Th Tsoi

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 Parkinsons 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.

Epileptic seizure after stroke in Chinese patients

Abstract.This was a hospitalbased cohort study aiming at determining the occurrence rate of poststroke seizures and the associated risk factors. From 27 July 1996 to 16 June 1998, the first 1000 consecutive patients in the acute stroke registry were retrospectively reviewed for one year after acute stroke to identify seizure occurrence. The demographic data, seizure onset time, seizure type, drug treatment, response to medication, electroencephalogram findings and cranial computed tomogram findings were collected. Thirty-four patients (3.4%) developed seizure within one year after acute stroke. Univariate analysis revealed that male, age greater than 65 years, total anterior circulation infarction, partial anterior circulation infarction, cortical location and large lesion were significantly associated with post-stroke seizure while multivariate analysis showed that only male (adjusted OR 3.21, p<0.01) and cortical location (adjusted OR 3.83, p<0.05) were significant independent risk factors. Fifty-six percent of early seizures were partial type whereas 72% of late seizures were generalized tonic-clonic type of undetermined onset. Seizures occurred in 3.4% of patients within one year after the onset of stroke. This percentage of seizure occurrence and associated risk factors were similar to other studies. However, intracerebral and subarachnoid haemorrhage were not shown to be risk factors in our study.

Familial Parkinsonism with digenic parkin and PINK1 mutations

To clarify the genetic correlation between parkin and PINK1, we screened for PINK1 mutations in 175 parkinsonism patients with parkin mutations. We detected two sibling pairs and one sporadic patient carrying both parkin and PINK1 mutations. The age at onset of Parkinsonism of patients with the digenic mutations was lower than that of patients with the same parkin mutation alone. In addition, two of three patients carrying both parkin and PINK1 mutations had schizophrenia. These findings indicate that PINK1 mutation might modify parkin mutation‐positive Parkinsonism, and PINK1 mutations might be associated withpsychiatric disorders.

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 I 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 200 1) 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.

The Lowest Effective Intensity of Prophylactic Anticoagulation for Patients with Atrial Fibrillation

Background: Stroke prevention trials in patients with atrial fibrillation (AF) mainly studied the use of warfarin in Caucasians, and the international normalized ratio (INR) was targeted in the range of 2–4. The result may not necessarily be applicable to other ethnic groups. This study aimed to determine the optimal intensity of anticoagulation for stroke prevention in Chinese patients. Methods: We performed a retrospective study on all Chinese patients with AF taking warfarin for stroke prevention in our hospital from January 1, 2000, to June 30, 2002. Patients with a mechanical heart valve were excluded. We systematically studied their indication of using warfarin, duration of therapy and all INR results. Only those patients whose indications of using warfarin were consistent with the ACC/AHA/ESC Executive Summary were included. Thrombo-embolic episodes, sudden death, major bleeding, intracranial haemorrhage and the INR at the time of the event were recorded. The INR range was divided into six categories: <1.5, 1.5–1.9, 2.0–2.5, 2.6–3.0, 3.1–3.5, >3.5. The number of events was recorded for each category, and this formed the numerator. The denominator was the summation of time each patient stayed in each category of INR. The event rate was then calculated for each INR category. Results: 555 patients were included in the analysis, they constituted 893 patient-years. The INR was kept below 2.6 in 84.9% of the time and between 1.5 and 1.9 in 35% of the time. The overall event rate in our patients was 6.0%, of which 3.9% were due to thrombo-embolic events and 2.1% were due to serious bleeding. The overall event rate was lowest in the INR range from 1.5 to 1.9. which is not significantly different from that of INR 2.0–2.5 and 2.6–3.0. The overall event rate was 3.6% in INR 1.5–3.0 which was significantly lower than 15.1% in INR <1.5 and 20.5% in INR >3.0 (p < 0.01). Conclusions: Our retrospective cohort showed that a lower INR range of 1.5–3.0 was safe and effective for stroke prevention in Chinese patients treated in a single hospital.

Cerebral venous thrombosis in Hong Kong.

Cerebral venous thrombosis (CVT) is a ‘relatively uncommon but nonetheless important condition’ [1]. The Chinese are considered less susceptible to venous thrombosis, and CVT in Chinese has not been systemically studied. To date, there is only one abstract reporting a case series from Taiwan [2]. Queen Mary, Ruttonjee and Pamela Youde Nethersole Eastern are the three district hospitals of Hong Kong Island that provide acute services to an urban population of 1.4 million. We reviewed retrospectively 13 consecutive adult patients presenting with CVT over 3 years (October 1995 to September 1998) to explore the clinical relevance of CVT in a Chinese community. Details of the patients are summarized in table 1. Hypercoagulation states were screened for in all cases. Laboratory evidence of type I natural anticoagulant protein deficiency was present in 3 patients. Patient 9 had a persistent thrombocytosis of undetermined cause. Six cases were on oral contraceptive pills (OCP) for various indications. Patient 13 was also taking an unknown herbal preparation for weight reduction. Patients 1 and 8 developed symptoms of CVT 18 and 14 days, respectively, after delivery. Patient 6 was an intravenous narcotic addict with a history of deep venous thrombosis related to selfinjection. She was admitted for septicaemic shock. Meningitis was excluded by lumbar puncture. Patient 11 was on a moderate dose of corticosteroid for suspected bronchiolitis obliterans organizing pneumonia. CT scan demonstrated the cord sign in patients 1 and 9, haemorrhagic infarction in patients 3, 9, 11 and 13, non-haemorrhagic venous infarction in patients 1 and 12, and hydrocephalus in patient 7. Thrombosed dural sinus was confirmed in all patients with MRI.

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 Todds 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 Todds 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.

Effects of Statins on Progression of Subclinical Brain Infarct

Background: Subclinical brain infarct (SBI) is associated with subsequent stroke and cognitive decline. A longitudinal epidemiological study suggests that statins may prevent development of SBI. We investigated the effects of statins upon development of brain infarct by performing a post-hoc analysis of the Regression of Cerebral Artery Stenosis (ROCAS) study. Methods: The ROCAS study is a randomized, double-blind, placebo-controlled study evaluating the effects of simvastatin 20 mg daily upon progression of asymptomatic middle cerebral artery stenosis among stroke-free individuals over 2 years. A total of 227 subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The number of brain infarcts as detected by MRI was recorded at baseline and at the end of the study. The primary outcome measure was the number of new brain infarcts at the end of the study. Results: Among the 227 randomized subjects, 33 (14.5%) had SBI at baseline. At the end of the study, significantly fewer subjects in the active group (n = 1) had new brain infarcts compared with the placebo group (n = 8; p = 0.018). The new brain infarcts of subjects in the active group were subclinical. Among the placebo group, the new brain infarcts of 3 subjects were symptomatic while those of the remaining 5 subjects were subclinical. Among putative variables, multivariate regression analysis showed that only the baseline number of SBIs (OR = 6.27, 95% CI 2.4–16.5) and simvastatin treatment (OR = 0.09, 95% CI 0.01–0.82) independently predicted the development of new brain infarcts. Conclusions: Consistent with findings of the epidemiological study, our study suggests that statins may prevent the development of a new brain infarct.

Single-nucleotide polymorphism of transient axonal glycoprotein-1 and its correlation with clinical features and prognosis in chronic inflammatory demyelinating polyneuropathy

The single‐nucleotide polymorphism (SNP) rs2275697 in the transient axonal glycoprotein‐1 (TAG‐1) gene was reported to be associated with responsiveness to intravenous immunoglobulin (IVIG) treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, it is not known if this SNP is associated with long‐term prognosis. We examined the case records of 32 Chinese CIDP patients. The overall response rate to IVIG, prednisolone, or plasmapheresis was 83%. After 5.4 years, 57% of patients were on maintenance immunotherapy. Patients with higher modified Rankin score and more prolonged distal motor latencies in the upper limbs on presentation had a higher risk (odds ratio [OR] 3.86, 95% confidence interval [CI] 1.23–12.11 and OR 1.04, 95% CI 1.01–1.07, respectively) of being on maintenance immunotherapy. Blood samples from 24 patients and 147 controls were examined for their genotypes of four non‐synonymous SNPs (rs41264871, rs36074532, rs5611135, and rs2275697) in the coding region of TAG‐1. The G allelic frequency of rs2275697 was similar between CIDP patients and controls (56% and 50%, respectively) and was not associated with treatment responsiveness, treatment dependence, disability, or mortality.