Background The association of HTRA1 rs11200638 and ARMS2 rs10490924 gene polymorphisms with response to intravitreal ranibizumab therapy among neovascular AMD (nAMD) subjects in Malaysia was determined in this study, followed by the expression of HTRA1 and ARMS2 genes. Results Both single nucleotide polymorphisms (SNPs) recorded a significant association between nAMD and controls with HTRA1 rs11200638 at P = 0.018 (OR = 1.52, 95% CI = 1.07–215) and ARMS2 rs10490924 at P < 0.001 (OR = 2.44, 95% CI = 1.75–3.42). An association was also observed in response to ranibizumab for both SNPs in a logistic regression analysis ( P < 0.001). The mRNA levels in the HTRA1 variant between responder and non-responder groups were significantly different for the homozygous non-risk GG genotype ( P = 0.032). Conclusions The HTRA1 rs11200638 and ARMS2 rs10490924 gene polymorphisms are associated with nAMD among Malaysians. Both gene polymorphisms were also correlated with response to intravitreal ranibizumab therapy based on visual and anatomical outcomes especially the HTRA1 rs11200638 variant.

Background: As the world witnessed the devastation caused by the coronavirus disease 2019 (COVID-19) outbreak, a growing body of literature on COVID-19 is also becoming increasingly available. Stroke has increasingly been reported as a complication of COVID-19 infection. However, a systematic synthesis of the available data has not been conducted. Therefore, we performed a systematic review and meta-analysis of currently available epidemiological, clinical, and laboratory data related to both stroke and COVID-19 infection. Methods: We systematically searched Medline, Cinahl, and PubMed for studies related to stroke and COVID-19 from inception up to June 4, 2020. We selected cohort studies, case series, and case reports that reported the occurrence of stroke in COVID-19 patients. A fixed-effects model was used to estimate the pooled frequency of stroke in COVID-19 patients with a 95% confidence interval (CI). Results: Twenty-eight studies were included in the systematic review and seven studies for the meta-analysis. The pooled frequency of stroke in COVID-19 patients was 1.1% (95% CI: 0.8, 1.3). The heterogeneity was low ( I 2 = 0.0%). Even though the frequency of stroke among patients having COVID-19 infection was low, those with concomitant COVID-19 infection and stroke suffered from a more severe infection and eventually had a poorer prognosis with a higher mortality rate (46.7%) than COVID-19 alone. Many COVID-19 patients shared the common traditional risk factors for stroke. We noted that ischemic stroke involving the anterior circulation with large vessels occlusion is the most common type of stroke with more strokes seen in multi-territorial regions, suggesting systemic thromboembolism. An elevated level of D-dimers, C-reactive protein, ferritin, lactic acid dehydrogenase, troponin, ESR, fibrinogen, and a positive antiphospholipid antibody were also noted in this review. Conclusions: The occurrence of stroke in patients with COVID-19 infection is uncommon, but it may pose as an important prognostic marker and indicator of severity of infection, by causing large vessels occlusion and exhibiting a thrombo-inflammatory vascular picture. Physicians should be made aware and remain vigilant on the possible two-way relationship between stroke and COVID-19 infection. The rate of stroke among patients with COVID-19 infection may increase in the future as they share the common risk factors.

Background Transverse myelitis (TM) is a relatively uncommon condition, and vaccine-associated myelitis is even rarer. Concern regarding neurological complications following vaccination escalated following the report of TM during the safety and efficacy trials of the COVID-19 vaccine. Case presentation We report the first case of Longitudinal Extensive Transverse Myelitis (LETM) in Malaysia following administration of the chimpanzee adenovirus-vectored (ChAdOx1 nCoV-19) vaccine. A 25-year-old female presented with bilateral lower limb weakness and inability to walk with a sensory level up to T8 with absent visual symptoms. Urgent gadolinium-enhanced magnetic resonance imaging (MRI) of the spine showed long segment TM over the thoracic region. Cerebrospinal fluid autoantibodies for anti-aquaporin-4 and anti-myelin-oligodendrocyte were negative. A diagnosis of LETM following vaccination was made, and the patient was started on a high dose of intravenous methylprednisolone. The patient eventually made a recovery following treatment. Conclusion LETM is a rare but serious adverse reaction following vaccination. Previously reported cases showed an onset of symptoms between 10 to 14 days post-vaccination, suggesting a delayed immunogenic reaction. However, the incidence of myelitis in COVID-19 is much more common, far greater than the risk associated with vaccination.

Objective To evaluate the efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as a migraine prevention by conducting a systematic review and meta-analysis. Background The efficacy of high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex as preventive migraine treatment remains debatable. Methods PubMed, Scopus, CINAHL, CENTRAL, and BioMed Central databases were searched from their inception until December 2020. Randomised trials comparing high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex with sham for migraine prevention were included. The risk of bias was assessed using the Cochrane guidelines. Headache days, pain intensity, acute medication intake, and disability were extracted as study outcomes and the mean difference with a random-effects model was used to determine the effect size. Results Meta-analysis revealed that high-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex significantly reduced acute medication intake (Mean Difference = 9.78, p = 0.02, 95%CI: 1.60, 17.96, p = 0.02) and functional disability (Mean Difference = 8.00, p < 0.05, 95%CI: 4.21, 11.79). However, no differences were found in headache days and pain intensity reduction, although there was a slight trend favouring high-frequency repetitive transcranial magnetic stimulation. Conclusion High-frequency repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex may be effective in reducing acute medication intake and disability. However, more studies are needed to strengthen this preliminary evidence.

Onchocerciasis and lymphatic filariasis (LF) are human filarial diseases belonging to the group of neglected tropical diseases, leading to permanent and long-term disability in infected individuals in the endemic countries such as Africa and India. Microfilaricidal drugs such as ivermectin and albendazole have been used as the standard therapy in filariasis, although their efficacy in eliminating the diseases is not fully established. Anti-Wolbachia therapy employs antibiotics and is a promising approach showing potent macrofilaricidal activity and also prevents embryogenesis. This has translated to clinical benefits resulting in successful eradication of microfilarial burden, thus averting the risk of adverse events from target species as well as those due to co-infection with loiasis. Doxycycline shows potential as an anti-Wolbachia treatment, leading to the death of adult parasitic worms. It is readily available, cheap and safe to use in adult non-pregnant patients. Besides doxycycline, several other potential antibiotics are also being investigated for the treatment of LF and onchocerciasis. This review aims to discuss and summarise recent developments in the use of anti-Wolbachia drugs to treat onchocerciasis and LF.