Exercise promotes growth and rescues volume deficits in the hippocampus after cranial radiation in young mice.

Human and animal studies suggest that exercise promotes healthy brain development and function, including promoting hippocampal growth. Childhood cancer survivors that have received cranial radiotherapy exhibit hippocampal volume deficits and are at risk of impaired cognitive function, thus they may benefit from regular exercise. While morphological changes induced by exercise have been characterized using magnetic resonance imaging (MRI) in humans and animal models, evaluation of changes across the brain through development and following cranial radiation is lacking. In this study, we used high-resolution longitudinal MRI through development to evaluate the effects of exercise in a pediatric mouse model of cranial radiation. Female mice received whole-brain radiation (7 Gy) or sham radiation (0 Gy) at an infant equivalent age (P16). One week after irradiation, mice were housed in either a regular cage or a cage equipped with a running wheel. In vivo MRI was performed prior to irradiation, and at three subsequent timepoints to evaluate the effects of radiation and exercise. We used a linear mixed-effects model to assess volumetric and cortical thickness changes. Exercise caused substantial increases in the volumes of certain brain regions, notably the hippocampus in both irradiated and nonirradiated mice. Volume increases exceeded the deficits induced by cranial irradiation. The effect of exercise and irradiation on subregional hippocampal volumes was also characterized. In addition, we characterized cortical thickness changes across development and found that it peaked between P23 and P43, depending on the region. Exercise also induced regional alterations in cortical thickness after 3 weeks of voluntary exercise, while irradiation did not substantially alter cortical thickness. Our results show that exercise has the potential to alter neuroanatomical outcomes in both irradiated and nonirradiated mice. This supports ongoing research exploring exercise as a strategy for improving neurocognitive development for children, particularly those treated with cranial radiotherapy.

Pre-operative cognitive burden as predictor of motor outcome following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

INTRODUCTION: The interrelationship between neurocognitive impairments and motor functions was observed in patients with advanced Parkinson's disease (PD). This study was conducted to identify pre-operative neurocognitive and clinical predictors of short-term motor outcome following subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: All consecutive PD patients who were eligible for bilateral STN-DBS from 2009 to 2019 were evaluated before and at 1 year following surgery. Standard motor evaluation and neurocognitive tests including global cognition, memory, executive functions (attention and category fluency), confrontational speech, visuospatial abilities, and mood were conducted at baseline. The post-operative STN-DBS effects were assessed at 1 year following the surgery. Multiple regression analysis was applied to identify baseline independent predictors of post-operative STN-DBS effect. RESULTS: A total of 82 patients were analyzed. It was found that younger age at operation, higher levodopa responsiveness at baseline based on UPDRS-III total score, and better baseline verbal delayed memory and category fluency predicted post-operative motor outcome at 1 year following STN-DBS (F = 9.639, p < 0.001, R2 = .340). CONCLUSION: Our findings demonstrated the role of baseline cognitive burden, especially cognitive processes related to frontostriatal circuits, was significant clinical predictors of short-term motor outcomes following STN-DBS. Profile analysis of neurocognitive functions at baseline is recommended.

Promoting community reintegration using narratives and skills building for young adults with stroke: a protocol for a randomised controlled trial.

BACKGROUND: Stroke in adults aged between 18 and 64 years old is increasing significantly worldwide. Studies have reported that this group of young stroke survivors encounters enormous difficulties reintegrating into their social roles. Individualised discussions with healthcare professionals and learning from other survivors are imperative for them to reconstruct their identities after stroke. There is also great demand for community support during their chronic stage of recovery to help them rebuild life skills to promote reintegration. METHODS/DESIGN: This is a randomised controlled trial to investigate the effects of a 24-week Narrative and Skills-building Intervention (NSI) on young stroke survivors' community reintegration and psychosocial outcomes. A total of 208 adults aged 18-64 years old with a first-ever or recurrent ischaemic or haemorrhagic stroke and have been discharged home will be recruited and randomly assigned to receive usual care or usual care with NSI. The NSI is grounded in Narrative Theory and Bandura's principles of Self-efficacy and Outcome Expectation, consisting of successive eight individual sessions over six months delivered by a trained facilitator (a registered nurse). Participants will be facilitated to narrate their survival experiences and rebuild core life skills. Videos of peer young stroke survivors' experiences of recovery will be provided. Outcomes including community reintegration, depressive symptoms, health-related quality of life, self-efficacy, outcome expectation and satisfaction with performance of self-management behaviours will be measured before (T0) and immediately after NSI (T1), then six (T2) and 12 months after NSI (T3). Generalised estimating equations models will be used to compare the differential changes in outcomes across time between the two groups. Focus group interviews will be conducted with the facilitator at T1 and with the participants in the intervention group at T1 and T3. DISCUSSION: This study will evaluate the short and long-term effects of a theory-based NSI on young stroke survivors' community reintegration and establish a new model of community reintegration after stroke to inform future research. The results will also provide valuable evidence to develop clinical guidelines for young stroke survivors' community reintegration. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04560140 , registered on 23 September, 2020.

Evidence of improved immediate verbal memory and diminished category fluency following STN-DBS in Chinese-Cantonese patients with idiopathic Parkinson's disease.

The present study investigated the neuropsychological effects of bilateral deep brain stimulation (DBS) on subthalamic nucleus (STN) in Chinese-Cantonese patients with idiopathic Parkinson's disease (PD). Twenty-seven patients were prospectively recruited from the Movement Disorder Clinic at the Hong Kong Prince of Wales Hospital. Neuropsychological evaluations were performed at baseline, 6 and 12 months following the DBS procedure. Assessment battery included standardized tests on global cognitive function, verbal memory, non-verbal memory, confrontation naming, visuospatial organization, attention and executive functions. Anxiety and depressive symptoms were measured by two self-reported questionnaires. Results demonstrated diminished performance on a category fluency task that occurred at 6 months post-operatively and persisted at 12-month re-evaluation; 29.6-33.3 % of patients showed reduction of more than 1 SD (standard deviation) at post-operative measure. Conversely, performance on an immediate recall task in a verbal memory test was found to improve significantly at the same time point and persisted through 12 months after surgery; 22.2-25.9 % showed an improvement (≥1 SD). Psychologically, anxiety symptoms were statistically decreased and the significant reduction occurred at 12 months after surgery. Patients who reported a moderate to severe level of anxiety reduced from 51.9 to 18.5 %. Our findings concurred with most evidences on the effects of STN-DBS on verbal fluency; on the other hand, we demonstrated improvement of immediate verbal memory that warranted further investigation.

Pallidal deep brain stimulation: an effective treatment in Chinese patients with tardive dystonia.

Tardive dystonia is an iatrogenic complication of dopamine receptor antagonist medication such as first-generation antipsychotics. It occurs in up to 2% of patients and only 10% recover after stopping medication. Deep brain stimulation for primary dystonia has proven to be effective and its application for secondary dystonias is gaining acceptance. We report our experience in treating three ethnic Chinese schizophrenia patients with severe medically refractory tardive dystonia by globus pallidus internus deep brain stimulation. Preoperatively, all required assistance with essential activities of daily living and two were bed-bound. The mean Burke-Fahn-Marsden Dystonia Rating Scale score was 61 (range, 44-80) and mean Global Dystonia Rating Scale score was 47 (range, 40-52). No procedure-related complications were encountered. By 3 months all could return to unassisted living and walk with support with a mean of 77% and 66% improvement in the Burke-Fahn-Marsden Dystonia Rating Scale and Global Dystonia Rating Scale scores, respectively. Quality-of-life assessment performed for two patients using the EuroQol-5 dimensions visual analogue scale showed a mean improvement of 86% at 3 months. On clinical follow-up, the effect was well maintained for a period of 3 to 10 years. Pallidal deep brain stimulation is a safe and highly effective form of symptomatic treatment for patients with medically refractory tardive dystonia.

Subthalamic nucleus deep brain stimulation for Parkinson's disease: evidence for effectiveness and limitations from 12 years' experience.

OBJECTIVE: To present the result and experience of subthalamic nucleus deep brain stimulation for Parkinson's disease. DESIGN: Case series. SETTING: Prince of Wales Hospital, Hong Kong. PATIENTS: A cohort of patients with Parkinson's disease received subthalamic nucleus deep brain stimulation from September 1998 to January 2010. Patient assessment data before and after the operation were collected prospectively. RESULTS: Forty-one patients (21 male and 20 female) with Parkinson's disease underwent bilateral subthalamic nucleus deep brain stimulation and were followed up for a median interval of 12 months. For the whole group, the mean improvements of Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III were 32.5% and 31.5%, respectively (P<0.001). Throughout the years, a multidisciplinary team was gradually built. The deep brain stimulation protocol evolved and was substantiated by updated patient selection criteria and outcome assessment, integrated imaging and neurophysiological targeting, refinement of surgical technique as well as the accumulation of experience in deep brain stimulation programming. Most of the structural improvement occurred before mid-2005. Patients receiving the operation before June 2005 (19 cases) and after (22 cases) were compared; the improvements in UPDRS part III were 13.2% and 55.2%, respectively (P<0.001). There were three operative complications (one lead migration, one cerebral haematoma, and one infection) in the group operated on before 2005. There was no operative mortality. CONCLUSIONS: The functional state of Parkinson's disease patients with motor disabilities refractory to best medical treatment improved significantly after subthalamic nucleus deep brain stimulation. A dedicated multidisciplinary team building, refined protocol for patient selection and assessment, improvement of targeting methods, meticulous surgical technique, and experience in programming are the key factors contributing to the improved outcome.

A retrospective comparison of cognitive performance in individuals with advanced Parkinson's Disease in Hong Kong and Canada.

A deeper understanding of the cross-cultural applicability of cognitive tests across countries and cultures is needed to better equip neuropsychologists for the assessment of patients from diverse backgrounds. Our study compared cognitive test scores in patients with advanced Parkinson's disease (PD) at the Prince of Wales Hospital (n = 63; Hong Kong) and the Foothills Medical Center (n = 20; Calgary, Canada). The groups did not differ in age or sex (p > .05), but Western patients had significantly more years of education (M = 14.2, SD = 2.7) than Asian patients (M = 10.33, SD = 4.4). Cognitive tests administered to both groups included: digit span, verbal fluency (animals), the Boston Naming Test, and verbal memory (California Verbal Learning Test or Chinese Auditory Verbal Learning Test). Testing was completed before and 12 months after deep brain stimulation surgery. Results showed cognitive performance was similar across time, but significant group differences were found on digit span forward (longer among patients from Hong Kong; F(1, 75) = 44.155, p < .001) and the Boston Naming Test (higher percent spontaneous correct among patients from Canada; F(1, 62) = 7.218, p = .009, η2 = 0.104), after controlling for age, sex, and years of education. In conclusion, our findings provide preliminary support for the similarity of Chinese versions of tests originally developed for Western populations. Also, we caution that some aspects of testing may be susceptible to cultural bias and therefore warrant attention in clinical practice and refinement in future test development for Asian patients.

Feasibility of a ballet-inspired low-impact at-home workout programme for adults with stroke: a mixed-methods exploratory study protocol.

INTRODUCTION: Balancing problems are prominent in stroke survivors with unilateral paresis. Recent evidence supports that dance interventions are associated with significant improvements in gait, stability and walking endurance in people with neurological conditions. The aim of this study is to explore the feasibility of a novel ballet-inspired at-home workout programme (Footprints to Better Balance (FBB)) for stroke survivors. METHODS AND ANALYSIS: A mixed-methods exploratory study incorporating a randomised controlled trial and qualitative evaluation will be conducted. We will recruit 40 adults with a first-ever ischaemic or haemorrhagic stroke and mild-moderate lower limb paresis from two acute stroke units. The intervention group will receive usual care plus FBB, an 8-week home-based programme with ballet-inspired workouts underpinned by Bandura's principles of self-efficacy and outcome expectation. FBB will be delivered by trained lay and peer volunteers, with the support of volunteer healthcare professionals. Multiple data will be collected: Recruitment rate, adherence to FBB, semi-structured interviews and questionnaires on outcomes (balance, gait and memory) assessed at baseline and immediately post-intervention. The generalised estimating equations model will be used to compare differential changes on outcomes across time points between the two arms. Qualitative data will be coded and grouped to form themes and subthemes. ETHICS AND DISSEMINATION: Ethical approval from the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee has been obtained. All eligible participants will provide written informed consent. Study results will be disseminated via publications in peer-reviewed journals and presentations at international conferences. TRIAL REGISTRATION NUMBER: NCT04460794.

Spatiotemporal Mapping of Early Volume Loss in the Mouse Brain after Cranial Irradiation.

Sequelae after pediatric cranial radiotherapy (CRT) result in long-term changes in brain structure. While past evidence indicates regional differences in brain volume change, it remains unclear how these manifest in the time course of change after CRT. In this study, we spatiotemporally characterized volume losses induced by cranial irradiation in a mouse model, with a dense sampling of measurements over the first week postirradiation. Wild-type mice received whole-brain irradiation (7 Gy) or sham irradiation (0 Gy) at 16 days of age. In vivo magnetic resonance imaging was performed at one time point before, and 2-4 time points postirradiation in each mouse, with a particular focus on sampling during the first week after cranial irradiation. Volume changes across the brain were measured, and the degree and timing of volume loss were quantified across structures from a predefined atlas. Volume measurements across the brain after cranial irradiation revealed a ∼2-day delay in which volume is not significantly altered, after which time volume change proceeds over the course of four days. Volume losses were 3% larger and emerged 40% slower in white matter than in gray matter. Large volume loss was also observed in the ventricles. Differences in the timing and magnitude of volume change between gray and white matter after cranial irradiation were observed. These results suggest differences in the mechanism and/or kinetics underlying the associated radio-response, which may have implications in development.

PHAIR: a biosensor for pH measurement in air-liquid interface cell culture.

In many biological systems, pH can be used as a parameter to understand and study cell dynamics. However, measuring pH in live cell culture is limited by the sensor ion specificity, proximity to the cell surface, and scalability. Commercially available pH sensors are difficult to integrate into a small-scale cell culture system due to their size and are not cost-effective for disposable use. We made PHAIR-a new pH sensor that uses a micro-wire format to measure pH in vitro human airway cell culture. Tungsten micro-wires were used as the working electrodes, and silver micro-wires with a silver/silver chloride coating were used as a pseudo reference electrode. pH sensitivity, in a wide and narrow range, and stability of these sensors were tested in common standard buffer solutions as well as in culture media of human airway epithelial cells grown at the air-liquid interface in a 24 well cell culture plate. When measuring the pH of cells grown under basal and challenge conditions using PHAIR, cell viability and cytokine responses were not affected. Our results confirm that micro-wire-based sensors have the capacity for miniaturization and detection of diverse ions while maintaining sensitivity. This suggests the broad application of PHAIR in various biological experimental settings.

Prolonged visual fixation as a surrogate marker of cholinergic deficit in Parkinson's disease: A 2-year follow-up study.

INTRODUCTION: The search for biomarkers of cognitive impairment in Parkinson's disease is driven by the potential clinical applications in disease prognostication. Various eye tracking studies on cognitive functions in Parkinson's disease suggest a promising role of eye movement parameters as a biomarker for cognitive decline but the clinical utility has not been validated in longitudinal studies. The present study aims to investigate the longitudinal progression of eye fixation duration in a visual search task and its correlation with domain-specific cognitive impairment. METHOD: This is a 2-year follow-up study on a group of non-demented Parkinson's disease patients, with baseline eye movement metrics and multi-domain cognitive functions measured, to assess the association between domain-specific cognitive impairment and progression of visual fixation duration. RESULTS: A total of 49 from the original 62 non-demented Parkinson's disease patients were re-examined at a 2-year follow-up. 15 cases (31%) were classified as having mild cognitive impairment. Visual fixation duration was significantly prolonged after 2 years. Using repeated measures ANOVA, impairment in semantic verbal fluency, visual and verbal recognition memory and orienting function of attention had a significant effect on prolonging visual fixation over time. CONCLUSION: Correlation between prolonged visual fixation and multiple domains of cognitive impairment related to cholinergic dysfunction in repeated measures over two years provides preliminary evidence for the eye tracking paradigm as a surrogate marker for cholinergic deficit in Parkinson's disease. The clinical utility in terms of disease prognostication is yet to be confirmed in prospective longitudinal studies with longer follow-up periods.

Special care units for dementia individuals with behavioural problems.

BACKGROUND: The behavioural problems of people with dementia are often considered as one of the most challenging issues in caring. Special Care Units (SCUs) have flourished since the 1980s with the aim of taking care of dementia patients, usually those with Alzheimer's disease, and in particular for those with behavioural problems. Although lacking a standard definition, SCUs are usually situated within nursing homes and commonly include the features of trained staffing, special programming, a modified physical environment, and family involvement. The costs of SCUs are commonly higher than for 'standard' nursing home care. However, evaluat ions of the outcomes of SCUs have yielded conflicting results. A systematic review of this evidence is therefore warranted . OBJECTIVES: To evaluate the effect of SCUs on behavioural problems, mood, use of restraints and psychotropic medication in patients with dementia. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO and CINAHL on 6 September 2007 using the search terms: Special Care Units or SCUs. The CDCIG Specialized Register contains records from major healthcare databases including MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL, and LILACS as well as many ongoing trial databases and grey literature sources. SELECTION CRITERIA: All randomized controlled trials (RCTs) in which the outcomes of SCUs were compared against traditional nursing units (nursing homes, skilled nursing facilities) were included. DATA COLLECTION AND ANALYSIS: Two reviewing authors independently read the full reports of the potentially eligible studies and selected those that met the inclusion criteria. Discrepancies were resolved by discussions among the two reviewing authors. Final consensus was reached with input from a third member of the team when necessary. MAIN RESULTS: No RCTs meeting the selection criteria were identified. Since it is unlikely, for ethical and practical reasons that an RCT of SCUs will be conducted, a systematic review of non-RCTs using the same protocol and criteria was conducted. There were eight non-RCTs that fulfilled the criteria for inclusion. Only four studies had data which could be extracted for pooling in meta-analysis. Differences between comparator groups in these nonRCTs ? for example in severity of dementia - w ere not adequately adjusted for and were common in the trial which accounted for almost all of the positive outcomes of SCUs (Nobili, 2006)All of the results of the outcomes came only from single studies except for "physical restraint use" at 6 months, which included data from two studies. A small improvement in total Neuropsychiatric Inventory scores, favouring SCU was noted in one study at 6, 12 and 18 months. The use of physical restraints was less common in SCUs at 6 and 12 months (OR= 0.46 (95% CI 0.27 to 0.80), p=0.006; and OR=0.49 (0.27 to 0.88), p=0.02 respectively). Patients in SCUs were less depressed at 3 months than those in traditional nursing home (WMD -6.30 (-7.88 to -4.72) Cornell points, p<0.00001). There was only one observation that favoured the control group: a small but significant effect favouring traditional nursing home care was observed at 6 months in the mean number of psychotropic medications used (WMD 0.20, CI 0.00 to 0.40, z=1.96, P=0.05). AUTHORS' CONCLUSIONS: There are no identified RCTs investigating the effects of SCUs on behavioural symptoms in dementia, and no strong evidence of benefit from the available non-RCTs. It is probably more important to implement best practice than to provide a specialized care environment. The routine collection of data on behaviour, restraint and psychotropic drug use across multiple nursing home settings offers the best modality for formal evaluation of the benefit or otherwise of SCUs.

Effectiveness and cost-effectiveness of a virtual multidisciplinary stroke care clinic for community-dwelling stroke survivors and caregivers: a randomised controlled trial protocol.

INTRODUCTION: The virtual multidisciplinary stroke care clinic (VMSCC) is the first nurse-led clinic developed to offer support to community-dwelling stroke survivors and caregivers, and to promote poststroke recovery. This two-arm randomised controlled trial will evaluate its effectiveness on survivors' self-efficacy (SE), survivors' and caregivers' health-related quality of life (HRQoL) and cost-effectiveness on emergency admissions and length of readmission hospital stay. METHODS AND ANALYSIS: A consecutive sample of 384 stroke survivor-caregiver dyads will be recruited from four hospitals. An online platform that embraces readily accessible and reliable information will be developed. Participants randomly assigned to the intervention group will receive usual care plus the VMSCC service. The service includes access to a tablet containing 30 videos demonstrating appropriate self-care strategies, communication with a registered nurse monthly through video and telephone calls and regular blood pressure monitoring. Primary outcomes include survivors' SE in self-management and survivors' and caregivers' HRQoL. Secondary outcomes include survivors' performance of self-management behaviours, depression and social participation; and caregivers' coping strategies, satisfaction with caring and depression. Data will be collected at baseline, and at 3 and 6 months after commencing the intervention. Survivors' and caregivers' satisfaction with the service will be assessed at 6-month follow-up. Multivariable regressions and generalised estimating equations model will be conducted. Survivors' emergency admissions and length of hospital stay will be evaluated during the 6-month follow-up period. Cost-effectiveness analysis will be performed on the average total cost incurred. DISCUSSION: The results will inform stakeholders about incorporating the VMSCC service into current stroke rehabilitation service. ETHICS AND DISSEMINATION: This protocol was approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No.: 2017.660). All participants will provide written informed consent. Results will be disseminated through scientific publications, and presentations at local and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR1800016101; Pre-results.

Eye movement parameters and cognitive functions in Parkinson's disease patients without dementia.

BACKGROUND: Cognitive deficits and eye movement abnormalities have been demonstrated to be detectable early clinical manifestations of Parkinson's disease. Understanding the relationship between these phenotypes may yield insight into the underlying anatomical pathways, assisting in the search for simple non-invasive markers of early neurodegeneration. OBJECTIVE: To explore the correlations between eye movement parameters with multi-domain cognitive functions in patients suffering from Parkinson's disease without dementia. METHOD: This is a cross-sectional case-control study of Parkinson's disease patients without dementia. Participants underwent global and domain-specific cognitive tests and an eye-tracking visual search task to characterize eye movement parameters. RESULTS: 62 Chinese Parkinson's disease patients without dementia and 62 sex-, age- and education-matched controls were recruited. The disease group performed worse in multiple cognitive tasks and exhibited a smaller saccadic amplitude. Negative correlations between the eye fixation duration and performance in semantic verbal fluency, verbal and visual recognition memory tasks were observed, though there was no moderation effect on the correlations due to the presence of Parkinson's disease. A common cholinergic deficit in the temporal and parietal regions may account for the observed correlations. The lack of association with predominantly frontal-executive tasks may suggest specificity of these correlations. CONCLUSION: Prolonged visual fixation duration is correlated with poorer performance in semantic verbal fluency, verbal and visual recognition memory tasks in Parkinson's disease patients without dementia, although these correlations are not specific. The clinical utility of eye movement parameters as an early marker for cognitive decline in Parkinson's disease warrants further exploration in longitudinal studies.

Low-molecular-weight heparin compared with aspirin for the treatment of acute ischaemic stroke in Asian patients with large artery occlusive disease: a randomised study.

BACKGROUND: Acute stroke patients with large artery occlusive disease (LAOD) have a distinct pathophysiology and may respond differently to anticoagulation treatments. We compared the efficacy of a low-molecular-weight heparin (LMWH), nadroparin calcium, with aspirin in Asian acute stroke patients with LAOD. METHODS: Acute ischaemic stroke patients with onset of symptoms less than 48 h and LAOD (diagnosed by transcranial doppler imaging, carotid duplex scan, or magnetic resonance angiography) were recruited. Patients were randomly assigned to receive either subcutaneous nadroparin calcium 3800 anti-factor Xa IU/0.4 mL twice daily or oral aspirin 160 mg daily for 10 days, and then all received aspirin 80-300 mg once daily for 6 months. This study is registered at www.strokecenter.org/trials (number 493). FINDINGS: Among 603 patients recruited, 353 (180 LMWH, 173 aspirin) had LAOD (300 had intracranial LAOD only, 42 had both intracranial and extracranial disease, and 11 had extracranial disease only). The proportion of patients with good outcomes at 6 months (Barthel index >or=85) was 73% in the LMWH group and 69% in the aspirin group (absolute risk reduction 4%; 95% CI -5 to 13). Analysis of prespecified secondary outcome measures showed a benefit in outcome for LMWH versus aspirin on the modified Rankin scale dichotomised at 0-1 (odds ratio 1.55, 95% CI 1.02-2.35). Haemorrhagic transformation of infarct and severe adverse events were similar in both groups. Post-hoc analyses of patients without LAOD, and all treated patients, showed similar proportions with a good outcome in aspirin and LMWH groups (78%vs 79% and 73%vs 75%, respectively). INTERPRETATION: Overall, the results do not support a significant benefit of LMWH over aspirin in patients with LAOD. The benefits indicated in most outcome measures warrant further investigation into the use of anticoagulation for acute stroke in patients with large artery atherosclerosis, particularly in intracranial atherosclerosis.

Prevalence of neutralising antibodies to interferon-beta and clinical response in Chinese patients with relapsing multiple sclerosis.

BACKGROUND: There are no data on neutralising antibodies to interferon-beta and its clinical implications in Chinese patients with multiple sclerosis (MS). OBJECTIVES: The objectives of this study were to investigate the prevalence of neutralising antibodies among Chinese patients with relapsing MS receiving interferon-beta (1a or 1b) and to study the association between neutralising antibodies and the clinical-radiological response. METHODS: We performed a cross-sectional study on MS patients who received interferon-beta for 9 months or more, and evaluated the clinical response by relapses and magnetic resonance imaging lesions. Blood samples were evaluated for myxovirus resistance protein A (MxA) gene expression by polymerase chain reaction, anti-interferon-beta binding antibodies by enzyme-linked immunosorbent assay, and neutralising antibodies by cell-based MxA protein induction and luciferase reporter gene assays. Assay performances were evaluated by receiver operating characteristic analysis. RESULTS: Among 78 subjects recruited, 61/77 (79%) had anti-interferon-beta binding antibodies, and 22/78 (28%) had neutralising antibodies by MxA protein induction assay. The presence of high-titre neutralising antibodies was associated with poor clinical outcome (odds ratio 6.1, 95% confidence interval 1.5-25.6, P = 0.013). The sensitivity and specificity for neutralising antibodies using MxA gene expression assay (cut-off 0.20) was 80% and 68%, respectively (area under the curve 0.71). CONCLUSIONS: Neutralising antibodies are associated with poor clinical outcome in Chinese patients with relapsing MS. MxA gene expression and protein induction assays are complimentary assays for neutralising antibody detection.

Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease in Hong Kong: A Prospective Territory-Wide 2-Year Follow-Up Study.

OBJECTIVE: We assessed the effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease at the 1-year and 2-year follow-up evaluations. Unified Parkinson's Disease Rating Scale (UPDRS) motor score at "off" medication ("on" DBS) and quality-of-life assessments (39-item Parkinson's Disease Questionnaire [PDQ-39]) were conducted. The percentage of awake "on" time and awake "off" time and levodopa requirement were also assessed. METHODS: A 2-year prospective study was conducted of 25 consecutive patients from 3 DBS referral centers in Hong Kong. The patients were treated with bilateral stimulation of the STN. Assessments were performed at 1 year and 2 years after DBS and were compared with the baseline. RESULTS: The 2-year outcome assessments were completed by 18 patients. The mean UPDRS motor score improvement was 57% in the first year and 45% in the second year. PDQ-39 showed significant improvement in quality of life for 2 consecutive years. The levodopa requirement decreased 63% in the first year and 55.9% in the second year. The awake "on" time was doubled in the first year and sustained in the second year. Awake "off" time was reduced from 28.1% to 5.9% in the first year and returned to 10.6% in the second year. Improvement of UPDRS motor score, reduction in awake "off" time, and decrease of daily levodopa dosage all were main factors correlated with the improvement in PDQ-39 summary index. CONCLUSIONS: The effects of STN DBS in patients with Parkinson disease in Hong Kong were satisfactory. The results showed that reduction in UPDRS motor score, awake "off"-time, and daily levodopa dosage were the major drivers of overall improvement in PDQ-39.

Anti-thyroid drugs-related myopathy: is carbimazole the real culprit?

INTRODUCTION: Anti-thyroid drugs (ATDs)-related myopathy is rarely reported in literature, but once developed, it can cause significant morbidity to patient. CASE PRESENTATION: A 28-year old Chinese female was treated with carbimazole (CMZ) for Graves' disease with hyperthyroidism. Two weeks later, she developed myalgia and proximal muscle weakness. Investigations showed evidence of myopathy. CMZ was stopped and rapid improvement of clinical condition and biochemical parameters ensued. CONCLUSIONS: Rapid decrement of thyroid hormone level is recognized as an important association for anti-thyroid drugs (ATDs)-related myopathy; however, the drug effects on muscle tissue cannot be excluded. Further elucidation of pathophysiology and identification of risk factors are needed. After commencing ATDs, early recognition of this rare condition and close monitoring are the essence of management. Different treatment strategies: dose reduction of ATDs, switching to alternative ATDs, with or without addition of thyroid hormone supplement can be applied depending on clinical situation.

Cost-effectiveness of subthalmic nucleus deep brain stimulation for the treatment of advanced Parkinson disease in Hong Kong: a prospective study.

BACKGROUND: Deep brain stimulation (DBS) is an effective but costly treatment for patients with advanced Parkinson disease (PD). This study examined the cost-effectiveness of DBS in relation to its improved effectiveness to help funding decision makers decide whether the treatment should be adopted. The incremental cost-effective ratio (ICER) per quality-adjusted life year has been benchmarked as being between US$50,000 and US$100,000 by US agencies, whereas it is less than €30,000 per quality-adjusted life year in Europe. OBJECTIVE: To provide cost-effectiveness information of subthalamic nucleus DBS for patients with advanced PD. MATERIALS: Direct medical expenses during the year before the DBS treatment were used to measure the baseline cost. Cost-effectiveness was measured by the ICER for the Unified Parkinson's Disease Rating Scale Part III and the ICER for the EuroQol Group's Health-Related Quality of Life measurement. RESULTS: Thirteen patients with advanced PD were recruited between January 2009 and January 2011. A 1-point improvement in the Unified Parkinson's Disease Rating Scale Part III score was associated with an ICER of US$926 in the first year and US$421 in the second year. A 1-point improvement on the EuroQol Group's Health-Related Quality of Life measurement was associated with an ICER of US$123,110 in the first year and US$62,846 in the second year. CONCLUSION: Cost-effectiveness of subthalamic nucleus DBS for treatment of advanced PD is greater during a 2-year period than 1 year only. These results can be used as a reference for the use of DBS for PD in a region with public health financing.