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Fulltext An update on HLA alleles as pharmacogenetic markers for antiepileptic drug-induced cutaneous adverse reaction

Then, Sue-Mian, Azman Ali Raymond

Neuroscience Research Notes, 2019;2(2):1-17.
MyJurnal

Epilepsy is a common neurological disorder affecting approximately 50 million people worldwide. Antiepileptic drugs (AEDs) are commonly used to treat the disease depending, mainlyon the type of seizure. However, the useof AEDs mayalso lead to cutaneous adverse drug reactions (cADR) such as toxic epidermal necrolysis (TEN), Stevens-Johnsonsyndrome (SJS), exfoliative dermatitis (ED) and drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), which are unwanted comorbidities in epilepsy. It was first discoveredthat the HLA-B*15:02 allele was strongly associatedwith carbamazepine(CBZ)-induced SJS/TEN amongHan Chinese and this ledto the discovery of other HLAallelesand cytochrome P450 (CYP) genes that were significantly associatedwith various AED-inducedcADRsacross variouspopulations. This mini-reviewis an update on the latest findings ofthe involvement of various HLA alleles and CYP alleles in cADRs caused by CBZ, phenytoin (PHT), oxcarbazepine (OXC) and lamotrigine(LTG) in different case-control studies around the world. From our review, we found that CBZ-and PHT-induced cADRsweremore commonly reportedthan the other AEDs.Therefore,there were morerobust pharmacogenetics studies related to these AEDs. OXC-and LTG-induced cADRswereless commonly reported,and somore studies are needed to validate the reported association of the newer reported HLA alleles with theseAEDs. It is also importantto considerthe allelic frequency within a given population before concludingthe use of thesealleles as genetic markers to prevent AED-induced cADR. Overall, the current body of research pointto a combination of alleles as a better pharmacogenetic marker comparedto the use of a single gene as a genetic marker for AED-induced cADR.
Fulltext Group B Streptococcal Meningitis in a Healthy Young Woman: A Case Report

Payus AO, Clarence C, Azman Ali R

Int J Gen Med, 2020;13:861-864.
PMID: 33116778 DOI: 10.2147/IJGM.S277394

Group B streptococcus (GBS) is a rare cause of meningitis in adults that commonly affects patients with multiple underlying comorbidities. Although it is uncommon, it typically progresses very rapidly and has a high mortality rate as compared to other causes of bacterial meningitis. Here, we report a patient with GBS meningitis who had no underlying medical illness and presented with multiple episodes of seizure within hours of developing fever. Cerebrospinal fluid analysis results were consistent with bacterial meningitis, and blood cultures grew GBS. She was treated with intravenous ceftriaxone for 2 weeks and made a great recovery without any sequalae. In conclusion, although GBS meningitis is uncommon in adults, it is a serious medical disease and associated with a high mortality rate. To the best of our knowledge, this patient represents one of the few reported cases of GBS meningitis in a previously healthy young adult.
Acute leukaemia masquerading as acute abdomen

S Abdul Wahid F, Cheong SK, Azman Ali R

Hosp Med, 2002 Jun;63(6):372-3.
PMID: 12096671 DOI: 10.12968/hosp.2002.63.6.2011
Fulltext A validation study of the Bahasa Malaysia version of the National Institute of Health Stroke Scale

Najma Kori, Wan Asyraf Wan Zaidi, Rabani Remli, Azman Ali Raymond, Norlinah Mohamed Ibrahim, Tan, Hui Jan, et al.

Neurology Asia, 2018;23(3):225-232.
MyJurnal

Background & Objectives: The National Institute of Health Stroke Scale (NIHSS) provides a valid and quick assessment of stroke severity in hyperacute stroke management. Stroke patients who are eligible for reperfusion therapy require prompt assessment. There is no validated Bahasa Malaysia (BM) version of the NIHSS that allows easier assessment by BM-speaking health professionals. This study aimed to translate and validate a BM version of the NIHSS.
Methods: The English NIHSS was translated to BM, then back translated to ensure linguistic accuracy. We also adapted the language assessment of the NIHSS to be more culturally appropriate. Training and certification videos were downloaded from the NIH website and dubbed into BM. We determined intra-class correlation and unweighted kappa as the best measure of reliability. Median scores were used in the analysis for language items.
Results: One hundred and one raters participated in the test-retest reliability study. Agreement between the original NIHSS and our translated version of the BM-NIHSS was good (ICC = 0.738, 95% CI: 0.611 to 0.823). Fair to moderate agreement was found on item-by-item analysis (unweighted κ=0.20-0.50) despite high observed agreement. Fifty patients participated in the language assessment arm. Scores were better in BM for reading, naming objects and repetition (Mdn = 100, p < 0.001). There was no difference in the median scores for the description component.
Conclusions: The BM-NIHSS is a valid translation of the NIHSS, and may be used in clinical practice by BM-speaking healthcare professionals.
Fulltext Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment

Golpich M, Amini E, Mohamed Z, Azman Ali R, Mohamed Ibrahim N, Ahmadiani A

CNS Neurosci Ther, 2017 Jan;23(1):5-22.
PMID: 27873462 DOI: 10.1111/cns.12655

Neurodegenerative diseases are a heterogeneous group of disorders that are incurable and characterized by the progressive degeneration of the function and structure of the central nervous system (CNS) for reasons that are not yet understood. Neurodegeneration is the umbrella term for the progressive death of nerve cells and loss of brain tissue. Because of their high energy requirements, neurons are especially vulnerable to injury and death from dysfunctional mitochondria. Widespread damage to mitochondria causes cells to die because they can no longer produce enough energy. Several lines of pathological and physiological evidence reveal that impaired mitochondrial function and dynamics play crucial roles in aging and pathogenesis of neurodegenerative diseases. As mitochondria are the major intracellular organelles that regulate both cell survival and death, they are highly considered as a potential target for pharmacological-based therapies. The purpose of this review was to present the current status of our knowledge and understanding of the involvement of mitochondrial dysfunction in pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) and the importance of mitochondrial biogenesis as a potential novel therapeutic target for their treatment. Likewise, we highlight a concise overview of the key roles of mitochondrial electron transport chain (ETC.) complexes as well as mitochondrial biogenesis regulators regarding those diseases.
Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease

Abdul Wahid SF, Law ZK, Ismail NA, Azman Ali R, Lai NM

Cochrane Database Syst Rev, 2016 11 08;11:CD011742.
PMID: 27822919

BACKGROUND: Amyotrophic lateral sclerosis (ALS), which is also known as motor neuron disease (MND) is a fatal disease associated with rapidly progressive disability, for which no definitive treatment as yet exists. Current treatment regimens largely focus on relieving symptoms to improve the quality of life of those affected. Based on data from preclinical studies, cell-based therapy is a promising treatment for ALS/MND.
OBJECTIVES: To assess the effects of cell-based therapy for people with ALS/MND, compared with placebo or no additional treatment.
SEARCH METHODS: On 21 June 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched two clinical trials' registries for ongoing or unpublished studies.
SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs), quasi-RCTs and cluster RCTs that assigned people with ALS/MND to receive cell-based therapy versus a placebo or no additional treatment. Co-interventions were allowable, provided that they were given to each group equally.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology.
MAIN RESULTS: No studies were eligible for inclusion in the review. We identified four ongoing trials.
AUTHORS' CONCLUSIONS: Currently, there is a lack of high-quality evidence to guide practice on the use of cell-based therapy to treat ALS/MND.We need large, prospective RCTs to establish the efficacy of cellular therapy and to determine patient-, disease- and cell treatment-related factors that may influence the outcome of cell-based therapy. The major goals of future research should be to determine the appropriate cell source, phenotype, dose, and route of delivery, as these will be key elements in designing an optimal cell-based therapy programme for people with ALS/MND. Future research should also explore novel treatment strategies, including combinations of cellular therapy and standard or novel neuroprotective agents, to find the best possible approach to prevent or reverse the neurological deficit in ALS/MND, and to prolong survival in this debilitating and fatal condition.