0.88-0.96)., Conclusion: Our results suggest that a smartphone tapping application is comparable to conventional methods for the assessment of motor dysfunction in PD and may be useful in clinical practice.

Postural dysfunctions are prevalent in patients with schizophrenia and affect their daily life and ability to work. In addition, sensory functions and sensory integration that are crucial for postural control are also compromised. This study intended to examine how patients with schizophrenia coordinate multiple sensory systems to maintain postural stability in dynamic sensory conditions. Twenty-nine patients with schizophrenia and 32 control subjects were recruited. Postural stability of the participants was examined in six sensory conditions of different level of congruency of multiple sensory information, which was based on combinations of correct, removed, or conflicting sensory inputs from visual, somatosensory, and vestibular systems. The excursion of the center of pressure was measured by posturography. Equilibrium scores were derived to indicate the range of anterior-posterior (AP) postural sway, and sensory ratios were calculated to explore ability to use sensory information to maintain balance. The overall AP postural sway was significantly larger for patients with schizophrenia compared to the controls [patients (69.62±8.99); controls (76.53±7.47); t1,59 = -3.28, p<0.001]. The results of mixed-model ANOVAs showed a significant interaction between the group and sensory conditions [F5,295 = 5.55, p<0.001]. Further analysis indicated that AP postural sway was significantly larger for patients compared to the controls in conditions containing unreliable somatosensory information either with visual deprivation or with conflicting visual information. Sensory ratios were not significantly different between groups, although small and non-significant difference in inefficiency to utilize vestibular information was also noted. No significant correlations were found between postural stability and clinical characteristics. To sum up, patients with schizophrenia showed increased postural sway and a higher rate of falls during challenging sensory conditions, which was independent of clinical characteristics. Patients further demonstrated similar pattern and level of utilizing sensory information to maintain balance compared to the controls.

Pigment epithelium-derived factor (PEDF) has been shown previously to prevent liver fibrosis and hepatic stellate cell (HSC) activation. By investigating the functional domains in PEDF, we identified a 34-mer peptide (residues Asp44-Asn77) that harbors the same function as the full-length PEDF protein. Not only did the 34-mer suppress the development of fibrosis in carbon tetrachloride (CCl4)-treated mouse liver but it also upregulated peroxisome proliferator-activated receptor-gamma (PPARγ) expression in HSCs in vivo. Platelet-derived growth factor (PDGF) plays a crucial role on the process of HSC activation in response to liver damage. The 34-mer suppressed PDGF-induced cell proliferation and expression of myofibroblastic marker proteins in primary rat HSC culture, increased the levels of PPARγ mRNA and protein in a dose-dependent manner and markedly reduced the level of active β-catenin protein, an HSC activating factor, in HSC-T6 cells. Similarly, IWR-1, an inhibitor of the Wnt response, displayed the same effect as the 34-mer in preventing HSC-T6 activation. The Wnt signaling-mediated PPARγ suppression was abolished by both the IWR-1 inhibitor and a small interfering RNA (siRNA) targeting β-catenin and the Wnt coreceptor, LRP6. Both PEDF and the 34-mer down-regulated PDGF receptor-α/β expression and blocked the PDGF-induced phosphorylation of Akt and ERK. Moreover, the inhibitory effect on PDGF receptor expression was abolished by PPARγ antagonists and PPARγ siRNA. Our observations indicate that the PEDF-derived 34-mer peptide can mimic PEDF in attenuating HSC activation. Investigation of this 34-mer peptide led to the identification of a signaling mechanism involving PPARγ induction, suppression of Wnt/β-catenin signaling and down-regulation of the PDGF receptor-α/β.

Aims: To investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (TBI), we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery., Materials and Methods: In this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury. Rats subjected to 6-Pa cerebral cortical fluid percussion injury were treated by using subcutaneous infusion pumps filled with either saline (sham group) or amantadine hydrochloride, with a releasing rate of 3.6 mg/kg/hour for 8 weeks. The dopamine-releasing conditions and metabolism were analyzed sequentially by fast scan cyclic voltammetry (FSCV) and high-pressure liquid chromatography (HPLC). Novel object recognition (NOR) and fixed-speed rotarod (FSRR) behavioral tests were used to determine treatment effects on cognitive and motor deficits after injury., Results: Sequential dopamine-release deficits were revealed in 6-Pa-fluid-percussion cerebral cortical injured animals. The reuptake rate (tau value) of dopamine in injured animals was prolonged, but the tau value became close to the value for the control group after amantadine therapy. Cognitive and motor learning impairments were shown evidenced by the NOR and FSRR behavioral tests after injury. Chronic amantadine therapy reversed dopamine-release deficits, and behavioral impairment after fluid percussion injuries were ameliorated in the rats treated by using amantadine-pumping infusion., Conclusion: Chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury.