A Pathophysiological Approach to Reduce Peritumoral Edema with Gamma Knife Radiosurgery for Large Incidental Meningiomas.

BACKGROUND: Peritumoral edema may be a prohibitive side effect in treating large incidental meningiomas with stereotactic radiosurgery. An approach that limits peritumoral edema and achieves tumor control with SRS would be an attractive management option for large incidental meningiomas. METHODS: This is a retrospective cohort study of patients with large incidental meningiomas (≥2 mL in volume and/or 2 cm in diameter) treated with gamma knife radiosurgery (GKRS) between 2000 and 2019 in Taiwan and followed up for 5 years. The outcomes of a pathophysiological approach targeting the dural feeding artery site with a higher marginal dose (18-20 Gy) to enhance vascular damage and the parenchymal margin of the tumor with a lower dose (9-11 Gy) to reduce parenchymal damage were compared with those of a conventional approach targeting the tumor center with a higher dose and tumor margin with a lower dose (12-14 Gy). RESULTS: A total of 53 incidental meningiomas were identified, of which 23 (43.4%) were treated with a pathophysiological approach (4 cases underwent a two-stage approach) and 30 (56.7%) were treated with a conventional approach. During a median follow-up of 3.5 (range 1-5) years, tumor control was achieved in 19 (100%) incidental meningiomas that underwent a single-stage pathophysiological approach compared with 29 (96.7%) incidental meningiomas that underwent a conventional approach (log-rank test: p = 0.426). Peritumoral edema developed in zero (0%) incidental meningiomas that underwent a single stage pathophysiological approach compared to seven (23.3%) incidental meningiomas that underwent a conventional approach (log-rank test: p = 0.023). CONCLUSIONS: Treatment of large incidental meningiomas with a pathophysiological approach with GKRS achieves similar rates of tumor control and reduces the risk of peritumoral edema. GKRS with a pathophysiological approach may be a reasonable management strategy for large incidental meningiomas.

Investigation of coenzyme Q10 status, serum amyloid-ß, and tau protein in patients with dementia.

Objectives: Dementia is an oxidative stress-related disease. Coenzyme Q10 is a nutrient that occurs naturally in the human body and acts as an antioxidant. The purpose of this study was to investigate the relationships of coenzyme Q10 status, biomarkers for dementia (amyloid ß and tau protein), and antioxidant capacity in patients with dementia. Methods: Eighty dementia patients aged ≥60 years and with a mini mental state examination (MMSE) score ≤ 26 were enrolled. The levels of coenzyme Q10, total antioxidant capacity (TAC), amyloid ß, and tau protein were measured. Results: A total of 73% of patients had a low coenzyme Q10 status. Patients with low coenzyme Q10 status had a significantly higher level of serum amyloid ß-42 and amyloid ß-42/40 ratio (p < 0.05). Coenzyme Q10 status was significantly correlated with the values of TAC, MMSE score, amyloid ß-42, and amyloid ß-42/40 ratio (p < 0.05) but not with tau protein. Additionally, a high proportion of moderate dementia patients were found to have low coenzyme Q10 status (p = 0.07). Conclusion: Patients with dementia suffered from coenzyme Q10 deficiency, and the degree of deficiency was related to the level of amyloid-ß and antioxidant capacity. Since adequate level of coenzyme Q10 may delay the progression of dementia, monitoring coenzyme Q10 status in patients with dementia is necessary.

Sarcopenic Obesity Tendency and Nutritional Status Is Related to the Risk of Sarcopenia, Frailty, Depression and Quality of Life in Patients with Dementia.

The purpose of this study was to investigate the nutritional status of dementia patients and examine the correlation with sarcopenia, frailty, depression, and quality of life. We enrolled patients aged 60 years and over with Mini Mental State Examination (MMSE) scores ≤ 26 (Taiwan), and dementia diagnosed by a neurologist or psychiatrist. Nutritional status was assessed with the Mini Nutritional Assessment (MNA). Muscle mass was measured by dual-energy X-ray absorptiometry. Muscle strength and endurance were evaluated by handgrip, leg-back strength, dumbbell curls, sit to stand test, and gait speed. Quality of life, frailty, and depression status were measured by questionnaires. Patients with moderate dementia (MMSE ≤ 20) had a significantly lower MNA score, muscle function, and quality of life than patients with mild dementia (p < 0.01). A lower MNA score was significantly associated with the risk of frailty (odds ratio: 4.76, p < 0.01), depression (odds ratio: 3.17, p = 0.03), and poor quality of life (odds ratio: 2.73, p < 0.05), and sarcopenia (odds ratio: 3.97, p = 0.03) after adjusting for potential confounders. In conclusion, patients with dementia were at risk of malnutrition, and nutritional status was associated to the risk of sarcopenia, frailty, depression, and quality of life.

Effectiveness of the 10 cm2 Rivastigmine Patch in Taiwanese Patients with Mild-to-Moderate Alzheimer's Dementia: A 48-Week Real-World Observational Study.

INTRODUCTION: The current study aimed to provide data on the effectiveness of the 10 cm2 rivastigmine patch in patients with Alzheimer's disease (AD) in a real-world setting in Taiwan. METHODS: This was a 48-week, single-arm, open-label, observational, and post-marketing study conducted across seven centers in Taiwan between May 5, 2016 and July 10, 2017. Eligible patients (aged 55-95 years) treated with the 10 cm2rivastigmine patch were enrolled based on physicians' judgment and according to the Taiwan reimbursement criteria of the drug. Data were prospectively collected at Week 0 (baseline), Week 24, and Week 48. The primary endpoint was the change in the cognitive assessment screening instrument (CASI) scores at Week 48 versus baseline. The changes from baseline in clinical dementia rating (CDR), mini-mental state examination (MMSE), and neuropsychiatric inventory (NPI) scores were evaluated, as were treatment persistence and the safety profile. RESULTS: Of the 285 eligible patients [full analysis set (FAS)], 216 (75.8%) completed the study protocol while 180 (63.2%) persisted on the 10 cm2 rivastigmine patch for the full 48 weeks. At baseline, 89.8% of patients had a CDR score of 0.5 or 1, while the change in CDR score at Week 48 was not significant. In the FAS, both the CASI and MMSE scores had numerical improvement at Week 24 but declined by 2.1 and 0.4 points, respectively, at Week 48 (p = 0.005 and p = 0.022). The increment in NPI scores was not significant. The most common drug-related adverse events (AEs) were pruritus (11.2%), nausea (3.5%), rash (3.2%), and vomiting (2.8%). CONCLUSIONS: The use of the 10 cm2 rivastigmine patch in the mild stage of AD maintained cognitive function at Week 24 and neuropsychiatric function at Week 48. The treatment persistency and safety profile support the clinical tolerability of the rivastigmine patch in the management of mild-to-moderate AD in Taiwan.

Associations of Chinese Herbal Medicine Usage with Risk of Dementia in Patients with Parkinson's Disease: A Population-Based, Nested Case-Control Study.

Background: Patients who have Parkinson's disease (PD) comorbid with dementia is common. With the prolonged life expectancy, dementia is gradually becoming prevalent and affects most patients' life qualities. However, the efficacy of current treatments in dementia of PD is limited. Previous studies indicated the potential roles of Chinese herbal medicine (CHM) in treating dementia, yet the correlation between CHM usage and risk of dementia in PD patients is unclear. Methods: This case-control study was nested within a National Health Insurance database of patients over 50 years with newly diagnosed PD from year 2000 to 2010. Among these PD patients, dementia and nondementia groups were discussed, respectively, in terms of the duration of taking CHM (≥90 vs. <90 days), age (50-64 vs. ≥65 years) and gender. Results: The risk of dementia in patients with PD is lower in CHM users compared with non-CHM users, especially in those taking CHM for more than 90 days (adjusted odds ratio [aOR] 0.58; 95% confidence interval [95% CI] 0.39-0.87). The use of CHM was significantly related to the lower risk of dementia in the subgroups of patients with age ≥65 years for CHM usage <90 days (aOR 0.68; 95% CI 0.53-0.88), patients with age ≥65 years for CHM usage ≥90 days (aOR 0.63; 95% CI 0.42-0.94), female patients using CHM for ≥90 days (aOR 0.43; 95% CI 0.22-0.84), and male patients using CHM for <90 days (aOR 0.62; 95% CI 0.43-0.88). Conclusions: The authors demonstrated the association of CHM usage with lower risk of dementia in patients with PD, especially in women with the usage of CHM for more than 90 days. Since no arbitrary causal conclusions could be drawn from retrospective cohort studies, the finding in this study could be used to generate a hypothesis for a subsequent design of prospective longitudinal study.

Exploring the Issues of Advance Directives in Patients with Mild Dementia in Taiwan.

Due to cultural traditions, most Taiwanese do not have an advance directive or healthcare proxy. We explored how patients with mild dementia in Taiwan may still make self-determined decisions concerning advance directives for their healthcare and end-of-life care choices as the disease progresses. We examined 260 respondents with mild dementia at a Taiwan medical center: 199 patients who agreed (and 61 patients who disagreed) with the concept of advance directives completed a structured questionnaire. Multiple logistic regression models to determine the between-group differences revealed that the following were positively associated with approval of end-of-life directives: maintaining one's quality of life (adjusted odds ratio [AOR], 2.44; 95% CI: 1.07-5.53), discussion with family members (AOR, 3.50; 95% CI: 1.49-8.26), and friend support networks (AOR, 3.36; 95% CI: 1.34-8.43). Cardiopulmonary resuscitation (AOR, 0.27; 95% CI: 0.09-0.79) was negatively associated with approval. There was also a positive association between the support of the legal validity of end-of-life directives (OR, 1.93; 95% CI: 1.07-3.48), without other confounding factors. In Taiwanese society, we remain mindful of cultural influences that may impact patients, including maintaining one's quality of life, discussion with family members, and friend/support networks. These influences may help dementia patients complete their advance directives.

Studies on a novel regimen for management of orofacial pain and morphine tolerance.

BACKGROUND/PURPOSE: The prevalence of orofacial pain is high but the etiology of orofacial pain is not well understood. Because of clinical treatment is not so effective, it is urgent to explore novel regimens with more effective and less side effects for clinical application. MATERIALS AND METHODS: Male mice (ICR strain) were injected with capsaicin (10µg/5 µl) in vibrissa pad. Spontaneous orofacial pain in 20 min was recorded after receiving capsaicin to quantify the nociceptive level. Green tea polyphenols (GTP 60 mg/kg), memantine (Mem 10 mg/kg), and GTPm (GTP 30 mg/kg plus Mem 3 mg/kg) were dissolved in 2% carboxymethyl cellulose, which was orally administered to mice twice per day and five times per week consecutively for 2 weeks. TruScan photobeam tracking was used to record changes of behavior and locomotor activities. RESULTS: GTPm by itself attenuated orofacial pain induced by capsaicin. Moreover, GTPm enhanced morphine analgesic effects, reduced morphine depressant side effects and delayed morphine tolerance. Along with this experiment, GTPm was tested on the hot plate (52 °C)-induced peripheral thermal pain. It was found that both memantine and GTPm reduced morphine-analgesia in hind paw thermal pain. CONCLUSION: In this study, GTP (60 mg/kg/day) orally administrated produced a significant analgesic effect on capsaicin-induced orofacial pain. Memantine combined with GTP synergistically not only reduced orofacial pain but also enhanced morphine analgesic effects. Thus, a new regimen of GTPm orally administered twice per day attenuated orofacial pain after consecutive 5 days.

Gamma Knife radiosurgery for large vestibular schwannomas greater than 3 cm in diameter.

OBJECTIVE Stereotactic radiosurgery (SRS) is an important alternative management option for patients with small- and medium-sized vestibular schwannomas (VSs). Its use in the treatment of large tumors, however, is still being debated. The authors reviewed their recent experience to assess the potential role of SRS in larger-sized VSs. METHODS Between 2000 and 2014, 35 patients with large VSs, defined as having both a single dimension > 3 cm and a volume > 10 cm3, underwent Gamma Knife radiosurgery (GKRS). Nine patients (25.7%) had previously undergone resection. The median total volume covered in this group of patients was 14.8 cm3 (range 10.3-24.5 cm3). The median tumor margin dose was 11 Gy (range 10-12 Gy). RESULTS The median follow-up duration was 48 months (range 6-156 months). All 35 patients had regular MRI follow-up examinations. Twenty tumors (57.1%) had a volume reduction of greater than 50%, 5 (14.3%) had a volume reduction of 15%-50%, 5 (14.3%) were stable in size (volume change < 15%), and 5 (14.3%) had larger volumes (all of these lesions were eventually resected). Four patients (11.4%) underwent resection within 9 months to 6 years because of progressive symptoms. One patient (2.9%) had open surgery for new-onset intractable trigeminal neuralgia at 48 months after GKRS. Two patients (5.7%) who developed a symptomatic cyst underwent placement of a cystoperitoneal shunt. Eight (66%) of 12 patients with pre-GKRS trigeminal sensory dysfunction had hypoesthesia relief. One hemifacial spasm completely resolved 3 years after treatment. Seven patients with facial weakness experienced no deterioration after GKRS. Two of 3 patients with serviceable hearing before GKRS deteriorated while 1 patient retained the same level of hearing. Two patients improved from severe hearing loss to pure tone audiometry less than 50 dB. The authors found borderline statistical significance for post-GKRS tumor enlargement for later resection (p = 0.05, HR 9.97, CI 0.99-100.00). A tumor volume ≥ 15 cm3 was a significant factor predictive of GKRS failure (p = 0.005). No difference in outcome was observed based on indication for GKRS (p = 0.0761). CONCLUSIONS Although microsurgical resection remains the primary management choice in patients with VSs, most VSs that are defined as having both a single dimension > 3 cm and a volume > 10 cm3 and tolerable mass effect can be managed satisfactorily with GKRS. Tumor volume ≥ 15 cm3 is a significant factor predicting poor tumor control following GKRS.

Post-infectious opsoclonus and reversible magnetic resonance imaging changes: a case report and review of the literatures.

PURPOSE: Opsoclonus is a rare neurological disorder in adult. The etiology of opsoclonus includes parainfectious, paraneoplastic, toxic, and metabolic disorders. We reported an old female with post-infectious opsoclonus who had a benign clinical course and reversible brain MRI lesions, and its review of the literature. CASE REPORT: A 67-year-old woman presented with opsoclonus and truncal ataxia for two weeks. The magnetic resonance imaging (MRI) showed the hyperintensity lesions in bilateral medial thalamus, hypothalamus, and tegmentum of pons on Fluid-attenuated inversion recovery (FLAIR) imaging. Investigations of neoplasm and autoimmune disorders showed negative findings. Clinical symptoms subsided in two-week duration and MRI abnormalities also disappeared one month later. CONCLUSION: A benign clinical course and reversible MRI lesions could be found in the patients with postinfectious opsoclonus such as our case. However, detailed investigations and long-term follow-up are needed to exclude paraneoplastic or other systemic and immunological disorders.

Impairment of cerebral hemodynamic response to the cold pressor test in patients with Parkinson's disease.

BACKGROUND AND PURPOSE: Disturbance of the autonomic nervous system (ANS) is frequently encountered in Parkinson's disease (PD). In this study, we examined changes in systemic and cerebral hemodynamics during the cold pressor test (CPT) to determine whether cerebrovascular reactivity, controlled by the sympathetic nervous system, is intact or impaired in patients with PD. METHODS: Forty-nine patients with PD and 49 sex- and age-matched non-PD subjects were evaluated. Measurements were performed in the resting state and over a period of 1min of CPT. The cerebral blood flow velocity (CBFV) and pulsatility index (PI) of the middle cerebral artery (MCA) were recorded by transcranial color-coded Doppler ultrasonography (TCCS). Mean arterial blood pressure (MAP), heart rate (HR), and end-tidal CO(2) (Et-CO(2)) were investigated simultaneously. The resistance of the cerebrovascular bed (CVR) was calculated as the ratio of mean arterial blood pressure to mean cerebral blood flow velocity (Vm). Changes of Vm, PI and CVR in response to the cold pressor test were evaluated. RESULTS: Baseline values for control and PD subjects showed no statistical difference. CPT induced a significant increase in MAP, HR, and Vm in both groups. Pulsatility index (PI) and CVR were decreased in both groups during CPT. Percent increases of Vm (P<0.001) and MAP (P=0.011) were significantly higher while the percent decreases of PI (P=0.002) and CVR (P=0.007) were significantly decreased more in the non-PD group. CONCLUSIONS: This study indirectly shows that ANS-mediated cerebrovascular reactivity is impaired in patients with PD. Further investigations are needed to confirm the hypothesis that using the cold pressor test to evaluate cerebrovascular reactivity might be beneficial in early diagnosis of impairment of ANS-mediated cerebrovascular autoregulation in patients with PD.

Atorvastatin administration after percutaneous coronary intervention in patients with coronary artery disease and normal lipid profiles: impact on plasma adiponectin level.

BACKGROUND: There is controversy about the effects of statins on plasma adiponectin, and the impact of percutaneous coronary intervention (PCI) on plasma adiponectin level is still unknown. We investigated the impact of Atorvastatin on plasma adiponectin levels in coronary artery disease (CAD) patients with stable angina and normal lipid profiles after PCI. METHODS: Sixty CAD patients with stable angina and normal lipid profiles scheduled for PCI, and not on statins, were randomly assigned to either no treatment (control group) or the Atorvastatin treatment (Atorvastatin group). Atorvastatin administration was started immediately after PCI. Blood samples were obtained immediately after PCI and again 3 and 6 mo later. Fasting plasma adiponectin concentrations were measured using a radioimmunoassay kit. RESULTS: After PCI, there were statistically significant decreases in adiponectin levels in the Atorvastatin group at 3 and 6 mo (8.66 +/- 0.69 versus 6.87 +/- 0.55 and 7.12 +/- 0.71 microg/mL at 0, 3, and 6 mo, respectively), despite the anti-inflammation and lipid-lowering effects of Atorvastatin. There were no statistically significant changes in adiponectin levels in the control group. There was significant positive association between baseline plasma adiponectin and high-density lipoprotein (HDL) levels. Changes of adiponectin level were not associated with the changes of high-sensitivity C-reactive protein (hs-CRP) and lipid profiles in the Atorvastatin group. CONCLUSIONS: Our study confirmed the benefits of Atorvastatin on anti-inflammation and anti-atherosclerosis, but we also found that Atorvastatin had a negative effect on the adiponectin system. The anti-inflammatory, anti-atherogenic effects of Atorvastatin are not affected by decreased adiponectin levels.

Prevalence of perinuclear antineutrophil cytoplasmic antibody in patients with Graves' disease treated with propylthiouracil or methimazole in Taiwan.

BACKGROUND AND PURPOSE: Antineutrophil cytoplasmic antibody (ANCA)-mediated vasculitis can be induced by propylthiouracil (PTU) and methimazole (MMI) for the treatment of Graves' disease. This study investigated the prevalence of ANCA positivity and its clinical correlates in Taiwanese patients with Graves' disease treated with PTU or MMI. METHODS: Eighty nine patients with Graves' disease who were currently being treated with PTU (n = 47) or MMI (n = 42) were included in the study. Sera were screened for ANCA by indirect immunofluorescence. The antigenic specificity of myeloperoxidase or proteinase-3 was measured by enzyme-linked immunosorbent assay. Thyroid autoantibodies against microsomal antibodies (AMA) and thyroglobulin antibodies were detected by indirect passive hemagglutination assays, and thyroid autoantibodies against thyrotropin receptor were detected by a radioreceptor assay. The correlations among ANCAs, clinical manifestations, gender, duration of treatment, and thyroid autoantibodies were analyzed by logistic regression. RESULTS: 20.2% of patients with Graves' disease receiving PTU and MMI were seropositive for ANCA; all of them were perinuclear-ANCA (p-ANCA)-positive. The frequency of p-ANCA-positive status in the PTU treatment group was significantly higher than in the MMI treatment group (31.9% vs 7.1%; p = 0.01). The mean duration of PTU treatment was 25 +/- 16 months, and was 30 +/- 21 months for the MMI treatment. In the PTU treatment group, the average duration of treatment in p-ANCA-positive patients was significantly longer than in p-ANCA negative patients (32.9 +/- 16.3 vs 19.6 +/- 12.1 months, p = 0.04). In addition, the prevalence of AMA positivity was significantly lower in p-ANCA-positive patients than in p-ANCA negative patients (53.3% vs 90.6%; p = 0.01). CONCLUSIONS: Only p-ANCA positivity was found in long-term treatment with PTU and MMI in Graves' disease. A higher frequency of p-ANCA positivity was found in the PTU treatment group than in the MMI treatment group. However, the presence of AMA was less frequent in p-ANCA-positive patients compared to p-ANCA-negative patients treated with PTU.

Diabetes mellitus has an additional effect on coronary artery disease.

We investigated whether plasma levels of adiponectin in patients with both coronary artery disease (CAD) and diabetes mellitus (DM) are lower than in patients with CAD alone. We examined plasma adiponectin levels in 113 patients, 82 with CAD (40 of whom had both CAD and type 2 DM) and 31 normal controls. We found differences in plasma adiponectin levels between CAD patients with and without DM (7.8 +/- 4.75 versus 12.1 +/- 6.87 microg/mL, P = 0.002), between patients with CAD and controls (10.0 +/- 6.27 versus 15.3 +/- 5.38 microg/mL, P < 0.0001), and between men and women (10.2 +/- 6.41 versus 13.1 +/- 6.22 microg/mL, P = 0.017). Plasma adiponectin levels were correlated negatively with body mass index, triglyceride, total cholesterol, hemoglobin A1c, and fibrinogen levels (r = -0.456, P < 0.0001; r = -0.355, P < 0.0001; r = -0.286, P = 0.002; r = -0.299, P < 0.0001; r = -0.400, P < 0.0001, respectively), but were not significantly correlated with high sensitivity C-reactive protein or low density lipoprotein levels (r = -0.088, P = 0.352; r = -0.167, P = 0.077, respectively). Plasma adiponectin levels correlated positively with high density lipoprotein levels (r = 0.410, P < 0.0001). Our study demonstrates that plasma adiponectin levels in patients with both CAD and DM are lower than in patients with CAD alone. We speculate that people who have very low plasma adiponectin levels may be at increased risk of developing both CAD and DM.