Validity of balance measures in cerebellar ataxia: A prospective study with 12-month follow-up.

INTRODUCTION: Balance deficits are common in cerebellar ataxia. Determining which balance outcome measures are psychometrically strong for this population remains an unmet need. OBJECTIVE: To evaluate the validity and responsiveness of two clinic-based balance measures (Berg Balance Scale [BBS] and balance sub-component of the Scale for the Assessment and Rating of Ataxia [SARA-bal]) and two laboratory-based balance measures (Sensory Organization Test [SOT] and Limits of Stability [LOS]) in cerebellar ataxia. DESIGN: Prospective cohort study. SETTING: Institutional study assessing 40 participants with cerebellar ataxia at baseline, and 6 and 12 months. MAIN OUTCOME MEASURES: Balance was assessed using the BBS, SARA-bal, SOT, and LOS; disease severity was assessed using the SARA; and Patients' Global Impression of Change (PGIC) was used to estimate responsiveness to disease progress at 6 and 12 months. RESULTS: BBS and SARA-bal (Spearman's correlation coefficient, ρS = -0.89, p < .01) demonstrated strong criterion validity. Convergent validity was moderate to high (ρS range: -0.75 to 0.92) and external validity was low (ρS range: -0.75 to 0.11). Composite SOT scores (SOT-COM; ρS = 0.29, p < .01) and maximal excursion (MXE-LOS) in the forward (F) and right (R) directions of the LOS (ρS = 0.18, p < .01) demonstrated moderate to low criterion and convergent validity. The area under the receiver-operating characteristic curve (AUCROC ) and its effect size (standard response mean [SRM]) for categorizing "stable" and "worsened" patients at 6 and 12 months were satisfactory for the BBS (AUCROC : 0.75; SRM-Stable: 1.06; SRM-Worsened: 1.16), SARA-bal (AUCROC : 0.76; SRM-Stable: 0.86; SRM-Worsened: 0.85), and MXE-LOS(R) (AUCROC : 0.29; SRM-Stable: 0.41; SRM-Worsened: 1.39). CONCLUSION: BBS and SARA-bal have moderate to strong criterion and convergent validity and adequate responsiveness to balance changes. Both laboratory-based measures (SOT and LOS) demonstrated a high floor effect. The SOT-COM and MXE-LOS(R) demonstrated moderate to low criterion validity, with only the MXE-LOS(R) displaying adequate responsiveness to balance changes after 6 and 12 months.

Effectiveness and cost of integrated cognitive and balance training for balance and falls in cerebellar ataxia: a blinded two-arm parallel group RCT.

Background: In patients with cerebellar ataxia (CA), dual-tasking deteriorates the performance of one or both tasks. Objective: Evaluate the effects of 4 weeks of cognitive-coupled intensive balance training (CIBT) on dual-task cost, dynamic balance, disease severity, number of falls, quality of life, cognition and cost among patients with CA. Methods: This RCT compared CIBT (Group 1) to single-task training (Group 2) among 32 patients with CA. The intervention included either dual-task (CIBT) or single-task training for 4 weeks followed by 6 months of unsupervised home exercises. Dual-task timed up-and-go test (D-TUG) assessed dual-task cost of the physical and cognitive tasks. Assessment time points included baseline 1 (Week 0:T1), baseline 2 (Week 6:T2), post-intervention (Week 10:T3), and follow-up (Week 34:T4). Results: Compared to single-task training CIBT improved the dual-task cost of physical task [MD -8.36 95% CI (-14.47 to -2.36, p < 0.01), dual-tasking ability [-6.93 (-13.16 to -0.70); p = 0.03] assessed using D-TUG, balance assessed using the scale for the assessment and rating of ataxia (SARAbal) [-2.03 (-4.04 to -0.19); p = 0.04], visual scores of the SOT (SOT-VIS) [-18.53 (-25.81 to -11.24, p ≤ 0.01] and maximal excursion [13.84 (4.65 to 23.03; p ≤ 0.01] of the Limits of Stability (LOS) in the forward direction and reaction time in both forward [-1.11 (-1.42 to -0.78); p < 0.01] and right [-0.18 (0.05 to 0.31); p < 0.01] directions following 4 weeks of training. CIBT did not have any additional benefits in reducing the number of falls, or improving disease severity, quality of life and cognition. The mean cost of intervention and healthcare costs for 7 months was HKD 33,380 for CIBT group and HKD 38,571 for single-task training group. Conclusion: We found some evidence to support the use of CIBT for improving the dual-tasking ability, dual-task cost of physical task and dynamic balance in CA. Future large fully-powered studies are needed to confirm this claim. Clinical trial registration: https://clinicaltrials.gov/study/NCT04648501, identifier [Ref: NCT04648501].

Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease.

OBJECTIVES: The predisposition of intracranial atherosclerotic disease (ICAD) to East Asians over Caucasians infers a genetic basis which, however, remains largely unknown. Higher prevalence of vascular risk factors (VRFs) in Chinese over Caucasian patients who had a stroke, and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD. METHODS: Unrelated symptomatic patients with ICAD were recruited for genome sequencing (GS, 60-fold). Rare and potentially deleterious single-nucleotide variants (SNVs) and small insertions/deletions (InDels) were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes. Rare aneuploidies, copy number variants (CNVs) and chromosomal structural rearrangements were also investigated. Lastly, candidate genes were used for pathway and gene ontology enrichment analysis. RESULTS: Among 92 patients (mean age at stroke onset 61.0±9.3 years), GS identified likely ICAD-associated rare genomic variants in 54.3% (50/92) of patients. Forty-eight patients (52.2%, 48/92) had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes. None of the 59 rare variants were identified in local subjects without ICAD (n=126). 31 SNVs/InDels were related to conventional VRFs, and 28 were discovered in genes related to other stroke subtypes. Our study also showed that rare CNVs (n=7) and structural rearrangement (a balanced translocation) were potentially related to ICAD in 8.7% (8/92) of patients. Lastly, candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process. CONCLUSIONS: Our GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.

Identification of Risk Loci for Parkinson Disease in Asians and Comparison of Risk Between Asians and Europeans: A Genome-Wide Association Study.

Importance: Large-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the largest population worldwide (ie, Asian). Objectives: To identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts. Design Setting, and Participants: Genome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson's Disease Society Brain Bank Criteria. Main Outcomes and Measures: Genotypes of common variants, association with disease status, and polygenic risk scores. Results: Of 31 575 samples identified, 6724 PD cases (mean [SD] age, 64.3 [10] years; age at onset, 58.8 [10.6] years; 3472 [53.2%] men) and 24 851 controls (age, 59.4 [11.4] years; 11 030 [45.0%] men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2C and WBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association for SV2C (rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21; P = 1.17 × 10-10 in meta-analysis of discovery and replication samples) but showed potential genetic heterogeneity at WBSCR17 (rs9638616; I2=67.1%; P = 3.40 × 10-3 for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%; P = 6.81 × 10-12). Conclusions and Relevance: This study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta-genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia.

Does integrated cognitive and balance (dual-task) training improve balance and reduce falls risk in individuals with cerebellar ataxia?

Frequent falls in people with cerebellar ataxia (CA) is a significant problem Therefore, an intervention that could improve balance and reduce the number of falls is of paramount importance from the patients' perspective. Combining cognitive training with physical training to improve balance is a new approach for reducing the risk of falls in patient populations who are at risk for falls. To determine if adding structured cognitive demands to conventional balance and coordination training we designed the Cognitive-coupled Intensive Balance Training (CIBT) program. We found that the more intensive and focused CIBT intervention reduced dual-task cost, improved balance, and reduced the number of falls in a sample of individuals with CA. We hypothesize that (1) CIBT will improve balance and reduce falls; and (2) CIBT will be a cost-effective treatment option for improving balance and reduce falls. To test these hypotheses, we propose conducting a randomized controlled trial (RCT) with economic evaluation . This paper reports the findings of our study testing the feasibility of the CIBT program, rationale for testing our hypothesis and an overview of our future study design to test the effectiveness and cost-effectiveness of the CIBT program.

Evaluation of novel Parkinson's disease candidate genes in the Chinese population.

Recent whole-exome sequencing studies in European patients with Parkinson's disease (PD) have identified potential risk variants across 33 novel PD candidate genes. We aim to determine if these reported candidate genes are similarly implicated in Asians by assessing common, rare, and novel nonsynonymous coding variants by sequencing all 33 genes in 198 Chinese samples and genotyping coding variants in an independent set of 9756 Chinese samples. We carried out further targeted sequencing of CD36 in an additional 576 Chinese and Korean samples. We found that only 8 of 43 reported risk variants were polymorphic in our Chinese samples. We identified several heterozygotes for rare loss-of-function mutations, including the reported CD36 p.Gln74Ter variant, in both cases and controls. We also observed 2 potential compound heterozygotes among PD cases for rare loss-of-function mutations in CD36 and SSPO. The other reported variants were common in East Asians and not associated with PD, completely absent, or only found in controls. Therefore, the 33 reported candidate genes and associated variants are unlikely to confer significant PD risk in the East Asian population.

Can pre-screening vestibulocerebellar involvement followed by targeted training improve the outcomes of balance in cerebellar ataxia?

Balance problems and frequent falls are common among clients with Cerebellar Ataxia (CA). CA is not a disease by itself but a collection of symptoms due to the involvement of cerebellum or its pathways. Presently the treatment for balance problems for CA is not standardized. Interventions available to improve balance are not specific to symptoms presentation. Functionally the cerebellum is divided into the spinocerebellum, vestibulocerebellum and corticocerebellum. Each functional zone has a distinct role in maintaining balance. Therefore, the presentation of symptoms will vary according to the functional zone involved. Pre-screening clients with CA for identifying the part of cerebellum involved will facilitate clinicians to provide tailor-made interventions for targeting specific symptoms for better outcomes. Pre-screening clients with CA according to the part of cerebellum involved is not in practice and our study will introduce this concept. We hypothesize pre-screening participants with spinocerebellar ataxia (SCA) for the involvement vestibulocerebellum followed by prescribing vestibulocerebellum targeted exercises will have better outcomes when compared to conventional balance training. We plan to conduct two related studies. In study 1 we will screen participants with CA for the involvement of vestibulocerebellum. In study 2, the effects of vestibulocerebellum targeted balance exercises on balance will be studied. We will assess the Subjective Visual Vertical (SVV) deviation and postural sway pattern to screen participants into people with and without vestibulocerebellar involvement. SVV deviation will be estimated using a computerized Subjective Visual Vertical (cSVV) device and postural sway pattern will be assessed using the limits of stability program of the Bertec© Balance system. The obtained SVV deviation scores will be used to derive at cut-off scores to discriminate clients with and without vestibulocerebellar involvement. The second study will test the treatment effects of conventional exercises plus vestibulocerebellum targeted exercises to improve balance by correcting SVV deviation in SCA with vestibulocerebellar involvement. The intervention is planned as 12 one-to-one sessions over three months period. Participants will be reassessed after the intervention and 3 months post-intervention. The findings of this cutting-edge research are extremely important to the clinicians, researchers and clients with SCA.

Converting MMSE to MoCA and MoCA 5-minute protocol in an educationally heterogeneous sample with stroke or transient ischemic attack.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA. METHODS: A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment. RESULTS: The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859. CONCLUSION: We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy.

Cross-Cultural Differences of the Non-Motor Symptoms Studied by the Traditional Chinese Version of the International Parkinson and Movement Disorder Society- Unified Parkinson's Disease Rating Scale.

BACKGROUND: Given the importance of ethnic differences in the evaluation of various aspects of symptoms in patients with Parkinson's disease (PD), we present the formal procedure for completing the traditional Chinese translation of the International and Parkinson and Movement Disorder Society/UPDRS (MDS-UPDRS) and highlight the discrepancy in nonmotor symptoms (NMS) between patients in Eastern and Western countries. METHODS: A total of 350 native Chinese-speaking PD patients were recruited from multiple hospitals in Eastern countries; they completed the MDS-UPDRS. The translation process was executed and factor analysis was performed to determine the structure of the scale. Chi-squared and t tests were used to compare frequency and severity of PD symptoms between the Chinese-speaking and English-speaking groups (n = 876). RESULTS: NMS and motor symptoms were more severe in the Western population (Part I: t(1205) = 5.36, P < 0.0001; and Part III: t(1205) = 7.64, P < 0.0001); however, the prevalence of cognitive dysfunction and impairments in activities of daily living were more frequent in the Eastern patients. The comparative fit index was 0.93 or greater, and the exploratory factor analysis revealed compatible results between the translated scale and the original version. CONCLUSION: The traditional Chinese version of the MDS-UPDRS can be designated as an official translation of the original scale, and it is now available for use. Moreover, NMS in PD constitute a major issue worldwide, and the pattern of NMS among the Chinese population is more marked in terms of cognition-based symptoms and activities of daily living.

Neuropsychiatric Symptom Clusters in Stroke and Transient Ischemic Attack by Cognitive Status and Stroke Subtype: Frequency and Relationships with Vascular Lesions, Brain Atrophy and Amyloid.

BACKGROUND: The objectives of this study are 1) to examine the frequencies of neuropsychiatric symptom clusters in patients with stroke or transient ischemic attack (TIA) by cognitive level and stroke subtype; and 2) to evaluate effect of demographic, clinical, and neuroimaging measures of chronic brain changes and amyloid upon neuropsychiatric symptom clusters. METHODS: Hospital-based, cross-sectional study. 518 patients were administered the Neuropsychiatric Inventory (NPI) 3-6 months post index admission. NPI symptoms were classified into four symptom clusters (Behavioral Problems, Psychosis, Mood Disturbance & Euphoria) derived from a confirmatory factor analysis of the 12 NPI items. Multivariable logistic regression was used to determine independent associations between demographic, clinical and neuroimaging measures of chronic brain changes (white matter changes, old infarcts, whole brain atrophy, medial temporal lobe atrophy [MTLA] and frontal lobe atrophy [FLA]) with the presence of NPI symptoms and all symptom clusters except euphoria. 11C-Pittsburg Compound B Positron Emission Tomography (11C-PiB PET) was performed in 24 patients to measure amyloid retention for Alzheimer's Disease (AD) pathology. RESULTS: 50.6% of the whole sample, including 28.7% cognitively normal and 66.7% of patients with mild cognitive symptoms, had ≥1 NPI symptoms. Frequencies of symptom clusters were largely similar between stroke subtypes. Compared to patients with cardioembolic stroke and intracranial haemorrhage, those with TIA had less frequent mood disturbance. Stroke severity at admission and MTLA were the most robust correlates of symptoms. FLA was associated with behavioral problems cluster only. Frequency of symptom clusters did not differ between patients with and without significant amyloid retention. CONCLUSION: Frequency of neuropsychiatric symptoms increased with level of cognitive impairment but was largely similar between stroke subtypes. Stroke severity and MTLA were associated with neuropsychiatric symptoms. AD pathology appeared to be unrelated to neuropsychiatric manifestations but further studies with larger sample size are required to substantiate this finding.

Relations between Recent Past Leisure Activities with Risks of Dementia and Cognitive Functions after Stroke.

BACKGROUND: Leisure activity participation has been shown to lower risks of cognitive decline in non-stroke populations. However, effects of leisure activities participation upon cognitive functions and risk of dementia after stroke are unclear. The purpose of this study is to examine the effects of recent past leisure activities participation upon cognitive functions and risk of incident dementia after stroke. METHODS: Hospital-based, retrospective cohort study. 88 of 1,013 patients with stroke or TIA having no prestroke dementia were diagnosed to have incident poststroke dementia (PSD) 3-6 months after stroke. Regular participation (≥3 times per week) in intellectual, recreational, social and physical activities over the year before the index stroke was retrospectively recorded at 3-6 months after stroke. RESULTS: Logistic regression analyses showed that regular participation in intellectual (RR 0.36, 95%CI 0.20-0.63) and stretching & toning physical exercise (0.37, 0.21-0.64) was significantly associated with a reduced risk of PSD after controlling for age, education, prestroke cognitive decline, stroke subtype, prior strokes and chronic brain changes including white matter changes, old infarcts and global atrophy. Results were similar in patients with past strokes in unadjusted models. Participation in increased number of activities in general (r = 0.41, p<0.01) and in intellectual (r = 0.40, p<0.01), recreational (r = 0.24, p<0.01), strenuous aerobic (r = 0.23, p<0.01) and mind-body (r = 0.10, p<0.01) activities was associated with higher poststroke Mini-mental State Examination scores in models adjusted for prestroke cognitive decline. CONCLUSIONS: Regular participation in intellectual activities and stretching & toning exercise was associated with a significantly reduced short-term risk of PSD in patients with and without recurrent strokes. Participation in greater number of recent past leisure activities was associated with better poststroke cognitive performance. Findings of this retrospective cohort study call for studies of activity intervention for prevention of cognitive decline in individuals at elevated risk of stroke.

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.

Delayed-onset dementia after stroke or transient ischemic attack.

INTRODUCTION: Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. METHODS: Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. RESULTS: Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. DISCUSSION: Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group.

Volumetric magnetic resonance imaging correlates of the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment neuropsychology protocols.

BACKGROUND: Vascular cognitive impairment (VCI) refers to the entire spectrum of cognitive dysfunction attributable to vascular changes in the brain. The objective of this study is to evaluate magnetic resonance imaging (MRI) correlates of performance on the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) VCI neuropsychology protocols. METHOD: Fifty ischemic stroke patients and 50 normal elderly persons completed the VCI protocols and MRI. Relationships between the four cognitive domains (executive/activation, language, visuospatial, and memory) and three protocol (60-, 30-, and 5-min) summary scores with MRI measures of volumes of white matter hyperintensities (WMH) and global brain and hippocampal atrophy were assessed using linear regression. RESULTS: All cognitive domain scores were associated with WMH volume and, with the exception of language domain, with global atrophy. Additional relationships were found between executive/activation and language domains with left hippocampal volume, visuospatial domain with right hippocampal volume, and memory domain with bilateral hippocampal volumes. All protocol summary scores showed comparable relationships with WMH and hippocampal volumes, with additional relationships found between the 60- and 30-min protocols with global brain volume. CONCLUSIONS: Performance on the NINDS-CSN VCI protocols reflects underlying volumetric brain changes implicated in cognitive dysfunctions in VCI.

Montreal Cognitive Assessment 5-minute protocol is a brief, valid, reliable, and feasible cognitive screen for telephone administration.

BACKGROUND AND PURPOSE: The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization working group proposed a brief cognitive protocol for screening of vascular cognitive impairment. We investigated the validity, reliability, and feasibility of the Montreal Cognitive Assessment 5-minute protocol (MoCA 5-minute protocol) administered over the telephone. METHODS: Four items examining attention, verbal learning and memory, executive functions/language, and orientation were extracted from the MoCA to form the MoCA 5-minute protocol. One hundred four patients with stroke or transient ischemic attack, including 53 with normal cognition (Clinical Dementia Rating, 0) and 51 with cognitive impairment (Clinical Dementia Rating, 0.5 or 1), were administered the MoCA in clinic and a month later, the MoCA 5-minute protocol over the telephone. RESULTS: Administration of the MoCA 5-minute protocol took 5 minutes over the telephone. Total score of the MoCA 5-minute protocol correlated negatively with age (r=-0.36; P<0.001) and positively with years of education (r=0.41; P<0.001) but not with sex (ρ=0.03; P=0.773). Total scores of the MoCA and MoCA 5-minute protocol were highly correlated (r=0.87; P<0.001). The MoCA 5-minute protocol performed equally well as the MoCA in differentiating patients with cognitive impairment from those without (areas under receiver operating characteristics curve for MoCA 5-minute protocol, 0.78; MoCA=0.74; P>0.05 for difference; Cohen d for group difference, 0.80-1.13). It differentiated cognitively impaired patients with executive domain impairment from those without (areas under receiver operating characteristics curve, 0.89; P<0.001; Cohen d=1.7 for group difference). Thirty-day test-retest reliability was excellent (intraclass correlation coefficient, 0.89). CONCLUSIONS: The MoCA 5-minute protocol is a free, valid, and reliable cognitive screen for stroke and transient ischemic attack. It is brief and highly feasible for telephone administration.

Evolution of intracranial atherosclerotic disease under modern medical therapy.

OBJECTIVE: Understanding how symptomatic intracranial atherosclerotic disease (ICAD) evolves with current medical therapy may inform secondary stroke prevention. METHODS: In a prospective academic-initiated study, we recruited 50 patients (mean age = 63.4 ± 9.0 years) with acute strokes attributed to high-grade (≥70%) intracranial atherosclerotic stenosis for 3-dimensional rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low-density lipoprotein ≤ 70mg/dl, glycosylated hemoglobin (HbA1c) ≤ 6.5%, and systolic blood pressure ≤ 140 mmHg. We analyzed infarct topography and monitored microembolic signal in recurrent strokes. The reference group was a published cohort of 143 ICAD patients. RESULTS: Overall, the stenoses regressed from 79% at baseline (interquartile range [IQR] = 71-87%) to 63% (IQR = 54-74%) in 1 year (p < 0.001). Specifically, the qualifying lesions (n = 49) regressed (stenosis reduced >10%) in 24 patients (49%), remained quiescent (stenosis same or ±10%) in 21 patients (43%), and progressed (stenosis increased >10%) in 4 patients (8%). There was no difference in intensity of risk factor control between groups of diverging clinical or angiographic outcomes. Higher HbA1c at baseline predicted plaque regression at 1 year (odds ratio = 4.4, 95% confidence interval = 1.4-14.5, p = 0.006). Among the 6 patients with recurrent strokes pertaining to the qualifying stenosis, 5 patients had solitary or rosarylike acute infarcts along the internal or anterior border zones, and 2 patients showed microembolic signals in transcranial Doppler ultrasound. INTERPRETATION: A majority of symptomatic high-grade intracranial plaques had regressed or remained quiescent by 12 months under intensive medical therapy. Artery-to-artery thromboembolism with impaired washout at border zones was a common mechanism in stroke recurrence.

Risk factors for incident dementia after stroke and transient ischemic attack.

BACKGROUND: We hypothesized that chronic brain changes are important substrates for incident dementia after stroke and transient ischemic attack (TIA). METHODS: We compared clinical and imaging features between patients with consecutive stroke/TIA with (n = 88) and without (n = 925) incident dementia at 3 to 6 months after a stroke/TIA. Pittsburg compound B (PiB) positron emission tomography was performed in 50 patients, including those with (n = 37) and without (n = 13) incident dementia. RESULTS: Age, history of diabetes mellitus, severity of white matter changes (WMCs), and medial temporal lobe atrophy (MTLA) were associated with incident dementia. Alzheimer's disease (AD)--like PiB retention was found in 29.7% and 7.7% (P = .032) of patients with and without incident dementia, respectively. CONCLUSIONS: Chronic brain changes including WMCs, MTLA, and AD pathology are associated with incident dementia after stroke/TIA. Interventions targeting these chronic brain changes may reduce burden of vascular cognitive impairment.

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.