Mitochondrial diseases in Hong Kong: prevalence, clinical characteristics and genetic landscape.

OBJECTIVE: To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region. METHODS: This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators. RESULTS: A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81-1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%. CONCLUSION: This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry.

Spontaneous Spinal Epidural Hematoma Mimicking Stroke and Its Outcome post Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: Spontaneous spinal epidural hematoma (SSEH) is a rare neurological emergency. Its presentation, depending on location of hematoma, could mimic stroke. While intravenous thrombolysis (IVT) is recommended to commence as early as possible in case of acute ischemic stroke, it is likely that it could be given to SSEH patients. We aimed to examine the prevalence, outcome, and prognosis of such patients. METHODS: We have retrospectively screened all patients given IVT from January 2008 to March 2021 admitted to United Christian Hospital, a tertiary hospital in Hong Kong. We reviewed the final diagnosis of all patients and included cases diagnosed with SSEH. Their clinical and radiological features, treatment, and outcome were analyzed. We further performed a literature review to search for all cases with SSEH given IVT and review their clinical features and outcome. RESULTS: Out of a total of 940 patients over the 12-year span, 2 patients were diagnosed with SSEH, accounting for 0.21% of cases. From our literature search, to date, there are only 10 cases that had been reported from 5 case reports where IVT was given to SSEH patients. Of the 12 cases, all presented with hemiparesis and 9 with pain. Of those with neck pain, 3 with initial computed tomography angiogram done showed SSEH which was missed initially. Eight were treated surgically and 4 conservatively. All recovered with no major disability. CONCLUSIONS: Though a rare disease, awareness toward SSEH presenting as stroke mimic should be raised.

Residual Stroke Risk in Patients with Atrial Fibrillation Treated with Non-Vitamin K Oral Anticoagulants: An 8-Year Retrospective Cohort Study.

BACKGROUND: Use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in non-valvular atrial fibrillation (NVAF) is common and significantly reduces stroke occurrence. Yet little is known about patients who have a stroke despite treatment. OBJECTIVE: The aim of this work was to study the epidemiology of patients with stroke despite being treated with NOACs. METHODS: We identified a cohort of patients with NVAF admitted to the United Christian Hospital for acute ischemic stroke (AIS) or transient ischemic attack (TIA) while on NOACs. The baseline characteristics, type of NOAC, compliance, duration of use, and dosage were reviewed. RESULTS: Of 2,090 patients admitted for AIS/TIA from 2012 to 2019, 143 were on NOACs before the index episode. After excluding patients with non-compliance and incomplete data, 109 patients were included in the analysis; 65.1% were female and 79.8% were never smokers, with a mean age of 78 years. The mean CHA2DS2-VASc score was 5; 83.5% had hypertension, 59.3% had hyperlipidemia, and 30.3% had diabetes mellitus. Overall, 52.9% presented with lacunar syndrome, suggesting an atherosclerotic cause of stroke. However, their risk factor control was unexpectedly good; none had HbA1c >7% and only 23.9% had a low-density lipoprotein cholesterol level higher than 2.6 mmol/L. CONCLUSIONS: Stroke developed in NVAF patients despite being on NOACs, with the majority being female, older, and hypertensive. Surprisingly, in general they had reasonable lipid and diabetic control.

Plaque morphology in acute symptomatic intracranial atherosclerotic disease.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is globally a major ischaemic stroke subtype with high recurrence. Understanding the morphology of symptomatic ICAD plaques, largely unknown by far, may help identify vulnerable lesions prone to relapse. METHODS: We prospectively recruited patients with acute ischaemic stroke or transient ischaemic attack attributed to high-grade ICAD (60%-99% stenosis). Plaque morphological parameters were assessed in three-dimensional rotational angiography, including surface contour, luminal stenosis, plaque length/thickness, upstream shoulder angulation, axial/longitudinal plaque distribution and presence of adjoining branch atheromatous disease (BAD). We compared morphological features of smooth, irregular and ulcerative plaques and correlated them with cerebral ischaemic lesion load downstream in MRI. RESULTS: Among 180 recruited patients (median age=60 years; 63.3% male; median stenosis=75%), plaque contour was smooth (51 (28.3%)), irregular (101 (56.1%)) or ulcerative (28 (15.6%)). Surface ulcers were mostly at proximal (46.4%) and middle one-third (35.7%) of the lesions. Most (84.4%) plaques were eccentric, and half had their maximum thickness over the distal end. Ulcerative lesions were thicker (medians 1.6 vs 1.3 mm; p=0.003), had steeper upstream shoulder angulation (56.2° vs 31.0°; p<0.001) and more adjoining BAD (83.3% vs 57.0%; p=0.033) than non-ulcerative plaques. Ulcerative plaques were significantly associated with coexisting acute and chronic infarcts downstream (35.7% vs 12.5%; adjusted OR 4.29, 95% CI 1.65 to 11.14, p=0.003). Sensitivity analyses in patients with anterior-circulation ICAD lesions showed similar results in the associations between the plaque types and infarct load. CONCLUSIONS: Ulcerative intracranial atherosclerotic plaques were associated with vulnerable morphological features and had a higher cumulative infarct load downstream.

De novo status epilepticus is associated with adverse outcome: An 11-year retrospective study in Hong Kong.

PURPOSE: To identify predictors of poor clinical outcome in patients presenting to the intensive care units with status epilepticus (SE), in particular for patients presenting with de novo status epileptics. METHODS: A retrospective review was performed on patients admitted to the intensive care units with status epilepticus in two hospitals in Hong Kong over an 11-year period from 2003 to 2013. RESULTS: A total of 87 SE cases were analyzed. The mean age of patients was 49.3 years (SD 14.9 years). Eighteen subjects (20.7%) had breakthrough seizure, which was the most common etiology for the status epilepticus episodes. Seventy-eight subjects (89.7%) had convulsive status epilepticus (CSE) and 9 subjects (10.3%) had non-convulsive status epilepticus (NCSE) on presentation. The 30-day mortality rate of all subjects was 18.4%. Non-convulsive status epilepticus was more common in patients with de novo status epilepticus when compared to those with existing history of epilepsy (15.5% Vs. 0%, p=0.03). Patients with de novo status epilepticus were older (52 Vs 43, p=0.009). De novo status epilepticus was associated with longer status duration (median 2.5 days, IQR 5 days), longer ICU stay (median 7.5 days, IQR 9 days) and poorer outcome (OR 4.15, 95% CI 1.53-11.2). CONCLUSIONS: For patients presenting to intensive care units with status epilepticus, those with de novo status epileptics were older and were more likely to develop non-convulsive status epilepticus. De novo status epilepticus was associated with poorer outcome. Continuous EEG monitoring would help identifying NCSE and potentially help improving clinical outcomes.

The role of the Ala746Thr variant in the ATP13A2 gene among Chinese patients with Parkinson's disease.

The association between idiopathic Parkinson's disease (PD) and the ATP13A2 (PARK9) Ala746Thr variant, associated with Kufor-Rakeb syndrome, is controversial. We investigated this association in 69 patients with early onset PD (EOPD; ≦50 years of age), 192 patients with late onset PD (LOPD; >50 years of age), and 180 healthy controls in the Chinese population in Hong Kong. The presence of the Ala746Thr variant in the ATP13A2 locus was examined in all participants. We detected the heterozygous Ala746Thr variant in one healthy control (0.6%), one patient with EOPD (1.4%, p=0.50), and one patient with LOPD (0.5%, p=0.96). We suggest that the ATP13A2 Ala746Thr variant is not a common risk factor for PD in the Chinese population in Hong Kong.

Effects of valproate or lamotrigine monotherapy on the reproductive endocrine and insulin-related metabolic profile in Chinese adults with epilepsy: a prospective randomized study.

Cross-sectional studies have suggested that valproate treatment may be associated with hyperinsulinemia and hyperandrogenism in women. Few prospective data are available. We evaluated the reproductive endocrine and insulin-related metabolic parameters in men and women with untreated epilepsy randomized to valproate (n=44) or lamotrigine (n=37) monotherapy for 12 months. On treatment, there was no significant difference in fasting serum insulin concentrations between the two groups. In women (n=40), there was no significant difference between the two groups in change from baseline in serum total testosterone, dehydroepiandrosterone sulfate, luteinizing hormone, or follicle-stimulating hormone. In men (n=41), follicle-stimulating hormone concentration significantly decreased in patients taking valproate compared with those on lamotrigine as early as 3 months after treatment. Greater attention should be paid to investigate the potential impact of valproate on reproductive function in men.