Tea Consumption Reduces the Incidence of Neurocognitive Disorders: Findings from the Singapore Longitudinal Aging Study.

OBJECTIVES: To examine the relationships between tea consumption habits and incident neurocognitive disorders (NCD) and explore potential effect modification by gender and the apolipoprotein E (APOE) genotype. DESIGN: Population-based longitudinal study. SETTING: The Singapore Longitudinal Aging Study (SLAS). PARTICIPANTS: 957 community-living Chinese elderly who were cognitively intact at baseline. MEASUREMENTS: We collected tea consumption information at baseline from 2003 to 2005 and ascertained incident cases of neurocognitive disorders (NCD) from 2006 to 2010. Odds ratio (OR) of association were calculated in logistic regression models that adjusted for potential confounders. RESULTS: A total of 72 incident NCD cases were identified from the cohort. Tea intake was associated with lower risk of incident NCD, independent of other risk factors. Reduced NCD risk was observed for both green tea (OR=0.43) and black/oolong tea (OR=0.53) and appeared to be influenced by the changing of tea consumption habit at follow-up. Using consistent non-tea consumers as the reference, only consistent tea consumers had reduced risk of NCD (OR=0.39). Stratified analyses indicated that tea consumption was associated with reduced risk of NCD among females (OR=0.32) and APOE ε4 carriers (OR=0.14) but not males and non APOE ε4 carriers. CONCLUSION: Regular tea consumption was associated with lower risk of neurocognitive disorders among Chinese elderly. Gender and genetic factors could possibly modulate this association.

Ten year survival and outcomes in a prospective cohort of new onset Chinese Parkinson's disease patients.

OBJECTIVE: The 10 year outcomes and impact of motor and non-motor features on survival of a cohort of new onset Chinese Parkinson's disease (PD) patients were prospectively studied. METHOD: A cohort of new onset PD patients from 1995 to 2002 was recruited from a regional hospital based movement disorder clinic. Subjects were classified into postural instability gait disorder (PIGD), tremor predominant type or mixed subtypes at presentation. All were evaluated yearly for development of sensory complaints, first significant fall, hallucinations, dementia, postural hypotension, speech disturbances, dysphagia and postural instability persisted during 'on' medication state (PIPon). Mortality and predictors of death were determined. RESULTS: 171 new onset PD patients were recruited. After a mean follow-up of 11.3±2.6 years, 50 (29%) patients died. The standardised mortality ratio was 1.1 (CI 0.8 to 1.5, p=0.34). 83 (49%) developed dementia, 81 (47%) had psychosis and 103 (60%) had sensory complaints. Postural hypotension was found in 58 (34%) patients, 108 (63%) had PIPon, 101 (59%) had falls, 102 (60%) had dysphagia, 148 (87%) had freezing of gait and 117 (68%) had speech disturbances. 46 (27%) were institutionalised whereas 54 (32%) lived independently. Dementia (HR 5.0, 95% CI 2.1 to 13.0), PIPon (HR 2.8, 95% CI 1.2 to 6.8), older onset (HR 1.05, 1 year increase in age, 95% CI 1.0 to 1.1) and PIGD type (HR 2.1, 95% CI 1.2 to 3.7) were independent predictors of death. CONCLUSIONS: 10 years into PD, a significant proportion of patients developed dopa resistant motor and non-motor features. Older onset, PIGD type, PIPon and dementia had a negative impact on survival. Standardised mortality ratio was 1.1.

Validation study of the Chinese Identification Pain Questionnaire for neuropathic pain.

OBJECTIVES: For diagnosing neuropathic pain, a simple 6-item patient-completed identification pain questionnaire has been validated among Caucasians. We aimed to study the validity and reliability of this questionnaire among Hong Kong Chinese patients. DESIGN: Questionnaire survey. SETTING: Two pain clinics and two neurology clinics in Hong Kong. PATIENTS: Patients with either neuropathic pain or nociceptive pain were recruited randomly from the four clinics. The patients completed the questionnaire themselves and the diagnosis of neuropathic pain and nociceptive pain was made by the pain specialists. We determined the optimal cutoff, positive and negative predictive values, sensitivity, specificity, the area under the receiver operating characteristic curve, and test-retest reliability of the translated version. RESULTS: Among the 92 participants, 60 (65%) had neuropathic pain and 32 (35%) had nociceptive pain. At an optimal cutoff score of 3 or higher, the positive predictive value was 87% while the negative predictive value was 55%, and it correctly classified 71% of cases. The specificity and sensitivity were 81% and 65%, respectively. The area under the curve was 0.78 (P<0.001). Test-retest reliability in the 10 randomly selected patients showed a good intraclass correlation of 0.72. CONCLUSION: The Chinese Identification Pain Questionnaire is a valid and reliable scale that may be used as an initial diagnostic tool for neuropathic pain among Hong Kong Chinese patients.

Impulse control disorders in Chinese Parkinson's disease patients: the effect of ergot derived dopamine agonist.

OBJECTIVE: We studied the prevalence and related risk factors of impulse control disorders in Chinese Parkinson's disease patients. METHOD: We screened all non-demented Parkinson's disease patients attending our Parkinson's disease clinic from August 2009 to March 2010. The clinical characteristics of patients with impulse control disorders and those without were compared. RESULTS: Of the 213 PD subjects screened, 15 (7.0%) with impulse control disorders were identified. Fourteen of these subjects were on both a dopamine agonist and Levodopa, and one was on Levodopa alone. Of the fourteen subjects on both a dopamine agonist and Levodopa, eleven were on bromocriptine and Levodopa; 10.5% of the subjects exposed to bromocriptine had impulse control disorder. Upon multivariate analysis, dose of dopamine agonist used, young age at onset of Parkinson's disease and a history of anxiety or depression were independent predictors for developing impulse control disorders. CONCLUSIONS: 7% of our Chinese PD subjects had impulse control disorders. When young Parkinson's disease patients with a history of anxiety or depression are treated with high dose of DA, they are at risk of developing impulse control disorders.

Association of diffusion weighted imaging abnormalities and recurrence in transient global amnesia.

Since the first description of transient global amnesia (TGA) in 1964, its etiology has remained obscure. Reversible diffusion weighted imaging (DWI) hyperintensities in the hippocampus have been found on MRI of some patients with TGA during acute events. The implication of this is not well understood. We identified 47 patients with TGA between November 2004 and November 2009, and enrolled 27 patients with brain MRI within 72 hours of symptom onset for analysis and recorded subsequent relapse or stroke occurrence during follow-up. Nine of the 27 patients had reversible hippocampal punctuate hyperintensities, with complete resolution noted on a second MRI on average 4 months after the initial TGA. Patients with a first relapse (their second TGA attack) had a significantly higher association of DWI hippocampal abnormalities (p=0.03) compared to patients with their first TGA event. None of the 27 patients had a stroke or further relapse during the mean follow-up period of 32.6 months. Thus, patients with recurrent TGA have a significantly higher association of reversible DWI abnormality.

Production and validation of Putonghua- and Cantonese-Chinese language National Institutes of Health Stroke Scale training and certification videos.

BACKGROUND AND PURPOSES: The National Institutes of Health Stroke Scale (NIHSS) is an integral part of acute stroke assessment. We report our experience with new Putonghua- and Cantonese-Chinese language NIHSS (PC-NIHSS and CC-NIHSS) training and certification videos. METHODS: A professional video production company was hired to create the training and certification videos for both PC-NIHSS and CC-NIHSS. Two training and certification workshops were held in Chengdu and Beijing, and two workshops in Hong Kong. The instruction, training and group A certification videos were presented to workshop attendees. Unweighted kappa statistics were used to measure the agreement among raters, and the inter-rater agreements for PC-NIHSS and CC-NIHSS videos were compared with those of original English language NIHSS (E-NIHSS) videos. RESULTS: The pass rates using PC-NIHSS and CC-NIHSS videos were 79% and 82%, respectively. All possible responses on individual scale items were included. Facial palsy and limb ataxia (13%) showed poor agreement, nine (60%) to 10 (67%) items showed moderate agreement (0.4

Star fruit intoxication successfully treated by charcoal haemoperfusion and intensive haemofiltration.

We report on a case of an elderly woman with chronic renal impairment, secondary to diabetic nephropathy, who developed a deep coma and seizure shortly after consumption of star fruit. She was managed in the intensive care unit, and her consciousness level improved dramatically after an 8-hour charcoal haemoperfusion and 30 hours of continuous haemofiltration. There were no long-term neurological or renal sequelae 9 months later. Early recognition of this condition, intensive dialytic therapy and supportive measures, as well as early initiation of charcoal haemoperfusion may improve the management of this potentially treatable condition.

Using the National Institutes of Health Stroke Scale (NIHSS) to predict the mortality and outcome of patients with intracerebral haemorrhage.

OBJECTIVES: To investigate whether the National Institutes of Health Stroke Scale (NIHSS) can be used to predict mortality and functional outcome in patients presenting with intracerebral haemorrhage. DESIGN: Retrospective study of a prospectively collected cohort. SETTING: Regional hospital, Hong Kong. PATIENTS: A cohort of 359 patients presented to our hospital from 1996 to 2001 with their first-ever stroke and intracerebral haemorrhage. MAIN OUTCOME MEASURES: The sensitivity and specificity of the NIHSS with a cut-off point of 20 in predicting mortality at 30 days and 5 years, and a favourable functional outcome at 5 years. RESULTS: A total of 359 patients were available for analysis and were divided into three subgroups according to the site and the size of the haematoma. The NIHSS can predict 30-day mortality with a sensitivity of 81% [corrected] and a specificity of 90% [corrected] The NIHSS can predict 5-year mortality with a sensitivity of 57% [corrected] and a specificity of 92% [corrected] In predicting favourable functional outcomes at 5 years, the NIHSS had a sensitivity of 98% [corrected] and a specificity of 16% [corrected] CONCLUSIONS: The NIHSS performed on admission can be used to predict mortality at 30 days and 5 years as well as favourable functional outcome at 5 years, all with an acceptable sensitivity and specificity.

Outcomes after first-ever stroke.

OBJECTIVES: To determine the outcomes after first-ever stroke, including mortality, dependence, and recurrence. DESIGN: Retrospective study on a prospectively collected cohort. SETTING: Regional hospital, Hong Kong. PATIENTS: A cohort of 755 patients presented to our hospital from 1996 to 1998 with their first-ever stroke. MAIN OUTCOME MEASURES: Mortality and stroke recurrence rate at 30 days, 1 year, and 5 years from the onset of the stroke. Dependence in activity of daily living at 5 years from the onset of stroke. RESULTS: The mortality rate was 15.1% at 30 days, 22.5% at 1 year, and 39.7% at 5 years from the onset of the first-ever stroke. The rate of stroke recurrence was 0.9% at 30 days, 7.0% at 1 year, and 21.2% at 5 years from the onset of first-ever stroke. Among patients presenting with ischaemic strokes, 109 (20.6%) had a recurrence, of which 92 (84%) were ischaemic strokes and 17 (16%) were haemorrhagic. Among patients presenting with intracerebral haemorrhage, 25 (23.1%) had a recurrence, of which 12 (48%) were haemorrhagic strokes and 13 (52%) patients were ischaemic. After 5 years, 11% of the patients were dependent in terms of activity of daily living. CONCLUSIONS: The long-term prognosis after first-ever stroke is poor--5 years after their stroke, 39.7% of patients had died and 10.7% were dependent in terms of activity of daily living; 136 (21%) who survived at least 30 days after the initial stroke, had a recurrence within 5 years.

Genetic and genomic insights into the role of benzoate-catabolic pathway redundancy in Burkholderia xenovorans LB400.

Transcriptomic and proteomic analyses of Burkholderia xenovorans LB400, a potent polychlorinated biphenyl (PCB) degrader, have implicated growth substrate- and phase-dependent expression of three benzoate-catabolizing pathways: a catechol ortho cleavage (ben-cat) pathway and two benzoyl-coenzyme A pathways, encoded by gene clusters on the large chromosome (boxC) and the megaplasmid (boxM). To elucidate the significance of this apparent redundancy, we constructed mutants with deletions of the ben-cat pathway (the DeltabenABCD::kan mutant), the boxC pathway (the DeltaboxABC::kan mutant), and both pathways (the DeltabenABCDDelta boxABC::kan mutant). All three mutants oxidized benzoate in resting-cell assays. However, the DeltabenABCD::kan and DeltabenABCD DeltaboxABC::kan mutants grew at reduced rates on benzoate and displayed increased lag phases. By contrast, growth on succinate, on 4-hydroxybenzoate, and on biphenyl was unaffected. Microarray and proteomic analyses revealed that cells of the DeltabenABCD::kan mutant growing on benzoate expressed both box pathways. Overall, these results indicate that all three pathways catabolize benzoate. Deletion of benABCD abolished the ability of LB400 to grow using 3-chlorobenzoate. None of the benzoate pathways could degrade 2- or 4-chlorobenzoate, indicating that the pathway redundancy does not directly contribute to LB400's PCB-degrading capacities. Finally, an extensive sigmaE-regulated oxidative stress response not present in wild-type LB400 grown on benzoate was detected in these deletion mutants, supporting our earlier suggestion that the box pathways are preferentially active under reduced oxygen tension. Our data further substantiate the expansive network of tightly interconnected and complexly regulated aromatic degradation pathways in LB400.

Growth substrate- and phase-specific expression of biphenyl, benzoate, and C1 metabolic pathways in Burkholderia xenovorans LB400.

Recent microarray experiments suggested that Burkholderia xenovorans LB400, a potent polychlorinated biphenyl (PCB)-degrading bacterium, utilizes up to three apparently redundant benzoate pathways and a C(1) metabolic pathway during biphenyl and benzoate metabolism. To better characterize the roles of these pathways, we performed quantitative proteome profiling of cells grown on succinate, benzoate, or biphenyl and harvested during either mid-logarithmic growth or the transition between the logarithmic and stationary growth phases. The Bph enzymes, catabolizing biphenyl, were approximately 16-fold more abundant in biphenyl- versus succinate-grown cells. Moreover, the upper and lower bph pathways were independently regulated. Expression of each benzoate pathway depended on growth substrate and phase. Proteins specifying catabolism via benzoate dihydroxylation and catechol ortho-cleavage (ben-cat pathway) were approximately an order of magnitude more abundant in benzoate- versus biphenyl-grown cells at the same growth phase. The chromosomal copy of the benzoyl-coenzyme A (CoA) (box(C)) pathway was also expressed during growth on biphenyl: Box(C) proteins were approximately twice as abundant as Ben and Cat proteins under these conditions. By contrast, proteins of the megaplasmid copy of the benzoyl-CoA (box(M)) pathway were only detected in transition-phase benzoate-grown cells. Other proteins detected at increased levels in benzoate- and biphenyl-grown cells included general stress response proteins potentially induced by reactive oxygen species formed during aerobic aromatic catabolism. Finally, C(1) metabolic enzymes were present in biphenyl-grown cells during transition phase. This study provides insights into the physiological roles and integration of apparently redundant catabolic pathways in large-genome bacteria and establishes a basis for investigating the PCB-degrading abilities of this strain.

An epidemiological study of motor neuron disease in Hong Kong.

Worldwide, the incidence of motor neuron disease (MND) has been increasing steadily over recent decades. We reported a follow-up epidemiology study of MND in this locality. We identified the subjects from the computer database of the government hospital system between 1 January 1997 and 31 January 2002 by searching the ICD code starting from 335.xx. Every retrieved case or their records were reviewed and validated by neurologist(s) of the responsible regional hospitals which the patients attended. One hundred and twenty cases from seven regional hospitals (serving 48.05% of the HKSAR population) were identified, validated and confirmed to be MND or related diseases. Ninety-eight new cases were diagnosed during the study period. Average age of onset was 58.76 years; SD 14.12 (28-89) years. Male to female ratio was 1.72:1. Peak age of onset was 60-64 years without sex difference. The adjusted incidence rate was 0.60/100,000/year. The adjusted point prevalence at the prevalence date (31 January 2001) was 3.04/100,000. Despite the incidence and prevalence of MND among Hong Kong Chinese, it remained low compared to worldwide figures, and our data suggested a significant rise of MND or related disease in the last decade. A territory-wide prospective epidemiological study is indicated.

Bath-related headache.

Bath-related headache (BRH) is a rare primary headache syndrome. We present our experience over seven years and review all reported cases of BRH. Thirteen patients, including six from our group, are described. BRH occurred exclusively in middle-aged or elderly Oriental women (mean age 51 years, range 32-67. Hong Kong 6 cases, Taiwan 4 cases, Japan 3 cases). The typical presentation was a uniphasic cluster of severe headache recurrently triggered by bathing or other activities involving contact with water. Each attack lasted 30 min to 30 h. Onset was hyperacute, consistent with that of thunderclap headache. Reversible multisegmental cerebral vasoconstriction was found in two patients. No underlying secondary causes were identified. Response to acute treatment was generally unsatisfactory, but headache could be prevented by avoiding the specific trigger(s). BRH runs a self-limiting course; all patients remitted within three months after onset. Nimodipine may shorten the duration of illness.

Biphenyl and benzoate metabolism in a genomic context: outlining genome-wide metabolic networks in Burkholderia xenovorans LB400.

We designed and successfully implemented the use of in situ-synthesized 45-mer oligonucleotide DNA microarrays (XeoChips) for genome-wide expression profiling of Burkholderia xenovorans LB400, which is among the best aerobic polychlorinated biphenyl degraders known so far. We conducted differential gene expression profiling during exponential growth on succinate, benzoate, and biphenyl as sole carbon sources and investigated the transcriptome of early-stationary-phase cells grown on biphenyl. Based on these experiments, we outlined metabolic pathways and summarized other cellular functions in the organism relevant for biphenyl and benzoate degradation. All genes previously identified as being directly involved in biphenyl degradation were up-regulated when cells were grown on biphenyl compared to expression in succinate-grown cells. For benzoate degradation, however, genes for an aerobic coenzyme A activation pathway were up-regulated in biphenyl-grown cells, while the pathway for benzoate degradation via hydroxylation was up-regulated in benzoate-grown cells. The early-stationary-phase biphenyl-grown cells showed similar expression of biphenyl pathway genes, but a surprising up-regulation of C(1) metabolic pathway genes was observed. The microarray results were validated by quantitative reverse transcription PCR with a subset of genes of interest. The XeoChips showed a chip-to-chip variation of 13.9%, compared to the 21.6% variation for spotted oligonucleotide microarrays, which is less variation than that typically reported for PCR product microarrays.

Clinical features of hereditary spinocerebellar ataxia diagnosed by molecular genetic analysis.

OBJECTIVE: To assess the frequency and clinical features of different types of hereditary spinocerebellar ataxia in Hong Kong. DESIGN: Cross-sectional study using a questionnaire and clinical examination, with the majority of the information retrospectively collected. SETTING: Three regional hospitals, Hong Kong. PARTICIPANTS: All patients with spinocerebellar ataxia that was confirmed by molecular genetic tests between January 2001 and October 2003. MAIN OUTCOME MEASURES: History, latest physical examination results, clinical investigation results, and genetic profiles. RESULTS: A total of 16 Chinese patients had received diagnoses of spinocerebellar ataxia. These patients had spinocerebellar ataxia type 1 (n=3), spinocerebellar ataxia type 3 (Machado-Joseph disease; n=12), and dentatorubro-pallidoluysian atrophy (n=1). The most common manifestation was ataxia (15/16), followed by pyramidal signs (12/16). Other features such as bulbar dysfunction, ophthalmoplegia, neuropathy, and cognitive impairment were present but variable. CONCLUSIONS: The clinical manifestations of different types of spinocerebellar ataxia overlap, and genetic study is necessary to confirm the diagnosis. The frequency of spinocerebellar ataxia type 3 is greater than that of other types among these Chinese patients. The age of onset of this type may correlate inversely with the number of CAG repeats.

Lateral temporal hyperperfusion in postictal psychosis assessed by 99mTc-HMPAO SPECT.

Postictal psychosis is a rare complication of epileptic seizure characterized by reversible psychotic symptoms after flurries of seizure attack. It has been attributed to a phenomenon similar to Todd's paralysis without definitive proof. We studied regional cerebral blood flow (rCBF) of six patients with postictal psychosis by (99m)Tc-HMPAO SPECT scan. Baseline rCBF was compared with the rCBF during postictal psychosis. An asymmetry index (ASI) was calculated as 200 x [(ipsilateral ROI count density - contralateral ROI count density)/(ipsilateral ROI count density + contralateral ROI count density)] %. Significant differences could be found between ASIs during postictal psychosis and interictal state SPECT scan over the lateral temporal neocortex region (P = 0.017). Although hyperperfusion abnormality in SPECT can be found in Todd's paralysis, such findings are more commonly found in cerebral hyperactivity conditions. Taking into account the clinical characteristics of postictal psychosis, namely a preceding lucid interval and crescendo-decrescendo clinical course, these may be an alternative psychopathogenic mechanism for the development of postictal psychosis.

Development of a Rhodococcus recombinant strain for degradation of products from anaerobic dechlorination of PCBs.

The Gram-positive bacterium Rhodococcus sp. strain RHA1, naturally containing the biphenyl pathway, was electroporated with a broad host range plasmid containing the 4-chlorobenzoate (4-CBA) degradation operon (fcb) isolated from Arthrobacter globiformis strain KZT1. The recombinant strain grew in medium containing 4-CBA and 4-chlorobiphenyl (4-CB) as the only source of carbon, with stoichiometric release of chloride and a molar growth yield on 4-CB that suggested utilization of both biphenyl rings. In resting cell assays, similar rates of degradation were observed for wild-type and recombinant strains for the most common eight congeners from the anaerobic dechlorination of Aroclor 1242, but the recombinant strain accumulated lower amounts of chlorinated meta-cleavage products and no 4-CBA. Recombinant cells inoculated at 10(4) cells/g into nonsterile soil amended with 4-CB grew to 6-10(5) cells/g, a density consistent with the 4-CB consumed. 4-CB was removed only in the inoculated soil, and the recombinant strain did not grow in the same soil when it was not amended with 4-CB. The fcb operon remained stable in the recombinant strain reisolated from soil after 60 days. This work provides proof of concept that a Rhodococcus strain constructed to grow on a PCB would grow in nonsterile soil if the appropriate chlorobiphenyl is available.

Cloning, expression, and nucleotide sequence of the Pseudomonas aeruginosa 142 ohb genes coding for oxygenolytic ortho dehalogenation of halobenzoates.

We have cloned and characterized novel oxygenolytic ortho-dehalogenation (ohb) genes from 2-chlorobenzoate (2-CBA)- and 2,4-dichlorobenzoate (2,4-dCBA)-degrading Pseudomonas aeruginosa 142. Among 3,700 Escherichia coli recombinants, two clones, DH5alphaF'(pOD22) and DH5alphaF'(pOD33), converted 2-CBA to catechol and 2,4-dCBA and 2,5-dCBA to 4-chlorocatechol. A subclone of pOD33, plasmid pE43, containing the 3,687-bp minimized ohb DNA region conferred to P. putida PB2440 the ability to grow on 2-CBA as a sole carbon source. Strain PB2440(pE43) also oxidized but did not grow on 2,4-dCBA, 2,5-dCBA, or 2,6-dCBA. Terminal oxidoreductase ISPOHB structural genes ohbA and ohbB, which encode polypeptides with molecular masses of 20,253 Da (beta-ISP) and 48,243 Da (alpha-ISP), respectively, were identified; these proteins are in accord with the 22- and 48-kDa (as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) polypeptides synthesized in E. coli and P. aeruginosa parental strain 142. The ortho-halobenzoate 1,2-dioxygenase activity was manifested in the absence of ferredoxin and reductase genes, suggesting that the ISPOHB utilized electron transfer components provided by the heterologous hosts. ISPOHB formed a new phylogenetic cluster that includes aromatic oxygenases featuring atypical structural-functional organization and is distant from the other members of the family of primary aromatic oxygenases. A putative IclR-type regulatory gene (ohbR) was located upstream of the ohbAB genes. An open reading frame (ohbC) of unknown function that overlaps lengthwise with ohbB but is transcribed in the opposite direction was found. The ohbC gene codes for a 48,969-Da polypeptide, in accord with the 49-kDa protein detected in E. coli. The ohb genes are flanked by an IS1396-like sequence containing a putative gene for a 39,715-Da transposase A (tnpA) at positions 4731 to 5747 and a putative gene for a 45,247-Da DNA topoisomerase I/III (top) at positions 346 to 1563. The ohb DNA region is bordered by 14-bp imperfect inverted repeats at positions 56 to 69 and 5984 to 5997.