Shung-Lon Lai

Serial Changes in Platelet Activation in Patients After Ischemic Stroke Role of Pharmacodynamic Modulation

Background and Purpose— Enhanced platelet activity has previously been reported in the acute phase after ischemic stroke. We tested the hypothesis that activated platelets (expressed by CD62p) are substantially increased in the acute stage after a stroke and decrease thereafter, and that antiplatelet therapies can suppress CD62p expression. Methods— We serially examined platelet CD62p expression using flow cytometry after acute ischemic stroke in 87 consecutive patients. The CD62p expression was also evaluated in 20 healthy volunteers and 33 at-risk control subjects. Results— CD62p expression was significantly higher in the acute phase after ischemic stroke than in normal and at-risk control subjects (both P < 0.0001). CD62p expression decreased to a significantly lower level on day 21, and to a substantially lower level on day 90. CD62p expression was not significantly suppressed by warfarin. However, CD62p expression was significantly suppressed by aspirin treatment (P = 0.024) and more substantially suppressed by clopidogrel (P < 0.0001) on day 90. Furthermore, only clopidogrel treatment (P = 0.0016) was significantly independently associated with decreased CD62p expression on day 90. Conclusions— Platelet activation was significantly increased in acute ischemic stroke and substantially decreased thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.

Association of plasma homocysteine concentration with cerebral white matter hyperintensity on magnetic resonance images in stroke patients.

BACKGROUND Homocysteine (Hcy) has been recognized as a risk factor for atherosclerosis. White matter hyperintensity (WMH) on MRI has been regarded as a hallmark for cerebral small vascular disease. The study is to investigate the relationship between plasma Hcy level and WMH on a hospital-based cohort of Taiwanese stroke patients. METHODS AND RESULTS A total of 352 consecutive stroke patients (64.7+/-11.2 years) were included. Severity of WMH was semi-quantitatively evaluated with a scoring system. The top WMH score tertile was defined as severe white matter change (sv-WMH). Associations between Hcy tertile levels and sv-WMH were examined, adjusting for demographics and atherosclerosis risk factors. Subjects in the top Hcy tertile (>10.25 micromol/L) had higher WMH scores and prevalence of sv-WMH than those in the middle and in the bottom tertile. The adjusted odds ratio of having sv-WMH was 2.04 (95% confidence interval 1.20-3.47, p=0.008) for the top Hcy level tertile than for the lower two tertiles combined. CONCLUSION Hcy is a risk factor for cerebral white matter lesion in stroke patients. Even mild hyperhomocysteinemia can significantly increase severity of cerebral microangiopathy.

Risk Factors of Oxcarbazepine-induced Hyponatremia in Patients With Epilepsy

Objectives:To determine the risk factors for hyponatremia in patients with epilepsy treated with oxcarbazepine (OXC). Methods:Seventy-three adult patients with epilepsy aged older than 17 years who received OXC therapy were enrolled in this study. Patients who had hyponatremia due to any etiology before OXC therapy and patients receiving OXC therapy for nonepileptic disorders were excluded from this study. The baseline level of serum sodium of the patients was measured before the OXC therapy. During OXC therapy, serum sodium levels were measured at least once per 3 months. Results:The frequency of hyponatremia (Na+, ≤134 mEq/L) was 24.7% (n = 18) in patients with OXC therapy, and 8.2% (n = 6) of the patients had severe hyponatremia (Na+, ≤128 mEq/L). The degree of decline in serum sodium concentration was significantly negatively correlated with the dosage of OXC. An increase of 1 mg in the dosage of OXC increased the risk of hyponatremia by 0.2%. Moreover, increasing the number of combination antiepileptic drugs increased the risk of hyponatremia. Conclusions:Higher dosages of OXC and the number of combination antiepileptic drugs may increase the risk of OXC-induced hyponatremia in patients with epilepsy. Most patients are asymptomatic, but if symptoms of hyponatremia, such as headache, general malaise, gait disturbance, and somnolence, are suspected, the serum sodium level should be measured; it may be necessary to decrease the OXC dose or to discontinue the drug.

Botulinum toxin type A treatment for Parkinsonian patients with moderate to severe sialorrhea.

PURPOSE To investigate the effect of botulinum toxin type A (BTX-A; Botox) in reducing saliva in patients with Parkinsonism. METHODS Fifteen patients with clinical diagnosis of idiopathic Parkinsons disease, dementia with Lewy bodies, or multiple system atrophy were enrolled in this open clinical trial. A total of 40-unit dose of Botox was injected into the bilateral parotid and submandibular glands. Objective measuring of saliva production with dental rods, subjective Drooling Score, personal impression of clinical improvement, and the duration of response were used for the global assessment of sialorrhea after BTX-A treatment. RESULTS All patients showed objective reduction in saliva production following BTX-A treatment and the mean production was reduced at a significant level. The severity of sialorrhea assessed by Drooling Score was 5.87 +/- 0.92 (range: 5-8) and 3.60 +/- 1.18 (range: 2-6) respectively (p<0.001) before and after BTX-A injection. The mean duration of BTX-A response extended for 16.3 +/- 5.7 weeks (range: 5-24). No severe adverse effect nor worsening of existing dysphagia was observed in all Parkinsonian patients. CONCLUSIONS Parkinsonian drooling may undermine patients health and daily activity. BTX-A local injection is a safe and effective measure in counteracting sialorrhea, even in patients associated with moderate dysphagia.

Association between MIF gene polymorphisms and carotid artery atherosclerosis

Atherosclerosis is a chronic inflammatory disorder. Macrophage migration inhibitory factor (MIF) is a potent cytokine that plays an important role in the regulation of immune responses. Polymorphisms including five- to eight-repeat CATT variants ((CATT)(5-8)) and G-173C in the promoter region of the MIF gene are associated with altered levels of MIF gene transcription. The purpose of the study is to investigate the relationship between promoter polymorphisms of the MIF gene and the severity of carotid artery atherosclerosis (CAA). The severity of CAA was assessed in 593 individuals with a history of ischemic stroke by using sonographic examination, and the MIF promoter polymorphisms of these individuals were genotyped. The carriage of (CATT)7 (compared to genotypes composed of (CATT)5, (CATT)6, or both), carriage of C allele (compared to GG), and carriage of the haplotype (CATT)7-C (compared to genotypes composed of (CATT)5-G, (CATT)6-G, or both) were significantly associated with an increase in the severity of CAA. We conclude that polymorphisms in the MIF gene promoter are associated with CAA severity in ischemic stroke patients. These genetic variants may serve as markers for individual susceptibility to CAA.

Neurologic and Non-neurologic Predictors of Mortality in Ischemic Stroke Patients Admitted to the Intensive Care Unit

BACKGROUND/PURPOSE Patients with severe strokes may have different associated medical comorbidities from those with mild strokes. This study evaluated the neurologic and non-neurologic medical predictors of mortality in patients with severe cerebral infarction in the acute stage. METHODS Patients admitted to a neurologic intensive care unit (ICU) due to cerebral infarction were included. Neurologic and non-neurologic predictors for in-unit mortality were determined by logistic regression analyses. Two models using (A) neurologic factors and (B) combined neurologic and non-neurologic factors as mortality predictors were developed. The performance of the models in predicting overall, neurologic and non-neurologic mortalities was compared by areas under the receiver-operating characteristic curves (AUC) of the derived regressive equations. RESULTS Of 231 patients with cerebral infarction admitted to the ICU, 34 (14.7%) died during ICU stay. Conscious state and acute physiologic abnormalities were significant predictors of mortality. The length of ICU stay in patients with non-neurologic mortality was longer than in those with neurologic mortality (p = 0.044). The AUC of Model B was larger than that of Model A in predicting overall (0.768 +/- 0.045 vs. 0.863 +/- 0.033, p = 0.005) and non-neurologic mortalities (0.570 +/- 0.073 vs. 0.707 +/- 0.074, p = 0.009), while there was no difference in predicting death from neurologic causes (0.858 +/- 0.044 vs. 0.880 +/- 0.032, p = 0.217). CONCLUSION Impaired consciousness and acute physiologic abnormalities are independent predictors of mortality for severe ischemic stroke during the acute stage. Neurologic factors predict early mortality from intrinsic cerebral dysfunction, while non-neurologic factors, especially the associated physiologic abnormalities, predict late mortality from medical complications.

Sleep quality and daytime sleepiness in patients with epilepsy.

PURPOSE Poor sleep quality and excessive daytime sleepiness (EDS) are common complaints of patients with epilepsy (PWE). This study aimed to evaluate possible predisposing factors for EDS and subjective sleep quality in PWE. METHODS One hundred and seventeen PWE were enrolled and 30 healthy volunteers were recruited as controls. EDS was evaluated by the Epworth Sleepiness Scale (ESS) while the Pittsburg Sleep Quality Index (PSQI) was designed to evaluate overall sleep quality. Clinical baseline data and possible risk factors for sleep disturbances were included in the statistical analysis. RESULTS Twenty percent of PWE (23/117) and 7% of healthy controls (2/30) had excessive daytime sleepiness (p = 0.007). PWE had significantly higher PSQI total scores (6.5 ± 3.8 vs. 3.7 ± 2.9), sleep latency (1.2 ± 0.8 vs. 0.6 ± 0.7) and sleep efficiency (0.8 ± 1.0 vs. 0.0 ± 0.2) scores than the controls (all p < 0.001). A significantly higher prevalence of poor sleep quality was found in the partial seizure, non-seizure-free, and polytherapy groups (all p < 0.05). Multivariate analysis showed that poor seizure control was the strongest independent risk factor for poor sleep quality (OR = 2.43, 95% CI = 1.15-5.15, p = 0.02). CONCLUSION EDS and poor sleep quality are common in PWE and are closely related to partial epilepsy, poor seizure control, and polytherapy. These relationships must be addressed in order to provide the best management of sleep disturbance in such patients.

Tetrodotoxin intoxication in a uraemic patient

Tetrodotoxin intoxication results from ingesting puffer fish or other animals containing the toxin. Clinical presentation is mainly acute motor weakness and respiratory paralysis. Death is common in the worst affected victims. Although the severity of the symptoms generally depends on the amount of toxin ingested, it may be influenced by the victim’s medical condition, as described in this report. The patient was a 52 year old uraemic woman. The uraemia was of undefined aetiology. Over the past 3 years she has received regular haemodialysis. One day both she and her husband, a healthy 55 year old man, ate a fish soup. About 4 hours after the meal she developed a headache and a lingual and circumoral tingling sensation and numbness at the distal parts of all four limbs. She was dizzy and unsteady, had difficulty in swallowing, and became very weak. She was taken to the emergency service and was placed on machine assisted ventilation as respiratory distress and cyanosis developed. Her husband remained asymptomatic throughout this time. Changes in the symptoms of poisoning in relation to each course of haemodialysis. Scales in the vertical axis represent the arbitrary measurements of severity of each …

Ictal paralysis with tonic eye gazing mimicking a pontine infarction.

PURPOSE Concomitant positive and negative motor phenomena in a single seizure have not been reported before. METHOD We used an extensive history review, neurological examination, EEG, MRI and SPECT study to demonstrate a rare combination of motor presentations as an ictal phenomenon. RESULT A 64-year-old male was brought to the emergency room with dizziness, progressive drowsiness and left hemiparesis. A spontaneous eye deviation to the left side with nystagmus was observed. A right pontine lesion was tentatively diagnosed. However, a focal motor seizure of the patients left face and limbs occurred 3.5h later. A brain MRI revealed a high signal in the right amygdala, hippocampus and thalamus, instead of the pons. An EEG showed periodic epileptic discharges in the right posterior temporal parietal region. Regional hyperperfusion was found by brain SPECT. The level of consciousness improved dramatically after adequate phenytoin treatment. CONCLUSION A posterior temporal-parietal seizure can present with a prolonged ictal paralysis, a positive ocular nystagmoid deviation and an altered level of consciousness. The EEG is essential for a correct diagnosis, especially with a negative or an unexplainable MRI study. The SPECT has an additional role for the differential diagnosis.

The Relation between Plasma Homocysteine Level and Cardiovascular Risk Factors in Cerebral Ischemia

PURPOSE Hyperhomocysteinemia (HHcy) is associated with a higher risk of cerebral ischemia and other vascular thrombosis. Homocysteine is greatly influenced by a broad spectrum of physiological and pathological conditions but the confounding factor for HHcy is unknown in our population, especially in normocreatininemic individuals. It is our aim in this study to elucidate the relation between homocysteine and cardiovascular risk factors, and also describe the distribution of plasma homocysteine level in cerebral ischemia patients with normal serum creatinine level. METHODS A retrospective study was conducted to understand the frequency of HHcy in cerebral ischemia patients, and the confounding cardiovascular risk factors in HHcy. Patients were classified into two groups by their plasma homocysteine levels; group I patients were those whose level was > or = 12 microM/L whereas group II < 12 microM/L. RESULTS A total of 218 patients were enrolled. Their plasma homocysteine level ranged from 3.57 to 46.37 microM/L (mean: 10.01 +/- 5.03 microM/L). Group I included 45 patients whereas group II 173 patients. The frequency of hypertension, diabetes mellitus and cardiac disease, as well as age, aminotransferases, total cholesterol, triglyceride, albumin, hematocrit, hemoglobin and leucocyte count did not differ between group I and II patients, except serum creatinine level was higher in group I patients (p < 0.01). Serum creatinine level correlated directly to and was an independent predictor for the plasma homocysteine level. CONCLUSIONS HHcy is common in our cerebral ischemia patients. Since renal function is a determinant for HHcy even in normocreatininemic patients, as a cardiovascular risk factor which detriments the renal function, it should be regularly monitored as HHcy is amenable for treatment.