Effects of interactive video-game-based exercise on balance in older adults with mild-to-moderate Parkinson's disease.

BACKGROUND: This study aimed to evaluate the effectiveness of a customized interactive video game-based (IVGB) training on balance in older adults with mild-to-moderate Parkinson's disease (PD). METHODS: In this 12-week crossover trial, PD patients ≥65 years of age were randomly divided into Group A (a 6-week intervention phase followed by a 6-week control phase) and Group B (a 6-week control phase followed by a 6-week intervention phase). Participants received IVGB exercise training during the intervention phase and no exercise during the control phase. Functional outcomes were measured using behavioral evaluation scales and questionnaires at baseline, week 6 and week 12. RESULTS: Twenty-four PD patients were included in this study, and were evenly divided into two groups. After Bonferroni adjustment, the changes in Modified Falls Efficacy Scale (MFES) and two subscales of Multi-Directional Reach Test were significantly different between two groups in the first 6-week period. In addition, the changes in Berg Balance Scale, MFES, and two subscales of Maximum Step Length were significantly different between two groups in the second 6-week period. Compared to controls, 6-week IVGB exercise intervention significantly improved different but overlapping functional outcomes in two groups of PD patients. CONCLUSIONS: The customized IVGB exercise training improves balance, postural stability and confidence in preventing falls in older adults with mild-to-moderate PD. However, this IVGB exercise doesn't have a significant impact on quality of life. TRIAL REGISTRATION: ClinicalTrials.gov. NCT03689764 . Registered 27 September 2018, retrospectively registered.

Serum lipid level is not associated with symptomatic intracerebral hemorrhage after intravenous thrombolysis for acute ischemic stroke.

BACKGROUND: This study assessed whether serum lipid levels are associated with the risk of symptomatic intracerebral hemorrhage (sICH) and functional outcomes in patients with acute ischemic stroke after receiving intravenous thrombolysis. METHODS: We retrospectively analyzed consecutive ischemic stroke patients who were treated with intravenous tissue plasminogen activator between January 2007 and January 2017. Lipid levels on admission, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels, as well as potential predictors of sICH were tested using univariate and multivariate analyses. RESULTS: Of the 229 enrolled patients (100 women, aged 68 ± 13 years), 14 developed sICH and 103 (45%) had favorable functional outcomes at 3 months. The patients with sICH more often had diabetes mellitus (71% vs. 26%, P = 0.01) and had more severe stroke (mean National Institutes of Health Stroke Scale [NIHSS] score of 16 vs. 13, P = 0.045). Regarding lipid subtype, total cholesterol, LDL-C, HDL-C, and triglyceride levels were not associated with sICH or functional outcomes. According to the results of multivariate analysis, the frequency of sICH was independently associated with diabetes mellitus (odds ratio [OR] = 6.04; 95% CI [1.31-27.95]; P = 0.02) and the NIHSS score (OR = 1.12; 95% CI [1.02-1.22]; P = 0.01). A higher NIHSS score was independently associated with unfavorable functional outcomes (OR = 0.86; 95% CI [0.81-0.91]; P < 0.001). CONCLUSIONS: Serum lipid levels on admission, including total cholesterol, LDL-C, HDL-C, and triglyceride levels, were not associated with sICH or 3-month functional outcomes after intravenous thrombolysis for acute ischemic stroke.

High exposure compared with standard exposure to metoclopramide associated with a higher risk of parkinsonism: a nationwide population-based cohort study.

AIMS: We conducted a cohort study utilizing a nationwide health insurance database to assess the European Medicines Agency's restrictions on using metoclopramide and its association with the risk of parkinsonism. METHODS: New oral metoclopramide users aged ≥20 years, and age- and gender-matched non-users were recruited between 2001 and 2011. Users were divided into high-exposure (dose >30 mg day-1 and/or duration >5 days) and standard-exposure (dose ≤30 mg day-1 and duration ≤5 days) groups. The adjusted hazard ratio (aHR) with 95% confidence interval (CI) estimated the risk of parkinsonism. RESULTS: During a 1-year period, 122 of 218 931 (0.06%) users of metoclopramide vs. 56 of 218 931 (0.03%) non-users developed parkinsonism (P < 0.001). Among the 122 cases of parkinsonism in users, 64 (0.04%) were from 168 566 standard-exposure users and 58 (0.12%) from 50 365 high-exposure users. Compared with non-users, the risk of parkinsonism was higher in users (aHR 2.16; 95% CI 1.54, 3.02), including standard-exposure (aHR 1.73; 95% CI 1.11, 2.70), and high-exposure (aHR 3.15; 95% CI 1.78, 5.57) users. High-exposure users had a higher risk of parkinsonism than standard-exposure users (aHR 1.83; 95% CI 1.28, 2.63). Within the high-exposure group, 45 233 of 50 365 (89.81%) users and 55 of 58 (94.83%) parkinsonism were from long-duration exposure; 5 132 of 50 365 (10.19%) users and 3 of 58 (5.17%) parkinsonism were from high-dose exposure and long-duration + high-dose exposure. CONCLUSIONS: The risk of parkinsonism in metoclopramide users, although extremely low (0.06%), is 2.16-fold greater than in non-users. High-exposure users have a 1.83-fold higher risk than standard-exposure users. As users in high-exposure group had a higher risk of parkinsonism than in standard-exposure group, and the majority of users and parkinsonism in high-exposure group were from long-duration exposure; thus, physician are advised to avoid prescribing metoclopramide for >5 days, even if the daily dose is ≤30 mg.

Timing of Symptomatic Infarct Swelling Following Intravenous Thrombolysis in Acute Middle Cerebral Artery Infarction: A Case-Control Study.

BACKGROUND: The risk of symptomatic infarct swelling has been reported to be higher in patients treated with recombinant tissue plasminogen activator (rt-PA). The aim of this study was to evaluate the timing of symptomatic infarct swelling after rt-PA treatment. METHODS: We retrospectively analyzed 14 868 patients with acute ischemic stroke from a stroke registry databank. We recruited patients with massive middle cerebral artery (MCA) infarction and symptomatic infarct swelling and excluded those with parenchymal or symptomatic hemorrhage. Multiple linear regression and multivariate logistic regression analyses were used to estimate the impact of rt-PA on the timing of symptomatic infarct swelling. RESULTS: A total of 23 patients with rt-PA treatment and 117 patients without rt-PA treatment were included. The rt-PA treatment group had a lower rate of coronary artery disease (8.7% vs 32.5%; P = .023), lower severity of baseline National Institutes of Health Stroke Scale score (19 vs 23; P = .014), shorter duration of infarct swelling (27.6 vs 45.4 hours; P < .001), and higher rate of hemicraniectomy surgery (65.2% vs 28.2%; P =.001) than those without rt-PA treatment. After adjusting for variables in multiple linear regression analysis, rt-PA treatment and an elevated C-reactive protein level were associated with early symptomatic infarct swelling ( P = .014 and P = .041, respectively). The rt-PA treatment was an independent factor related to early symptomatic infarct swelling within 36 hours ( P = .005; odds ratio [OR]: 5.3; confidence interval [CI]: 1.65-17.0) or 48 hours ( P = .009; OR: 16.4; CI: 2.00-134). CONCLUSION: Intravenous rt-PA treatment may hasten the onset of cerebral edema and subsequent cerebral herniation in large MCA territory infarction.

Epicatechin isolated from Tripterygium wilfordii extract reduces tau-GFP-induced neurotoxicity in zebrafish embryo through the activation of Nrf2.

Tau plays important roles in the assembly and stabilization of the microtubule structure to facilitate axonal transport in mammalian brain. The intracellular tau aggregates to form paired helical filaments leading to neurodegenerative disorders, collectively called tauopathies. In our previous report, we established a zebrafish model to express tau-GFP to induce neuronal death, which could be directly traced in vivo. Recently, we used this model to screen 400 herbal extracts and found 45 of them to be effective on reducing tau-GFP-induced neuronal death. One of the effective herbal extracts is the Tripterygium wilfordii stem extract. HPLC analysis and functional assay demonstrated that epicatechin (EC) is the major compound of Tripterygium wilfordii stem extract to decrease the neurotoxicity induced by tau-GFP. Using a luciferase reporter assay in the zebrafish, we confirmed that EC could activate Nrf2-dependent antioxidant responses to significantly increase the ARE-controlled expression of luciferase reporter gene. These data suggest that EC from the Tripterygium wilfordii stem extract could diminish tau-GFP-induced neuronal death through the activation of Nrf2.

Zebrafish cyclin Dx is required for development of motor neuron progenitors, and its expression is regulated by hypoxia-inducible factor 2α.

Cyclins play a central role in cell-cycle regulation; in mammals, the D family of cyclins consists of cyclin D1, D2, and D3. In Xenopus, only homologs of cyclins D1 and D2 have been reported, while a novel cyclin, cyclin Dx (ccndx), was found to be required for the maintenance of motor neuron progenitors during embryogenesis. It remains unknown whether zebrafish possess cyclin D3 or cyclin Dx. In this study, we identified a zebrafish ccndx gene encoding a protein which can form a complex with Cdk4. Through whole-mount in situ hybridization, we observed that zccndx mRNA is expressed in the motor neurons of hindbrain and spinal cord during development. Analysis of a 4-kb promoter sequence of the zccndx gene revealed the presence of HRE sites, which can be regulated by HIF2α. Morpholino knockdown of zebrafish Hif2α and cyclin Dx resulted in the abolishment of isl1 and oligo2 expression in the precursors of motor neurons, and also disrupted axon growth. Overexpression of cyclin Dx mRNA in Hif2α morphants partially rescued zccndx expression. Taken together, our data indicate that zebrafish cyclin Dx plays a role in maintaining the precursors of motor neurons.

Multiple signaling factors and drugs alleviate neuronal death induced by expression of human and zebrafish tau proteins in vivo.

BACKGROUND: The axonal tau protein is a tubulin-binding protein, which plays important roles in the formation and stability of the microtubule. Mutations in the tau gene are associated with familial forms of frontotemporal dementia with Parkinsonism linked to chromosome-17 (FTDP-17). Paired helical filaments of tau and extracellular plaques containing beta-amyloid are found in the brain of Alzheimer's disease (AD) patients. RESULTS: Transgenic models, including those of zebrafish, have been employed to elucidate the mechanisms by which tau protein causes neurodegeneration. In this study, a transient expression system was established to express GFP fusion proteins of zebrafish and human tau under the control of a neuron-specific HuC promoter. Approximately ten neuronal cells expressing tau-GFP in zebrafish embryos were directly imaged and traced by time-lapse recording, in order to evaluate the neurotoxicity induced by tau-GFP proteins. Expression of tau-GFP was observed to cause high levels of neuronal death. However, multiple signaling factors, such as Bcl2-L1, Nrf2, and GDNF, were found to effectively protect neuronal cells expressing tau-GFP from death. Treatment with chemical compounds that exert anti-oxidative or neurotrophic effects also resulted in a similar protective effect and maintained human tau-GFP protein in a phosphorylated state, as detected by antibodies pT212 and AT8. CONCLUSIONS: The novel finding of this study is that we established an expression system expressing tau-GFP in zebrafish embryos were directly imaged and traced by time-lapse recording to evaluate the neurotoxicity induced by tau-GFP proteins. This system may serve as an efficient in vivo imaging platform for the discovery of novel drugs against tauopathy.

Treadmill Training Improves Forward and Backward Gait in Early Parkinson Disease.

OBJECTIVE: The aim of this study was to examine effects of treadmill training (TT) and lasting duration of training effects on forward walking (FW) and backward walking (BW) gait in Parkinson disease (PD). DESIGN: Twenty-six early PD patients undertook a 12-wk intensive TT program using FW. A repeated-measures design compared GAITRite-measured FW and BW gait before TT, within 1 wk, and at 4 and 12 wks after TT. RESULTS: Twenty-three PD patients, after completing TT, walked forward and backward with increased velocity, enlarged stride length, prolonged swing phase, and decreased double support phase; improvements occurred within 1 wk and remained at 4 and 12 wks after training (P < 0.01 or < 0.001). In addition, trends toward reduced posttraining swing time variability and stride length variability occurred in both directions and sustained for 12 wks. Posttraining FW and BW gait improvements were comparable. BW deficits, regardless of training, constantly exceeded FW deficits. Cadence did not differ before and after training in FW (P = 0.195) and BW (P = 0.229) and between FW and BW irrespective of TT (P = 0.124). CONCLUSIONS: A 12-wk TT program improves the 12-wk duration of FW and BW gait and can be considered a part of a rehabilitation strategy to overcome gait disturbances in early PD.

Memory consolidation and inducible nitric oxide synthase expression during different sleep stages in Parkinson disease.

BACKGROUND: Parkinson disease (PD) is a neurodegenerative disease characterized by motor and nonmotor dysfunctions, which include sleep disturbances. Rapid eye movement (REM) sleep is associated with numerous physiologic changes such as memory consolidation. Compelling evidence suggests that nitric oxide (NO) is crucial to both sleep regulation and memory consolidation. In our study, we explored changes in biologic molecules during various sleep stages and the effects of sleep on memory consolidation in PD. METHODS: Ten PD patients and 14 volunteers without PD participated in our study. The gene expression of inducible NO synthase (iNOS) in all sleep stages was measured using realtime polymerase chain reaction (PCR) based on polysomnography (PSG)-guided peripheral blood sampling. In addition, the efficiency of memory consolidation during the sleep of the participants was measured using the Wechsler Memory Scale, third edition (WMS-III). RESULTS: The iNOS expression increased in all sleep stages among the PD patients compared to the control participants, in whom iNOS expression decreased during REM sleep. Regarding memory consolidation, the performance of the controls in logic memory and the patients in visual reproduction tasks improved after sleep. CONCLUSIONS: The iNOS synthase expression was different from control participants among PD patients, and the expression was dissimilar in various sleep stages. Sleep might enhance memory consolidation and there are different memory consolidation profiles between PD and control participants demonstrating distinct memory consolidation profiles.

Identification of TLR downstream pathways in stroke patients.

OBJECTIVE: Toll-like receptors (TLRs) are important molecules for detecting both pathogen invasion and tissue damage. The expression of TLR4 is upregulated in ischemic stroke, at least in the subacute stage. However, the TLR downstream pathways in the context of stroke have not been well studied in previous research. The purpose of this study is to elucidate the TLR4 downstream pathways following ischemic stroke. DESIGN AND METHODS: In this study, 12 ischemic stroke patients and 12 controls were selected from among 89 ischemic stroke patients and 166 controls. The chosen subjects had the highest levels of TLR4 mRNA in the peripheral blood. The differences in the TLR downstream signaling pathways, which were studied by using an RT2 Profiler TM PCR array system (Qiagen), were analyzed. The differentially expressed genes were analyzed by using GeneSpring GX and visualized based on the TLR pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: The genes upregulated in stroke patients were found to be involved in the MyD88-independent pathway and in UBE2V1-TRAF6 ubiquitin-mediated proteolysis. The genes were more expressed in extracellular space, receptor binding, and cytokine receptor binding by use of gene ontology (GO) terms than in control patients. CONCLUSIONS: We found that the MyD88-independent pathway and the ubiquitin-mediated proteolysis pathway, especially TRAF6, may be the most vital molecules among TLR downstream pathways in incidences of ischemic stroke.

Multiscale entropy analysis of electroencephalography during sleep in patients with Parkinson disease.

Sleep disorders are frequently seen in patients with Parkinson disease (PD), including rapid eye movement (REM) behavior disorder and periodic limb movement disorder. However, knowledge about changes in non-REM sleep in patients with PD is limited. This study explored the characteristics of electroencephalography (EEG) during sleep in patients with PD and non-PD controls. We further conducted multiscale entropy (MSE) analysis to evaluate and compare the complexity of sleep EEG for the 2 groups. There were 9 patients with PD (Hoehn-Yahr stage 1 or 2) and 11 non-PD controls. All participants underwent standard whole-night polysomnography (PSG), which included 23 channels, 6 of which were for EEG. The raw data of the EEG were extracted and subjected to MSE analysis. Patients with PD had a longer sleep onset time and a higher spontaneous EEG arousal index. Sleep stage-specific increased MSE was observed in patients with PD during non-REM sleep. The difference was more marked and significant at higher time scale factors (TSFs). In conclusion, increased biosignal complexity, as revealed by MSE analysis, was found in patients with PD during non-REM sleep at high TSFs. This finding might reflect a compensatory mechanism for early defects in neuronal network control machinery in PD.

OnabotulinumtoxinA improves tactile and mechanical pain perception in painful diabetic polyneuropathy.

OBJECTIVES: Diabetic neuropathic pain may be relieved by onabotulinumtoxinA (BoNT/A). However, whether BoNT/A changes sensory perception in neuropathic patients remains unknown. This study used a double-blind crossover design to explore the possible effect of BoNT/A on sensory perception. METHODS: Eighteen patients with painful diabetic polyneuropathy underwent 2 consecutive 12-week periods of treatment either in the sequence of saline (control) and then BoNT/A (SB cohort, n=9) or BoNT/A followed by saline (BS cohort, n=9). Sensory perception was assessed according to the tactile threshold [TT, logarithmized force (g) of von Frey filaments] and mechanical pain threshold [PT, logarithmized weight (g) of weighted syringes], both being averages from 4 individual measurements of bilateral medial and lateral feet obtained at baseline (before injections) and at weeks 1, 4, 8, and 12 after treatment. RESULTS: In either the SB or the BS cohort, there was a decrease in the TT and the PT after treatment with BoNT/A but not with saline. In the analysis merging both cohorts (n=18), BoNT/A resulted in a significant decrease in TT and PT at weeks 1, 4, 8, and 12 (all Ps<0.05 vs. saline). The longitudinal effect of BoNT/A on TT and PT remained significant when baseline values, treatment sequences, and periods were controlled using generalized estimating equations. DISCUSSION: BoNT/A may improve tactile and mechanical pain perception in painful diabetic polyneuropathy. The beneficial effects of BoNT/A deserves further study to elucidate the exact mechanism and potential for preventing insensate injuries.

Increase of toll-like receptor 4 but decrease of interleukin-8 mRNA expression among ischemic stroke patients under aspirin treatment.

OBJECTIVES: Toll-like receptors (TLRs) are molecules conserved in evolution for detecting pathogen invasions and tissue damage and are involved in atherogenesis. This study explores the mRNA expression of TLRs and their probable role in further disease occurrence among ischemic stroke patients. DESIGN AND METHODS: A total of 89 ischemic stroke patients and 166 controls were recruited for this study. Total RNA was extracted and mRNA was reverse-transcribed to cDNA and was analyzed for TLRs and interleukin 8 (IL8). RESULTS: The TLR4 mRNA expression level is significantly higher in the stroke group. Conversely, IL-8 mRNA levels decreased significantly in the patient group. CONCLUSION: Our results suggest that TLR4 overexpression in mRNA levels is observed in stroke patients, which might account for the probable inflammatory injury before or after stroke. A reduction of IL-8 expression could result from the downregulatory effects of aspirin.

Comparisons of forward and backward gait between poorer and better attention capabilities in early Parkinson's disease.

This study compared forward and backward gait between Parkinson's disease (PD) patients with poorer and better attention capabilities. PD and healthy control (HC) participants received a dual-stimuli attention task. The results were assessed using principal component analysis to quantify and rank attention capability. Accordingly, 22 PD and 42 HC subjects were equally divided into poorer (14 PD-P, 18 HC-P) and better (8 PD-B, 24 HC-B) attention capabilities. To analyze the spatiotemporal gait parameters, each participant walked forwards and backwards on a GAITRite(®) walkway. Compared to HC, PD performed worse in the dual task and exhibited slower velocity, less swing, and shorter stride in both walking directions. Notably, PD-P experienced all these gait defects, regardless of directions. PD-B walked worse than HC-B backwards, and displayed comparable gait to HC-P in both directions. In PD and HC, velocity, stride, and swing decreased perceptibly when walking backwards compared to forwards, and the same was true for velocity and stride in PD-P and PD-B. Backward strides were reduced evidently more in PD-P than in PD-B. However, backward swing reductions in PD-P and PD-B were statistically insignificant. Cadence in both directions was similar within the groups and between the groups, and there were little alterations between directions within each group and between groups. These results suggest that attention capability may affect PD gait. Poorer attention exacerbates gait defects and better attention improves gait in both directions. These results may support the application of cuing strategies in PD to enhance attention capability and improve walking gait.

Amyloid-ß peptide alteration of tau exon-10 splicing via the GSK3ß-SC35 pathway.

Amyloid-beta peptide (Aß) and Tau protein are the lead constituents in the pathogenesis of Alzheimer's disease (AD). However, their inter-relationship in the disease process remains to be established. Tauopathy refers to a characteristic neurodegenerative process in AD. In tauopathy, Tau accumulates as a consequence of altered pre-mRNA splicing of tau exon 10, resulting in 3R (without exon 10)/4R (with exon 10) imbalance. We studied Aß effects on tau exon 10 pre-mRNA splicing and relevant signaling events. This is the first demonstration of Aß alteration of tau exon 10 splicing with an increase in 3R/4R ratio caused by reduced 4R expression. This Aß ï€ action is causally related to its activation of GSK-3ß which in turn phosphorylates SC35, an enhancer in tau exon 10 splicing. The establishment of the Aß-GSK-3ß-SC35 cascade broadens insight into development of novel strategies to modulate Aß action on tau exon 10 splicing for possible prevention of tauopathy.

Expression of inducible nitric oxide synthase (iNOS) and period 1 (PER1) clock gene products in different sleep stages of patients with cognitive impairment.

Circadian and sleep disturbances are common behavioural and psychological symptoms of dementia; circadian rhythm-related molecules may be altered in dementia patients. This study investigated the expression of the period 1 clock gene product (PER1), which is involved in circadian rhythms, and inducible nitric oxide synthase (iNOS), thought to generate nitric oxide, important in rapid eye movement (REM) sleep regulation. Specifically, we investigated the difference in expression of these two genes between patients with cognitive impairment and controls. We studied iNOS and PER1 mRNA expression using real-time polymerase chain reaction in peripheral leukocytes during REM sleep, non-REM sleep and wake stages in patients with Alzheimer's disease (AD, n=5), patients with mild cognitive impairment (MCI, n=8) and controls (n=9) during polysomnography examination. Expression of iNOS significantly increased during REM sleep in AD patients compared to MCI patients and controls. There were no significant differences in PER1 expression between the three groups, but an increase in PER1 expression during the wake stage was observed for all participants. Increased expression of iNOS during REM sleep of patients with AD might be a compensation mechanism for maintaining REM sleep. However, the precise role of nocturnal expression of iNOS in patients with AD requires further investigation.

Methylenetetrahydrofolate reductase polymorphisms and plasma homocysteine in levodopa-treated and non-treated Parkinson's disease patients.

Genetic C677T and A1298C polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR) and levodopa therapy in Parkinson's disease (PD) may increase homocysteine (Hcy) level. We examined whether connecting both polymorphisms influences the effect of levodopa on Hcy. MTHFR genotypes and Hcy, vitamin B(12), and folate levels were determined in 48 levodopa-treated PD patients (PD-L), 28 non-treated PD patients (PD-N) and 110 controls. Hcy was remarkably higher in PD-L than in PD-N and controls (p<0.001); similarly, the differences were seen in different age subgroups and in both genders. Furthermore, Hcy differences between PD-L and PD-N were evident in 677C/T, T/T, C/T + A/A, T/T + A/A (all p<0.05), and 1298A/A (p<0.001), but not in others such as 677C/C, and C/C + A/A. Hcy in PD-N and controls was comparable for all genotypes. In PD-L, Hcy was the highest in 677T/T, then in C/T, and in C/C with a significant difference from T/T (p=0.014), but was not different among A1298C genotypes. Likewise, Hcy was the highest in 677T/T+1298A/A, intermediate in C/T+A/A, and the lowest in C/C+A/A. In PD-N, Hcy was similar among all genotypes. In conclusion, Hcy elevation may be caused by levodopa administration, and further promoted by 677C/T and T/T, but not by A1298C genotypes. The promoting elevation in 1298A/A is attributed to combining the 677T allele. Neither C677T nor A1298C genotypes contribute to elevating Hcy in PD-N.

Predictors for outcome and treatment delay in patients with tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is a challenge for clinicians because of the difficulty in making an early diagnosis and the severe consequences of delaying treatment. The objective of this study was to assess predictors of outcome and to evaluate factors critical to treatment delay of TBM. METHODS: One hundred and five adult patients with TBM, between 1997 and 2006, were retrospectively studied. Treatment delay was defined as progression of stage and physician delay between the initial presentation and the start of antituberculosis therapy. Factors contributing to the outcome, progression of stage, and prolonged physician delay were evaluated using univariate and multivariate analyses. RESULTS: Fifty patients (47.6%) experienced prolonged physician delay, and 38 (36.2%) had progression of stage. Thirty-four patients (32.4%) had an acute clinical course, and 76 (72.4%) received initial antibacterial therapy. Prolonged physician delay and progression of stage were important prognostic factors for poor outcome. Stage I at admission and prolonged physician delay were important factors contributing to progression of stage. An acute clinical course and an initial antibacterial therapy were important factors contributing to prolonged physician delay. CONCLUSIONS: Rapid diagnosis and early treatment before the occurrence of progression of stage are crucial for the outcome of TBM. TBM may present with an acute course, and when discrimination from bacterial meningitis is difficult, it is mandatory to start antituberculosis and antibacterial therapy simultaneously or lower the threshold for early antituberculosis therapy when persistent fever, deteriorated consciousness status, or progression of stage occurs during antibacterial therapy.

Low sleep efficiency in patients with cognitive impairment.

Alzheimer's disease (AD) is the most common cause of dementias. Mild cognitive impairment (MCI) indicates the situation that a person has memory complaints and mild objective cognitive impairment but no evidence of dementia. Sleep disturbance, one of the behavioral and psychological symptoms of dementia (BPSD), frequently occurs in patients with AD or MCI. The alteration of sleep architectures in AD patients remains inconclusive. In this study, we conducted the polysomnography. (PSG) examination among patients with mild AD with cholinesterase inhibitors (N=10) or MCI (N=12) and age-matched nondemented controls (N=13). The results showed sleep efficiency, which was one of the important parameters for sleep quality was significantly lower in patients with MCI and AD (N=22), 79.14 +/- 11.06 % vs. 67.07 +/- 19.10 %, p=0.046. There were no statistic differences of sleep architecture but a trend of REM insufficiency in patients with MCI or AD. The mean scores of geriatric depression score (GDS) and Epworth sleepiness scale (ESS) did not differ among the three groups. Our study implicated maintenance of sleep was impaired in patients with cognitive impairment and it was independent with depressive symptoms.