Vertebrobasilar insufficiency by persistent trigeminal artery stenosis

Persistent trigeminal artery is an embryonic remnant of the anastomotic channel linking the internal carotid artery and the basilar artery. Cases of vertebrobasilar insufficiency caused by the persistent trigeminal artery with internal carotid artery stenosis has been described previously, but vertebrobasilar insufficiency entirely due to in situ stenosis of the persistent trigeminal artery has not been reported. A 71-year-old man presented with frequent dizzy episodes. The brain MRI showed no parenchymal lesions. MR angiography showed poor visualization of vertebrobasilar system. He was diagnosed as having vertebrobasilar insufficiency. Cerebral angiography revealed that there was complete occlusion at the vertebrobasilar junction, and the basilar artery was supplied by the persistent trigeminal artery which had severe stenosis at its origin. There was no stenosis of the internal carotid artery of both sides. We believe that this is the first report of vertebrobasilar insufficiency due to stenosed persistent trigeminal artery, without internal carotid artery stenosis.

Neuropathologic and Clinical Features of Human Medial Temporal Lobe Epilepsy

BACKGROUND AND PURPOSE: There is recent evidence of various types of morphological changes in the hippocampus of a rodent model of medial temporal lobe epilepsy (mTLE). However, little is known about such changes in humans. We examined the histological changes [i.e., neuronal loss, cell genesis, and granule cell dispersion (GCD)] in surgical hippocampal specimens taken from patients with mTLE. METHODS: Nissl staining, and nestin and Prox1 immunohistochemistry were performed on human hippocampal specimens obtained from patients with medically intractable mTLE, thus allowing the analysis of neuronal loss, cell genesis, and GCD, respectively. We also assessed the correlations between clinical parameters and the histopathologic findings. RESULTS: The degree of cell genesis in the granule cell layer was significantly correlated with the severity of GCD, history of childhood febrile seizures, and frequent generalized seizures. Cell genesis was not correlated with cell death, age at seizure onset, duration of epilepsy, or the mean frequency of all seizures. CONCLUSIONS: Our results indicate that cell genesis in the dentate gyrus of patients with mTLE is associated with GCD and is influenced by the presence of febrile seizures during childhood and the frequency of episodes of generalized seizures.

Increased Circulating Endothelial Microparticles and Carotid Atherosclerosis in Obstructive Sleep Apnea

BACKGROUND AND PURPOSE: Endothelial impairment is a linking mechanism between obstructive sleep apnea (OSA) and cardiovascular diseases. Profiles of endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment. The aims of this study were to measure the levels of EMPs and progenitor cells in OSA, determine the correlations between these factors and OSA severity and the degree of atherosclerosis, and document any changes in these factors after therapy. METHODS: Subjects with (n=82) and without (n=22) OSA were recruited prospectively. We measured the number of colony-forming units (CFU) in cell culture as the endothelial progenitor cell index, and the number of EMPs using flow cytometry with CD31 [platelet endothelial cell adhesion molecule (PECAM)], CD42 (platelet glycoprotein), annexin V, and CD62E (E-selectin) antibodies at baseline and after 4-6 weeks of continuous positive airway pressure (CPAP) therapy. Carotid intima-media thickness (IMT) was regarded as a marker of atherosclerosis. RESULTS: The levels of PECAM+CD42- (p<0.001), PECAM+annexin V+ (p<0.001), and E-selectin+ microparticles (p=0.001) were higher in OSA subjects than in non-OSA subjects. The number of CFU did not differ between the two groups. OSA severity independently predicted the levels of PECAM+CD42- (p=0.02) and PECAM+annexin V+ (p=0.004). Carotid IMT was correlated with OSA severity (p<0.001), PECAM+CD42- (p=0.03), and PECAM+annexin V+ (p=0.01). Neither OSA severity nor carotid IMT was correlated with either the number of CFU or E-selectin+. CPAP therapy decreased the occurrence of E-selectin+ (p<0.001) in 21 of the OSA subjects, but had no effect on the other microparticles of the number of CFU. CONCLUSIONS: OSA led to the overproduction of EMPs, which moderately correlated with OSA severity and the degree of atherosclerosis, and partly responded to therapy. The endothelial impairment might contribute to future cardiovascular events.

Stroke Mimicking Encephalopathy as an Initial Manifestation of Diffuse Large B-Cell Lymphoma

BACKGROUND: Systemic lymphoma can be difficult to recognize due to its diverse manifestations. Paraneoplastic leukoencephalopathy has rarely been reported in the context of lymphoma. CASE REPORT: We report a 45-year-old man with systemic lymphoma whose initial manifestation was sudden-onset leukoencephalopathy, mimicking stroke. This patient, who was eventually diagnosed with diffuse large B-cell lymphoma, initially presented with sudden cognitive impairment and gait disturbance. Radiological studies suggested a paraneoplastic leukoencephalopathy. Chemotherapy for lymphoma resulted in clinical and radiological improvement. CONCLUSIONS: The presented case indicates that diffuse large B-cell lymphoma may initially appear as a treatable leukoencephalopathy.

Circulating Endothelial Progenitor Cells in Cerebrovascular Disease

Stroke is associated with high disability and mortality burdens worldwide, but there are few effective and widely available therapies. There is therefore a need to develop treatments that promote the repair and regeneration of ischemic brain tissue. In this regard, a population of adult stem cells-called endothelial progenitor cells (EPCs)-has been identified in peripheral blood that could provide novel approaches in regenerative medicine for curing patients with acute ischemic stroke. There is accumulating evidence that EPCs can repair damaged endothelia and attenuate the development and progression of atherosclerosis. Also, EPCs can be recruited in response to acute ischemic events and participate in reparative vasculogenesis. Most studies related to EPCs have involved patients with cardiovascular diseases, and there is emerging evidence that EPCs represent a risk marker and a potential therapeutic agent in cerebrovascular disease. Here we review the characteristics and biology of EPCs in cerebrovascular disease and discuss the challenges that must be addressed to clarify the role and therapeutic applicability of EPCs in cerebrovascular disease.

Truncal Contrapulsion in Pretectal Syndrome

Truncal contrapulsion in association with pretectal syndrome has not been described previously. We report a patient with vertical-gaze palsy and severe truncal contrapulsion due to an infarction in the mesodiencephalic junction. Truncal contrapulsion in this patient may have resulted from the disruption of the ascending fibers in the crossed cerebellothalamic tract.

Analysis of 10,811 Cases with Acute Ischemic Stroke from Korean Stroke Registry: Hospital-Based Multicenter Prospective Registration Study

BACKGROUND: Although several hospital-based stroke studies were published, there has not been any reliable data representing the clinical characteristics of stroke in Korea. We analyzed the clinical characteristics of patients with ischemic stroke registered in the Korean Stroke Registry (KSR), which is the largest prospective hospital-based nation-wide stroke registry in Korea. METHODS: The KSR provided standardized protocols for collecting data, which includes the data of demographics, subtypes of stroke, risk factors, and neurological outcome at discharge. The brain imaging studies, including CT or MRI, were performed in all cases. RESULTS: KSR registered 10,811 patients of acute ischemic stroke between Nov. 2002 and Jun. 2004. The large-artery atherosclerosis was the most common subtype (37.3%), followed by small vessel occlusion (30.8%). Hypertension (65.4%) was the most common risk factor, followed by smoking (34.5%) and diabetes (28.3%). Although most of the hypertensive and diabetic patients had been diagnosed before the stroke, less than 45.4% and 32.5% of them were under regular control. The steno-occlusive lesion of extracranial carotid artery was only 29.3% and the ratio of intra- to extracranial artery disease was more than 2 in KSR. Only 20.5% of patients were admitted within 3 hours after stroke onset and 2.1% were treated with intravenous thrombolysis. In-hospital case-fatality was 5.2%, which is relatively comparable to those of previous studies. CONCLUSIONS: The KSR provided informative data in understanding the clinical characteristics of ischemic stroke in Korea. Further analysis of KSR will facilitate clinical trials and development of guidelines for the management of stroke patients.

Endogenous Neural Stem Cell Proliferation after Intracerebral Hemorrhage in Rat Model

BACKGROUND: Focal and global ischemia was shown to be potent in inducing neurogenesis in the subventricular zone (SVZ). However, it is unknown whether these new neurons can replace those lost following damage, such as intracerebral hemorrhage (ICH). We tested the hypothesis that ICH leads to an increase of cell proliferation in the SVZ and that the new neurons migrate into the damaged area of the hemorrhagic striatum. METHODS: Experimental ICH was induced by an intrastriatal administration of collagenase in adult rats. Proliferating cells were labeled with intraperitoneal injections of 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU) over 3-day periods before sacrificing the animals, 0, 6, 9, 12 or 15 days after ICH. BrdU+ cells in the dorsolateral SVZ and the striatum were counted in three coronal sections per animal. RESULTS: BrdU+ cells were found in the bilateral SVZs, the third ventricle, and ipsilateral cortex near the needle insertion site. The number of BrdU+ cells in the damaged striatum and the ipsilateral SVZ reached maximum counts 9 days after ICH. The BrdU+ cells were double-labeled with a neuronal marker, neuronal nuclear antigen (NeuN), and a glial marker, the glial fibrillary acidic protein (GFAP), in the hemorrhagic hemisphere. The percentage of BrdU+ cells that expressed NeuN and GFAP was about 13% and about 72%, respectively. CONCLUSIONS: These results suggest new evidence that endogenous neural stem cells are activated in the dorsolateral SVZ after ICH, and that the newly formed cells play a role for ICH-induced neurogenesis in what may be an adaptive process that contributes to recovery after a hemorrhagic stroke.

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.

Forntal Lobe Epilepsy Presenting with Blinking and Leg Jerking

Eye blinking is a rare semiology in frontal lobe epilepsy. However, eye blinking with leg jerking as a manifestation of simple partial seizure has not been reported. We report a patient with frontal oligodendroglioma who showed simple partial seizure presenting with eye blinking and leg jerking.

Neural Stem Cells for Neurological Disorders

Recent progress shows that neurons suitable for transplantation can be generated from neural stem cells (NSCs) in culture, and that the adult brain produces new neurons from its own stem cells in response to injury. In this article, we discuss how the subventricular zone of the forebrain is the most active neurogenetic area and the richest source of NSCs. This review also focuses on the nature and functional properties of NSCs of the adult mammalian brain, and we propose our views on the strategy from bench to the clinic with particular concerns and considerations.

Optical Imaging in the Field of Molecular Imaging

Molecular imaging is leading an important role in the era of molecular medicine. Optical imaging, a rising star in the filed of molecular imaging, largely consists of fluorescent imaging and bioluminescent imaging. In the fluorescence imaging, an illuminating light excites fluorescent reporters in the living subject, and a charged coupled device (CCD) camera collects an emission light of shifted wavelength. In the bioluminescent imaging, reporter genes code for the luciferase that is responsible for fireflies' glow. After the injection of the substrate iuciferin, animals carrying the luciferase gene are imaged with a supersensitive CCD camera to pick up the small number of photons transmitted through tissues. It has been shown that well aimed and creatively built reporters let researchers explore and answer a lot of biologically important questions in living subjects. Despite its relatively short history, optical imaging is rapidly being implemented in various clinical areas as well as research fields.

Limb-Shaking Transient Ischemic Attack due to Stenosis of the Middle Cerebral Artery: Case Report

We present a case of a 51-year-old man with frequent left limb-shaking transient ischemic attacks due to severe stenosis of the right proximal middle cerebral artery(MCA). The involuntary movement was provoked by walking and it was relieved by adopting a squatting posture. Initially, we tried antiepileptic medication, but it did not eliminate the involuntary movement. Cerebral angiography and single photon emission computed tomography demonstrated decreased perfusion and reserve capacity of the right cerebral hemisphere which correspond to stenotic proximal MCA territory. After superficial temporal artery to MCA anastomosis, the decreased reserve capacity was restored and his limb-shaking attack completely disappeared. His history of radiotherapy for craniopharyngioma, in addition to hypercholesterolemia and diabetes mellitus, seems to have contributed to gradual stenosis of right MCA.

Human Neural Stem Cells Transplantation in Experimental Intracerebral Hemorrhage

BACKGROUND: Intracerebral hemorrhage (ICH) is associated with a considerable proportion of stroke and head injuries, but except for supportive care, there is no medical therapy available. Transplantation of human neural stem cells (NSCs) can be used to reduce behavioral deficit in experimental ischemic infarct model. However, effect of stem cell transplantation in experimental intracerebral hemorrhage (ICH) is unknown. We hypothesized that NSCs could migrate and differentiate into neurons or glial cells, and improve functional outcome in ICH. METHODS: Experimental ICH was made by intrastriatal administration of bacterial collagenase in adult rats. Animals were randomized to receive intravenously either immortalized Lac-Z positive human NSCs (5x1 06 in 500microL, n=15) or same volume of saline (n=12) on the following day. Animals were evaluated for 8 weeks after surgery with behavioral test battery. After 8 weeks, animals were sacrificed and the brains were sectioned. Transplanted NSCs were detected by X-gal histochemistry or beta-gal immunohistochemistry, and differentiation of grafted NSCs were evaluated by double labeling of GFAP, NeuN, or neurofilament. RESULTS: Transplanted NSCs migrated to the side of peri-hematomal areas, and differentiated into neurons and astrocytes. NSCs injection group showed improved performances on rotarod test after 2 weeks and on limb placing test after 5 weeks compared with control group (p<0.05) and these effect persisted up to 8 weeks. CONCLUSIONS: Intravenously injected NSCs enter rat brain with ICH, and differentiate into astrocytes or neuronal cell, which lead to functional recovery. These findings show the possibility that NSCs can be used to reduce neurological deficits in the experimental ICH.

Delayed Up-regulation of Vascular Endothelial Growth Factor and flk-1 after Global Cerebral Ischemia in Mongolian Gerbil: Possible roles in neuroangiogenesis?

BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen and a potent mediator of vascular permeability. Flk-1, one of the receptors for VEGF, is important in vascular development. Increased expression of VEGF is related with reactive astrogliosis, which stimulates the proliferation of neural progenitor cells. VEGF expression increases in the acute phase of cerebral ischemia, however the expression of VEGF together with flk-1 in subacute stage is still unknown. This study is done to demonstrate the spatial/cellular patterns of expression for VEGF/flk-1 up to subacute stages and to find out the role of VEGF in ischemia. METHODS: Transient global ischemia was induced by a 10 min-occlusion/reperfusion of the bilateral carotid arteries in the Mongolian gerbil. Immunohistochemistry and western blot were performed to ensure the expression of VEGF and flk-1 on the day 1, 3, 7, 14, and 28. RESULTS: Both VEGF and flk-1 initially increased at day1, and decreased at day 3. Thereafter, VEGF gradually increased again to the initial level at day 7 and to the peak level after day 14. Flk-1 showed a peak expression at day 14, and then decreased at day 28. Immunohistochemical staining for VEGF showed immunoreactivity mainly on the cytoplasm of neurons and endothelium in cortex and hippocampus at day 1, and neuron, endothelium, and glial cell from day 14 to 28. The distribution and chronological patterns of flk-1 expression were similar to that of VEGF expression. CONCLUSIONS: We suggest that global cerebral ischemia can induce a delayed up-regulation of VEGF and flk-1, which may be associated with neuroangiogenesis and repair process.

Stroke Awareness in Korea : The Results of Survey in the Second Stroke Prevention Campaign

BACKGROUND: Assessing public knowledge concerning stroke and its risk factors is the starting point in developing the effective stroke prevention program. The aim of this study was to investigate the awareness of stroke risk factors and factors influencing it. METHODS: All who participated in the second stroke prevention campaign were encouraged to answer the survey. It was performed using a standard questionnaire designed to assess the awareness of stroke risk factors, its correlation with usual demographic characteristics, history of stroke, and self-assessment of stroke risk. The number of established risk factors on an open question estimated the awareness of stroke risk factors. RESULTS: Nationwide 4065 persons took part in the campaign and 43% of them (1749) responded the survey (age=65.4+/-12.2, male=34.2%). A total of 986 responders (56.4%) correctly listed at least one of the established stroke risk factors to open question. Age and schooling were the significant predictors for listing at least one of the established stroke risk factors on multivariate analysis. Number of classic risk factors of stroke in each subject was significantly correlated with self-assessment of stroke risk. Most of the individual risk factors of stroke were also correlated with self-assess-ment of stroke risk but smoking and old age (65 years or more) were not. CONCLUSIONS: This study suggests that the level of stroke risk awareness in Korea is not high, especially among the elderly and the lowly educated. The systematic public education program is warranted.

Cerebrovascular Disease : Overview and Classification

Stroke is a common cause of death in South Korea. The etiology of stroke affects prognosis, outcome, and management. Trials of therapies for patients with acute stroke should include measurement of responses as influenced by the subtypes of stroke. Stroke can be classified into ischemic and hemorrhagic stroke. Ischemic stroke classification denotes five subtypes of ischemic stroke : ① large-artery atheromatous disease, ② cardioembolism, ③ lacunes, ④ stroke of other causes, and ⑤ transient ischemic attack. Hemorrhagic stroke can be classified into ① intracerebral hemorrhage, ② subarachnoid hemorrhage, and ③ other hemorrhages. Stroke is a syndrome with various etiologies, and proper classification is important for the treatment and prognosis. Risk factors for stroke such as hypertension, heart disease, smoking, diabetes, and hypercholesterolemia should be controlled properly. Clinical trials testing new treatment for acute stroke are on-going worldwide, and it is appropriate to standardize the classification of stroke.

Expression and Neuroprotection of Vascular Endothelial Growth Factor in an in vitro Ischemia

BACKGROUND: Vascular endothelial growth factor (VEGF) is an angiogenic peptide that enhances microvascular perfusion. Recently, VEGF is known to have neurotrophic effect and rescues neurons from cell death induced by serum deprivation. To investigate the serial changes in VEGF expression and neuroprotective properties of VEGF during acute ischemia. METHODS: Human cortical-neuroblastoma hybrid cell line (A1G11), human neuroglioma cell line (H4), and human vascular endothelial cell line (ECV304) were placed in the glucose/serum free media and incubated in the hypoxic chamber (94% N2/5% CO2/1% room air) at 37 degrees C. Cell viability was determined by MTT assay. Western blot analysis was performed to detect VEGF and its receptor (VEGFR) expression. To test the protective effect of VEGF, human recombinant VEGF165 was used. RESULTS: Morphological changes and the decrease of cell viability were observed following 6 hr ischemia. In A1G11 cells, VEGF expression was not noted until 3 hr ischemia, but was induced after 6hr and continued to 12 hr and then diminished. In H4 and ECV304, the change of VEGF expression was not observed. VEGFR-2/Flk-1 expression was induced from 6 hr (peak level) to 12 hr in A1G11, and induced after 3 hr and continued to 12hr in ECV304. Administration of VEGF increased cell viability in A1G11 cells at 6 hr, 12 hr and 18 hr ischemia (p=0.009, p=0.01 p=0.013), but not in H4 or ECV304 cells ( p>0.05). CONCLUSION: Ischemia induces VEGF production in neurons and VEGF may exert a direct neuron-specific protective effect through VEGFR-2/Flk receptors during the acute phase of ischemic neuronal injury.

Combined Effect of Hypothermia and Hyperglycemia onTransient Focal Cerebral Ischemia of the Rat

BACKGROUND: In experimental cerebral ischemia, hypothermia protects the brain, while hyperglycemia aggravates ischemic damage. Clinical studies have also reported worse outcomes in ischemic stroke patients with hyperglycemia or fever and improved outcomes with hypothermic therapy. However, it is not well known what will happen if these opposite effects exist together. METHODS: Sixty male Sprague-Dawley rats were used. Focal cerebral ischemia was induced for 2 hours by an intraluminal thread followed by reperfusion for 4 hours. Rats were divided into 4 groups; 1) normo-glycemic normothermic (NGNT), 2) normoglycemic hypothermic (low temperature) (NGLT), 3) hyperglycemic normothermic (HGNT), and 4) hyperglycemic hypothermic (HGLT) groups (n=15 for each group). Hyperglycemia wasmade by intraperitoneal injection of streptozotocin (60 mg/kg) 3 days before ischemia. The body temperature was maintained at 37+/-1 degrees C in normothermic animals, while lowered at 32+/-1 degrees C in hypothermic animals during the ischemic period. Following reperfusion, 2-mm thick coronal slices were obtained and stained by triphenyltetrazolium chloride. The infarct volume was measured using an image analyzer. RESULTS: Mean glucose levels (mean+/-SD in mg/dl) were 77.9+/-9.3 in NGNT, 77.7+/-11.5 in NGLT, 311.0+/-69.2 in HGNT, and 355.3+/-57.7 in HGLT. Mean infarct volumes (mean+/-SD in mm 3) were 168.2+/-44.2 in NGNT, 66.2+/-24.2 in NGLT, 417.6+/-123.2 in HGNT, and 337.2+/-89.3 in HGLT. The protective effect of hypothermia was less evident in hyperglycemic rats and the aggravating effect of hyper-glycemia was more evident in hypothermic rats. Infarct volume of HGLT was 2-fold bigger than that of NGNT (p<0.05). CONCLUSIONS: Our results suggest that the detrimental effect of hyperglycemia may override the protective effect of hypothermia in transient focal cerebral ischemia.

Neuronal Cytoskeletal Abnormalities and Neurotrophin Receptor Immunoreactivity in Severe Cerebral Cortical Dysplasia

BACKGROUND: Cerebral cortical dysplasia (CD) is one of the important causes of intractable epilepsies and characterized histologically by disorganized cortical lamination and cytomegalic dysplastic neurons. Although various cytoskeletal abnormalities have been found in dysplastic neurons of CD, the pathogenetic role of dysplastic neurons has rarely been investigated. METHODS: In this study, immunohistochemical analysis was performed using antibodies against non-phosphorylated high- or medium-molecular weight neurofilament protein and microtubule-associated protein 2 (MAP-2) in surgical specimens of CD. In order to know the possible relationship of dysplastic neurons with cytoskeletal abnormalities and various neurotrophin receptors, NGFR p75, trkA, trkB, and trkC immunoreactivities were also analyzed. RESULTS: Dysplastic neurons showed strong immunoreactivities for non-phosphorylated high- or medium-molecular weight neurofilament protein and MAP-2, which might reflect abnormal outgrowth and altered plasticity of the dysplastic neurons. TrkB and trkC were strongly expressed in dysplastic neurons and NGFR p75 was also strongly expressed in some dysplastic neurons. CONCLUSIONS: Since it has been known that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have effects on the differentiation of neuronal precursor cells from the cortex and on dendritic and axonal arborization, increased expression of trkB and trkC may play a role in cytoskeletal abnormalities and altered synaptic transmission in dysplastic neurons.