Clinical and pathological characterization of FLNC-related myofibrillar myopathy caused by founder variant c.8129G>A in Hong Kong Chinese.

FLNC-related myofibrillar myopathy could manifest as autosomal dominant late-onset slowly progressive proximal muscle weakness; involvements of cardiac and/or respiratory functions are common. We describe 34 patients in nine families of FLNC-related myofibrillar myopathy in Hong Kong ethnic Chinese diagnosed over the last 12 years, in whom the same pathogenic variant c.8129G>A (p.Trp2710*) was detected. Twenty-six patients were symptomatic when diagnosed; four patients died of pneumonia and/or respiratory failure. Abnormal amorphous material or granulofilamentous masses were detected in half of the cases, with mitochondrial abnormalities noted in two-thirds. We also show by haplotype analysis the founder effect associated with this Hong Kong variant, which might have occurred 42 to 71 generations ago or around Tang and Song dynasties, and underlain a higher incidence of myofibrillar myopathy among Hong Kong Chinese. The late-onset nature and slowly progressive course of the highly penetrant condition could have significant impact on the family members, and an early diagnosis could benefit the whole family. Considering another neighboring founder variant in FLNC in German patients, we advocate development of specific therapies such as chaperone-based or antisense oligonucleotide strategies for this particular type of myopathy.

Clinical manifestation of late onset Pompe disease patients in Hong Kong.

Late onset Pompe disease is a rare inherited metabolic disease with diverse clinical manifestation. However, there is a lack of local data in Hong Kong. We aimed at performing an in-depth review of natural history of all patients in Hong Kong. Eleven patients were diagnosed to have the disease in Hong Kong from 2000 to 2013. All case records were reviewed and face-to-face interviews were conducted to complete a questionnaire regarding the clinical manifestation and diagnosis of the disease. The estimated birth incidence was 1/300,000. The age of diagnosis ranged from 9 to 44 years; all patients were ethnic Chinese. The median ages of first symptoms and first medical attention were 20.5(6-44) and 29(9-44) years respectively. The most common initial complaint was decreased exercise tolerance. Two patients' first complaint was difficulty with getting up from lying position and failure to perform sit up. The mean time from first medical attention to diagnosis was 1.3 years but one patient was diagnosed 8 years later. Half of the patients sought medical attention due to progressive shortness of breath and all of them developed type 2 respiratory failure requiring ventilator support during the first admission. Two patients became chair-bound and seven patients required assisted ventilation. Late onset Pompe disease tends to have an earlier and more aggressive clinical presentation in Chinese and lower birth incidence was found in Hong Kong.

Can botulinum toxin decrease carer burden in long term care residents with upper limb spasticity? A randomized controlled study.

OBJECTIVE: To evaluate whether botulinum toxin can decrease the burden for caregivers of long term care patients with severe upper limb spasticity. METHOD: This was a double-blind placebo-controlled trial with a 24-week follow-up period. SETTING: A 250-bed long term care hospital, the infirmary units of 3 regional hospitals, and 5 care and attention homes. PARTICIPANTS: Participants included 55 long term care patients with significant upper limb spasticity and difficulty in basic upper limb care. INTERVENTIONS: Patients were randomized into 2 groups that received either intramuscular botulinum toxin A or saline. MAIN OUTCOME MEASURES: The primary outcome measure was provided by the carer burden scale. Secondary outcomes included goal attainment scale, measure of spasticity by modified Ashworth score, passive range of movement for shoulder abduction, and elbow extension and finger extension. Pain was assessed using the Pain Assessment in Advanced Dementia Scale. RESULTS: A total of 55 patients (21 men; mean age = 69, SD =18) were recruited. At week 6 post-injection, 18 (60%) of 30 patients in the treatment group versus 2 (8%) of 25 patients in the control group had a significant 4-point reduction of carer burden scale (P < .001). There was also significant improvement in the goal attainment scale, as well as the modified Ashworth score, resting angle, and passive range of movement of the 3 regions (shoulder, elbow, and fingers) in the treatment group which persisted until week 24. There were also fewer spontaneous bone fractures after botulinum toxin injection, although this did not reach statistical significance. No significant difference in Pain Assessment in Advanced Dementia scale was found between the 2 groups. No serious botulinum toxin type A-related adverse effects were reported. CONCLUSION: Long term care patients who were treated for upper limb spasticity with intramuscular injections of botulinum toxin A had a significant decrease in the caregiver burden. The treatment was also associated with improved scores on patient-centered outcome measures.

Young-onset parkinsonism in a Hong Kong Chinese man with adult-onset Hallervorden-Spatz syndrome.

Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of disorders varied in genetic etiologies, clinical presentations, and radiological features. NBIA is an iron homeostasis disorder with progressive iron accumulation in the central nervous systems and is clinically characterized by extrapyramidal movement abnormalities, retinal pigmentary changes, and cognitive impairment. Panthothenate kinase-associated neurodegeneration (Hallervorden-Spatz disease) is the commonest disorder of NBIA with a prevalence of one-three per million. Clinically, it is classified into early-onset childhood, atypical late-onset, and adult-onset type. Adult-onset type is rarer. We report the first case of adult-onset panthothenate kinase-associated neurodegeneration in Hong Kong in a 28-year-old Chinese man who presented with pure young-onset parkinsonism. Magnetic resonance imaging (MRI) of the brain showed the presence of eye-of-the-tiger sign. Two compound heterozygous mutations PANK2 NM_153638.2: c.445G > T; NP_705902.2: p.E149X and PANK2 NM_153638.2: c.1133A > G; NP_705902.2: p.D378G were detected. Parkinsonism per se is a very heterogeneous phenotypic group. In view of the readily available genetic analysis of PANK2, panthothenate kinase-associated neurodegeneration should be considered in adult patients with young-onset parkinsonism with or without the eye-of-the-tiger sign. The exact diagnosis offers a different management approach and genetic counseling. NBIA is likely under- or misdiagnosed in Hong Kong Chinese.

Bickerstaff's brainstem encephalitis complicating Salmonella Paratyphi A infection.

Patients with enteric fever frequently develop neurological complications during their illness. Among them, majority has encephalopathy, but focal deficits or peripheral nervous involvements are occasionally encountered. We describe a young woman who developed a neurological syndrome consistent with Bickerstaff's brainstem encephalitis, with symptoms and signs including convulsion, impaired consciousness, external ophthalmoplegia, ataxia, bulbar palsy and pyramidal signs, following Salmonella Paratyphi A infection. This is the first case report of this syndrome after S. Paratyphi A infection, and it is the second case of Bickerstaff's brainstem encephalitis complicating enteric fever reported in the literature. This case also demonstrated, for the first time, a positive anti-GQ1b IgG response in a patient with Bickerstaff's brainstem encephalitis and related disorders that appear as complications during enteric fever.

The co-occurrence of serologically proven myasthenia gravis and Miller Fisher/Guillain Barré overlap syndrome: a case report.

The co-occurrence of myasthenia gravis (MG) and Guillain Barré syndrome (GBS) is uncommon with a few reported cases in the literature. There is only one reported case of MG and Miller Fisher variant of GBS. We described an 84 year old Chinese woman with underlying seropositive myasthenia gravis (MG) who presented with ophthalmoplegia, areflexia and acute neuromuscular weakness. She was proved to have co-occurrence of MG and GBS/Miller Fisher overlap syndrome with positive anti-GQ1b antibody. The unusual finding in this patient raises an interesting question on their pathogenesis with the possibility that prior activation of the immune system may predispose the development of autoantibodies against other antigens within the same set of muscles.

The clinical course of multiple sclerosis patients in Hong Kong.

BACKGROUND: Multiple sclerosis (MS) has a low prevalence in Hong Kong. OBJECTIVE: To reassess MS prevalence in Hong Kong and to examine associated risk factors for relapsing-remitting type MS patients to reach Kurtzke's Extended Disability Status Scale (EDSS) of 6.0, i.e. when walking aid was needed. DESIGN: Retrospective observational study on MS patients over 11 years. SETTING: Three tertiary hospitals in Hong Kong. RESULTS: A hundred and six patients were recruited. Female to male ratio was 3.2:1 and the prevalence was 4.8 per 100,000. 95 were relapsing-remitting (RR) type. The mean disease duration was 12.7 years (range: 1-45 years) and the duration of follow up was 11.0+/-0.8 (mean+/-SE) years. The initial mean EDSS was 1.59 and the latest mean EDSS was 4.26. 38 (40%) RR type MS patients progressed to EDSS 6.0 after a mean duration of 6.0 years. With Cox regression analysis, patients with older age (>35y) of onset (HR 2.57; 95% CI:1.29-5.11), higher EDSS of 2.0 or more upon presentation (HR 2.19; 95%CI: 1.12-4.26) were associated with progression to EDSS of 6.0, while there was a tendency towards slower disease progression for patients initially presenting with optic symptoms (HR 0.52; 95%CI: 0.23-1.16). The number of relapses and use of interferon could not be shown to have significant effect on disease progression. CONCLUSIONS: The local period prevalence ratio of MS was 4.8 per 100,000. Older age of onset and higher EDSS upon initial presentation were independent predictors for progression to EDSS of 6.0.

Coexisting cerebral infarction in Alzheimer's disease is associated with fast dementia progression: applying the National Institute for Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences Neuroimaging Criteria in Alzheimer's Disease with Concomitant Cerebral Infarction.

OBJECTIVES: To determine whether patients with Alzheimer's disease (AD) and coexisting cerebral infarction (CI) that satisfy the National Institute for Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) neuroimaging criteria for vascular dementia (VaD) progress faster than those who do not satisfy the neuroimaging criteria. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary memory clinic in a tertiary hospital. PARTICIPANTS: One hundred thirty consecutive patients with AD, with or without CI, followed up regularly for more than 1 year. MEASUREMENTS: The patients were classified according to the distribution and severity of CI as defined according to the NINDS-AIREN neuroimaging criteria into those with AD and no CI (AD-N), those with AD and CI not fulfilling neuroimaging criteria (AD-I), and those with AD and CI fulfilling neuroimaging criteria (AD-V), and their differences in dementia progression were tested. The loss of independence, indicated by institution admission or a clinical dementia rating (CDR) score of 3, was defined as the endpoint for a poor outcome. RESULTS: The mean age was 75.8, and 68.5% were women. The initial Mini-Mental State Examination (MMSE) score was 15.3+/-0.4, and the average duration of follow up was 30.4 months. Fifty-four patients had reached study endpoint at the time of analysis. AD-V (hazard ratio (HR)=3.1, 95% confidence interval (CI)=1.2-8.2), use of psychotropic drugs (HR=2.7, 95% CI=1.1-6.4), and initial MMSE score (HR=0.9, 95% CI=0.8-1.0) were independent predictors of poor outcome in the Cox regression model. CONCLUSION: In AD, co-occurrence of CI with distribution and severity as defined in the NINDS-AIREN neuroimaging criteria for VaD is associated with faster dementia progression.

Topiramate for migraine prophylaxis among Chinese population.

We evaluated the efficacy and safety of topiramate for migraine prophylaxis among Chinese patients in a multicenter prospective observational study. We found that topiramate at low doses was effective in preventing migraine headache in Chinese patients and was generally well tolerated. There was no difference in baseline headache frequency or intensity between responders and nonresponders.

Simple clinical tests may predict severe oropharyngeal dysphagia in Parkinson's disease.

OBJECTIVE: To determine if simple screening tests can predict severe oropharyngeal dysphagia in subjects with Parkinson's disease. METHODOLOGY: Forty-five subjects (26 females) of average age 75 (range: 65-94) who were classified as Modified Hoehn and Yahr stages 2 to 5 were enrolled. The presence of oropharyngeal dysphagia was assessed by a symptom questionnaire, 50 ml water swallowing test and videofluroscopic swallowing study. RESULTS: Six of the subjects had severe oropharyngeal dysphagia in videofluroscopic swallowing study. Subsequent multivariate analysis showed that 3 factors could independently predict severe oropharyngeal dysphagia. These included higher Modified Hoehn and Yahr stage (P = 0.042), low Body mass index (P = 0.014), and increased difficulty in keeping food or drink in the mouth (P = 0.047). The regression model had a positive predictive power of 96% (sensitivity: 83.3%, specificity: 97.4%). CONCLUSION: A combination of 3 simple clinical parameters may be useful for screening for severe oropharyngeal dysphagia as shown radiologically in subjects with Parkinson's disease.

The effects of disease severity, use of corticosteroids and social factors on neuropsychiatric complaints in severe acute respiratory syndrome (SARS) patients at acute and convalescent phases.

OBJECTIVE: To evaluate the effects of disease severity, corticosteroids and social factors on neuropsychiatric complaints in severe acute respiratory syndrome (SARS) patients, both during acute and convalescent phases. SUBJECTS AND METHODS: Self-administered mail questionnaires survey to 308 SARS patients after discharging from hospital. Both patients and their families were asked about symptoms related to various neuropsychiatric domains, and the questions covered both acute and convalescent phases. RESULTS: Among the 102 (33%) valid replies, 65% had strong symptoms in convalescent phase as indicated by GHQ28 score >/= 5. In multiple linear regression analysis, use of pulse steroid and total dosages of pulse steroid during hospitalisation were predictive for anxiety-depression, psychosis and behavioural symptoms in acute phase, the effects persisted in convalescent phase. Disease severity had direct correlation with symptoms in all neuropsychiatric domains at acute phase and anxiety-depression and cognition at convalescent phase. Health care workers had more neuropsychiatric complaints in both phases. Severity of symptoms, corticosteroids and social factors explained about half of the variances (R(2) = 52) in anxiety-depression at acute phase and 33% at convalescent phase. CONCLUSION: Severe disease, high dose corticosteroids and being health care workers were independent predictors of neuropsychiatric complaints in both acute and convalescent phases.

Adjustment outcomes in Chinese patients following one-month recovery from severe acute respiratory syndrome in Hong Kong.

This study aimed to examine the short-term adjustment outcomes including distress, self-esteem, and quality of life among Chinese patients after 1-month recovery from severe acute respiratory syndrome (SARS) in Hong Kong and to investigate the predictive abilities of a set of selected variables on the outcomes. At 1-month recovery, 100 SARS survivors (mean age = 37; 66 women) and 184 community subjects completed self-administered questionnaires. In the General Health Questionnaire-28, 61% of the SARS survivors were identified as distressed cases under a conservative cutoff score of 6. Compared with the community sample, SARS survivors had significantly more distress and poor quality of life. Being a healthcare worker, severity of SARS symptoms, steroid dosage, and social support accounted for a portion of variances of different measures. Early psychiatric screening and intervention may be beneficial for the adjustment of SARS survivors after short-term recovery. Future research on the long-term impact of SARS is recommended.

Possible central nervous system infection by SARS coronavirus.

On day 22 of illness, generalized tonic-clonic convulsion developed in a 32-year-old woman with severe acute respiratory syndrome (SARS). Cerebrospinal fluid tested positive for SARS coronavirus (SARS-CoV) by reverse transcriptase-polymerase chain reaction. SARS-CoV may have caused an infection in the central nervous system in this patient.