Long-term observation of lateral medullary infarction due to vertebral artery dissection assessed with multimodal neuroimaging.

A 33-year-old man presented with a lateral medullary infarction, vertigo, and nausea. At the time of hospital admission, he had Wallenberg syndrome. Although initial magnetic resonance imaging showed no abnormalities, subsequent diffusion-weighted magnetic resonance imaging showed a high-intensity area in the right lateral medulla oblongata. The right vertebral artery was shown to be dilated on basi-parallel anatomical scanning but to be stenosed on magnetic resonance angiography (MRA). Cerebral angiography 7 days after onset showed the "pearl and string sign" in the right vertebral artery. Follow-up MRA showed gradual improvement of the stenosis in the right vertebral artery. Multiple neuroimaging studies, such as MRA, basi-parallel anatomical scanning, 3-dimensional computed tomographic angiography, and cerebral angiography, should be performed soon after onset in suspected cases of cerebral artery dissection. In addition, serial imaging examinations increase diagnostic accuracy, and the medical history and neurological examination are important.

Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer's disease.

Stem cell transplantation therapy is currently in clinical trials for the treatment of ischemic stroke, and several beneficial aspects have been reported. Similarly, in Alzheimer's disease (AD), stem cell therapy is expected to provide an efficient therapeutic approach. Indeed, the intracerebral transplantation of stem cells reduced amyloid-ß (Aß) deposition and rescued memory deficits in AD model mice. Here, we show that intravenous transplantation of bone marrow-derived mononuclear cells (BMMCs) improves cognitive function in two different AD mouse models, DAL and APP mice, and prevents neurodegeneration. GFP-positive BMMCs were isolated from tibiae and femurs of 4-week-old mice and then transplanted intravenously into DAL and APP mice. Transplantation of BMMCs suppressed neuronal loss and restored memory impairment of DAL mice to almost the same level as in wild-type mice. Transplantation of BMMCs to APP mice reduced Aß deposition in the brain. APP mice treated with BMMCs performed significantly better on behavioral tests than vehicle-injected mice. Moreover, the effects were observed even with transplantation after the onset of cognitive impairment in DAL mice. Together, our results indicate that intravenous transplantation of BMMCs has preventive effects against the cognitive decline in AD model mice and suggest a potential therapeutic effect of BMMC transplantation therapy.

Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer's disease.

Oxidative stress is known to play a prominent role in the onset and early stage progression of Alzheimer's disease (AD). For example, protein oxidation and lipid peroxidation levels are increased in patients with mild cognitive impairment. Here, we created a double-transgenic mouse model of AD to explore the pathological and behavioral effects of oxidative stress. Double transgenic (APP/DAL) mice were constructed by crossing Tg2576 (APP) mice, which express a mutant form of human amyloid precursor protein (APP), with DAL mice expressing a dominant-negative mutant of mitochondrial aldehyde dehydrogenase 2 (ALDH2), in which oxidative stress is enhanced. Y-maze and object recognition tests were performed at 3 and 6 months of age to evaluate learning and memory. The accumulation of amyloid plaques, deposition of phosphorylated-tau protein, and number of astrocytes in the brain were assessed histopathologically at 3, 6, 9, and 12-15 months of age. The life span of APP/DAL mice was significantly shorter than that of APP or DAL mice. In addition, they showed accelerated amyloid deposition, tau phosphorylation, and gliosis. Furthermore, these mice showed impaired performance on Y-maze and object recognition tests at 3 months of age. These data suggest that oxidative stress accelerates cognitive dysfunction and pathological insults in the brain. APP/DAL mice could be a useful model for exploring new approaches to AD treatment.

Acute vertebral artery origin occlusion leading to basilar artery thrombosis successfully treated by angioplasty with stenting and thrombectomy.

Few reports have described the successful treatment of stroke caused by acute vertebral artery (VA) origin occlusion by endovascular surgery. We describe the case of a 68-year-old man who experienced stroke due to left acute VA origin occlusion. Cerebral angiography showed that the left VA was occluded at its origin, the right VA had hypoplastic and origin stenosis, and the basilar artery was occluded by a thrombus. The VA origin occlusion was initially passed through with a 0.035-inch guide wire. An angioplasty was performed, and a coronary stent was appropriately placed. The VA origin was successfully recanalized. A balloon-assisted guiding catheter was navigated through the stent and a thrombectomy was performed using the Penumbra system. The patient's symptoms gradually improved postoperatively. Balloon-assisted catheter guidance through a vertebral artery stent permitted a successful thrombectomy using the Penumbra system and may be useful for treating stroke due to VA origin occlusion.

Aortic arch atherosclerosis in ischaemic stroke of unknown origin affects prognosis.

BACKGROUND: Cerebral infarction of unknown origin at admission accounts for half of all cerebral infarction cases in some institutions. However, the factors associated with cerebral infarction prognosis have not been sufficiently examined. Here, we investigated whether aortic arch plaques (AAPs) on transoesophageal echocardiography (TOE) were associated with the prognosis of cerebral infarction of unknown origin at admission. METHODS: Of 571 patients who were hospitalised between June 2009 and September 2011, 149 (age: 67 ± 14 years; 95 men) with cerebral infarctions of unknown origin at admission underwent TOE and were enrolled in this study. We examined their clinical characteristics, the incidence of intermittent atrial fibrillation detected on 24-hour electrocardiography, and the echographic findings of the carotid artery in the hospital. A poor prognostic outcome was defined as a modified Rankin Scale score of ≥3 after 90 days. RESULTS: In all, 110 patients (74%) showed good prognoses and 39 patients (26%) showed poor outcomes. A National Institutes of Health Stroke Scale score of >6 on admission [odds ratio (OR) = 6.77; 95% confidence interval (CI): 2.59-18.8; p < 0.001] and AAPs of ≥4 mm (OR = 2.75; 95% CI: 1.19-6.91; p = 0.024) showed significant associations with a poor prognosis of cerebral infarction of unknown origin at admission. CONCLUSIONS: Thick AAPs could be a factor in the prediction of a poor prognosis of cerebral infarction of unknown origin at admission. The establishment of international standards for aortogenic brain embolisms is required. Future prospective studies should examine cerebral infarctions of unknown origin.

The effect of cilostazol and aspirin pre-treatment against subsequent transient focal cerebral ischemia in rat.

OBJECTIVES: Among several anti-platelet drugs to prevent recurrent stroke, cilostazol has shown various effects besides its anti-platelet activity. We examined whether 7 days of oral administration of cilostazol protects against subsequent cerebral ischemia, and whether or not the effect of combination therapy with aspirin is more protective. METHODS: We used Sprague-Dawley (SD) rats and assigned them to four groups: vehicle, aspirin, cilostazol, and aspirin plus cilostazol combination therapy. After oral administration of anti-platelets for 7 days, we performed transient middle cerebral artery occlusion (MCAO) for 90 minutes, and examined infarct volume, neurological symptoms, and regional cerebral blood flow (rCBF). Immunostaining of Bax, Bcl-2, TUNEL, 4-HNE, 8-OHdG, and COX-2 was performed 24 hours after ischemia. RESULTS: The cilostazol group and the combination therapy group showed significant decreases of infarct volume and significant improvements of rCBF during ischemia, compared with the vehicle or aspirin group. Significant decreases of Bax, TUNEL, 8-OHdG, and 4-HNE expression in the combination therapy group, compared with those in the vehicle or aspirin group, were shown in the boundary zone. COX-2 expression was unexpectedly increased in the combination therapy group. DISCUSSION: Aspirin co-administration did not inhibit this effect. The addition of the oral administration of cilostazol either alone or with aspirin administration may be beneficial for subsequent cerebral ischemic damage in terms of reducing infarct volume, improving rCBF during ischemia, inhibiting the apoptotic pathway, and reducing oxidative stress.

Continuous oral administration of atorvastatin ameliorates brain damage after transient focal ischemia in rats.

AIMS: Pre-treatment with statins is known to ameliorate ischemic brain damage after experimental stroke, and is independent of cholesterol levels. We undertook pre- vs post-ischemic treatment with atorvastatin after focal cerebral ischemia in rats. MAIN METHODS: Male Sprague-Dawley rats underwent transient 90-min middle cerebral artery occlusion (MCAO). Atorvastatin (20mg/kg/day) or vehicle was administered orally. Rats were divided into vehicle-treated, atorvastatin pre-treatment, atorvastatin post-treatment, and atorvastatin continuous-treatment groups. In the pre-treatment, rats were given atorvastatin or vehicle for 7 days before MCAO. In the post-treatment, rats received atorvastatin or vehicle for 7 days after MCAO. Measurement of infarct volume, as well as neurological and immunohistochemical assessments, were done 24h and 7 days after reperfusion. KEY FINDINGS: Each atorvastatin-treated group demonstrated significant reductions in infarct and edema volumes compared with the vehicle-treated group 24h after reperfusion. Seven days after reperfusion, infarct volumes in the post-treatment group and continuous-treatment group (but not the pre-treatment group) were significantly smaller than in the vehicle-treated group. Only the continuous-treatment group had significantly improved neurological scores 7 days after reperfusion compared with the vehicle group. Post-treatment and continuous-treatment groups had significantly decreased lipid peroxidation, oxidative DNA damage, microglial activation, expression of tumor necrosis factor-alpha, and neuronal damage in the cortical ischemic boundary area after 7 days of reperfusion. SIGNIFICANCE: These results suggest that continuous oral administration (avoiding withdrawal) with statins after stroke may reduce the extent of post-ischemic brain damage and improve neurological outcome by inhibiting oxidative stress and inflammatory responses.

Multiple vascular accidents including rupture of a sinus of valsalva aneurysm, a minor ischemic stroke and intracranial arterial anomaly in a patient with systemic congenital abnormalities: a case report.

A 39-year-old man with a history of rupture of a sinus of Valsalva aneurysm experienced an ischemic stroke. Although the patient presented left-sided hemiparesis for a week, no abnormal signals were indicated on diffusion-weighted imaging with repeated magnetic resonance scans. Carotid ultrasound and cerebral angiography were conducted, and they revealed hypoplasty of the left internal carotid artery with a low-lying carotid bifurcation at the level of the C6 vertebra. In addition, he was diagnosed with intellectual disabilities, evaluated by the Wechsler Adult Intelligence Scale-III, and congenital velopharyngeal insufficiency. We herein present the first report of a patient with cardio-cerebrovascular abnormalities, intellectual disabilities, and an otorhinolaryngological abnormality.

Low serum n-3 polyunsaturated fatty acid/n-6 polyunsaturated fatty acid ratio predicts neurological deterioration in Japanese patients with acute ischemic stroke.

BACKGROUND: Epidemiological and clinical trials have shown that n-3 polyunsaturated fatty acids (PUFAs) reduce the incidence of coronary heart disease or stroke. However, the association between PUFAs and acute-phase stroke has not yet been thoroughly studied. We investigated the impact of serum PUFAs on early neurological deterioration (END) in patients with acute ischemic stroke. METHODS: In this retrospective study, we enrolled 281 Japanese patients (mean age: 75 ± 13 years; 165 males) with acute ischemic stroke diagnosed within 24 h of onset. General blood examinations, including PUFAs (n-3 PUFAs: eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA, and n-6 PUFAs: arachidonic acid, AA), were performed on admission. Other risk factors and comorbidities were also examined. END was defined as a ≥2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score within a 72-hour period. Statistical significance between the END and non-END group was assessed using Wilcoxon rank sum tests or Student's t tests for categorical variables. Multiple logistic regression analyses were performed to identify predictors of END. RESULTS: END was observed in 75 patients (26.7%). Diabetes mellitus (p = 0.003), high-sensitivity C-reactive protein (hs-CRP) level (p < 0.001), prior stroke (p = 0.035), ischemic heart disease (p = 0.029), EPA/AA ratio (p = 0.003), DHA/AA ratio (p = 0.002), EPA+DHA/AA ratio (p = 0.002), diagnosis of small vessel disease (p = 0.004) and admission NIHSS score (p < 0.001) were significantly associated with END. We used separate multiple logistic regression analyses for the EPA/AA, DHA/AA and EPA+DHA/AA ratios, because EPA and DHA are considered covariant factors (r = 0.544; p < 0.0001). Multiple logistic regression analyses showed that END was positively associated with diabetes mellitus, hs-CRP level and NIHSS score on admission, and negatively associated with the EPA/AA ratio (odds ratio, OR: 0.18; 95% confidence interval, CI: 0.05-0.58; p = 0.003), DHA/AA ratio (OR: 0.045; 95% CI: 0.006-0.30; p = 0.001), EPA+DHA/AA ratio (OR: 0.45; 95% CI: 0.26-0.74; p = 0.002) and diagnosis of small vessel disease. CONCLUSIONS: Our data suggest that a low serum n-3 PUFA/n-6 PUFA ratio on admission may predict neurological deterioration in Japanese patients with acute ischemic stroke. Large-scale prospective studies are further required to clarify the role of PUFAs in the acute phase of ischemic stroke.

Successful treatment of cerebral venous thrombosis associated with ulcerative colitis.

Thromboembolic complications, such as deep venous thrombosis and pulmonary embolism, are well described in patients with inflammatory bowel disease, but cerebral venous thrombosis (CVT) is a rare but potentially devastating complication. The authors describe the case of a 36-year-old Japanese man presenting with CVT associated with ulcerative colitis (UC) that was successfully treated with a combination of continuous anticoagulant and pulse steroid therapy. Our observations suggest that aggressive therapy for inducing acute UC remission is vitally important for CVT associated with UC.

Valproic acid attenuates ischemia-reperfusion injury in the rat brain through inhibition of oxidative stress and inflammation.

Valproic acid (VPA), widely used in clinical contexts for the treatment of seizures and bipolar mood disorder, has neuroprotective properties in cellular and animal models. However, the precise mechanisms underlying its neuroprotection against stroke remain unknown. In the present study, we explored the effect of VPA on experimental ischemic stroke. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 90 min, followed by reperfusion. The animals received a single injection of VPA (300 mg/kg) immediately, 90, or 270 min after the induction of ischemia. Vehicle-treated animals underwent the same procedure with physiological saline. Infarct volume and neurological symptoms were evaluated 24 h after reperfusion. Immunohistochemical staining for myeloperoxidase (MPO), microglia (Iba1), 4-hydroxy-2-nonenal (4-HNE), or 8-hydroxy-deoxyguanosine (8-OHdG) was performed. Ischemic boundary zone cell death was determined by TUNEL staining. VPA injected immediately or 90 min after ischemia induction significantly reduced infarct volume and improved neurological deficit compared with vehicle (P<0.05). VPA was ineffective when given 270 min after ischemia induction. VPA significantly reduced TUNEL-positive cells, MPO-positive cells, Iba1-positive cells, 4-HNE-positive cells, and 8-OHdG-positive cells compared with vehicle in the ischemic boundary zone (P<0.05). The therapeutic time window for single injection of VPA is between 0 and 90 min in this model. Our results demonstrate that single injection of VPA may have anti-inflammatory as well as antioxidative effects, leading to reduced cell death in ischemia-reperfusion injury.

Administration of cilostazol, an antiplatelet, to patients with acute-stage cerebral infarction and its effects on plasma substance P level and latent time of swallowing reflex.

BACKGROUND AND OBJECTIVE: It has been reported that medical treatment with cilostazol (cilo) as an antiplatelet may increase a substance P level in the striatum to shorten the latent time of swallowing reflex (LTSR). We undertook a pilot study to confirm whether cilo administration to patients with cerebral infarction is effective in increasing their plasma substance P level and then in ameliorating the status of LTSR. METHODS AND SUBJECTS: Eligible subjects were recruited, after informed consents, from 20 hospitalized patients with acute-phase cerebral infarction within 72 hours from the onset. At the start of treatment, the subjects were assigned at random to those given aspirin alone (non-cilo group) and those given aspirin plus cilo (cilo group). Plasma substance P levels and LTSR values were measured at the starting point (baseline), 28 days after, and 180 days after. RESULTS AND DISCUSSION: No significant time-dependent change in plasma substance P level was found probably because of large individual differences but, 28 days after the start of treatment, this value tended to become higher in cilo group than in non-cilo group (P<0.10). Whereas, in terms of fold changes of LTSR in cilo group, there was a significant between-term difference at P<0.05, indicating that this medication is effective in ameliorating the swallowing function is improved in the long run. CONCLUSION: The LTSR values was significantly shortened within 180 days after the start of cilo treatment, but the result was not well explained by substance P levels as far as these were measured using the plasma, probably because this substance had diluted during blood circulation. However, it will become clinically usable as a single swallowing index, if in the future some ingeneus method of its measurement is developed. A larger-scale study would also be needed to confirm our conclusion from this pilot study.

Brain protection therapy in acute cerebral infarction.

Many drugs for cerebral infarction that were shown to be effective in animal experiments have shown negative results in human clinical trials. For this reason, a completely new approach is needed to develop brain protection therapies against cerebral infarction. Brain protection therapies can be categorized into 3 types: 1) lengthening the therapeutic time window for thrombolytic therapy, 2) reducing the side effects of thrombolytic therapy, and 3) brain protection drug therapy for patients with contraindications for thrombolytic therapy (including combination therapy). Here, we show our recent results of brain protection therapy. First, combination therapy with 2 effective drugs was tried, and time-lag administration was performed. Combination therapy was effective and lengthened the therapeutic time window. Next, a completely new approach to improve cerebral ischemic damage, namely, H2 gas inhalation therapy, was tried. This therapy was also effective, even in the ischemic core.

Blood pressure control in patients with chronic kidney disease.

Chronic kidney disease (CKD) is defined as either kidney damage or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 for more than 3 months. Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies. CKD is classified as stage 1 to 5 on the basis of eGFR. Cardiovascular disease (CVD) carries a reciprocal risk of loss of kidney function in patients with chronic kidney disease (CKD) and with the development of kidney disease. CVD is a major cause of morbidity and mortality in patients with CKD. Blood pressure control in patients with CKD aims to prevent CVD and provide renoprotection. The renin-angiotensin system (RAS) is involved in every stage of the progression of CKD and is, therefore, a critical link in the pathologic relationship between hypertension and renal disease. The first-line agents for controlling blood pressure are inhibitors of the RAS: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. These agents have been shown to have renoprotective effects in addition to their ability to control blood pressure. In CKD, the target blood pressure is less than 130/80 mm Hg, or 125/75 mm Hg, if amount of urinary protein is more than 1 g/day. To achieve the target blood pressure, other classes of antihypertensive agents, such as diuretics and calcium channel blockers, should be administered in addition to angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers.

A case of dural arteriovenous fistulas at the craniocervical junction presenting with occipital/neck pain associated with sleep.

Venous congestive myelopathy associated with spinal dural arteriovenous fistulas (DAVFs) is a treatable disorder that can be controlled without sequelae if it is diagnosed at an early stage. It is important to consider spinal DAVFs in the differential diagnosis based on clinical history and neurologic examination. We report the unique case of a patient with DAVFs at the craniocervical junction presenting with occipital/neck pain associated with sleep.

Mild hypothermia enhanced the protective effect of protein therapy with transductive anti-death FNK protein using a rat focal transient cerebral ischemia model.

We previously reported that the protein transduction domain fused FNK (PTD-FNK) protein, which was derived from anti-apoptotic Bcl-xL protein and thereby gained higher anti-cell death activity, has a strong neuroprotective effect on rat focal brain ischemia models. The aim of this study was to investigate the effect of PTD-FNK protein and hypothermia combined therapy on cerebral infarction. Male SD rats were subjected to 120min middle cerebral artery occlusion (MCAO) with intraluminal thread. Rats were divided into 4 groups: 1) 37°C vehicle administration (37V); 2) 37°C PTD-FNK administration (37F); 3) 35°C vehicle administration (35V); and 4) 35°C PTD-FNK administration (35F). PTD-FNK protein was intravenously administered 60min after the induction of MCAO. Hypothermia (35°C) was applied during 120min MCAO. Rats were sacrificed 24h later; infarct volumes were measured, and Bax, Bcl-2, TUNEL and caspase-12 immunostaining was evaluated. There was significant infarct volume reduction in 37F, 35V, and 35F groups compared to 37V. There was also a significant difference between 37F and 35F. This suggests that hypothermia enhanced the effect of PTD-FNK. Similar results were found in neurological symptoms. Caspase-12 and TUNEL staining showed a significant difference between 37F and 35F; however, Bax and Bcl-2 staining failed to show a difference. In this study we showed an additive protective effect of hypothermia on PTD-FNK treatment, and immunohistological results showed that the protective mechanisms might involve the inhibition of apoptotic pathways through caspase-12, but not through Bcl-2.

FK506 ameliorates oxidative damage and protects rat brain following transient focal cerebral ischemia.

OBJECTIVE: The immunosuppressant FK506 (tacrolimus) is neuroprotective in experimental models of cerebral ischemia. However, the precise mechanisms underlying this neuroprotection remain unknown. In the present study, we hypothesized that FK506 treatment could protect rat brain from oxidative injuries through antioxidative and anti-inflammatory pathways after ischemia-reperfusion injury. METHODS: Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 120 minutes, followed by reperfusion. Animals received a single injection of FK506 (0·3 mg/kg) or vehicle intravenously at 30 minutes after ischemic induction. Infarct volume and neurological performance were evaluated at 24 hours after reperfusion. Immunohistochemical analysis for 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-deoxyguanosine (8-OHdG), ionized calcium-binding adapter molecule 1 (Iba-1), and tumor necrosis factor-alpha (TNF-alpha) were conducted at 24 hours after reperfusion. RESULTS: FK506 significantly reduced infarct volume (61·7%; P=0·01) and improved neurological deficit scores (P<0·05) 24 hours after reperfusion compared to vehicle. In FK506-treated rats, accumulation of 4-HNE (P<0·01) and 8-OHdG (P<0·01) was significantly suppressed in the cerebral cortex 24 hours after reperfusion. In addition, FK506 markedly reduced microglial activation (P<0·01) and TNF-alpha expression (P<0·01). DISCUSSION: These results demonstrate that FK506 may have antioxidant as well as anti-inflammatory effects and reduces ischemic damage following cerebral infarction.

Combination therapy with bone marrow stromal cells and FK506 enhanced amelioration of ischemic brain damage in rats.

AIMS: Transplantation of bone marrow stromal cells (MSCs) has been shown to ameliorate ischemic brain injury in animals. In the present study, we investigated whether the transplantation of MSCs combined with FK506, a clinically used immunosuppressant, enhanced neuroprotective effects in rat experimental stroke. MAIN METHODS: Male Sprague-Dawley rats underwent transient 90 min middle cerebral artery occlusion (MCAO). Two or 6h after ischemia onset, the rats were randomly assigned to receive intravenous administration of MSCs plus FK506, MSCs alone, FK506 alone, or vehicle. Infarct volume, and neurological and immunohistological assessments were performed to examine the effects of these therapies. KEY FINDINGS: In 2-hour post-ischemia treatment groups, significant improvement of infarct volume and neurological scores were observed 1 day after combination therapy compared with monotherapy, and this neuroprotection continued for 7 days. Combination therapy significantly reduced the number of TUNEL-positive apoptotic cells, increased Bcl-2 expression, decreased Bax expression, and suppressed neutrophil infiltration and microglia/macrophage activation compared to monotherapy. In 6-hour post-ischemia treatment groups, a significant reduction of infarct volume, edema index, and neurological score was observed only in the combination therapy group. Moreover, the number of engrafted MSCs on day 7 with combination therapy was significantly higher than with MSCs alone. SIGNIFICANCE: Combination therapy using FK506 enhanced the anti-apoptotic and anti-inflammatory effects of MSCs and increased the survival of transplanted cells, leading to expansion of the therapeutic time window for MSCs.

Hepatic encephalopathy with reversible focal neurologic signs resembling acute stroke: case report.

A 64-year-old female with a history of primary biliary cirrhosis and esophageal varices starting at age 39 was brought to our Stroke Care Unit by ambulance with right-side weakness and speech difficulty. Physical examination revealed right hemiparesis (including the face), sensory disturbances, pathological reflexes, and slightly decreased consciousness, with a Glasgow Coma Scale rating of E3V4M6. Flapping tremors and speech disturbance, as well as anarithmia, construction apraxia, and ideomotor apraxia, were noted, and her National Institutes of Health Stroke Scale score was 13. Initially, the patient was diagnosed with acute stroke and treated accordingly; however, subsequent findings from clinical images and electroencephalography led to a diagnosis of focal neurologic signs due to hepatic encephalopathy (HE). The patient had significantly reduced cerebral blood flow in the left side of the brain, probably due to microsurgical repair of an aneurysm done 2 years earlier. HE with exaggerated chronic liver damage might have made the previously silent ischemia clinically apparent. This interpretation is supported by the fact that the patient's neurologic deficits resolved once HE was adequately controlled. This case illustrates the need for careful assessment of background pathophysiology when diagnosing patients with stroke-like symptoms.

Statin treatment decreased serum asymmetric dimethylarginine (ADMA) levels in ischemic stroke patients.

AIM: It remains unclear whether the decrease in the ADMA level associated with statin treatment results from the LDL-C-lowering effect or the pleiotropic effects of statins. A prospective, controlled study was conducted to examine whether statin treatment affects serum ADMA concentrations in ischemic stroke patients. METHODS: Consecutive outpatients with non-cardiogenic ischemic stroke who had never been treated with statins and whose LDL-cholesterol level was higher than 140 mg/dL were enrolled and compared with control patients whose LDL-cholesterol level was lower than 140 mg/dL. Overall, 114 patients were enrolled in the study (56 and 58 in statin-treated and non-statin-treated groups, respectively). Patients in the statin group were treated with pravastatin 10 mg/day (n=15), fluvastatin 20 mg/day (n=14), pitavastatin 1 mg/day (n=14), or atorvastatin 10 mg/day (n=13). RESULTS: The serum ADMA concentration and LDL-C level were significantly decreased by statin treatment (p=0.003 and p< 0.001, respectively), and the ADMA concentration in subjects treated with statins was significantly lower than that of the control (p=0.028). Multiple linear regression analysis showed that age (ß=0.26, p< 0.05) and statin use (ß=-0.20, p< 0.05) were independently associated with the ADMA level. CONCLUSIONS: A significant relation between statin treatment and decreased levels of ADMA was demonstrated in ischemic stroke patients with an adequately controlled lipid profile, suggesting the statin treatment might prevent atherosclerotic disease in ischemic stroke patients through suppression of ADMA concentration.