Benjamin K.C. Ong

Electroencephalographic changes and seizures in familial hemiplegic migraine patients with the CACNA1A gene S218L mutation.

The S218L CACNA1A mutation has been previously described in two families with familial hemiplegic migraine. We present three siblings with the mutation with the novel association of childhood seizures, and highlight the dynamic changes seen on electroencephalography during hemiplegic migraine attacks. Depressed activity contralateral to the hemiparesis was seen on electroencephalography during acute hemiplegic migraine attacks, which may be due to changes to calcium channels caused by the S218L mutation. Both parents were asymptomatic and did not carry the S218L mutation in their blood. This suggests the presence of mosaicism in the transmitting parent.

Oxidative Damage in Ischemic Stroke Revealed Using Multiple Biomarkers

Background and Purpose— We investigated changes in oxidative damage after ischemic stroke using multiple biomarkers. Methods— Serial blood and urine samples of ischemic stroke subjects and age-matched control subjects were assayed for F2-isoprostanes, hydroxyeicosatetraenoic acid products, F4-neuroprostanes, 24-hydroxycholesterol, allantoin, and urate. Results— Sixty-six stroke subjects (mean age, 65 years; median National Institutes of Health Stroke Scale 17) and 132 control subjects were recruited. A bimodal pattern of change was observed in plasma and urinary F2-isoprostanes and plasma 24-hydroxycholesterol. The rise in plasma hydroxyeicosatetraenoic acid products, F4-neuroprostanes, and allantoin was highest 6 to 12 hours after stroke onset, whereas plasma urate was significantly lower than controls on Days 1 to 3. After adjusting for age and baseline National Institutes of Health Stroke Scale, baseline plasma esterified hydroxyeicosatetraenoic acid products (OR, 1.01; 95% CI, 1.01 to 1.02), plasma urate (1.01; 1.00 to 1.01), and plasma free F4-neuroprostanes (2.73; 1.76 to 3.93) were associated with 90-day good functional recovery (modified Rankin Scale ⩽1). Conclusions— Multiple markers of oxidative damage are increased immediately after stroke and remain elevated for several days. Recognition of these temporal changes may help design better antioxidant treatment trials for acute ischemic stroke.

Feasibility and Safety of Intravenous Thrombolysis in Multiethnic Asian Stroke Patients in Singapore

Treatment rates with intravenously administered tissue plasminogen activator (IV-tPA) in acute ischemic stroke (IS) remain low in Asian populations. Various logistic obstacles and higher anticipated bleeding risk in Asians are major concerns. We report on the feasibility and safety of IV-tPA therapy at our tertiary care center. Consecutive acute IS patients eligible for thrombolysis were treated with low-dose (maximum 50 mg) IV-tPA between January 2000 and September 2006 and with standard-dose (maximum 90 mg) IV-tPA between October 2006 and May 2008. The efficacy of IV-tPA was assessed by the modified Rankin Scale (mRS) score at 3 months and by absolute changes in the National Institute of Health Stroke Scale (NIHSS) score at hospital discharge and 3 months. The safety of IV-tPA was assessed by the rate of symptomatic intracranial hemorrhage (SICH). A total of 130 patients were included (mean age, 60±13 years; 60% males; median NIHSS score, 14). A total of 48 patients received low-dose IV-tPA, and 82 patients received standard-dose IV-tPA. The median onset to treatment time was 160 minutes. Some 59% of the patients achieved functional independence (mRS score 0-1) at 3 months with standard-dose tPA, compared with 35% in the low-dose group (P=.011). SICH occurred more frequently with the low dose (14.5%) than with the standard dose (1.2%; P=.004). In a multivariate logistic regression model, lower admission NIHSS score (odds ratio [OR]=0.78 per 1-point increase; 95% confidence interval [CI]=0.70-0.88), lower pretreatment blood glucose level (OR=0.76 per 1 mmol/L increase; 95% CI=0.60-0.95), shorter time from symptom onset to IV-tPA bolus (OR=0.97 per 1-minute increase; 95% CI=0.94-1.0), and standard-dose IV-tPA (OR=12.49; 95% CI=2.9-53.89) were associated with a higher likelihood for functional independence at 3 months. Our data indicate that standard-dose IV-tPA (0.9 mg/kg) was feasible and safe for treating acute IS in our multiethnic Asian population in Singapore.

Stroke Risk Factors and Outcomes Among Various Asian Ethnic Groups in Singapore

Data on interethnic differences in the Asian stroke population are limited. We evaluated the relationships among various cardiovascular risk factors, stroke subtypes, and outcomes in a multiethnic Singaporean population comprising consecutive ischemic stroke patients presenting to our tertiary center over a 1-year period. Strokes were classified based on criteria used in the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Functional independence at hospital discharge was defined as a modified Rankin Scale (mRS) score of 0-2. The ethnic distribution of the study population (n = 481; mean age, 64.1 ± 11.9 years) was 74% Chinese, 17% Malay, and 9% Indian. The prevalence of risk factors was similar in the 3 ethnic groups except for diabetes (Chinese, 39.8%; Malay, 67.5%; Indian, 52.3%; P < .001). Hypertension and hypercholesterolemia were the most common cardiovascular risk factors. Lacunar stroke was the most frequent stroke subtype (47.9%). Large-artery atherosclerotic infarctions were more prevalent in Indians (25.0%), whereas lacunar infarctions occured more frequently in Chinese (51.8%; P < .01). No differences in in-hospital mortality and functional independence at discharge were seen among the 3 ethnic groups. Despite the differences in risk factors and in stroke subtypes classified by location or underlying etiology, short-term outcome measures were similar in the 3 different Asian ethnicities in Singapore.

Recanalization Therapies in Acute Ischemic Stroke: Pharmacological Agents, Devices, and Combinations

The primary aim of thrombolysis in acute ischemic stroke is recanalization of an occluded intracranial artery. Recanalization is an important predictor of stroke outcome as timely restoration of regional cerebral perfusion helps salvage threatened ischemic tissue. At present, intravenously administered tissue plasminogen activator (IV-TPA) remains the only FDA-approved therapeutic agent for the treatment of ischemic stroke within 3 hours of symptom onset. Recent studies have demonstrated safety as well as efficacy of IV-TPA even in an extended therapeutic window. However, the short therapeutic window, low rates of recanalization, and only modest benefits with IV-TPA have prompted a quest for alternative approaches to restore blood flow in an occluded artery in acute ischemic stroke. Although intra-arterial delivery of the thrombolytic agent seems effective, various logistic constraints limit its routine use and as yet no lytic agent have not received full regulatory approval for intra-arterial therapy. Mechanical devices and approaches can achieve higher rates of recanalization but their safety and efficacy still need to be established in larger clinical trials. The field of acute revascularization is rapidly evolving, and various combinations of pharmacologic agents, mechanical devices, and novel microbubble/ultrasound technologies are being tested in multiple clinical trials.

Response to Letter Regarding Article, “External Carotid Artery–Internal Jugular Vein Fistula: A Complication of Internal Jugular Cannulation”

We appreciate the comments and the issues raised by Thalhammer et al in their letter regarding our case report.1 Our patient presented with an episode of transient right-sided weakness. Carotid duplex was performed as part of the stroke work-up and to explore the cause of the bruit on the right side of her neck. The fistula between the external carotid …

Computer-based testing of the modified essay question: the Singapore experience

Background: The modified essay question (MEQ), featuring an evolving case scenario, tests a candidates problem-solving and reasoning ability, rather than mere factual recall. Although it is traditionally conducted as a pen-and-paper examination, our university has run the MEQ using computer-based testing (CBT) since 2003. Aims: We describe our experience with running the MEQ examination using the IVLE, or integrated virtual learning environment (https://ivle.nus.edu.sg), provide a blueprint for universities intending to conduct computer-based testing of the MEQ, and detail how our MEQ examination has evolved since its inception. Methods: An MEQ committee, comprising specialists in key disciplines from the departments of Medicine and Paediatrics, was formed. We utilized the IVLE, developed for our university in 1998, as the online platform on which we ran the MEQ. We calculated the number of man-hours (academic and support staff) required to run the MEQ examination, using either a computer-based or pen-and-paper format. Results: With the support of our universitys information technology (IT) specialists, we have successfully run the MEQ examination online, twice a year, since 2003. Initially, we conducted the examination with short-answer questions only, but have since expanded the MEQ examination to include multiple-choice and extended matching questions. A total of 1268 man-hours was spent in preparing for, and running, the MEQ examination using CBT, compared to 236.5 man-hours to run it using a pen-and-paper format. Despite being more labour-intensive, our students and staff prefer CBT to the pen-and-paper format. Conclusions: The MEQ can be conducted using a computer-based testing scenario, which offers several advantages over a pen-and-paper format. We hope to increase the number of questions and incorporate audio and video files, featuring clinical vignettes, to the MEQ examination in the near future.

Novel chloride channel mutations leading to mild myotonia among Chinese

We describe two Chinese families with a mild form of the myotonia congenita due to novel chloride channel (ClCN1) mutations. In one case, heterozygous I553F and H555N mutations were found. The patient shared the I553F mutation with his healthy father, and his mother had a history of mild myotonia when she was younger. In another family, autosomal dominant myotonia congenita was due to a L844F change. The physiological effects of the mutations were examined by using the two-electrode voltage-clamp technique after expression of the channels in Xenopus oocytes. All mutations drastically shifted the voltage required for half-maximal activation, more under conditions mimicking the homozygous situation, than under conditions mimicking the heterozygous situation. The larger effect was seen in the compound heterozygous situation combining the I553F and the H555N mutations. Our data suggest that myotonia congenita caused by CLCN1 mutations in Chinese have similar variable features to those found in the West.

External Carotid Artery–Internal Jugular Vein Fistula A Complication of Internal Jugular Cannulation

A 75-year-old female patient was admitted to our hospital after an episode of transient right-sided weakness. Her medical history was significant for ischemic heart disease, with coronary artery bypass grafting having been performed 4 years previously. She had experienced progressive dyspnea and decreased effort tolerance in the preceding 2 years, with 2 admissions due to congestive heart failure in the past year despite medical treatment. The physical examination was remarkable for a raised jugular venous pressure on the right side, bilateral ankle edema, and basal crackles in the lungs. A right carotid bruit was heard on auscultation during systole, although no thrill was …A 75-year-old female patient was admitted to our hospital after an episode of transient right-sided weakness. Her medical history was significant for ischemic heart disease, with coronary artery bypass grafting having been performed 4 years previously. She had experienced progressive dyspnea and decreased effort tolerance in the preceding 2 years, with 2 admissions due to congestive heart failure in the past year despite medical treatment. The physical examination was remarkable for a raised jugular venous pressure on the right side, bilateral ankle edema, and basal crackles in the lungs. A right carotid bruit was heard on auscultation during systole, although no thrill was …

Spontaneous thoracic extradural haematoma presenting as the Brown-Sequard syndrome.

Sirs: Complete hemisection of the spinal cord, classically described as the Brown-Sequard syndrome, results in ipsilateral weakness and loss of proprioceptive and vibratory sensation due to disruption of the corticospinal tracts and dorsal columns. Pain and temperature sensation are lost on the contralateral side because of the affected spinothalamic tract, which decussates at the level of the lesion or one space above. Often however, the clinical syndrome is incomplete, with intact proprioceptive and vibratory sensation, as a result of compression of the spinal cord, sparing the dorsal columns. The Brown-Sequard syndrome can be caused by intraand extramedullary lesions, and is commonly reported in association with spinal neoplasms and trauma [1]. Spontaneous spinal extradural haematoma is defined as extradural haemorrhage occurring in the absence of identifiable etiologies such as anticoagulation, hemophilia, neoplasia, arteriovenous malformation or trauma [2]. The extent of the hematoma may be small and localized, or may extend over many vertebral levels. The Brown-Sequard syndrome as a presenting feature of a spontaneous extradural hematoma is rare. We report the case history and MR images of a patient with extradural hematoma, who presented initially with the Brown-Sequard syndrome localized to the 10th thoracic cord level, and rapidly progressed to develop flaccid paraplegia. A 51-year-old woman developed weakness of sudden onset in the right lower limb and numbness in the contralateral limb on awakening. She presented to another hospital where complete paralysis and loss of vibration sense of the right lower limb and loss of sensation to pain in the contralateral limb were documented, and the diagnosis of the Brown-Sequard syndrome was made. Within the next thirty minutes, her weakness and numbness progressed to involve both lower limbs, and she developed urinary and fecal incontinence. She was referred to our neurosurgical unit and examination revealed flaccid paraplegia with a sensory level at L1 bilaterally. Apart from a blood pressure of 180/110 mmHg, the examination of her other systems was unremarkable. Her medical history consisted of a 30-year history of hypertension, for which she was receiving atenolol. She was in good health prior to this presentation and did not consume any antiplatelet or anticoagulant agents. She denied overt trauma and any symptoms prior to going to sleep. All laboratory data were within normal limits, including CBC, electrolytes, blood urea nitrogen, creatinine and coagulation studies. The electrocardiogram disclosed left ventricular hypertrophy. Magnetic resonance imaging (MRI) within 6 hours of symptom onset revealed a right ventrolateral extradural mass extending from the inferior border of T10 to the mid-body of T12 with spinal cord compression (Fig. 1). The mass was isointense on T1-weighted imaging and hyperintense on T2-weighted imaging. Venogram and arteriogram did not reveal a vascular malformation. A diagnosis of spontaneous extradural hematoma was made on the basis of the clinical history and MRI findings. She underwent decompressive laminectomy to T10-T12 within 8 hours from the onset of her symptoms. Intra-operatively, coagulated blood was observed, and an extensive search grossly and with histopathologic assessment did not reveal any vascular abnormalities. Despite surgery, pre-operative dexamethasone at the emergency room and post-operative methylprednisolone coverage at 30 mg/kg bolus followed by a 5 mg/kg/hour infusion for a period totaling 3 days, neurological deficits persisted with no recovery of power and sensation of both lower limbs. Resolution of the extradural hematoma was documented on post-operative MRI of the spine 2 weeks later. We describe a patient who acutely developed the Brown-Sequard syndrome and flaccid paraplegia that were attributable to an acute compression of the spinal cord from a spontaneous extradural hematoma. Spontaneous hemorrhage into the extradural compartments is uncommon and a majority of cases have previously been reported in association with trauma, anticoagulant therapy, hemorrhagic diathesis, vascular malformation, lumbar puncture and tumor hemorrhage [3]. Spontaneous extradural hematoma rarely presents with the Brown-Sequard syndrome, and a review of the literature revealed only 5 cases previously reported. We summarize the clinical characteristics and clinical course of these patients in Table 1, and postulate the possible mechanisms of spontaneous extradural hematoma. There are conflicting reports and hypotheses on the mechanisms responsible for extradural hematoma, with some suggesting LETTER TO THE EDITORS