Cardiovascular Biomarkers during Acute Periods of Ischemic Stroke due to Non-Valvular Atrial Fibrillation

BACKGROUND: A subanalysis study of the ENGAGE AF-TIMI 48 trial showed that cardiac troponin I, N-terminal proB-type natriuretic peptide, and D-dimer, were powerful predictors of cerebrovascular adverse events. We aimed to evaluate D-dimer and cardiac troponin I levels during the acute period of ischemic stroke in anticoagulation-naïve patients with non-valvular atrial fibrillation (NVAF) and also studied the association between these biomarkers and stroke severity. METHODS: Consecutive anticoagulation-naïve patients with acute ischemic stroke due to NVAF were enrolled within two days after each stroke event, and all patients were stratified into either moderate-to-severe or mild neurologic deficit groups using the National Institutes of Health Stroke Scale (NIHSS) at admission. RESULTS: A total of 98 patients were enrolled in this study. The median value for the D-dimer was above the upper limit of the normal reference range, but the troponin I value was within the normal range for all patients. After adjusting for CHA2DS2-VASc risk factors, the log-transformed values for D-dimer were positively correlated with an increasing NIHSS score (r=0.233; P=0.051). In the multivariate logistic analysis, the log-transformed D-dimer was positively associated with more severe strokes (odds ratio, 30.1; 95% confidence interval [CI], 1.9–486.2 and 29.7; 95% CI, 2.0–430.8 in the upper two quartiles respectively). The log-transformed values for troponin I did not correlate with the NIHSS score. CONCLUSION: D-dimer levels were higher and an independent risk factor for severe stroke in anticoagulation-naïve patients with NVAF related stroke. In contrast, troponin I levels were normal and were not associated with stroke severity.

Cardiovascular Autonomic Dysfunction in Mild and Advanced Parkinson's Disease

OBJECTIVE: The purpose of the present study was to investigate cardiovascular autonomic dysfunction in patients with Parkinson's disease (PD) with mild to severe stages of motor symptoms and to compare cardiovascular autonomic dysfunction between drug-naïve and dopaminergic drug-treated groups. METHODS: This study included 188 PD patients and 25 age-matched healthy controls who underwent head-up tilt-testing, 24-h ambulatory blood pressure (BP) monitoring and 24-h Holter monitoring. Autonomic function test results were evaluated among groups categorized by motor symptom severities (mild vs. moderate vs. severe) and treatment (drug-naïve or dopaminergic drug treatment). RESULTS: Orthostatic hypotension and supine hypertension were more frequent in patients with PD than in healthy controls. The frequencies of orthostatic hypotension, supine hypertension, nocturnal hypertension and non-dipping were not different among groups. Additionally, no significant differences were detected in supine BP, orthostatic BP change, nighttime BP, nocturnal BP dipping, or heart rate variabilities among groups. CONCLUSIONS: Cardiovascular autonomic dysfunction is not confined to moderate to severe PD patients, and starts early in the course of the disease in a high proportion of PD patients. In addition, dopaminergic drug treatments do not affect cardiovascular autonomic function.

Bilateral Thalamic Lesions in Hashimoto's Encephalopathy

No abstract available.

Blood Pressure and Heart Rate Variability in Alzheimer's Disease

BACKGROUND AND PURPOSE: Altered blood pressure (BP) and heart rate variations (HRVs) have been reported in Alzheimer's disease (AD). However, it is unclear how these two manifestations are associated with AD. Therefore, the objective of this study was to investigate BP and heart rate variability in AD compared to that in normal controls, patients with subjective memory impairment (SMI), and patients with mild cognitive impairment (MCI). METHODS: Case-control comparisons were made among AD (n=37), MCI (n=24), SMI (n=17), and controls (n=25). All patients underwent clinical and neuropsychological assessments with 24-h ambulatory BP and Holter monitoring. RESULTS: Patients with AD had higher pulse pressures than those in other groups. In addition, AD patients experienced blunted nocturnal BP dipping associated with declining cognitive status. AD patients also had larger ranges of HRV in parasympathetic domains compared to other groups, especially at night. CONCLUSIONS: Our results suggest that diurnal sympathetic and parasympathetic cardiac variability were significantly disturbed in mild cholinesterase-naive AD patients. This may be an indirect sign of disturbed integrity to the sleep-wake cycle in mild AD.

Supra-Additive Neuroprotection by Renexin, a Mixed Compound of Ginkgo Biloba Extract and Cilostazol, Against Apoptotic White Matter Changes in Rat after Chronic Cerebral Hypoperfusion

BACKGROUND AND PURPOSE: White-matter (WM) lesions are known to potentiate cognitive impairment in poststroke patients. The present study was designed to assess whether Ginkgo biloba extract (GB) and cilostazol, which were evaluated alone and in a combination formula (Renexin), can attenuate the WM lesions and cognitive decline caused by chronic hypoperfusion in the rat. METHODS: Animals were divided into five treatment groups: cilostazol (25 mg/kg/day), GB (20 mg/kg/day), Renexin (25 mg/kg/day cilostazol + 20 mg/kg/day GB), vehicle, and sham. The animals received the treatments orally 1 day after bilateral common carotid artery occlusion [two-vessel occlusion (2VO); except for the sham group, which underwent the surgery but the arteries were not occluded], and then the same dose every day for 21 days thereafter. Prior to sacrificing the rats, repetitive eight-arm radial maze testing was performed to examine their cognitive abilities. After drug administration and cognitive testing, brain tissues were isolated for Kluver-Barrera and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end-labeling (TUNEL) staining, immunohistochemical assessment of glial fibrillary acidic protein (GFAP) and CD11b (OX-42), and to assay free-radical scavenging activity. RESULTS: We found that the significant WM lesions induced by 2VO was ameliorated significantly by treatment with cilostazol, GB, and Renexin, in association with increased TUNEL-positive cells. In addition, chronic cerebral hypoperfusion caused a large increase in the degree of GFAP and OX-42 immunoreactivity and free-radical activity in the optic tract. These abnormalities were significantly reversed by the three drugs, but most prominently by Renexin, suggesting a markedly enhanced or supra-additive effect of cilostazol and GB when administered together. CONCLUSIONS: Significant attenuation of cytoarchitectural damage and apoptotic cell death was found with GB and cilostazol, but a markedly enhanced effect was seen for treatment with their combination in the WM of rat brains after bilateral occlusion of the common carotid arteries. We suggest that combination therapy with GB and cilostazol provides enhanced neuroprotective effects and induces subsequent cognitive improvement in patients with chronic ischemic conditions.

Differential Expression of Activating Transcription Factor-2 and c-Jun in the Immature and Adult Rat Hippocampus Following Lithium-Pilocarpine Induced Status Epilepticus

PURPOSE: Lithium-pilocarpine induced status epilepticus (LPSE) causes selective and age-dependent neuronal death, although the mechanism of maturation-related injury has not yet been clarified. The activating transcription factor-2 (ATF-2) protein is essential for the normal development of mammalian brain and is activated by c-Jun N-terminal kinase (JNK). It induces the expression of the c-jun gene and modulates the function of the c-Jun protein, a mediator of neuronal death and survival. Therefore, we investigated the expression of c-Jun and ATF-2 protein in the immature and adult rat hippocampus to understand their roles in LPSE-induced neuronal death. MATERIALS AND METHODS: Lithium chloride was administrated to P10 and adult rats followed by pilocarpine. Neuronal injury was assessed by silver and cresyl violet staining, performed 72 hours after status epilepticus. For evaluation of the expression of ATF-2 and c-Jun by immunohistochemical method and Western blot, animals were sacrificed at 0, 4, 24, and 72 hours after the initiation of seizure. RESULTS: Neuronal injury and expression of c-Jun were maturation-dependently increased by LPSE, whereas ATF-2 immunoreactivity decreased in the mature brain. Since both c-Jun and ATF-2 are activated by JNK, and targets and competitors in the same signal transduction cascade, we could speculate that ATF-2 may compete with c-Jun for JNK phosphorylation. CONCLUSION: The results suggested a neuroprotective role of ATF-2 in this maturation-related evolution of neuronal cell death from status epilepticus.

The Effect of 1, 25-Dihydroxyvitamin D3 on Dopaminergic Neurons and Microglial Activation in Parkinsonian Rat Model Induced by 6-Hydroxydopamine

BACKGROUND: Recent studies have shown increasing evidence for microglial activation in neuronal degeneration in Parkinson's disease (PD), although the cause of PD remains unclear. Recent studies have also shown that 1alpha, 25-dihydroxyvitamin D3 (vitamin D3) exert neuroprotective effects by inducing an increased expression of neurotrophic factors, suggesting the possibility of vitamin D3 for the treatment of PD and other neurodegenerative diseases. The purpose of this study was to investigate the effect of vitamin D3 on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity and microglial activation in adult rats. METHODS: Adult male Sprague-Dawley rats were subcutaneously injected with vitamin D3 or 0.1% ethanol for seven consecutive days and then infused unilaterally with 6-OHDA in the medial forebrain bundle. After 7 days of injection with 6-OHDA, the substantia nigra was examined by immunohistochemistry. RESULTS: The number of tyrosine hydroxylase (TH)-positive neurons in the lesioned substantia nigra pars compacta of vitamin D3 and ethanol groups was 84.8 +/- 18.84 and 52.6 +/- 13.23, respectively, fewer than that of the contralateral side (122.35 +/- 9.79 and 123.81 +/- 12.11, respectively) (P<0.05). The vitamin D3 group showed significantly higher numbers of the TH-positive neurons than that of the ethanol group (P<0.05). CD11b-positive microglial immunoreactivity was stronger in the lesion side than that of the normal side, and it was much weaker in the vitamin D3 group than that of the ethanol group (P<0.05). CONCLUSIONS: These results indicate that vitamin D3 protects dopaminergic neurons from the neuronal injury induced by 6-OHDA, possibly by the mechanism involving microglial activation.

Argatroban Treatment in Acute Ischemic Stroke: Multicenter, Randomized, Aspirin-Controlled Study

BACKGROUND: Argatroban, a direct thrombin inhibitor, has been suggested to be beneficial in acute ischemic stroke by preventing microthrombi formation. The aim of this multicenter, aspirin-controlled, randomized trial is to determine the safety and the efficacy of argatroban compared with aspirin in acute ischemic stroke. METHODS: The patients within 48 hours of noncardioembolic ischemic stroke were recruited from 8 centers. Argatroban was infused continuously at 2.5 mg/hr for the first 48 h, and then 10mg of argatroban was infused over 3 h twice a day on days 3-7. Control group received aspirin 300 mg/day for 7 days. The primary outcome was the NIHSS at 30 days and the secondary outcome was Barthel index (BI) and modified Rankin scale (mRS) at 90 days. The safety was evaluated by the incidence of bleeding complication. RESULTS: A total of 236 patients (123 for argatroban and 113 for aspirin) were included. NIHSS at 30 days, BI at 90 days and mRS at 90 days did not show significant difference between the argatroban and the aspirin group (3.1 +/- 3.1 vs 3.5 +/- 3.0, 88.9 +/- 22.5 vs 86.2 +/- 23.8, 1.4 +/- 1.1 vs 1.6 +/- 1.3, p>0.3, respectively). Post hoc analysis revealed that as for the patients who were treated within 24 hours after onset, numbers of patients with NIHSS=1 at 30 days were larger in the argatroban group (23 of 49) than in the aspirin group (10 of 40) (p=0.03). Bleeding complication was not different between the two groups (2 of 123 vs 0 of 113: p>0.4). CONCLUSIONS: Argatroban treatment is relatively safe in acute ischemic stroke. The efficacy of argatroban is not superior to aspirin. However, argatroban may be more beneficial in some subgroup of stroke patients than aspirin.

Perioperative Stroke in the Brain and Spinal Cord Following an Induced Hypotension

A 49-year-old woman presented with stupor and paraplegia following an induced hypotension. The temporal relationship to the induced hypotension and the absence of a clear embolic source on diagnostic tests support a causal association between the hypotensive episode and the ischemic infarct. However, despite the association, a cause-and-effect relationship could not be automatically inferred.

Levosulpiride-induced Parkinsonim

The present report discusses four cases of chronic renal failure, which developed symptoms of parkinsonism in response to levosulpiride. The temporal relationship between levosulpiride discontinuation and the disappearance of parkinsonism suggests a causal link. In addition, decreased striatal dopamine transporter bindings assessed by [I-123] IPT SPECT were observed in two patients suggesting that a dopamine blocking agent causes the dysfunction of nigrostriatal dopaminergic neurons and that such injury may be involved in the pathogenesis of drug-induced parkinsonism.

Protective Effects of the Green Tea Polyphenol(-)-epigallocatechin Gallate Against Ischemia Reperfusion Injury Induced by Middle Cerebral Artery Occlusion in Rats

BACKGROUND: EGCG(epigallocatechin gallate), a major green tea extract, is a potent free radical scavenger which has been shown to reduce free radical-induced lipid peroxidation. The purpose of this study was to examine whether EGCG reduces focal ischemia/reperfusion-induced brain injury in rats. METHODS: Male Wistar rats were anesthetized with ketamine and xylazine and subjected to 120 min of temporary middle cerebral artery occlusion by an intraluminal nylon suture coated with poly-L-lysine. The drug (EGCG, n=8) or vehicle (normal saline, n=8) was administered iv.(as a 50 mg/kg bolus) immediately after the onset of middle cerebral artery occlusion. Neurologic status was evaluated 2 hours after occlusion and 24 hours after. Twenty-four hours after ischemia, the brain was perfusion-fixated and the infarct volume was determined. RESULTS: EGCG significantly improved the neurological status at 24 hours after middle cerebral artery occlusion.(p<0.05), and reduced total infarct volumes (p<0.01). CONCLUSIONS: These results demonstrate the neuroprotective effect of EGCG in a rat model of transient focal cerebral ischemia.

A Case of Purple Toe Syndrome Associated with Warfarin Sodium

No abstract available.

A Case of Right Middle Cerebral Artery Infarction with Quadriparesis / 대한뇌혈관학회지

Diaschisis is classically defined as a sudden inhibition of function, produced by an acute focal disturbance in a remote area which is anatomically connected through fiber tracts. Transhemispheric diaschisis can underlie some diffuse symptoms of acute supratentorial stroke such as agitation, confusion, and coma. We experienced a patient with right middle cerebral artery infarction, presenting a quadriparesis and hypoesthesia at sensory level. This case suggests the diaschisis exacerbate the initial focal deficit such as weakness and sensory loss.

Apolipoprotein E4 Genotype in Patient with IschemicCerebrovascular Disease in Korea: A Preliminary Study

BACKGROUND: The apolipoprotein E (APOE) epsilon4 allele is over-represented in Alzheimer's disease, atherosclerosis, and ischemic heart disease. We investigated whether specific APOE polymorphism is a risk factor for ischemic cerebrovas-cular disease in the Korean population. METHODS: We compared 98 patients with ischemic cerebrovascular disease with 209 controls similar in age and dwelling areas. APOE genotypes were determined by restriction fragment-length poly-morphism analysis. The association of the APOE with: stroke subtypes, white matter hyperintensities, lipid profiles, and potential vascular risk factors, including: age, sex, hypertension, diabetes mellitus, lipid disorders, smoking habit, cardiac diseases, presence of past history and family history of ischemic cerebrovascular diseases, was examined. RESULTS: Overall, patients with ischemic cerebrovascular disease had no difference in APOE allele frequency with controls (p>0.05). Also, neither stroke subtypes nor white matter high signal intensities were associated with APOE polymorphism (p>0.05). APOE epsilon4 carriers exhibited more frequent personal stroke histories compared with non-epsilon4 subjects (p<0.01). CONCLUSIONS: Our data suggests that the APOE epsilon4 is not associated with ischemic cerebrovascular disease in the Korean population. However, an association between APOE epsilon4 and personal history supports the possibility that the APOE is a susceptibility locus for the risk of ischemic cerebrovascular diseases. (J Korean Neurol Assoc 19(1):19~23, 2001

Measurement of Changes in Cerebral Blood Flow Velocity During Hemodialysis / 대한신장학회잡지

Hemodialysis is a safe and effective treatment for uremic patients but hemodynamic changes during hemodialysis is suggested to be the possible cause of encephalopathy. However, few studies have evaluated the cerebral circulation of and the effects of hemodialysis. Therefore, this study was performed to evaluate the cerebral blood flow by transcranial doppler. The study populations were 12 male patients who ranged in age from 28 to 58 years(mean:57) and were receiving maintenance hernodialysis for 3.8 years(0.5-11.5 years). Mean blood flow velocity(MFV), pulsatility index(PI) and resistance index(RI) were measured in carotid artery(CA), middle cerebral artery(MCA), anterior cerebral artery(ACA) and posterior cerebral artery(PCA) before, during and after hemodialysis. Simultaneously, we also checked variables(body weight, blood pressure, arterial blood gases, hematocrits, and other biochemical parameters) which might affect cerebral blood flow. MFV during(70.5+/-20.3 vs. 60.0+/-211cm/sec) and after(vs. 60.6+/-13.7cm/sec, p<0.01) hemodialysis in CA showed significant reduction as compared to the that of before hemodialysis, but other vessels(MCA, ACA and PCA) showed no significant changes. There were no significant changes in PI and RI before, during and after hemodialysis. Body weight, PaCO(2), blood urea nitrogen and hematocrit changed significantly during and after hemodialysis as compared to those of before hemodialysis, but correlation between changes of MFV and these variables was not observed. Hemodialysis and its associated physiologic changes are not associated with cerebral blood flow, and this result suggests the well-preservation of autoregulation of cerebral blood flow during and after hemodialysis.

Stable Xenon-CT Cerebral Blood Flow Imaging in Patients with Cerebral nfarction

BACKGROUND: Stable xenon-CT has been known to be a useful technique for measuring cerebral blood flow (CBF) and its direct correlation with CT anatomy. We evaluated the usefulness and limitations of stable xenon-CT cerebral hemodynamic status. METHODS: Xenon-CT was administered to 23 patients. Ten were normal controls and 13 were stroke patients (acute 4, subacute 5, chronic 2, hemorrhagic 2). Time dependent Xenon concentrations within various tissue segments of the brain was used to derive both the local partition-coefficient (lamda) and CBF in each tissue volume (voxel) of the CT image. RESULTS: In the controls, the regional CBF (rCBF) (ml/100 gm/min) was as follows: frontal 22.9+/-7.3(Mean+/-SD), inferior temporal 23.9+/-3.2, superior temporal 27.4+/-7.3, parietal 30.0+/-10.1, occipital 24.3+/-8.4, cerebellar hemisphere 24.3+/-8.3, thalamus 31.1+/-7.1, and corona radiata 18.1+/-4.7. The cortical differences was within 10%. In the stroke patients, the rCBF in the infarcted area ranged from 0 to 26.5 ml/100 gm/min and interhemispheric cortical difference was above 50%. The routine CT revealed no abnormalitiy, particularly in acute stroke (within 6 hours after onset). However, a xenon-CBF showed perfusion defect which correlated with clinical signs. CONCLUSIONS: With xenon CT, CBF can be obtained within a few hours of stroke onset, result of which can be correlated with CT. In an acute stroke state, a Xenon-CBF map can be a more sensitive method than routine CT imaging. Low value of blood-flow and patient's in cooperation may limit use of Xe-CT.

Neurofibromatosis Type 1 with Spinal Arteriovenous Malformation

Neurofibromatosis is a heterogenous hereditary disease with autosomal dominant transmission divided into two distinct types on the basis of genetic and clinical characteristics. Cervical vessels are rarely involved in neurofibromatosis type 1 (von Recklinghausen's disease). In the present paper, we report a 32-year-old female patient of neurofibromatosis type 1 with spinal arteriovenous malformation (AVM). She suffered from posterior neck pain and paresthesia on her right 3rd, 4th, and 5th fingers for a half a year. MRI showed ectasia of the right dural sac and signal void tortuous tubular structures at the cervical level. The right vertebral artery fed this cervical AVM in angiography.

Central Hypoventilation Syndrome during Awake and Sleep

Central hypoventilation syndrome (CHS) can be caused by any lesions to the medullary respiratory centers, cerebral cortex, corticospinal pathways, and their connections. We report 5 patients with central hypoventilation syndrome and analyzed 26 patients who experienced central hypoventilation syndrome during sleep and waking states. We compared initial clinical symptoms and signs, maximal neurologic deficits, brain MRI and pathologic findings, and associated autonomic dysfunctions. The patients with respiratory failure during waking states showed quadriplegia, a rapidly progressing respiratory failure. The patients who had automatic respiratory failure showed mild hemiparesis, bulbar dysfunction, dysautonomia, and subacute to chronic recurrent respiratory failures. These results support the concept of two separate respiratory systems: a voluntary system and an automatic system. The respiratory management of these patients with central hypoventilation syndrome should be considered critical to their survival.

Two Cases of Invasive Aspergillosis of Sino-nasal Origin

Cerebral aspergillosis is a rare condition that affects primarily the immunocompromised host. Most of cerebral aspergillosis is developed by hematogenous dissemination from extracranial foci, but aspergillosis of sino-nasal origin rarely affects the CNS. In case 1, wel symptom of tumor recurrence was unilateral numbness of the chin. A 65-year-old male was admitted because of paresthesia around the left chin and left lower lip. Neurologic examination revealed hypesthesia on the left side of chin, lower lip and buccal mucous mem-brane. Bone scan (Tc-99m MDP) showed focal hot uptakes on the left mandible and left first rib. Brain CT with bone window setting showed a focal osteolytic lesion in the bone marrow of the left mandibular canal without destruction of bone cortex. Both coronal T1 weighted image and axial T2 weighted image showed focal low signal intensities on the left ramus. The pathophysiologic mechanism could be understood by identification of the pathologic focus.

Two Cases with Carbamazepine-induced Unusual Side Effects-Encephalopathy and Myoclonic Jerks

Central nervous system toxicity is the most commonly recognized problem during treatment with carbamazepine (CBZ). The most common side effects of CBZ are drowsiness, incoordination, and vertigo. However, unusual conditions such as movement disorders, seizure aggravation, and encephalopathy have also been attributed to CBZ therapy. In case 1, cognitive dysfunction and exacerbation of preexisting gait disturbance were observed in a 63-year-old female who had frontal lobe epilepsy, schizencephaly, and lissencephaly treated with CBZ. The neurological symptoms were resolved 24 hours after the withdrawal of CBZ and induced with the reintroduction of CBZ. In case 2, myoclonic jerks occurred in a 37-year-old female when CBZ was readministered after a 4-day-withdrawal period of CBZ. The myoclonic jerks disappeared 12 days after CBZ was discontinued. In both cases, plasma CBZ levels were within the therapeutic range. We report two cases with encephalopathy and myoclonic jerks as unusual side effects of CBZ, with the plasma levels of CBZ being within the therapeutic range.