Post-stroke upper limb recovery is correlated with dynamic resting-state network connectivity.

Motor recovery is still limited for people with stroke especially those with greater functional impairments. In order to improve outcome, we need to understand more about the mechanisms underpinning recovery. Task-unbiased, blood flow-independent post-stroke neural activity can be acquired from resting brain electrophysiological recordings and offers substantial promise to investigate physiological mechanisms, but behaviourally relevant features of resting-state sensorimotor network dynamics have not yet been identified. Thirty-seven people with subcortical ischaemic stroke and unilateral hand paresis of any degree were longitudinally evaluated at 3 weeks (early subacute) and 12 weeks (late subacute) after stroke. Resting-state magnetoencephalography and clinical scores of motor function were recorded and compared with matched controls. Magnetoencephalography data were decomposed using a data-driven hidden Markov model into 10 time-varying resting-state networks. People with stroke showed statistically significantly improved Action Research Arm Test and Fugl-Meyer upper extremity scores between 3 weeks and 12 weeks after stroke (both P < 0.001). Hidden Markov model analysis revealed a primarily alpha-band ipsilesional resting-state sensorimotor network which had a significantly increased life-time (the average time elapsed between entering and exiting the network) and fractional occupancy (the occupied percentage among all networks) at 3 weeks after stroke when compared with controls. The life-time of the ipsilesional resting-state sensorimotor network positively correlated with concurrent motor scores in people with stroke who had not fully recovered. Specifically, this relationship was observed only in ipsilesional rather in contralesional sensorimotor network, default mode network or visual network. The ipsilesional sensorimotor network metrics were not significantly different from controls at 12 weeks after stroke. The increased recruitment of alpha-band ipsilesional resting-state sensorimotor network at subacute stroke served as functionally correlated biomarkers exclusively in people with stroke with not fully recovered hand paresis, plausibly reflecting functional motor recovery processes.

Prophylaxis for paediatric emergence delirium in desflurane-based anaesthesia: a network meta-analysis.

PURPOSE: The prevalence of postoperative emergence delirium in paediatric patients (pedED) following desflurane anaesthesia is considerably high at 50-80%. Although several pharmacological prophylactic strategies have been introduced to reduce the risk of pedED, conclusive evidence about the superiority of these individual regimens is lacking. The aim of the current study was to assess the potential prophylactic effect and safety of individual pharmacotherapies in the prevention of pedED following desflurane anaesthesia. METHODS: This frequentist model network meta-analysis (NMA) of randomized controlled trials (RCTs) included peer-reviewed RCTs of either placebo-controlled or active-controlled design in paediatric patients under desflurane anaesthesia. RESULTS: Seven studies comprising 573 participants were included. Overall, the ketamine + propofol administration [odds ratio (OR) = 0.05, 95% confidence intervals (95%CIs) 0.01-0.33], dexmedetomidine alone (OR = 0.13, 95%CIs 0.05-0.31), and propofol administration (OR = 0.30, 95%CIs 0.10-0.91) were associated with a significantly lower incidence of pedED than the placebo/control groups. In addition, only gabapentin and dexmedetomidine were associated with a significantly higher improvement in the severity of emergence delirium than the placebo/control groups. Finally, the ketamine + propofol administration was associated with the lowest incidence of pedED, whereas gabapentin was associated with the lowest severity of pedED among all of the pharmacologic interventions studied. CONCLUSIONS: The current NMA showed that ketamine + propofol administration was associated with the lowest incidence of pedED among all of the pharmacologic interventions studied. Future large-scale trials to more fully elucidate the comparative benefits of different combination regimens are warranted. TRIAL REGISTRATION: PROSPERO CRD42021285200.

High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis.

Migraine is a highly prevalent neurologic disorder with prevalence rates ranging from 9% to 18% worldwide. Current pharmacologic prophylactic strategies for migraine have limited efficacy and acceptability, with relatively low response rates of 40% to 50% and limited safety profiles. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered promising therapeutic agents for migraine prophylaxis. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various dosages of EPA/DHA and other current Food and Drug Administration-approved or guideline-recommended prophylactic pharmacologic interventions for migraine. Randomized controlled trials (RCTs) were eligible for inclusion if they enrolled participants with a diagnosis of either episodic or chronic migraine. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed were 1) changes in migraine frequency and 2) acceptability (i.e., dropout for any reason). Secondary outcomes included response rates, changes in migraine severity, changes in the frequency of using rescue medications, and frequency of any adverse events. Forty RCTs were included (N = 6616; mean age = 35.0 y; 78.9% women). Our analysis showed that supplementation with high dosage EPA/DHA yields the highest decrease in migraine frequency [standardized mean difference (SMD): -1.36; 95% confidence interval (CI): -2.32, -0.39 compared with placebo] and the largest decrease in migraine severity (SMD: -2.23; 95% CI: -3.17, -1.30 compared with placebo) in all studied interventions. Furthermore, supplementation with high dosage EPA/DHA showed the most favorable acceptability rates (odds ratio: 1.00; 95% CI: 0.06, 17.41 compared with placebo) of all examined prophylactic treatments. This study provides compelling evidence that high dosage EPA/DHA supplementation can be considered a first-choice treatment of migraine prophylaxis because this treatment displayed the highest efficacy and highest acceptability of all studied treatments. This study was registered in PROSPERO as CRD42022319577.

Effects of bihemispheric transcranial direct current stimulation on motor recovery in subacute stroke patients: a double-blind, randomized sham-controlled trial.

BACKGROUND: Bihemispheric transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) can simultaneously modulate bilateral corticospinal excitability and interhemispheric interaction. However, how tDCS affects subacute stroke recovery remains unclear. We investigated the effects of bihemispheric tDCS on motor recovery in subacute stroke patients. METHODS: We enrolled subacute inpatients who had first-ever ischemic stroke at subcortical regions and moderate-to-severe baseline Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score 2-56. Participants between 14 and 28 days after stroke were double-blind, randomly assigned (1:1) to receive real (n = 13) or sham (n = 14) bihemispheric tDCS (with ipsilesional M1 anode and contralesional M1 cathode, 20 min, 2 mA) during task practice twice daily for 20 sessions in two weeks. Residual integrity of the ipsilesional corticospinal tract was stratified between groups. The primary efficacy outcome was the change in FMA-UE score from baseline (responder as an increase ≥ 10). The secondary measures included changes in the Action Research Arm Test (ARAT), FMA-Lower Extremity (FMA-LE) and explorative resting-state MRI functional connectivity (FC) of target regions after intervention and three months post-stroke. RESULTS: Twenty-seven participants completed the study without significant adverse effects. Nineteen patients (70%) had no recordable baseline motor-evoked potentials (MEP-negative) from the paretic forearm. Compared with the sham group, the real tDCS group showed enhanced improvement of FMA-UE after intervention (p < 0.01, effect size η2 = 0.211; responder rate: 77% vs. 36%, p = 0.031), which sustained three months post-stroke (p < 0.01), but not ARAT. Interestingly, in the MEP-negative subgroup analysis, the FMA-UE improvement remained but delayed. Additionally, the FMA-LE improvement after real tDCS was not significantly greater until three months post-stroke (p < 0.01). We found that the individual FMA-UE improvements after real tDCS were associated with bilateral intrahemispheric, rather than interhemispheric, FC strengths in the targeted cortices, while the improvements after sham tDCS were associated with predominantly ipsilesional FC changes after adjustment for age and sex (p < 0.01). CONCLUSIONS: Bihemispheric tDCS during task-oriented training may facilitate motor recovery in subacute stroke patients, even with compromised corticospinal tract integrity. Further studies are warranted for tDCS efficacy and network-specific neuromodulation. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov: (ID: NCT02731508).

Treatment, Outcome, and Relapse of Spontaneous and Nonspontaneous Cerebrospinal Fluid Leak.

Cerebrospinal fluid (CSF) leak can be spontaneous or nonspontaneous. The management options include conservative treatments, blood patch, and surgical repairs. We compared clinical symptoms, image findings, management options, hospitalization, and relapse rates among different causes of CSF leaks. Eighty-one patients were recruited: 20 with spontaneous and 61 with nonspontaneous CSF leaks. Nonspontaneous causes included lumbar puncture, surgery, and trauma. Surgery sites comprised sphenoid, spine, skull base, and calvaria. Spontaneous CSF leak came from the sphenoid or spine. Age, gender, body mass index, initial symptoms, hospitalization, treatment courses, and recurrence rates showed no difference between the groups. The spontaneous group had higher CSF accumulations on their MRIs. MRI pachymeninge enhancement showed the highest sensitivity (78.6%) for intracranial hypotension. Meningitis occurred in 1/3 of sphenoid, skull base, and calvarian surgeries. Earlier reoperation was correlated with shorter hospitalization (r = 0.651), but the recurrence rates were similar. Longer intervals between surgery and CSF leak encouraged reoperation. Among the spontaneous spine and lumbar puncture-related CSF leaks, 57.1% of them responded to 4 days of conservative treatment. Among the trauma-related CSF leaks, 90.9% of them required surgical repair. The demographic data and symptoms were similar in various groups of CSF leak. The symptom onset durations and treatment strategies were different. However, the recurrence rates were similar.

Orthostatic myoclonus - A retrospective study of Asian patients.

BACKGROUND/PURPOSE: Orthostatic myoclonus (OM) is myoclonic jerks in both legs during standing. It may relate to gait unsteadiness and may be associated with various diagnoses, including neurodegenerative, systemic, and musculoskeletal diseases. Diagnosis is based on the surface electromyography (SEMG). METHODS: From January 2016 to June 2020, we retrospectively reviewed 35 patients diagnosed with OM based on the SEMG criteria and analyzed the electrophysiological data. RESULTS: The mean age was 75.3±8.9. Disease duration ranged from 2 days to several years. Genders were equally affected. The most common symptom was gait disturbance, and the next was leg tremulous sensation, followed by backward disequilibrium. 28.6% of our patients had falls. Electrophysiologically, bursting duration shorter than 100 ms supported the myoclonic origin from the cortex. The bursting activity occurred only on the upright and weight-bearing leg. The associated diagnoses included lumbosacral radiculopathy (28.6%), lumbosacral radiculopathy plus myasthenia gravis (2.9%), lumbosacral radiculopathy plus vascular parkinsonism (5.7%), diabetic polyneuropathy (5.7%), vascular parkinsonism (17.1%), Parkinson's disease (PD) (14.2%), normal pressure hydrocephalus (5.7%), medication-induced parkinsonism (2.9%), cervical myelopathy (2.9%), medication-related myoclonus (2.9%), and unknown (11.4%). In PD, OM was present before, along with, or after PD diagnosis. The myoclonic activity disrupted the parkinsonian tremor upon standing on SEMG. CONCLUSION: OM is a syndrome instead of a diagnosis. It is more prevalent in the elderly with gait disturbance and patients will not necessarily fall. It is associated with central and peripheral nerve system disorders, systemic diseases, and medication use. We hypothesize that OM is a pathological disintegration of motor circuit.

Efficacy of pharmacologic treatment in tinnitus patients without specific or treatable origin: A network meta-analysis of randomised controlled trials.

BACKGROUND: Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear. METHODS: The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5th, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742. FINDINGS: Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control. INTERPRETATION: The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin. FUNDING: none.

Comparison of nerve conduction study and transcranial magnetic stimulation for early diagnosis and prognosis prediction of idiopathic facial palsy.

OBJECTIVE: Multiple electrophysiologic studies have been conducted in the evaluation of facial neuropathy. In our study, the diagnostic and prognostic values of nerve conduction studies (NCSs) and transcranial magnetic stimulation (TMS) were compared for idiopathic unilateral facial neuropathy. METHOD: We recruited patients with newly diagnosed idiopathic unilateral facial neuropathy and performed a blink reflex test, facial NCSs, and TMS. The amplitude of facial compound muscle action potential (CMAP) and motor evoked potential (MEP) between the affected and unaffected sides of the face was compared. RESULT: A total of 30 patients were enrolled in the final analysis. TMS yielded a better detection rate, and MEP reduction rate was significantly higher than CMAP reduction rate, early in the course of the disease. Poor prognosis was positively associated with the CMAP reduction rate. The cutoff value of the CMAP reduction rate in the prediction of poor prognosis was established as 0.42. CONCLUSION: Facial TMS could detect idiopathic unilateral facial neuropathy with a high sensitivity when used as an early diagnostic tool. Facial NCS could predict prognosis, and the CMAP reduction rate was significantly associated with poor short-term prognosis.

Renal Function-Dependent Associations of Statins with Outcomes of Ischemic Stroke.

AIM: Chronic kidney disease (CKD) is associated with unfavorable outcomes in patients with ischemic stroke. One major metabolic derangement of CKD is dyslipidemia, which can be managed by statins. This study aimed to investigate whether the association of statins with post-stroke outcomes would be affected by renal function. METHODS: We evaluated the association of statin therapy at discharge with 3-month outcomes according to the estimated glomerular filtration rate (eGFR) of 50,092 patients with acute ischemic stroke from the Taiwan Stroke Registry from August 2006 to May 2016. The outcomes were mortality, functional outcome as modified Rankin Scale (mRS), and recurrent ischemic stroke at 3 months after index stroke. RESULTS: Statin therapy at discharge was associated with lower risks of mortality (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.34 to 0.50) and unfavorable functional outcomes (mRS 3-5; aHR, 0.80; 95% CI, 0.76 to 0.84) in ischemic stroke patients. After stratification by eGFR, the lower risk of mortality associated with statins was limited to patients with an eGFR above 15 mL/min/1.73 m2. Using statins at discharge was correlated with a lower risk of unfavorable functional outcomes in patients with an eGFR of 60-89 mL/min/1.73 m2. Statin therapy in patients with an eGFR of 60-89 mL/min/1.73 m2 may be associated with a higher risk of recurrent ischemic stroke compared with nonusers (aHR, 1.29; 95% CI, 1.07 to 1.57). CONCLUSIONS: In patients with acute ischemic stroke, the associations of statins with mortality and functional outcomes was dependent on eGFR.

Peroxisome Proliferator-Activated Receptor γ Coactivator 1α Activates Vascular Endothelial Growth Factor That Protects Against Neuronal Cell Death Following Status Epilepticus through PI3K/AKT and MEK/ERK Signaling.

Status epilepticus may cause molecular and cellular events, leading to hippocampal neuronal cell death. Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) is an important regulator of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2), also known as fetal liver kinase receptor 1 (Flk-1). Resveratrol is an activator of PGC-1α. It has been suggested to provide neuroprotective effects in epilepsy, stroke, and neurodegenerative diseases. In the present study, we used microinjection of kainic acid into the left hippocampal CA3 region in Sprague Dawley rats to induce bilateral prolonged seizure activity. Upregulating the PGC-1α pathway will increase VEGF/VEGFR2 (Flk-1) signaling and further activate some survival signaling that includes the mitogen activated protein kinase kinase (MEK)/mitogen activated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways and offer neuroprotection as a consequence of apoptosis in the hippocampal neurons following status epilepticus. Otherwise, downregulation of PGC-1α by siRNA against pgc-1α will inhibit VEGF/VEGFR2 (Flk-1) signaling and suppress pro-survival PI3K/AKT and MEK/ERK pathways that are also accompanied by hippocampal CA3 neuronal cell apoptosis. These results may indicate that the PGC-1α induced VEGF/VEGFR2 pathway may trigger the neuronal survival signaling, and the PI3K/AKT and MEK/ERK signaling pathways. Thus, the axis of PGC-1α/VEGF/VEGFR2 (Flk-1) and the triggering of downstream PI3K/AKT and MEK/ERK signaling could be considered an endogenous neuroprotective effect against apoptosis in the hippocampus following status epilepticus.

Association of Central Noninvasive Brain Stimulation Interventions With Efficacy and Safety in Tinnitus Management: A Meta-analysis.

Importance: Tinnitus has a prevalence of 10% to 25% and is frequently associated with numerous complications, such as neuropsychiatric disease. Traditional treatments have failed to meet the needs of patients with tinnitus. Noninvasive brain stimulation (NIBS) can focally modify cortical functioning and has been proposed as a strategy for reducing tinnitus severity. However, the results have been inconclusive. Objective: To evaluate the association between different central NIBS therapies and efficacy and acceptability for treatment of tinnitus. Data Sources: ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, and Web of Science databases were searched from inception to August 4, 2019. No language restriction was applied. Manual searches were performed for potentially eligible articles selected from the reference lists of review articles and pairwise meta-analyses. Study Selection: Randomized clinical trials (RCTs) examining the central NIBS method used in patients with unilateral or bilateral tinnitus were included in the current network meta-analysis. The central NIBS method was compared with sham, waiting list, or active controls. Studies that were not clinical trials or RCTs and did not report the outcome of interest were excluded. Data Extraction and Synthesis: Two authors independently screened the studies, extracted the relevant information, and evaluated the risk of bias in the included studies. In cases of discrepancy, a third author became involved. If manuscript data were not available, the corresponding authors or coauthors were approached to obtain the original data. This network meta-analysis was based on the frequentist model. Main Outcomes and Measures: The primary outcome was change in the severity of tinnitus. Secondary outcomes were changes in quality of life and the response rate related to the NIBS method in patients with tinnitus. Results: Overall, 32 unique RCTs were included with 1458 unique participants (mean female proportion, 34.4% [range, 0%-81.2%]; mean age, 49.6 [range, 40.0-62.8] years; median age, 49.8 [interquartile range, 48.1-52.4] years). The results of the network meta-analysis revealed that cathodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex combined with transcranial random noise stimulation over the bilateral auditory cortex was associated with the greatest improvement in tinnitus severity (standardized mean difference [SMD], -1.89; 95% CI, -3.00 to -0.78) and quality of life (SMD, -1.24; 95% CI, -2.02 to -0.45) compared with the controls. Improvement in tinnitus severity ranked more favorably for continuous theta-burst stimulation (cTBS) over both auditory cortices (SMD, -0.79; 95% CI = -1.57 to -0.01) than cTBS over only the left auditory cortex (SMD, -0.30; 95% CI, -0.87 to 0.28), compared with controls. Repetitive transcranial magnetic stimulation with priming had a superior beneficial association with tinnitus severity compared with the strategies without priming. None of the investigated NIBS types had a significantly different dropout rate compared with that of the control group. Conclusions and Relevance: This network meta-analysis suggests a potential role of NIBS interventions in tinnitus management. Future large-scale RCTs focusing on longer follow-up and different priming procedure NIBS are warranted to confirm these findings.

Neurophysiological signatures of hand motor response to dual-transcranial direct current stimulation in subacute stroke: a TMS and MEG study.

BACKGROUND: Dual transcranial direct current stimulation (tDCS) to the bilateral primary motor cortices (M1s) has potential benefits in chronic stroke, but its effects in subacute stroke, when behavioural effects might be expected to be greater, have been relatively unexplored. Here, we examined the neurophysiological effects and the factors influencing responsiveness of dual-tDCS in subacute stroke survivors. METHODS: We conducted a randomized sham-controlled crossover study in 18 survivors with first-ever, unilateral subcortical ischaemic stroke 2-4 weeks after stroke onset and 14 matched healthy controls. Participants had real dual-tDCS (with an ipsilesional [right for controls] M1 anode and a contralesional M1 [left for controls] cathode; 2 mA for 20mins) and sham dual-tDCS on separate days, with concurrent paretic [left for controls] hand exercise. Using transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), we recorded motor evoked potentials (MEPs), the ipsilateral silent period (iSP), short-interval intracortical inhibition, and finger movement-related cortical oscillations before and immediately after tDCS. RESULTS: Stroke survivors had decreased excitability in ipsilesional M1 with a relatively excessive transcallosal inhibition from the contralesional to ipsilesional hemisphere at baseline compared with controls, as quantified by decreased MEPs and increased iSP duration. Dual-tDCS led to increased MEPs and decreased iSP duration in ipsilesional M1. The magnitude of the tDCS-induced MEP increase in stroke survivors was predicted by baseline contralesional-to-ipsilesional transcallosal inhibition (iSP) ratio. Baseline post-movement synchronization in α-band activity in ipsilesional M1 was decreased after stroke compared with controls, and its tDCS-induced increase correlated with upper limb score in stroke survivors. No significant adverse effects were observed during or after dual-tDCS. CONCLUSIONS: Task-concurrent dual-tDCS in subacute stroke can safely and effectively modulate bilateral M1 excitability and inter-hemispheric imbalance and also movement-related α-activity.

Effects of anti-epileptic drugs on spreading depolarization-induced epileptiform activity in mouse hippocampal slices.

Epilepsy and spreading depolarization (SD) are both episodic brain disorders and often exist together in the same individual. In CA1 pyramidal neurons of mouse hippocampal slices, induction of SD evoked epileptiform activities, including the ictal-like bursts, which occurred during the repolarizing phase of SD, and the subsequent generation of paroxysmal depolarization shifts (PDSs), which are characterized by mild depolarization plateau with overriding spikes. The duration of the ictal-like activity was correlated with both the recovery time and the depolarization potential of SD, whereas the parameters of PDSs were not significantly correlated with the parameters of SD. Moreover, we systematically evaluated the effects of multiple anti-epileptic drugs (AEDs) on SD-induced epileptiform activity. Among the drugs that are known to inhibit voltage-gated sodium channels, carbamazepine, phenytoin, valproate, lamotrigine, and zonisamide reduced the frequency of PDSs and the overriding firing bursts in 20-25 min after the induction of SD. The GABA uptake inhibitor tiagabine exhibited moderate effects and partially limited the incidence of PDSs after SD. AEDs including gabapentin, levetiracetam, ethosuximide, felbamate, and vigabatrin, had no significant effect on SD-induced epileptic activity. Taken together, these results demonstrate the effects of AEDs on SD and the related epileptiform activity at the cellular level.

Determinants of generic and specific health-related quality of life in patients with Parkinson's disease.

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.

Responsiveness of the short-form health survey and the Parkinson's disease questionnaire in patients with Parkinson's disease.

BACKGROUND: The responsiveness of a measurement instrument is important for understanding its ability to detect changes in the progression of a disease. We examined and compared the internal and external responsiveness of the 36-item Short-Form Health Survey (SF-36) and the 39-item Parkinson's Disease Questionnaire (PDQ-39) in patients with Parkinson's Disease (PD). METHODS: Seventy-four patients with PD were evaluated using the SF-36 and PDQ-39 at baseline and again after one year. In addition, their motor signs, motor difficulties of daily living, and depressive symptoms were assessed as external criteria. The internal responsiveness was examined using effect size, standardized response mean, and the Wilcoxon signed rank test. The external responsiveness was examined using receiver operating characteristic curves, correlation analyses, and regression models. RESULTS: Both instruments were partially sensitive to changes during the 1-year follow-up and able to discriminate between patients with improved versus deteriorated motor signs. In addition, both were similarly responsive to changes in the motor difficulties of daily living; the SF-36 appeared to be more sensitive than the PDQ-39 to changes in depressive symptoms. CONCLUSIONS: The SF-36 and the PDQ-39 were acceptably internally and externally responsive during the 1-year follow-up.

Impact of MCA stenosis on the early outcome in acute ischemic stroke patients.

BACKGROUND: Asians have higher frequency of intracranial arterial stenosis. The present study aimed to compare the clinical features and outcomes of ischemic stroke patients with and without middle cerebral artery (MCA) stenosis, assessed by transcranial sonography (TCS), based on the Taiwan Stroke Registry (TSR). METHODS: Patients with acute ischemic stroke or transient ischemic attack registered in the TSR, and received both carotid duplex and TCS assessment were categorized into those with stenosis (≥50%) and without (<50%) in the extracranial internal carotid artery (ICA) and MCA, respectively. Logistic regression analysis, Kaplan-Meier method and Cox proportional hazard model were applied to assess relevant variables between groups. RESULTS: Of 6003 patients, 23.3% had MCA stenosis, 10.1% ICA stenosis, and 3.9% both MCA and ICA stenosis. Patients with MCA stenosis had greater initial NIHSS, higher likelihood of stroke-in-evolution, and more severe disability than those without (all p<0.001). Patients with MCA stenosis had higher prevalence of hypertension, diabetes and hypercholesterolemia. Patients with combined MCA and extracranial ICA stenosis had even higher NIHSS, worse functional outcome, higher risk of stroke recurrence or death (hazard ratio, 2.204; 95% confidence intervals, 1.440-3.374; p<0.001) at 3 months after stroke than those without MCA stenosis. CONCLUSIONS: In conclusion, MCA stenosis was more prevalent than extracranial ICA stenosis in ischemic stroke patients in Taiwan. Patients with MCA stenosis, especially combined extracranial ICA stenosis, had more severe neurological deficit and worse outcome.

Low cholesterol level associated with severity and outcome of spontaneous intracerebral hemorrhage: Results from Taiwan Stroke Registry.

The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with <160, 160-200 and >200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC <160 mg/dL. Patients with TC <160 mg/dL presented more often severe neurological deficit (NIHSS >15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41-2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11-1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI) <22 kg/m2 had higher risk of 3-month mortality (aOR 3.94, 95% CI 1.76-8.80). Prior use of lipid-lowering drugs (2.8% of the ICH population) was not associated with initial severity and 3-month outcomes. A total cholesterol level lower than 160 mg/dL was common in patients with acute ICH and was associated with greater neurological severity on presentation and poor 3-month outcomes, especially with lower BMI.

Cholesterol Levels Are Associated with 30-day Mortality from Ischemic Stroke in Dialysis Patients.

BACKGROUND: We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients. METHODS: From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013. RESULTS: Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of <120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of <120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. CONCLUSIONS: Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or <120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Effective and Cheap Behavioral Modification Therapy to Manage Complicated Polydipsia and Seizures in a Chronic Mental Health Institute.

PURPOSE: Polydipsia is one of the most serious and complicated problems causing morbidity and mortality in chronic mental health institutes. The pathophysiology of polydipsia in chronic schizophrenia remains unclear; as a result, no effective methods exist to deal with this serious problem. This report describes a patient with schizophrenia with polydipsia and seizures who benefitted from a behavioral modification program at a chronic mental health institute. CASE REPORT: A 56-year-old schizophrenic man did not have a history of physical illnesses or seizures and developed seizures following polydipsia. Despite drug adjustment, his polydipsia was uncontrolled and he suffered from generalized tonic convulsions. After introducing a "water restriction program," his polydipsia and seizures were controlled. CONCLUSION: The "water restriction program" consisted of daily body weight monitoring and frequent checking of electrolyte data, both of which are inexpensive and simple. This program can be carried out by untrained nursing staff, who are the primary caregivers in chronic mental health institutes. Our case highlights an effective and inexpensive behavior modification program to deal with the difficult and complicated problems of polydipsia and seizures in chronic mental health institutes.

State-dependent increase in the levels of neurotrophin-3 and neurotrophin-4/5 in patients with bipolar disorder: A meta-analysis.

Bipolar disorder (BD) is one of the most serious psychiatric disorders in the world, but its pathophysiology is still unclear. Regulation of neurotrophic factors have been thought to play a role in this process. There have been inconsistent findings regarding the differences in blood neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) between patients with BD and healthy controls (HCs). The aim of the current meta-analysis is to examine the changes in the levels of NT-3 and NT-4/5 in BD patients at different affective states. Eight articles (including 465 BD patients and 353 HCs) were included in the analysis, and their results were pooled by using a random effects model. We found the levels of both NT-3 (p = 0.0046) and NT-4/5 (p = 0.0003) were significantly increased in BD patients, compared to HCs. Through subgroup analysis, this increase persisted only in patients in depressed state (p = 0.0038 for NT-3 and p = 0.0001 for NT-4/5), but not in manic or euthymic state. In addition, we found the differences in NT-3 and NT-4/5 were significantly associated with the duration of illness, but not by the mean age or female proportion. Our results suggest a state-dependent increase in NT-3 and NT-4/5 levels in patients with BD. Further studies are needed to examine dynamic changes of these neurotrophins in BD patients along the disease course.