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Fulltext Stem cell therapy in neurodegenerative diseases: From principles to practice

Sakthiswary R, Raymond AA

Neural Regen Res, 2012 Aug 15;7(23):1822-31.
PMID: 25624807 DOI: 10.3969/j.issn.1673-5374.2012.23.009

The lack of curative therapies for neurodegenerative diseases has high economic impact and places huge burden on the society. The contribution of stem cells to cure neurodegenerative diseases has been unraveled and explored extensively over the past few years. Beyond substitution of the lost neurons, stem cells act as immunomodulators and neuroprotectors. A large number of preclinical and a small number of clinical studies have shown beneficial outcomes in this context. In this review, we have summarized the current concepts of stem cell therapy in neurodegenerative diseases and the recent advances in this field, particularly between 2010 and 2012. Further studies should be encouraged to resolve the clinical issues and vague translational findings for maximum optimization of the efficacy of stem cell therapy in neurodegenerative diseases.
Fulltext Factors affecting adherence to antiepileptic drugs therapy in Malaysia

Tan, XC, M Makmor-Bakry, Lau, CL, Tajarudin, FW, Raymond, AA

Neurology Asia, 2015;20(3):235-241.
MyJurnal

Poor adherence to antiepileptic drug (AED) therapy can lead to various undesirable complications. Identifying the contributing factors of poor adherence is beneficial in assisting health care professionals to provide optimal interventions to control the seizures. This study aimed to identify the prevalence and factors affecting the adherence level to AED therapy in a multiracial population with epilepsy. This cross-sectional study was conducted at the neurology clinic of a tertiary care setting. Researcher-assisted questionnaire was utilised. Adherence level was assessed using validated Modified Morisky Adherence Scale-8. A total of 145 patients with epilepsy were included in this study. The prevalence of poor adherence to AED therapy was 64.1%. Poor adherence level was significantly associated with younger age (χ2 = 7.609, p = 0.022), medication adverse effects (χ2 = 5.075, p = 0.020), shorter duration of epilepsy (r = 0.180, p = 0.030) and uncertainty about the necessity for AEDs (χ2 = 11.803, p = 0.001).
Conclusion, prevalence of poor adherence to antiepileptic drugs was high and factors associated with poor adherence to AEDs were identified for a multiracial population with epilepsy.
Study site: Neurology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Fulltext The clinical significance of vitamin D in systemic lupus erythematosus: a systematic review

Sakthiswary R, Raymond AA

PLoS One, 2013;8(1):e55275.
PMID: 23383135 DOI: 10.1371/journal.pone.0055275

BACKGROUND: Vitamin D deficiency is more prevalent among SLE patients than the general population. Over the past decade, many studies across the globe have been carried out to investigate the role of vitamin D in SLE from various clinical angles. Therefore, the aim of this systematic review is to summarise and evaluate the evidence from the published literature; focusing on the clinical significance of vitamin D in SLE.
METHODS: THE FOLLOWING DATABASES WERE SEARCHED: MEDLINE, Scopus, Web of Knowledge and CINAHL, using the terms "lupus", "systemic lupus erythematosus", "SLE and "vitamin D". We included only adult human studies published in the English language between 2000 and 2012.The reference lists of included studies were thoroughly reviewed in search for other relevant studies.
RESULTS: A total of 22 studies met the selection criteria. The majority of the studies were observational (95.5%) and cross sectional (90.9%). Out of the 15 studies which looked into the association between vitamin D and SLE disease activity, 10 studies (including the 3 largest studies in this series) revealed a statistically significant inverse relationship. For disease damage, on the other hand, 5 out of 6 studies failed to demonstrate any association with vitamin D levels. Cardiovascular risk factors such as insulin resistance, hypertension and hypercholesterolaemia were related to vitamin D deficiency, according to 3 of the studies.
CONCLUSION: There is convincing evidence to support the association between vitamin D levels and SLE disease activity. There is paucity of data in other clinical aspects to make firm conclusions.
Fulltext The risk factors of gastrointestinal bleeding in acute ischaemic stroke

Hamidon BB, Raymond AA

Med J Malaysia, 2006 Aug;61(3):288-91.
PMID: 17240577 MyJurnal

Gastrointestinal (GI) bleeding is one of the most serious complications after an acute ischaemic stroke and may affect stroke outcome. We identified predictors and the eventual outcome of gastrointestinal bleeding during the in-patient period following the commencement of aspirin. This was a study of patients with acute ischaemic stroke admitted to Universiti Kebangsaan Malaysia Hospital from June 2000 to January 2001. A single observer, using predefined diagnostic criteria recorded information on demography, risk factors and GI bleeding that occurred during the inpatient period. One hundred and fifteen patients with acute ischaemic stroke were enrolled in the study. Gastrointestinal bleeding was observed in 6 (5.2%) patients. Using univariate analysis, the independent predictors of gastrointestinal bleeding were age (OR 1.25; 95% CI 1.07 to 1.50), and middle cerebral artery (MCA) territory infarcts (OR 9.47; 95% CI 1.62 to 55.5). Using multivariate analysis, the presence of gastrointestinal bleeding increased mortality (OR 24.97; 95% CI 1.97 to 316.91). Older age, and large MCA infarct predict the development gastrointestinal bleeding. Stroke mortality was independently predicted by gastrointestinal bleeding. Prophylactic treatment in elderly patients with large cerebral infarcts may be an area for further investigation.
Fulltext The use of nerve conduction studies in determining the short-term outcome of Bell's palsy

Prakash KM, Raymond AA

Med J Malaysia, 2003 Mar;58(1):69-78.
PMID: 14556328

Bell's palsy is a common neurological problem causing considerable loss of self-esteem among patients. A prospective observational study was conducted to determine the short-term outcome of Bell's palsy at 1 month and 2 months after the onset and the relationship between these outcomes with facial nerve degeneration. We also determined if gender, age, diabetes, systolic and diastolic blood pressure influence the severity of facial nerve degeneration and the clinical outcome at 2 months after the onset. After clinically grading the newly diagnosed unilateral Bell's palsy patients using the House-Brackmann facial nerve grading system, nerve conduction studies of the facial nerve were done to determine the severity of facial nerve degeneration. The recovery of the facial paralysis was clinically graded again at the end of 1 month and 2 months from the onset. A total of 37 patients were recruited. There was a strong positive correlation between facial nerve degeneration and the clinical outcome of Bell's palsy at 1 month (r = 0.794; p < 0.0005) and 2 months (r = 0.732; p < 0.0005) after the onset. There was no significant correlation between either the facial nerve degeneration or the clinical outcome at 2 months with the patients' age (p = 0.288 and p = 0.799 respectively), systolic blood pressure (p = 0.425 and p = 0.933 respectively) or diastolic blood pressure (p = 0.243 and p = 0.579 respectively). Neither the severity of facial nerve degeneration nor the clinical outcome at 2 months were significantly different between male and female patients (p = 0.460 and p = 0.725 respectively) or diabetic and non-diabetic patients (p = 0.655 and p = 0.655 respectively).
EEG features of focal malformations of cortical development

Raymond AA, Fish DR

J Clin Neurophysiol, 1996 Nov;13(6):495-506.
PMID: 8978621

Recent advances in neuroimaging have allowed the detection and characterization of focal malformations of cortical developmental in a significant proportion of patients with epilepsy, many of whom were previously labelled as cryptogenic, allowing a better description of the associated electroencephalogram (EEG) features. Alpha activity is usually preserved, although superficial gyral abnormalities are often associated with overlying localized polymorphic delta activity, and occasionally abnormal fast activity. Most affected patients with epilepsy show interictal spikes. These are often broadly concordant with the structural abnormality but may show a wider anatomic distribution and be multifocal, or occasionally appear only in anatomically distant sites. In many patients the spikes are frequent and sometimes they occur continuously or in long trains. EEG findings are often stable over time, but some patients only show the development of slow wave changes or interictal spikes when followed serially for several years. A small proportion of patients with focal malformations of cortical development have EEG features mimicking idiopathic generalized epilepsy, and occasionally patients exhibit continuous generalized spike and slow wave activity in sleep. Electrocorticography studies confirm the often widespread nature of interictal spiking, but may also show highly epileptogenic patterns recorded directly from dysplastic cortex. The intrinsic epileptogenicity of areas of cortical developmental abnormalities has also been demonstrated by chronic intracranial studies and in vitro recordings of slices obtained from resected human dysplastic cortex. In this regard such developmental abnormalities are fundamentally different from acquired lesions such as tumors/vascular anomalies that usually exert their effects through changes in adjacent cortex.
Fulltext Acute disseminated encephalomyelitis (ADEM) presenting with seizures secondary to anti-tetanus toxin vaccination

Hamidon BB, Raymond AA

Med J Malaysia, 2003 Dec;58(5):780-2.
PMID: 15190671

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system (CNS) that is known to occur spontaneously in association with specific and non-specific viral illnesses and after vaccination against various pathogens. Although it is often a self-limited monophasic illness, the fatality rate is estimated to be as high as 20%, and many patients suffer residual neurologic impairment 1. The diagnosis is mainly based on clinical and radiological findings. The clinical presentation varies from merely, an asymptomatic condition to loss of consciousness, seizures, ataxia, optic neuropathy, cranial nerve palsies, and motor dysfunction. MRI of the brain is the single most important diagnostic radiological investigation and can facilitate early diagnosis and prompt treatment. This case report describes a patient with ADEM presenting with only seizures after vaccination with anti-tetanus toxin.
Fulltext Risk factors and complications of acute ischaemic stroke patients at Hospital Universiti Kebangsaan Malaysia (HUKM)

Hamidon BB, Raymond AA

Med J Malaysia, 2003 Oct;58(4):499-505.
PMID: 15190624

In Malaysia, there is limited information on the mortality and morbidity after an acute stroke in hospitalised patients. The objective of the study was to identify the type, time of onset, and frequency of medical and neurological complications following an acute ischaemic stroke. Consecutive patients with acute ischaemic stroke who were admitted to Hospital Universiti Kebangsaan Malaysia from June 2000 to January 2001 were observed. The complication rate was 20.9%. The most common individual complication was pneumonia (12.3%), followed by septicaemia (11.0%), urinary tract infection (4.3%), and upper gastrointestinal haemorrhage (3.7%). The overall mean length of stay was 7.48 days. The independent risk factors for complications were diabetes mellitus (OR 2.87; 95%CI 1.06 to 7.78), middle cerebral artery (MCA) infarcts (OR 10.0; 95%CI 4.1 to 24.3), and Glasgow coma score (GCS) less than 9(OR 3.8; 95%CI 1.03 to 14.3). Infection was the commonest complication observed. Patients with diabetes mellitus, poor GCS and large MCA infarcts had a higher risk of developing complications.
Fulltext The impact of diabetes mellitus on in-hospital stroke mortality

Hamidon BB, Raymond AA

J Postgrad Med, 2003 Oct-Dec;49(4):307-9; discussion 309-10.
PMID: 14699227

Background and purpose: Diabetes mellitus is a strong risk factor for stroke. However, the prognosis in terms of mortality after a stroke is still unclear, especially in diabetic patients. The main purpose of this study was to compare and evaluate the features of stroke in patients having diabetes mellitus with those without diabetes mellitus and to identify factors that influence survival following a stroke.

Subjects and methods: In a prospective hospital-based study consecutive patients with acute ischaemic stroke were enrolled. A single observer, using predefined diagnostic criteria recorded the demographics, risk factors and the type of stroke and deaths that occurred during the in-patient period.

Results: One hundred and sixty-three patients with acute ischaemic stroke were enrolled in the study. Type 2 diabetes mellitus was present in 90 (55.2%) patients. Diabetes was a significant independent predictor of mortality (OR 4.88; 95%CI 1.25-19.1). Among the diabetic patients middle cerebral artery (MCA) territory infarct (OR 34.8, 95%CI 4.5-269.4) and Glasgow coma score (GCS) less than 9 (OR 12.3, 95%CI 3.7-198.1) were independent predictors of mortality.

Conclusions: MCA infarcts and poor conscious level increase the mortality in diabetic patients with stroke. Mortality is also significantly related to a high level of blood glucose at admission.
Fulltext Risk factors for stroke and predictors of one-month mortality

Ong TZ, Raymond AA

Singapore Med J, 2002 Oct;43(10):517-21.
PMID: 12587706

Stroke is the third most common cause of death in Malaysia.The prevalence of risk factors and predictors of mortality of stroke in Malaysia are poorly understood.
Fulltext The predictors of subclinical cerebral infarcts in ischaemic stroke patients

Hamidon BB, Joseph JP, Raymond AA

Med J Malaysia, 2007 Jun;62(2):114-6.
PMID: 18705441

Subclinical cerebral infarcts (SCI) have been increasingly shown to cause a significant clinical impact. However, there are limited data available on Asian patients. The objectives of this study were to determine the prevalence of SCI in ischaemic stroke patients seen in the Hospital Universiti Kebangsaan Malaysia (HUKM) and to identify its associated risk factors. We evaluated the brain computed tomography (CT) evidence of subclinical infarcts in ischaemic stroke patients. The patients were selected from those who were on regular follow up in the neurology clinic following an ischaemic stroke. The risk factors associated with subclinical infarct were documented. The brain CTs were done during acute admission and reviewed for SCI. Sixty-one patients were enrolled in this study. Twenty-two (36.1%) out of the 61 patients had SCI. The risk factors for SCI in our study were hypertension (OR 14.16 CI 2.04-97.89), diabetes mellitus (OR 12.48; CI 1.95-79.77) and leukoaraiosis (OR 28.39; CI 2.33-284.16). Subclinical cerebral infarcts were present in about one third of our ischaemic stroke patients. This finding is higher than in previous studies done on Caucasians. Hypertension, diabetes mellitus and leukoaraiosis independently predict SCI.

Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)
Fulltext Risk factors and outcome of dysphagia after an acute ischaemic stroke

Hamidon BB, Nabil I, Raymond AA

Med J Malaysia, 2006 Dec;61(5):553-7.
PMID: 17623955 MyJurnal

Dysphagia occurs frequently after a stroke. It is a major problem as patients are at risk of malnutrition and aspiration pneumonia. We aimed to identify the risk factors for and outcome of dysphagia over the first one month after an acute ischaemic stroke. Patients with acute first-ever ischaemic stroke admitted to the medical ward of Hospital Universiti Kebangsaan Malaysia (HUKM) between July 2004 and December 2004 were prospectively examined. Observation was done using pre-defined criteria. Demographic data, risk factors, and type of stroke were recorded on admission. The assessment of dysphagia was made using standardized clinical methods. All patients were followed up for three months. One hundred and thirty four patients were recruited in the study. Fifty-five patients (41%) had dysphagia at presentation. This number was reduced to 29 (21.6%) patients at one month. Logistic regression analysis revealed that age of more than 75 years [OR 5.20 (95% CI 1.89 - 14.30)], diabetes mellitus [OR 2.91 (95% CI 1.07 - 7.91)] and MCA infarct [OR 2.48 (95% CI 1.01-6.14)] independently predicts the occurrence of dysphagia after an acute stroke. Dysphagia at presentation was found to be an independent predictor of mortality at one-month [OR 5.28 (95% CI 1.51-18.45)] post ischaemic infarct. Dysphagia occurred commonly in ischaemic stroke. Advance age, diabetes mellitus and large infarcts were independently associated with the presence of dysphagia. Early stroke mortality can be independently predicted by the presence of dysphagia.
Fulltext The prognostic value of C-reactive protein (CRP) levels in patients with acute ischaemic stroke

Hamidon BB, Sapiah S, Nawawi H, Raymond AA

Med J Malaysia, 2004 Dec;59(5):631-7.
PMID: 15889566 MyJurnal

Increasing evidence suggests that inflammation plays an important role in the development of both cardiovascular and cerebrovascular events. Recently C-reactive protein (CRP) levels have been reported to be a prognostic factor for cerebrovascular and cardiovascular events. The main objective of the study was to evaluate the prognostic value of CRP levels in a first ever ischaemic stroke at one month. All ischaemic stroke patients who were admitted to Hospital Universiti Kebangsaan Malaysia (HUKM) between May 2002 and July 2002 were eligible for the study. CRP levels were taken within 72 hours after an acute ischaemic stroke. The functional ability was assessed using the Barthel Index (BI) after one month of stroke. During the study period 84 patients were admitted to HUKM with the diagnosis of ischaemic stroke; 49 patients were enrolled and 35 were excluded. Twenty-nine patients (59.2%) had elevated CRP levels (median 1.64+/-3.07 mg/dL, range 0.06 to 16.21 mg/dL). Elevated CRP levels were found to be a predictor of severe functional disability (BI<5) and were also associated with larger infarcts. In conclusion, elevated CRP levels are associated with poorer functional outcome and predict a larger infarct size.
An unusual cause of tremor in an elderly man

Fadilah SA, Raymond AA, Cheong SK

Postgrad Med J, 2001 Apr;77(906):268-269; discussion 277-8.
PMID: 11264499
Rapidly progressing tetraparesis in a young male patient with pyrexia

Fadilah SA, Cheong SK, Raymond AA

Postgrad Med J, 2000 Mar;76(893):170-3.
PMID: 10684332
Fulltext Guillain-Barré syndrome

Payus AO, Jan TH, Raymond AA

Clin Med (Lond), 2020 11;20(6):e281.
PMID: 33199345 DOI: 10.7861/clinmed.Let.20.6.6
A review of idiopathic inflammatory myopathy cases in Terengganu, Malaysia: A single centre experience

Nor Hashimah AMM, Mohd A, Raymond AA

Med J Malaysia, 2021 07;76(4):488-492.
PMID: 34305109

INTRODUCTION: The purpose of this study was to analyse the clinical characteristics of patients with idiopathic inflammatory myopathy (IIM) in Hospital Sultanah Nurzahirah (HSNZ), Terengganu, Malaysia. It also aimed to describe the disease manifestations in association with malignancy and other CTD.
METHODS: This was a retrospective descriptive study involving all IIM patients who were managed by the Rheumatology Unit HSNZ from January 2010 to December 2019.
RESULTS: In this review we described 15 cases wherein malignancy was detected in 4 patients after the diagnosis of IIM was made and 4 patients with overlap syndrome. One third of patients with malignancy and overlap syndrome had poor treatment response and succumbed to complications of the disease. Almost all of patients received corticosteroid as the first line therapy and nearly two thirds of them responded well to either corticosteroid alone or with combination therapy.
CONCLUSION: Although this study did not represent the whole population in Malaysia, it does provide a better understanding of the disease manifestation, treatment and disease complications in our cohort of patients.
Fulltext Aspirin resistance in patients with acute coronary events: risk factors and prevalence as determined by whole blood multiple electrode aggregometry

Ibrahim O, Maskon O, Darinah N, Raymond AA, Rahman MM

Pak J Med Sci, 2013 Nov;29(6):1319-22.
PMID: 24550945

OBJECTIVES: To determine the prevalence of aspirin resistance and associated risk factors based on biochemical parameters using whole blood multiple electrode aggregometry.
METHODS: The study was conducted at the outpatients cardiology clinic of the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from August 2011 to February 2012. Subjects on aspirin therapy were divided into two groups; first-ever coronary event and recurrent coronary event. Aspirin resistance was measured by a Multiplate(®) platelet analyser.
RESULTS: A total of 74 patients (63 male, 11 female), with a mean age of 57.93 ± 74.1years were enrolled in the study. The patients were divided into two groups -first-ever coronary event group (n=52) and recurrent coronary event group (n=22). Aspirin resistance was observed in 12 out of 74 (16%) of the study patients, which consisted of 11 patients from the first-ever coronary event group and one patient from the recurrent coronary event group. There were significant correlations between aspirin resistance and age (r = -0.627; p = 0.029), total cholesterol (r = 0.608; p = 0.036) and LDL (r = 0.694; p = 0.012). LDL was the main predictor for area under the curve (AUC) for aspirin resistance. However, there was no association between aspirin resistance and cardiovascular events in both groups in this study.
CONCLUSIONS: Aspirin resistance was observed in 16% of the study population. LDL was the major predictor of aspirin resistance. No association was found in the study between aspirin resistance with recurrent coronary events.
KEYWORDS: Aspirin resistance; Multiplate® platelet analyser; aspirin responsiveness; first-ever coronary event; recurrent coronary event
Fulltext Short QTc in epilepsy patients without cardiac symptoms

Teh HS, Tan HJ, Loo CY, Raymond AA

Med J Malaysia, 2007 Jun;62(2):104-8.
PMID: 18705439

Epilepsy patients have a higher mortality rate than the general population. Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality for these patients. The possibility of cardiac involvement in the pathogenesis of SUDEP has been suggested by many previous studies. This study compared the QT interval in epilepsy patients and normal controls, and identified the factors that affected the QT interval. Standard 12-lead ECGs were recorded from 70 consecutive epilepsy patients from the neurology clinic of HUKM and 70 age, race and gender matched controls. The mean QT interval corrected for heart rate (QTc) was calculated and compared. The mean QTc among the epilepsy patients was 0.401 +/- 0.027s. It was significantly shorter than the QTc (0.420 +/- 0.027s) in the control group (p<0.0005). Thirty five epilepsy patients (50%) and 17 matched controls (24.3%) had a mean QTc shorter than 0.40s (p=0.001). Among the epilepsy patients, the mean QTc did not significantly differ between patients in the duration (F=0.836, p=0.438) of the epilepsy, frequency (F=0.273, p=0.845) and types of seizures (p=0.633). There was no significant difference in the mean QTc between the epilepsy patients on different number of antiepileptic agents (F=0.444, p=0.643). Patients with cryptogenic epilepsy had a mean QTc of 0.392 +/- 0.029s, which was significantly shorter than patients with symptomatic epilepsy (QTc = 0.410 +/- 0.027s, p = 0.015). The mean QTc of the same subjects showed no significant interobserver difference (p=0.661). This study, for the first time, demonstrates that epilepsy patients have a significantly shorter QTc than controls, particularly in the subgroup of patients with cryptogenic epilepsy.
Study site: Neurology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Fulltext The electroencephalogram changes in migraineurs

Tan HJ, Suganthi C, Dhachayani S, Rizal AM, Raymond AA

Med J Malaysia, 2007 Mar;62(1):56-8.
PMID: 17682573 MyJurnal

Migraine is associated with a variety of electroencephalographic (EEG) changes. Previous studies using analogue EEG and old diagnostic criteria may under or over report the prevalence of EEG changes in migraine. The objective of this study was to reevaluate the EEG changes in migraine patients diagnosed by applying the new International Classification of Headache Disorder -2 criteria. This was a case control study involving 70 migraine patients and 70 age and gender matched control who were subjected to scalp EEG. The EEG changes during hyperventilation (HV), which were significantly more common in the migraine group were theta activity (34 vs 22, p = 0.038) and frontal intermittent rhythmic delta activity (FIRDA) (10 vs 3, p = 0.042). Applying the new ICHD -2 diagnostic criteria and digital EEG, this study yielded previously unrecognized features including FIRDA during HV on EEG.

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