Erle C.H. Lim

Diagnosing carpal tunnel syndrome--clinical criteria and ancillary tests.

Damage to the median nerve within the carpal tunnel gives rise to carpal tunnel syndrome (CTS), which is associated with a wide spectrum of symptoms. The predominant classic symptoms are nocturnal pain of the hand, and sensory disturbances within the distribution of the median nerve, both of which are characteristically relieved by hand movements. Ancillary tests, including nerve conduction studies (NCS) and imaging techniques, are mainly indicated when the classic defining features are absent. NCS are less accurate in the early stages of CTS, and in younger patients. Imaging tests (ultrasound and MRI), while still having a lower diagnostic accuracy than NCS, are proving to be useful for explaining persistence of symptoms following surgical relief. Supplementary tests of small nerve fiber function and measurement of intracarpal pressure might, in the future, improve early recognition of CTS, especially in the absence of well-defined symptoms.

Oxidative damage in dengue fever

Oxidative stress may be important in the pathogenesis of dengue infection. Using accurate markers of oxidative damage, we assessed the extent of oxidative damage in dengue patients. The levels of hydroxyeicosatetraenoic acid products (HETEs), F(2)-isoprostanes (F(2)-IsoPs), and cholesterol oxidation products (COPs) were measured in 28 adult dengue patients and 28 age-matched study controls during the febrile, defervescent, and convalescent stages of infection. We compared the absolute and the percentage change in these markers in relation to key clinical parameters and inflammatory markers. The levels of total HETEs and total HETEs/arachidonate, total F(2)-IsoPs/arachidonate, and COPs/cholesterol were higher during the febrile compared to the convalescent level. Total HETEs correlated positively with admission systolic blood pressure (r=0.52, p<0.05), whereas an inverse relationship was found between 7beta-hydroxycholesterol and systolic and diastolic blood pressure (r=-0.61 and -0.59, respectively, p<0.01). The urinary F(2)-IsoP level was higher in urine during the febrile stage compared to the convalescent level. Despite lower total cholesterol levels during the febrile stage compared to convalescent levels, a higher percentage of cholesterol was found as COPs (7beta-, 24-, and 27-hydroxycholesterol). The levels of platelet-activating factor-acetylhydrolase activity, vascular cellular adhesion molecule-1, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein were higher during the febrile stage compared to their convalescent levels (p<0.01). Markers of oxidative damage are altered during the various stages of dengue infection.

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.

Oral zinc supplementation does not improve oxidative stress or vascular function in patients with type 2 diabetes with normal zinc levels

OBJECTIVE There is considerable controversy about what constitutes optimal zinc intakes in patients with type 2 diabetes mellitus. Several studies suggest that higher zinc intakes improve vascular function and decrease oxidative damage. We aimed to assess the effects of zinc supplementation using a range of reliable biomarkers of oxidative damage and vascular function in patients with type 2 diabetes. METHODS Forty male type 2 diabetic patients were supplemented either with 240 mg/day of zinc as zinc gluconate (n=20) or with placebo (n=20) for 3 months. Blood and spot urine samples were taken at baseline, days 3 and 7, months 1, 2 and 3 during supplementation and 1 month after cessation. Serum zinc, reliable biomarkers of oxidative damage (F(2)-isoprostanes, neuroprostanes, cholesterol oxidation products, allantoin) as well as hydroxyeicosatetraenoic acid products and vascular-related indices (augmentation index, pulse wave velocity and aortic pressure) were measured. RESULTS Despite significantly higher levels of serum zinc in the treatment group, markers of oxidative damage, levels of hydroxyeicosatetraenoic acid products and vascular indices were unchanged by zinc supplementation during the four-month study period. CONCLUSION Improving the zinc status in patients with type 2 diabetes with normal zinc levels did not have any impact on oxidative damage and vascular function, and such supplementation may not be generally beneficial in these individuals.

Use of botulinum toxin in the neurology clinic.

Botulinum neurotoxin (BoNT) is an effective treatment for conditions associated with overactivity of glandular, smooth or skeletal muscle, and this toxin can also ameliorate certain painful conditions. Electromyography, endoscopy and imaging techniques such as ultrasonography and fluoroscopy have been used to increase the accuracy of BoNT injections. This Review assesses the mechanisms of action of BoNT, and examines the use of BoNT injections in numerous neurological conditions, including dystonia, spasticity, headaches and other painful disorders, hemifacial spasm, essential tremor, motor tics, hyperhidrosis, and sialorrhea and drooling. Important practical aspects, such as the reconstitution of BoNT, dosing, and methods of administration, are also addressed.

Markers of oxidative damage are not elevated in otherwise healthy individuals with the metabolic syndrome.

OBJECTIVE The role of oxidative damage in the pathogenesis of metabolic syndrome is poorly understood. RESEARCH DESIGN AND METHODS A detailed cross-sectional study was performed to assess the relationship between lipid oxidation products, γ-glutamyltransferase, high-sensitivity C-reactive protein (hs-CRP), and phospholipase activities with respect to the metabolic status in a cohort of otherwise healthy individuals. RESULTS A total of 179 individuals (87 men and 92 women) aged 43 ± 14 years (mean ± SD) participated in this study. There were no differences in the levels of plasma F2-isoprostanes, hydroxyeicosatetraenoic acids, cholesterol oxidation products, and phospholipase activities in individuals with features of metabolic syndrome. In multivariate analyses, serum hs-CRP was a consistent independent predictor of metabolic syndrome. CONCLUSIONS Minimal changes were observed in multiple markers of oxidative damage in a well-characterized cohort of individuals with features of metabolic syndrome.

Relationship between circulating vascular endothelial growth factor and its soluble receptors in adults with dengue virus infection: a case–control study

BACKGROUND We performed a case-control study to assess the relationship between vascular endothelial growth factor (VEGF) and its soluble receptors (sVEGFR-1 and 2) in adult patients with dengue fever (DF) and dengue hemorrhagic fever (DHF). METHODS We recruited 60 adult patients (34 DF and 26 DHF) with serologically-confirmed dengue infections, 10 patients with non-hemorrhagic infections, and 31 community-based healthy volunteers. The levels of VEGF, sVEGFR-1, and sVEGFR-2 were measured and the differences in these markers were compared using one-way analysis of variance (ANOVA), which was adjusted for multiple comparisons. RESULTS We observed lower VEGF levels in DF and DHF compared to study controls (p<0.01). sVEGFR-1 was higher in DHF than DF, whilst sVEGFR-2 was lower in DF and DHF compared to study controls (all p<0.01). In DHF, lower VEGF levels were observed in older patients. The use of a single marker, sVEGFR-1>350 pg/ml, was predictive of DHF. CONCLUSION The changes in VEGF and its soluble receptors highlight the importance of vascular permeability cytokines in the pathogenesis of DHF.

Acute effects of cigarette smoking on insulin resistance and arterial stiffness in young adults

BACKGROUND It is unclear whether changes in insulin sensitivity or arterial stiffness in cigarette smokers could explain the link between cigarette smoking and diabetes mellitus. The purpose of the study was to evaluate the acute effects of cigarette smoking on insulin resistance and arterial stiffness in a cohort of young healthy adults. METHODS Metabolic risk components, hemodynamic parameters, plasma nitrite/nitrate and high-sensitivity C-reactive protein (hsCRP) levels, were compared between smokers and age- and gender-matched controls (non-smokers). In smokers, these levels were determined 8-h following cigarette abstinence and an hour after smoking. RESULTS One hundred nineteen smokers and age-matched non-smokers (mean age, 32 years; 83% men) were included in this study. Compared with non-smokers, smokers had a significantly higher number of abnormal metabolic risk components, HOMA-IR index and total nitrite/nitrate levels. There were no differences in brachial/central blood pressure, augmentation index and hsCRP between smokers and non-smokers. An hour after smoking, smokers had significantly higher levels of HOMA-IR, total nitrite/nitrate, hsCRP and heart rate compared with baseline levels. By contrast, brachial/central blood pressure and augmentation index were unchanged after cigarette smoking. Baseline vascular and insulin resistance status predicted the extent of rise in the HOMA-IR and augmentation indices acutely after cigarette smoking (adjusted R(2) 0.358 and 0.124, p < 0.001 respectively). CONCLUSIONS Individuals with more advanced vascular damage and insulin resistance are vulnerable to the acute effects of cigarette smoking.

Brain seizes, heart ceases: a case of ictal asystole

Epileptic seizures commonly result in changes of cardiac rate.1-4Although tachycardias are much more frequent, ictal bradycardia and asystole may be life threatening and contribute to the syndrome of sudden unexplained death in epileptic patients.5Differentiation between primary cardiac and cerebrogenic bradyarrhythmia is possible with the use of simultaneous EEG and ECG recording. The correct identification of ictal bradycardia and asystole is important as treatment needs to consider both optimal anticonvulsant therapy and the implantation of a cardiac demand pacemaker. We report ictal asystole in a patient with a left temporal lobe seizure identified by simultaneous ECG and scalp EEG recording. A 74 year old Malay man was first admitted in January 1992 to the Neurosurgery Department for evacuation of bilateral chronic subdural haematomas sustained after several accidental falls. Recovery was uneventful until July 1992, when he was admitted for a possible seizure. Brain CT disclosed a right cerebral peduncular infarct. A clinical diagnosis of post-traumatic epilepsy was made, and he was started on 300 mg phenytoin at night. Over the next 5 years, he had one seizure, whereas between 1997 and 1998, he had four seizures. The four were attributed to poor compliance with medications. In June 1999, he was admitted to the Neurology Department after another generalised tonic-clonic seizure. Neurological and cardiac examination were unremarkable. Clinically, he …

Accurate targeting of botulinum toxin injections: how to and why.

Botulinum toxin (BTX), the exotoxin of the obligate anaerobe, Clostridium botulinum, is used to ameliorate pain and treat conditions associated with glandular, smooth and skeletal muscle overactivity. The benefits derived from the injection of BTX may be negated by unintended weakness of uninjected muscles. Performance of BTX injections may be facile, requiring only surface marking or clinical-localisation techniques but may be more technically demanding, necessitating the use of equipment, such as electromyography (EMG) or ultrasonography (U/S). Less often, endoscopic, fluoroscopic or computed tomographic (CT) guidance may be required. Despite evidence to support the efficacy of BTX injections in treating many conditions, there is no evidence to support the superiority of any one injection technique over needle localisation using surface anatomy. This is possibly due to the lack of well-designed controlled studies, that is, current studies are hampered by small patient numbers, lack of consistency of injection technique and the application of different rating scales. Intuitively, certain injection techniques are more suited to injection of specific muscles or conditions, for example, U/S or passive-monitoring EMG should be used to treat cervical dystonia, active-monitoring EMG applied for strabismus injections, whereas either active-monitoring EMG or endoscopy is indicated when giving BTX for spasmodic dysphonia. Finally, electrical-stimulation EMG or U/S (or a combination of both) would be most suitable when injecting the forearm muscles for spasticity or writers cramps.