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.

Efficacy upon 12-weeks after achievement of maximal dose and tolerability of lacosamide as an adjunctive therapy in epilepsy: Real world clinical experience.

Lacosamide (LCM) is a new generation antiepileptic drug. It has only been available in Asia in recent years. A retrospective study at two hospitals in Hong Kong was performed to investigate the post-marketing efficacy and tolerability of the drug. A total of 81 subjects were recruited, among which 88% had drug-resistant epilepsy. The most common type of epilepsy was focal with unknown etiology. All patients used LCM as adjunctive therapy. The 50% responder rate was 42% at 12 weeks after achievement of maximal dose of LCM. No specific factor correlated with responsiveness including concomitant enzyme-inducing or sodium channel blocking anticonvulsants. Withdrawal rate within first 12 weeks after drug initiation was 14% while that at any time upon follow-up was 23%. Two cases of uncommon adverse reaction of myoclonus were also reported. The mechanism was postulated to be the sodium channel inhibiting action of LCM. Our study has shown LCM to have comparable efficacy and tolerability in post-marketing experience when compared with the landmark randomized controlled trials.

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.