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Demography and clinical course of ulcerative colitis in a multiracial Asian population: a nationwide study from Malaysia

Hilmi I, Singh R, Ganesananthan S, Yatim I, Radzi M, Chua AB, et al.

J Dig Dis, 2009 Feb;10(1):15-20.
PMID: 19236542 DOI: 10.1111/j.1751-2980.2008.00357.x

To establish the clinical course of ulcerative colitis (UC) in the Malaysian population, comparing the three major ethnic groups: Malay, Chinese and Indian.
Fulltext A case of Hashimoto encephalopathy in a Malay woman with Graves disease

Ngiu CS, Ibrahim NM, Yahya WN, Tan HJ, Mustafa N, Basri H, et al.

BMJ Case Rep, 2009;2009.
PMID: 21709844 DOI: 10.1136/bcr.01.2009.1501

Hashimoto encephalopathy (HE) is a poorly recognised steroid-responsive encephalopathy, with prominent neuropsychiatric features. Diagnosis is often difficult due to its heterogeneous clinical presentation, especially since the thyroid status or anti-thyroid antibody titres may not be related to the disease state. Here, the case of a 23-year-old Malay woman with Graves disease who presented with progressive encephalopathy diagnosed as HE is presented. She responded dramatically to high dose intravenous and then oral corticosteroid. A month after the initiation of treatment, she regained full independency.
Fulltext First Reported Case of Neuroleptospirosis Complicated With Anton's Syndrome

Saeed N, Khoo CS, Remli R, Law ZK, Periyasamy P, Osman SS, et al.

Front Neurol, 2018;9:966.
PMID: 30564184 DOI: 10.3389/fneur.2018.00966

Leptospirosis is a spirochetal zoonotic disease with a wide clinical spectrum, often underdiagnosed especially when presented as an acute neurological manifestation. We report a case of a 24-year-old man with serologically positive leptospirosis, who presented with altered sensorium, seizures and subsequently developed cortical blindness. His brain MRI revealed bilateral occipital and later parietal lobe cerebritis.
Knowledge of Acute Stroke Management Among Healthcare Professionals: Development and Validation of Acute Stroke Management Questionnaire (ASMaQ)

Sim CY, Wan Zaidi WA, Shah SA, Wan Yahya WNN, Tan HJ

J Stroke Cerebrovasc Dis, 2021 Jan;30(1):105421.
PMID: 33160125 DOI: 10.1016/j.jstrokecerebrovasdis.2020.105421

BACKGROUND: Around 15.0% of all strokes occurred in hospitalised patients and studies showed significant delay in the stroke recognition and lack of awareness on thrombolytic therapy for acute ischaemic stroke (AIS) which lead to higher mortality for in-hospital stroke. We aimed to develop and validate a new instrument known as acute stroke management questionnaire (ASMaQ) to evaluate the awareness of healthcare professionals in managing acute ischaemic stroke cases.
METHODS: This study consisted of 3 steps; the formulation of ASMaQ draft, content validation and construct validity. A total of 110 questions were drafted with 5-point Likert scale answers. From the list, 31 were selected and subsequently tested on 158 participants. The results were analysed and validated using exploratory factor analysis on SPSS. Components were extracted and questions with low factor loading were removed. The internal consistency was then measured with Cronbach's alpha.
RESULTS: Following analysis, 3 components were extracted and named as general stroke knowledge, hyperacute stroke care and advanced stroke management. Two items were deleted leaving 29 out of 31 questions for the final validated ASMaQ. Internal consistency showed high reliability with Cronbach's alpha of 0.82. Our respondents scored a total cumulative mean of 113.62 marks or 66.6%. A sub analysis by occupation showed that medical assistants scored the lowest in the group with a score of 57% whilst specialists including neurologists scored the highest at 79.4%.
CONCLUSION: The ASMaQ is a newly developed and validated questionnaire consisting of 29 questions testing the respondents' acute stroke management knowledge.
Fulltext Myasthenia gravis and premature ovarian failure - a causal link

Mohamed Arifin N, Khoo CS, Leong D, Tee TY, Tan HJ

Neurol Neurochir Pol, 2021;55(2):233-235.
PMID: 33555605 DOI: 10.5603/PJNNS.a2021.0015
CYP3A5 genetic variants and their associations with carbamazepine and valproic acid response in Malaysian epileptic patients

Miyata-Nozaka Y, Tan HJ, Wong SW, Raymond AA, Omar H, Zain SM

Int J Clin Pharmacol Ther, 2021 Jan;59(1):8-16.
PMID: 33026315 DOI: 10.5414/CP203761

OBJECTIVE: Epilepsy is a common chronic neurological condition characterized by recurrent seizures. Approximately 30 - 40% of epileptic patients do not respond to antiepileptic drugs. Previous studies suggest that CYP3A5 polymorphisms affect carbamazepine metabolism.
MATERIALS AND METHODS: To examine this hypothesis, in the present study, the associations between CYP3A5 variants (rs776746 and rs1419745) and response to carbamazepine and valproic acid monotherapy in Malaysian epileptic patients were evaluated.
RESULTS: A total of 288 Malaysian epileptic patients were recruited and further reviewed, of whom 63 patients were on carbamazepine monotherapy, and 85 patients were on valproic acid monotherapy. There was no patient with drug hypersensitivity syndrome within the population. Subjects were genotyped by using Sequenom MassARRAY platform. This study found a significant association of CYP3A5 rs776746 with the carbamazepine treatment response in total patients (p = 0.026) and Malay ethnic subgroup (p = 0.006). In addition, a marginal significant association of CYP3A5 rs1419745 with carbamazepine treatment response was reported in the Malays. Similarly, CYP3A5 rs776746 was associated with valproic acid response in total patients (p = 0.037) and Malays (marginal p = 0.05).
CONCLUSION: Our findings suggest that CYP3A5 polymorphisms affect carbamazepine and valproic acid response in Malaysian epileptic patients.
Fulltext Rome III survey of irritable bowel syndrome among ethnic Malays

Lee YY, Waid A, Tan HJ, Chua AS, Whitehead WE

World J Gastroenterol, 2012 Nov 28;18(44):6475-80; discussion p. 6479.
PMID: 23197894 DOI: 10.3748/wjg.v18.i44.6475

To survey irritable bowel syndrome (IBS) using Rome III criteria among Malays from the north-eastern region of Peninsular Malaysia.
Fulltext Prevalence and Factors Influencing Visual Memory Dysfunction among Epilepsy Patients-A Single-Center Study

Beh HC, Tan HJ, Hod R, Khoo CS, Mohamad K

Neurol India, 2020 7 10;68(3):581-585.
PMID: 32643667 DOI: 10.4103/0028-3886.289011

Background: Epilepsy is associated with cognitive impairment due to the disease itself or side-effects of antiepileptic drugs.
Objective: We aimed to study the prevalence of visual memory dysfunction among epilepsy patients and identify the predictors that could contribute to the impairment.
Materials and Methods: This was a cross-sectional study. We analyzed 250 patients with epilepsy from neurology clinic at our tertiary center. Assessment of visual memory was done using Wechsler Memory Scale-IV (WMS-IV) with scores from subsets of visual reproduction I, II and designs I, II contributing to visual memory index (VMI) score. The correlation between continuous variables was analyzed using Pearson correlation; whereas the VMI scores of different factors were analyzed via a 1-way ANOVA test. The statistical significance was set at P < 0.05.
Results: The prevalence of visual memory dysfunction in our epilepsy population was 37.2%. Analysis of individual predictors showed that older patients, lower educational level, combined generalized and focal types of epilepsy, longer duration of epilepsy, greater number of antiepileptic drugs (AEDs) used, and abnormal neuroimaging contributed to poor visual memory. Multiple logistic regression analysis showed that educational level, types of epilepsy, and the number of AEDs used were significant predictors for visual memory impairment.
Conclusion: Visual memory dysfunction in patients with epilepsy was due to manifold confounding factors. Our findings enabled us to identify patients with visual memory dysfunction and modifiable factors that contribute to it. WMS-IV is a suitable assessment tool to determine visual memory function, which can help clinicians to optimize the patients' treatment.
Fulltext MOG Antibody-Associated Disease with Recurrent Optic Neuritis and Multiple Cranial Neuropathies: A Rare Clinical Phenotype

Razali AM, Zain AM, Din NM, Tan HJ, Ng CF

Neurol India, 2020 3 20;68(2):500-501.
PMID: 32189702 DOI: 10.4103/0028-3886.280641
Fulltext Stevens-Johnson Syndrome following Failure of Genetic Screening prior to Carbamazepine Prescription

Nasir SA, Tan HL, Tan HJ, Hussaini HM, Ramli R

Case Rep Dent, 2017;2017:4201357.
PMID: 28473929 DOI: 10.1155/2017/4201357

Failure to screen susceptible individuals for human leucocyte allele B∗1502 leads to the onset of Stevens-Johnson syndrome (SJS). We report a case of a 27-year-old Malay female who was treated with carbamazepine following the diagnosis of trigeminal neuralgia without a genetic screening. She was prescribed 150 mg of carbamazepine initially and the dose was increased to 300 mg following the initial dose. A sudden development of skin and mucous membrane ulcers was observed and this warranted immediate hospitalization. A diagnosis of SJS was made and she was treated immediately with intravenous corticosteroids. Genetic screening prior to carbamazepine prescription is essential especially in susceptible populations.
Fulltext EEG is sensitive in early diagnosis of anti NMDAR encephalitis and useful in monitoring disease progress

Abdullah S, Lim KS, Wong WF, Tan HJ, Tan CT

Neurology Asia, 2015;20(2):167-175.
MyJurnal

Background& Objective: Investigation modalities, such as MRI and CSF examination, are neither sensitive nor specific in the early phase of anti-NMDAR encephalitis. Nuclear imaging may be useful to monitor the response to treatment but limited by the availability.We aimed to determine the role of EEG as a tool for early diagnosis as well as a tool to assess disease progression and response to treatment. Methods: A total of 99 EEGsdone in 16 patients diagnosed with anti-NMDAR encephalitis throughout the course of illness, were reviewed retrospectively. The EEG changes were correlated with the clinical presentations and response to treatment. Sixteen EEGs of patients with schizophrenia and mood disorder, and 10 EEGs of patients with infective encephalitis were included as control. Results: EEGs performed during the psychiatric and cognitive dysfunctionphase in patient with anti-NMDAR encephalitis, showed diffuse background slowing in the delta-theta range in all the patients. Serial EEGs showed that the dominant background frequency improved with improvement in cognitive status. Nine patients had complete recovery with normalisation of the EEG abnormalities. Eight patients had their typical clinical seizure recorded during EEG monitoring, but only 2 (25.0%) with EEG correlation. Ten patients had status epilepticus (62.5%), 5 had EEG recorded during their status epilepticus, of which only one with EEG correlation (20.0%). Eleven patients had asymmetric background (68.8%), but only 1 has correlation with focal changes in the MRI brain (9.1%). Even though the EEGs of patients with infective encephalitis also showed background slowing, their CSF analysis was supportive of an infective cause. EEGs of patients with established psychiatric disorder were within normal limits.
Conclusion: EEG abnormality has a good correlation with the degree of psychiatric and cognitive dysfunction in patient with anti-NMDAR encephalitis, and is useful in early diagnosis, monitoring the progress and the response to treatment. However, it has poor correlation with clinical seizures.
Fulltext Pioneering Annual Colorectal Cancer Screening and Treatment Targeting Low Income Communities in Malaysia (20102015)

Tze CN, Fitzgerald H, Qureshi A, Tan HJ, Low ML

Asian Pac J Cancer Prev, 2016;17(7):3179-83.
PMID: 27509948

The aim of this study was to assess the rate of uptake of a customised annual Colorectal Cancer Awareness, Screening and Treatment Project (CCASTP) using faecal immunohistochemical test (FIT) kits in low income communities in Malaysia. The immediate objectives were (1) to evaluate the level of adherence of CRC screening among lowincome groups, (2) to assess the knowledge and awareness of the screened population and (3) to assess the accuracy of FIT kits. A total of 1,581 FIT kits were distributed between years 2010 to 2015 to healthy asymptomatic participants of the annual CCASTP organized by Empowered the Cancer Advocacy Society of Malaysia. Data for sociodemographic characteristics, critical health and lifestyle information of the registered subjects were collected. Findings for use of the FIT kits were collected when they were returned for stool analyses. Those testingd positive were invited to undergo a colonoscopy examination. A total of 1,436 (90.8%) of the subjects retuned the FITkits, showing high compliance. Among the 129 subjects with positive FIT results, 92 (71.3%) underwent colonoscopy. Six cases (6.5%) of CRC were found. Based on the data collected, the level of awareness of stool examination and knowledge about CRC was poor amongst the participants. Gender, age group, ethnicity and risk factors (i.e. smoking, lack of exercise and low consumption of fresh fruits) were associated with positive FITkit results. In conclusion, CRC screening can be performed in the community with a single FITkit. Although CRC knowledge and awareness is poor in lowincome communities, the average return rate of the FIT kits and rate of colonoscopy examination were 91.2% and 70.3%, respectively.
Prevalence and factors of verbal learning and memory dysfunction in patients with epilepsy - A single centre study

Subramaniam SR, Khoo CS, Raymond AA, Che Din N, Syed Zakaria SZ, Tan HJ

J Clin Neurosci, 2020 Mar;73:31-36.
PMID: 32094071 DOI: 10.1016/j.jocn.2020.02.003

The objective of this study is to determine prevalence and factors leading to verbal learning and memory dysfunction among patients with epilepsy. A total of 211 subjects were recruited. Their verbal memory was assessed by Rey's Auditory Verbal Learning Test (RAVLT). This test was further subdivided into four major spheres for analysis, namely the verbal learning, interference list, immediate memory and delayed memory. All data collected were analyzed using Statistical Package for Social Sciences. Among the 211 patients, 55% (n = 116) had focal seizures and the remaining 45% (n = 95) had generalized seizures. Prevalence of verbal learning and memory impairment was high at 39.97% overall, and found most commonly in patients with focal impaired awareness seizures. Verbal learning and immediate memory dysfunction were significantly lower in focal impaired awareness group compared to others. Age more than 50 years, exposure to three or more antiepileptic drugs and use of carbamazepine more than 1000 mg a day were the predictors in poor verbal memory outcome. No statistical difference was observed in the mean RAVLT scores among the gender and hand dominance groups. Between patients with and without electroencephalogram changes as well as brain magnetic resonance imaging changes, the mean RAVLT scores showed no statistically significant difference. Verbal learning and memory impairment is prevalent among the epilepsy patients. The consequences of the memory impairment can be as debilitating as the seizure control. RAVLT is a reliable and practical test in the clinical setting.
Fulltext Cerebral Lupus and Cryptococcal Meningitis in a Pregnant Woman

Khoo CS, Marzukie MM, Yap SS, Wan Yahya WNN, Tan HJ

J Neurosci Rural Pract, 2020 Jan;11(1):183-186.
PMID: 32140026 DOI: 10.1055/s-0039-3402895

Systemic lupus erythematosus (SLE) is a chronic autoimmune and multisystem disorder, which frequently affects young women. During pregnancy, SLE flares could occur up to 65%, with renal and hematological manifestations being the most common. However, reports on neuropsychiatric lupus in pregnant women are scarce. We herein report a 26-year-old lupus pregnant woman, who had cerebral lupus with concurrent cryptococcal meningitis. This case highlights the complexity in diagnosing and managing our patient to achieve the best outcome for both the mother and infant.
Internal carotid artery injury during endonasal sinus surgery: our experience and review of the literature

Lum SG, Gendeh BS, Husain S, Gendeh HS, Ismail MR, Toh CJ, et al.

Acta Otorhinolaryngol Ital, 2019 Apr;39(2):130-136.
PMID: 30745587 DOI: 10.14639/0392-100X-1312
A case series of super-refractory status epilepticus successfully treated with electroconvulsive therapy

Tan HJ, Tee TY, Husin M, Khoo CS, Woon LS

Epileptic Disord, 2020 Dec 01;22(6):828-833.
PMID: 33337333 DOI: 10.1684/epd.2020.1233

Super-refractory status epilepticus (SRSE) is a neurocritical emergency, associated with significant morbidity and mortality. The precise pathophysiology is still not completely understood. The likelihood of spontaneous seizure termination reduces with time, and it is of paramount importance to abort status in order to prevent permanent long-term neurological sequelae and death. A few neuroprotective strategies, such as general anaesthesia, steroids, ketogenic diet and hypothermia, have been used to treat SRSE, however, the clinical outcome remains inconclusive. We herein present two cases of SRSE, which were successfully treated with electroconvulsive therapy (ECT) after failing all pharmacological measures.
Tuberculous meningitis mimicking Creutzfeldt-Jakob disease

Khoo CS, Krishnan L, Ng CF, Teh PC, Norlinah MI, Tan HJ

Rev Neurol (Paris), 2021 03;177(3):319-321.
PMID: 32747046 DOI: 10.1016/j.neurol.2020.05.013
SCN1A, SCN2A and SCN3A gene polymorphisms and responsiveness to antiepileptic drugs: a multicenter cohort study and meta-analysis

Haerian BS, Baum L, Kwan P, Tan HJ, Raymond AA, Mohamed Z

Pharmacogenomics, 2013 Jul;14(10):1153-66.
PMID: 23859570 DOI: 10.2217/pgs.13.104

Aim: Approximately a third of newly diagnosed epilepsy patients do not respond to antiepileptic drugs (AEDs). Evidence suggests that low penetrance variants in the genes of drug targets such as voltage-gated sodium channels may be involved in drug responsiveness. To examine this hypothesis, we compared data from two epilepsy cohorts from Malaysia and Hong Kong, as well as a meta-analysis from published data.

Materials & methods: Genotype analysis of 39 polymorphisms located in the SCN1A, SCN2A and SCN3A genes was performed on 1504 epilepsy patients from Malaysia and Hong Kong who were receiving AEDs. Meta-analysis was performed for pooled data of SCN1A rs3812718 and rs2298771, and SCN2A rs17183814 polymorphisms.

Results: Our data from the Hong Kong and Malaysia cohorts showed no significant allele, genotype and haplotype association of polymorphisms in the SCN1A, SCN2A, and SCN3A genes with drug responsiveness in epilepsy. This finding was supported by a meta-analysis for SCN1A rs3812718 and rs2298771, and for SCN2A rs17183814 polymorphisms.

Conclusion: Our comprehensive study suggests that common polymorphisms in SCN1A, SCN2A and SCN3A do not play major roles in influencing response to AEDs.
Fulltext Immune-mediated neurological syndrome in SARS-CoV-2 infection: a review of literature on autoimmune encephalitis in COVID-19

Payus AO, Jeffree MS, Ohn MH, Tan HJ, Ibrahim A, Chia YK, et al.

Neurol Sci, 2021 Dec 01.
PMID: 34853897 DOI: 10.1007/s10072-021-05785-z

INTRODUCTION: The novel Coronavirus Disease 2019 (COVID-19) is an infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which has been spreading rapidly amongst humans and causing a global pandemic. The notorious infection has shown to cause a wide spectrum of neurological syndrome, including autoimmune encephalitis.
OBJECTIVE: Here, we systematically review the literature on autoimmune encephalitis that developed in the background of SARS-CoV-2 infections and also the possible pathophysiological mechanisms of auto-immune mediated damage to the nervous system.
METHODOLOGY: An exhaustive search was made in Medline/PubMed, Embase, Scopus and other medical databases, and 28 relevant published articles were selected according to the strict inclusion criteria.
RESULTS: Autoimmune encephalitis can occur via three possible proposed pathophysiological mechanism and can manifest during or after the acute infection period. It is more common in adult but can also occur in the paediatric patients. There were various spectra of autoantibody panels reported including antineuronal antibody, anti-gangliosides antibody and onconeural antibody. Majority of the patients responded well to the immunomodulating therapy and achieved good recovery.
CONCLUSION: In conclusion, SARSCoV-2 infection can induce various spectrum of autoimmune encephalitis. It is a major concern since there is very limited long-term study on the topic. Hence, this review aims to elucidate on the potential long-term complication of SARS-CoV-2 infection and hopefully to improve the management and prognosis of COVID-19.
Prevalence and associated risk factors of undiagnosed depression among people with epilepsy in a multiethnic society

Tan JK, Khoo CS, Beh HC, Hod R, Baharudin A, Yahya WNNW, et al.

Epilepsy Res, 2021 Dec;178:106772.
PMID: 34763265 DOI: 10.1016/j.eplepsyres.2021.106772

BACKGROUND: Depression is the most frequent psychiatric comorbidity of epilepsy. However, clinicians often neglect to screen for depressive symptoms among patients with epilepsy and, therefore, fail to detect depression. Many studies have described the risks associated with depression in patients with epilepsy, but few studies have elaborated whether these risks are similar in those with undiagnosed depression, especially in a multiethnic community.
METHODS: In the present cross-sectional study conducted at a tertiary teaching hospital, we aimed to investigate the prevalence and associated risk factors of undiagnosed depression in patients with epilepsy. We recruited patients with epilepsy aged 18-65 years after excluding those with background illnesses that may have contributed to the depressive symptoms. In total, 129 participants were recruited. We collected their demographic and clinical details before interviewing them using two questionnaires-the Neurological Disorders Depression Inventory for Epilepsy and Beck's Depression Inventory-II. Subsequently, if a participant screened positive for depression, the diagnosis was confirmed using the Diagnostic and Statistical Manual of Mental Disorders questionnaire, and a psychiatric clinic referral was offered.
RESULTS: Among the 129 participants, 9.3 % had undiagnosed major depressive disorder, and there was a female preponderance (66.7 %). The risk factors for undiagnosed depression among patients with epilepsy included low socioeconomic background (p = 0.026), generalized epilepsy (p = 0.036), and temporal lobe epilepsy (p = 0.010). Other variables such as being underweight and unmarried were more common among patients diagnosed with depression than without but no statistically significant relationship was found.
CONCLUSION: The prevalence of undiagnosed depression among patients with epilepsy was higher than that in population-based studies conducted in Western countries. Although questionnaires to screen for depression are widely available, some clinicians rarely use them and, therefore, fail to identify patients who may benefit from psychosocial support and treatment that would improve their disease outcomes and quality of life. The present study indicated that clinicians should use screening questionnaires to identify undiagnosed depression in people with epilepsy.

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