We have developed and characterised a mouse model of Japanese encephalitis virus (JEV) infection via
footpad inoculation in order to better mimic viral transmission by mosquito bites. Two-week-old and
5-week-old mice consistently developed signs of infection such as ruffled fur, weight loss, hunchback
posture, tremors, mask-like facies and occasionally, hindlimb paralysis at 4 days post infection (dpi)
and 11-13 dpi, respectively. Most of the animals died within 24 to 48 hours following the onset of signs
of infection, with mortalities of 100% and 33.3% in 2-week-old and 5-week-old mice, respectively.
Mild meningitis and variable parenchymal inflammation with formation of microglial nodules, focal
necrosis and neuronophagia, and perivascular cuffing by inflammatory cells were observed in the
caudate nucleus, putamen, thalamus, cerebral cortex, brainstem, and spinal cord. Viral antigens/RNA
were demonstrated by immunohistochemisty and in situ hybridization, respectively, in most of these
areas as well as in the hippocampus and cerebellum, albeit more focally. The pathological findings in
this mouse model were generally similar to human Japanese encephalitis (JE) and other established JE
models but perhaps, compared to other JEV mouse models, it demonstrates lethal encephalitic infection
more consistently. We believe that our mouse model should be useful to study the pathogenesis of JE,
and for testing anti-viral drugs and vaccines
Background: Impulse control behaviours are repetitive and excessive activities that may be sub-syndromal and not fulfil the criteria for impulse control disorder. These activities have potential to negatively impact on the daily lives of sufferers. We conducted a study to investigate the prevalence of impulse control behaviours and its associated features in Parkinson’s disease in our population. Methods: We conducted a prospective cross-sectional study on consecutive patients attending neurology clinic. Inclusion criteria include idiopathic Parkinson’s disease patients with Hoehn & Yahr stage I-IV. Eighty patients were enrolled and screened for impulse control behaviours using the Questionnaire for Impulsive-Compulsive Disorder for Parkinson’s disease (QUIP). Results: Prevalence of impulse control behaviours among our cohort was 11.3%; the features significantly associated with it were higher level of education (p=0.02), advanced stage of disease (p=0.03) and higher levodopa dosage (p= 0.01). The commonest impulse control behaviour in our cohort was compulsive medication use (7.5%), followed by hobbyism (6.3%), hypersexuality (5%), compulsive buying (3.75%), punding (2.5%), walkabout (2.5%), compulsive eating (1.25%) and pathological gambling (1.3%).
Conclusions: There is an association between impulse control behaviour and higher levodopa dosage in a study on patients with Parkinson’s disease in Malaysia. We also found a low prevalence of pathological gambling as compared to studies performed in the West.
Study site: Neurology clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Adult-onset metachromatic leukodystrophy is often a diagnostic challenge to many clinicians. It may be presented with psychiatry symptom before other evidences of leukodystrophy are uncovered. We report a 53-year-old patient who presented with 7-year history of manic-like presentation in addition to progressive neurocognitive deterioration. Diagnosis was made eventually with neuroimaging. Mutational analysis showed compound heterozygous of ARSA gene. This case demonstrated the challenge in diagnosing this condition due to its complex neuropsychiatric presentation.
Faciobrachial dystonic seizures are pathognomonic of leucine-rich glioma inactivated-1 (LGi1) antibody, non-paraneoplastic limbic encephalitis. Faciobrachial dystonic seizures usually precede limbic encephalitis by about a month. It is unknown whether, if untreated, faciobrachial dystonic seizures inevitably progress to limbic encephalitis. We present an LGi1 seropositive patient with a year’s history of faciobrachial dystonic seizures, who achieved remission spontaneously without immunotherapy or antiepileptic drug treatment, and did not develop evidence of limbic encephalitis over a three-year follow-up.
Background & Objective: Posterior reversible encephalopathy syndrome (PRES) is associated with
immunosuppressive agents used in children with haemato-oncological diseases. There are no reports
to date from the South Asia and South East Asia region. We report a Malaysian tertiary centre case
series of children with haemato-oncological disease who developed PRES. Methods: Retrospective
study of children seen with haemato-oncology diseases seen at the University Malaya Medical Centre
Kuala Lumpur who developed PRES from 2011 – 2013. Clinical details were obtained from medical
records and brain neuroimaging was reviewed. Results: Five patients met the inclusion criteria. All
5 patients had significant hypertension acutely or subacutely prior to neurology presentation. Four
presented with acute seizures and the remainder 1 presented with encephalopathy.Three patients
were on chemotherapy, 1 had renal impairment and 1 had prior immunosupression for bone marrow
transplantation. A full recovery was seen in 4 patients and 1 patient had mild residual quadriplegia.
Conclusion: Our case series expands the clinico-radiological spectrum of PRES in children with
underlying haemato-oncological disorders. It is the first to show that prior cyclosporin intake as long
as 2 months is a potential risk factor for PRES. Clinicians need to be vigilant for development of
PRES and closely monitor the blood pressure in these children who are receiving or recently had
immunosuppressive drugs and present with acute neurological symptoms.
Coxsackievirus A16 (CV-A16) is the leading cause of hand-foot-mouth disease (HFMD), which usually
presents as mild and self-limiting symptoms in young children. Rarely, CV-A16 has been reported
to cause severe and fatal neurological complications but little is known about these complications.
In the present study, 1-day and 7-day old mouse models of CV-A16 were developed using a clinical
strain via subcutaneous inoculation. All infected mice exhibited clinical signs of infection, including
reduced mobility, limb weakness and paralysis between 3 to 6 days post-infection. Pathologically,
the main organs involved were the central nervous system (CNS), skeletal muscles and brown fat. In
the CNS, viral antigens as demonstrated by immunohistochemistry, were localized mainly to neurons
in the brain stem and spinal cord, suggesting that CV-A16 is neurotropic although inflammation is
very mild. The skeletal muscles showed necrosis and myositis due to viral infection as evidenced by
the dense viral antigens. Focal viral antigens were also detected in the brown fat. These preliminary
pathological findings indicate that our mouse models can be further developed to be useful models
for pathogenesis studies, and vaccine and anti-viral drug evaluation.
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
A 28-year-old Malay woman presented with severe loss of vision in both eyes associated with periocular pain on eye movement. She was completely blind at presentation and examination showed optic discs
swelling. Optic nerve imaging showed ‘doughnut sign’, characteristic of optic perineuritis. Steroid was
given over six months. Visual function improved gradually and was maintained at one year follow-up.
This case highlights the importance of differentiation between optic neuritis and optic perineuritis as
visual recovery depends on prolonged management with corticosteroid in optic perineuritis.
There are 50-100 million dengue infections each year, but dengue encephalitis is relatively
uncommon. The aetiology of neuronal injury is proposed to be due to direct viral neurotropism or
host immune response-mediated inflammation causing neuronal damage. We report a case of severe
dengue encephalitis, presenting during the acute viraemic phase of the disease. This was associated
with inflammation and haemorrhage of the internal medullary lamina of both thalami which, to our
knowledge, has not yet been reported in other infections of the central nervous system.
Sleep quality can vary in relation to one’s general well-being and in the elderly, it is often affected by the presence of medical or psychological conditions. This study aims to determine the frequency of different components of sleep quality in the elderly, and their relationships with psychosocial and medical attributes. A cross-sectional study was conducted on 123 attendees aged 60 years and above at Pusat Perubatan Primer Universiti Kebangsaan Malaysia. Sleep quality and psychological distress were assessed using the validated Malay versions of Pittsburgh sleep quality index (PSQI) and Hamilton anxiety depression scale (HADS) respectively. Information on medical comorbidities and medications were obtained from the participants, their doctors and medical notes. Almost half of the patients experienced poor sleep quality (47.2%) which was significantly associated with older mean age (69.5 ±4.55). There was no statistical significance between sleep quality and other sociodemographic characteristics (gender, ethnicity and living arrangement). Most patients described their sleep quality as subjectively generally “fairly good” (69.1%) despite PSQI scores indicating poor sleep quality. A majority of the patients (59.3%) were on follow-up for 3 or more medical illnesses, with heart disease as the only medical comorbidity significantly associated with poor sleep quality. Most of them also complained of only “mild difficulty” with their sleep. Among the 7 sleep components of PSQI, “sleep disturbance” was the most frequent experience. Most experienced mild sleep disturbance (87.8%) and usage of hypnotic agents was low (6.5%). Only 23.6% of patients had significant psychological distress (HADS scores ≥ 8), with positive correlation with sleep quality.
Study site: Pusat Perubatan Primer, Universiti Kebangsaan Malaysia (PPPUKM), Kuala Lumpur, Malaysia
Background & Objective: Symptomatic sarcocystosis has been said to be rare until recent years, when there were reports of outbreaks of febrile myositis for travellers returning from the Malaysian island resorts. In 2012, an outbreak of Sarcocystis nesbitti infection involving 92 college students and staff occurred after returning from Pangkor Island, Malaysia. A few months after recovering from the febrile illness, some patients complained of hair loss. This study aimed to determine the prevalence, clinical features and outcome of this disorder.
Methods: All patients who became sick in the outbreak were asked whether they had the hair loss. For those who had, they were interviewed with standard questionnaires, examined and investigated. Patients were followed-up via an online survey 2 years later.
Results: Out of 89 patients who were ill, 19 patients (21.4%) complained of alopecia. The mean peak onset was 4 months after the initial illness. Eleven patients (57.9%) reported the hair fall of more than 100 per day. The other symptoms were itch 10 (52.6%), scaling 10 (52.6%), erythema 4 (21.1%), none had scarring. Eleven patients (57.8%) had positive antinuclear factor with high titre (speckled or nucleolar pattern). Two years after the event, 10 had complete or near complete spontaneous recovery, 1 had partial response and 1 had no improvement.
Conclusions: A delayed transient diffuse alopecia is seen in close to half of patients with Sarcocystis nesbittiinfection. This high frequency of positive ANF suggested an immune-mediated mechanism.
Study site: Dermatology Clinic, Universiti Malaya Medical Centre (UMMC)
Objective: To determine the validity and reliability of the Chinese parent proxy and child self-report
health related quality of life measure for children with epilepsy (CHEQOL-25) in Malaysia. Methods:
Face and content validity of the Chinese parent proxy and child self-report CHEQOL-25 was verified
by an expert panel, and piloted in five children with epilepsy (CWE). The Chinese CHEQOL-25 was
then administered to 40 parent proxies and their CWE (aged 8-18 years), from two tertiary hospitals,
at baseline and 2 weeks later. Results: Forty parents and their CWE were recruited. Cronbach’s alpha
for each subscale ranged from 0.56-0.83. At test-retest, the interclass correlation for all items ranged
from 0.68-0.97. Items 8 and 25 were removed as their corrected item-total correlation values were
Background & Objective: Modulation of cortical excitability by low frequency repetitive transcranial
magnetic stimulation (rTMS) has demonstrated therapeutic use in epilepsy. This study aimed to evaluate
the efficacy of low-frequency rTMS on refractory epilepsy in a group of Malaysian subjects. Methods:
Nine patients with refractory epilepsy completed the study. All patients received 10 sessions of 1Hz
rTMS (1000 pulses per session) at 90% of resting motor threshold. Outcome measures included seizure
frequency, Symptom Checklist-90 (SCL-90), Beck Depression Inventory II (BDI II) and Quality of
Life in Epilepsy-31 (QOLIE-31). Responders were defined as having ≥ 50% seizure reduction. Results:
The mean age was 33.8 years (SD 11.7), with 4 male. Three patients had mesial temporal sclerosis
(MTS); 4 with focal cortical dysplasia (FCD) and two lesion-negative. Three patients achieved >50%
seizure reduction at 8 weeks post-treatment, with 2 of them had improvement in the number of IED.
All of the responders had FCD. The responders were younger (mean 24.7 vs. 38.3 years old), had
shorter duration of illness (mean 15.7 vs. 30.5 years) and had less frequent seizure frequency prior to
treatment (mean 5.5 vs. 10.8 attacks per week), as compared to the non-responders. Six patients had
improvement in BDI-II scores, two in QOLIE-31 and four in SCL-90 post treatment, irrespective of
seizure control. The mean scores in BDI-II improved significantly with treatment (p
Migraine with aura is one of the major subtypes of migraine, and can be associated with ischaemic brain infarction. Use of oral contraceptive pills (OCPs) increases the risk of infarction in this type of migraine. Seizures and migraine also have a complex relationship, one element of which is migraine- triggered seizures. We report a case of bilateral occipital lobe infarction and migraine-triggered seizures, most likely precipitated by oral contraceptive pills (OCPs) in a patient with migraine with visual aura. OCPs, triptans and ergotamines should be used cautiously in these patients. Methods of birth control other than OCPs should be considered.
Background and Objective: There is a lack of international collaborative studies on young adults with ischaemic stroke in Asia. The aim of this study was to investigate risk factors, aetiology and outcome at hospital discharge of these patients across 8 participating countries in Asia. Methods: This was a prospective, observational, multicentre, hospital based cohort study. Consecutive young stroke patients with confirmed cerebral infarction between the ages of 18-49 were recruited from December 2011 to May 2012. Data was collected for patient demography, risk factors, investigations, clinical profile and TOAST classification. Outcome measures were death and independence (modified Rankin score≤ 2) at hospital discharge. Results: Two hundred and eighteen patients with the mean age was 40.8±6.7 years were recruited. There was a larger proportion of male patients with a ratio of 1.9:1. Traditional risk factors observed were hypertension (n=103; 47.3%), dyslipidaemia (n=93; 42.4%), smoking (n=85; 38.8%), diabetes (n=53; 24.3%), alcohol use (n=33; 15.0%), a previous history of stroke and transient ischaemic attacks (6.4%), family history (n=12; 5.5%), migraine (n=6;2.8%), pregnancy related (n=5; 2.3%) and numerous cardiac risk factors (0.9-5.5%). The majority suffered arterial infarction; n=216 (99.4%) while n=2 (0.6%) had venous strokes. The predominant stroke subtypes were large artery atherosclerosis (LAA); 29.8% and small vessel occlusion (SVO); 20.2%. LAA and SVO accounted for 37.5% of all stroke subtypes in the ≤36 year age-group. Cardioembolism (15.1%) and stroke of determined aetiology (14.7%) contributed to the other categories of identified stroke subtypes. Mortality on hospital discharge was 3.1% while 65.1% of patients were independent on discharge. Conclusion: This study demonstrated the substantial presence of premature atherosclerosis and conventional risk factors in young ischaemic stroke patients from 8 Asian cities. Venous infarction from cerebral venous thrombosis was rare in this study. Outcome on hospital discharge was poorer compared to Western studies. Detection of vascular risk factors and primary prevention measures should be initiated during late adolescence or early adulthood in urban Asia.
Introduction: None of the quantitative scale for public attitudes toward epilepsy was translated to Chinese language. This study aimed to translate and test the validity and reliability of a Chinese version of the Public Attitudes Toward Epilepsy (PATE) scale. Methods: The translation was performed according to standard principles and tested in 140 Chinese-speaking adults aged more than 18 years for psychometric validation. Results: The items in each domain had similar standard deviations (equal item variance), ranged from 0.85-0.95 in personal domain and 0.75-1.04 in general domain. The correlation between an item and its domain was 0.4 and above for all, and higher than the correlation with the other domain. Multitrait analysis showed the Chinese PATE had a similar variance, floor and ceiling effects, and relative relationship between the domains, as the original PATE. The Chinese PATE scale showed a similar correlation with almost all demographic variable except age. Item means were generally clustered in the factor analysis as hypothesized. The Cronbach’s α values was within acceptable range (0.773) in the personal domain and satisfactory range (0.693) in the general domain. Conclusion: The Chinese PATE scale is a validated and reliable translated version in measuring the public attitudes toward epilepsy.
We report a patient who presented with severe cold-induced allodynia and hyperhidrosis, and found to have acquired neuromyotonia (Isaacs syndrome) with high voltage-gated potassium channel (VGKC) antibody titre,positive contactin-associated protein 2 (CASPR2) and leucine-rich glioma-inactivated 1 (LGI1) antibodies. The patient also had positive anti-dsDNA and acetylcholine receptor (AChR) antibodies without clinical features of SLE or myasthenia gravis, suggesting a strong underlying autoimmune tendency. CT thorax showed no thymoma. Her symptoms improved with intravenous immunoglobulin infusion but recurred despite maintenance oral corticosteroids and carbamazepine. She has since been on regular IVIG infusions. Cold allodynia is an unusual presentation in acquired neuromyotonia.
This is a case of an adult patient with hypertensive intraventricular haemorrhages complicated by hydrocephalus that failed to respond to endoscopic third ventriculostomy (ETV). High-resolution 3D Fast Imaging Employing Steady State Acquisition (FIESTA) magnetic resonance imaging (MRI) revealed underlying multiloculated hydrocephalus. This case report highlights the appropriate sequence and its attributes that offer adequate preoperative information detailing the ventricular system.
Background and objectives: Radiation treatment in nasopharyngeal carcinoma (NPC) is known to be associated with increased prevalence of carotid stenosis. The objectives of the study was to determine the prevalence of radiation-induced extracranial carotid stenosis, plaque, carotid intima thickness (CIMT) in NPC patients; to explore whether the stenosis is due to direct effect of radiation rather than general tendency to atherosclerosis. Methods: This was a cross-sectional study conducted in the University Malaya Medical Centre from July 2011 to February 2012. The study subjects consisted of 47 NPC patients who were treated with radiation, and 47 healthy control. The patients and control had carotid duplex ultrasound and transcranial Doppler (TCD). Results: The mean age of the patients was 55.1 years, the time lapse from radiation was 76.7 ± 95.3 months. Internal carotid artery (ICA) and common carotid artery (CCA) stenosis of ≥50% was seen in 17.0% of patients vs 2.1 % of controls (p = 0.031), with 61.7% of patients and 19.1% of controls having plaque in ICA and CCA (p=0.004). CIMT was increased in 70.2% of patients and 44.7% of controls (p =0.022). Both the patient group and control had similar rate of intracranial stenosis of 12.8% in TCD.
Conclusion: Extracranial internal carotid artery is the most common site of stenosis following radiotherapy in NPC. This suggests that local trauma from irradiation is the most important factor in predisposition to atherosclerosis following radiation therapy.
Myopathies, although presenting more commonly in the younger age group, can occur and contribute significantly to disability in the elderly. To describe the spectrum of elderly myopathies, we reviewed 52 elderly patients (> 65 years) from the University of Malaya Medical Centre muscle biopsy databank, constituting 6.8% of 759 adult patients (> 18 years) who underwent muscle biopsy between 1992 and 2012. Commonest were the inflammatory myopathies (41/52, 78.8%), of which 43.9% had dermatomyositis; 23.9% polymyositis; 14.6% sporadic inclusion body myositis; 9.8% undifferentiated myositis and 2.4% overlap myositis. Seven patients (13.4%) had genetic myopathy; 2 muscular dystrophy and 5 chronic progressive external ophthalmoplegia, while 4 patients (7.7%) had drug-associated myopathy, 3 with statins. Malignancies were seen in 9.8% of inflammatory myopathies at diagnosis. Both acquired and genetic myopathies are seen in elderly Malaysians of all ethnicities and should not be misdiagnosed as some are potentially treatable and/or associated with malignancy.