Jun Hong Lee

Cilostazol Prevents the Progression of the Symptomatic Intracranial Arterial Stenosis The Multicenter Double-Blind Placebo-Controlled Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis

Background and Purpose— Cilostazol, a phosphodiesterase inhibitor, has been reported to reduce restenosis rate after coronary angioplasty and stenting. This study was performed to investigate the effect of cilostazol on the progression of intracranial arterial stenosis (IAS). Methods— We randomized 135 patients with acute symptomatic stenosis in the M1 segment of middle cerebral artery or the basilar artery to either cilostazol 200 mg per day or placebo for 6 months. Aspirin 100 mg per day was also given to all patients. Patients with potential embolic sources in the heart or extracranial arteries were excluded. IAS was assessed by magnetic resonance angiogram (MRA) and transcranial Doppler (TCD) at the time of recruitment and 6 months later. The primary outcome was the progression of symptomatic IAS on MRA and secondary outcomes were clinical events and progression on TCD. Results— Thirty-eight patients were prematurely terminated. Dropout rates and reasons for dropouts were similar between the cilostazol and placebo groups. There was no stroke recurrence in either cilostazol or placebo group, but there was 1 death and 2 coronary events in each group. In cilostazol group, 3 (6.7%) of 45 symptomatic IAS progressed and 11 (24.4%) regressed. In placebo group, 15 (28.8%) of symptomatic IAS progressed and 8 (15.4%) regressed. Progression of symptomatic IAS in cilostazol group was significantly lower than that in placebo group (P=0.008) Conclusion— Our study suggests that symptomatic IAS is a dynamic lesion and cilostazol may prevent its progression.

Association of the metabolic syndrome with intracranial atherosclerotic stroke

To investigate the impact of metabolic syndrome (MetSD) on the development of intracranial atherosclerotic stroke, the authors evaluated the components of the MetSD in 512 patients with stroke. The MetSD was observed most frequently in patients with intracranial atherosclerosis (p = 0.007). In multiple regression analysis, the MetSD, but not conventional risk factors, was independently associated with intracranial atherosclerosis (p = 0.005). The results suggest that treatment of metabolic abnormalities may be an important prevention strategy for intracranial atherosclerosis.

Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B

Background: Subcortical vascular dementia (SVaD) is considered the most common type of vascular dementia and often follows a slowly progressive course, simulating Alzheimer disease (AD). Whether the progressive cognitive decline is associated with pure SVaD or concomitant AD remains unknown. The purpose of this study was to determine what proportion of patients with SVaD lack abnormal amyloid imaging, and to examine differences in the clinical or MRI features between subjects with SVaD with cortical amyloid deposition and those without. Methods: We measured brain amyloid deposition using 11C-Pittsburgh compound B (PiB) PET in 45 patients (men: women = 19:26; mean age 74.2 ± 7.6 years) with SVaD. They all met DSM-IV criteria for vascular dementia and had severe white matter high signal intensities without territorial infarction or macrohemorrhage on MRI. Results: Thirty-one (68.9%) of 45 patients with SVaD were negative for cortical PiB binding. There was significant difference between 11C-PiB-positive and 11C-PiB-negative groups in terms of age (79.5 vs 71.9 years), Mini-Mental State Examination score (18.6 vs 22.6), the number of lacunes (3.9 vs 9.0), and the visual rating scale of hippocampal atrophy (3.1 vs 2.3). The neuropsychological assessments revealed that patients with 11C-PiB-negative SVaD performed better on the delayed recall of both the verbal and visual memory test than did those with 11C-PiB-positive scan. Conclusion: SVaD without abnormal amyloid imaging was more common than expected. Patients with SVaD with and without abnormal amyloid imaging differed in clinical and MRI features, although there was considerable overlap.

A Computerized In-Hospital Alert System for Thrombolysis in Acute Stroke

Background and Purpose— An effective stroke code system that can expedite rapid thrombolytic treatment requires effective notification/communication and an organized team approach. We developed a stroke code program based on the computerized physician order entry (CPOE) system and investigated whether implementation of this CPOE-based program is useful for reducing the time from arrival at emergency departments (ED) to evaluation steps and the initiation of thrombolytic treatment in various hospital settings. Methods— The CPOE-based program was implemented by 10 hospitals. Time intervals from arrival at the ED to blood tests, computed tomography scanning, and thrombolytic treatment during the 1-year period before and the 1-year period after the program implementation were compared. Results— Time intervals from ED arrival to evaluation steps were significantly reduced after implementation of the CPOE-based program. Times from ED arrival to CT scan, complete blood counts, and prothrombin time testing were reduced by 7.7 minutes, 5.6 minutes, and 26.8 minutes, respectively (P<0.001). The time from ED arrival to intravenous thrombolysis was reduced from 71.7±33.6 minutes to 56.6±26.9 minutes (P<0.001). The number of patients who were treated with thrombolysis increased from 3.4% (199/5798 patients) before the CPOE-based program to 5.8% (312/5405 patients) afterward (P<0.001). The CPOE implementation also improved the inverse relationship between onset-to-door time and door-to-needle time. Conclusions— The CPOE-based stroke code could be successfully implemented to reduce in-hospital time delay in thrombolytic therapy in various hospital settings. CPOE may be used as an efficient tool to facilitate in-hospital notification/communication and an organized team approach.

Single photon emission computed tomography-EEG relations in temporal lobe epilepsy

addition to marked hyperperfusion at the focus, a relative decrease in perfusion around the hyperperfused region is a useful additional sign, again when compared with the interictal examination.5J2 This sign is clearly seen in their Cases 14 and 17 and should be incorporated in the interpretation. Thirdly, in seizures where there is bilateral ictal spread and early EEG termination on the side of the focus, ictal SPECT may show a corresponding “postictal” pattern with mesial hyperperfusion and lateral hypoperfusion on the side of the focus, while the contralateral side may show obvious hyperperfusion. We agree that cases with bilateral change can be difficult to interpret, as reflected by the fact that their two masked readers had initial discordant interpretations on three of the six mislateralized cases. Knowledge of the complex patterns of ictal perfusion will avoid incorrect lateralization of ictal SPECT. This emphasizes the need for comparison with the interictal examination and evaluation of the entire ictal scan, not just identifying the area of maximum perfusion. Finally, 16 of their 19 cases were studied with ethyl cysteinate dimer (ECD) (Neurolite) rather than hexamethyl-propylenamine oxime (HMPAO) (Ceretec), the ligand on which most experience has been accumulated to date. As Lee et al. note,’ there appear to be differences in the pharmacologic properties of these two tracers. Differences in uptake of ECD compared to HMPAO, particularly in the mesial temporal region, have been reported in healthy c ~ n t r o l s . ’ ~ J ~ Differences in uptake of these two isotopes in strokeI5 and brain tumors16 have also been reported. There has been no direct comparison of ECD and HMPAO in ictal SPECT, but our limited experience suggests that ECD images may be more diffcult to interpret and less definitive than HMPAO studies. Our long experience with HMPAO suggests that in approximately 95% of cases of temporal lobe epilepsy, ictal studies yield correct localization. Because of these concerns, we believe that further experience and comparative studies are required before ECD can be regarded as a substitute for HMPAO in ictal SPECT.

Subdural hematoma in spontaneous CSF hypovolemia

Of 67 consecutive patients with spontaneous CSF hypovolemia (SCH), 11 (16.4%) had subdural hematoma (SDH). Patients with SDH were older (p = 0.005), more likely to be male (p = 0.035), and displayed longer time to diagnosis of SCH (p = 0.019) than those without SDH. All patients with SDH showed the findings of pseudo–subarachnoid hemorrhage on CT and responded favorably to epidural blood patches and neurosurgical drainage.

Distribution of the corticobulbar tract in the internal capsule

It is generally thought that the corticobulbar tract descends through the genu of the internal capsule (IC). There have been several reports that genu lesions cause bulbar symptoms such as facial palsies, dysarthria, and dysphagia. However, the precise location of the corticobulbar tract in the IC remains controversial. The purpose of our study is to assess whether the corticobulbar tract passes through the IC genu. We reviewed 26 patients with selective IC infarction and located the sites related to bulbar symptoms. In addition, using diffusion tensor imaging, we reconstructed tracts passing through the IC in ten subjects without cerebral infarction. Patients with genu infarction, which extended to more than half of the posterior limb of the IC, showed bulbar symptoms. However, patients with genu infarction, which was limited to the genu, did not have bulbar symptoms. In contrast, patients with lesions limited to the posterior limb may show bulbar symptoms. According to statistical maps of the region of interest, the lesions related to bulbar symptoms were localized to areas that were beyond the midpoint of the posterior limb of the IC. In diffusion tensor imaging of subjects without cerebral infarctions, the corticobulbar and corticospinal tracts did not pass through the IC genu. Our data provide evidence that the corticobulbar tract does not pass through the IC genu. The proposed location of the corticobulbar tract in the level of the IC lies beyond the midpoint of the posterior limb.

Effect of cilostazol in acute lacunar infarction based on pulsatility index of transcranial Doppler (ECLIPse): a multicenter, randomized, double-blind, placebo-controlled trial.

Background: This study is intended to evaluate the propensities of cilostazol to reduce the pulsatility index (PI) in patients with acute lacunar infarction using the serial transcranial Doppler (TCD) examinations. Methods: In a multicenter, randomized, double-blind, placebo-controlled trial, patients were randomly assigned to receive either placebo or 100 mg cilostazol twice a day as well as aspirin 100 mg a day. The primary outcomes were the changes of middle cerebral artery (MCA) and basilar artery (BA) PIs at 14 and 90 days from the baseline TCD study. This study is registered with ClinicalTrials.gov (NCT00741286). Results: Trial medication was given to 203 patients, with 100 receiving cilostazol and 103 receiving placebo, and 164 were included in the per-protocol analysis of the primary outcome. Results from the linear mixed model showed that significant effects were obtained for time-by-group interactions (p = 0.008 in right MCA, p = 0.015 in left MCA, p = 0.002 in BA), suggesting that changes of PIs from the baseline to the 90-day study were different across the groups. Conclusions: Cilostazol further decreased TCD PIs at 90 days from baseline compared to placebo in acute lacunar infarction. This result may be related to pleiotropic effects, such as vasodilation, beyond its antiplatelet activity.

IL-1β and IL-6 activate inflammatory responses of astrocytes against Naegleria fowleri infection via the modulation of MAPKs and AP-1

Naegleria fowleri, a free‐living amoeba, has been found in diverse habitats throughout the world. It causes primary amoebic meningoencephalitis in children and young adults. The amoeba attaches to nasal mucosa, migrates along olfactory nerves and enters the brain. Astrocytes are involved in the defence against infection and produce inflammatory responses. In this study, we focus on the mechanism of immune responses in astrocytes. We showed, using RNase protection assay, RT‐PCR and ELISA in an in vitro culture system, that N. fowleri lysates induce interleukin‐1beta (IL‐1β) and IL‐6 expression of astrocytes. In addition, cytokine levels of astrocytes gradually decreased due to extracellular signal‐regulated kinase (ERK), c‐Jun N‐terminal kinase (JNK) and p38 inhibitors. To determine the transcription factor, we used transcription inhibitor (AP‐1 inhibitor), which downregulated IL‐1β and IL‐6 expression. These results show that AP‐1 is related to IL‐1β and IL‐6 production. N. fowleri‐mediated IL‐1β and IL‐6 expression requires ERK, JNK and p38 mitogen‐activated protein kinases (MAPKs) activation in astrocytes. These findings show that N. fowleri‐stimulated astrocytes in an in vitro culture system lead to AP‐1 activation and the subsequent expressions of IL‐1β and IL‐6, which are dependent on ERK, JNK and p38 MAPKs activation. These results may imply that proinflammatory cytokines have important roles in inflammatory responses to N. fowleri infection.

Identification of oxidized serum albumin in the cerebrospinal fluid of ischaemic stroke patients

Background and purpose:  Extensive evidence has shown that oxidative stress mediates neuronal death in animal models of hypoxic–ischaemia. Brain biomarkers of oxidative stress need to be identified in order to better understand and treat brain damage in human stroke patients. The present study was conducted to identify potential target proteins of oxidative stress in the cerebrospinal fluid (CSF) of stroke patients with acute ischaemic brain injury.