Successful Reperfusion with Endovascular Therapy Has Beneficial Effects on Long-Term Outcome Beyond 90 Days.

BACKGROUND AND PURPOSE: Recent studies have demonstrated that endovascular reperfusion therapy improves clinical outcomes at 90 days after ischemic stroke. However, the effects on long-term outcomes are not well known. We hypothesized that successful reperfusion might be associated with long-term improvement beyond 90 days after endovascular therapy. To assess the long-term effects beyond 90 days, we analyzed the association of successful reperfusion with a temporal change in modified Rankin Scale (mRS) score from 90 days to 1 year after endovascular therapy. METHODS: We retrospectively analyzed a database of consecutive patients with acute ischemic stroke who received endovascular therapy between April 2006 and March 2016 at 4 centers. We compared the incidences of improvement and deterioration in patients with successful reperfusion (i.e., modified thrombolysis in cerebral infarction score of 2b or 3) with those in patients with unsuccessful reperfusion. We defined improvement and deterioration as decrease and increase on the mRS score by 1 point or more from 90 days to 1 year after endovascular therapy respectively. RESULTS: A total of 268 patients were included in the current study. The rate of patients with improvement tended to be higher in patients with successful reperfusion than in patients with unsuccessful reperfusion (20% [34/167 patients] vs. 12% [12/101], p = 0.07). The rate of patients with deterioration was lower in patients with successful reperfusion than in patients with unsuccessful reperfusion (25% [42/167] vs. 42% [42/101], p < 0.01). After adjustment for confounders, successful reperfusion was associated with improvement (adjusted OR 2.65; 95% CI 1.23-5.73; p < 0.05) and deterioration (adjusted OR 0.33; 95% CI 0.18-0.62; p < 0.01), independent of the 90-day mRS score. CONCLUSIONS: Successful reperfusion has further beneficial legacy effects on long-term outcomes beyond 90 days after stroke.

Alberta Stroke Program Early CT Score-Time Score Predicts Outcome after Endovascular Therapy in Patients with Acute Ischemic Stroke: A Retrospective Single-Center Study.

BACKGROUND: Clinical outcomes after successful endovascular therapy in patients with acute ischemic stroke are associated with several factors including onset-to-reperfusion time (ORT), the National Institute of Health Stroke Scale (NIHSS) score, and the Alberta Stroke Program Early CT Score (ASPECTS). The NIHSS-time score, calculated as follows: [NIHSS score] × [onset-to-treatment time (h)] or [NIHSS score] × [ORT (h)], has been reported to predict clinical outcomes after intravenous recombinant tissue plasminogen activator therapy and endovascular therapy for acute stroke. The objective of the current study was to assess whether the combination of the ASPECTS and the ORT can predict the outcomes after endovascular therapy. METHODS: The charts of 117 consecutive ischemic stroke patients with successful reperfusion after endovascular therapy were retrospectively reviewed. We analyzed the association of ORT, ASPECTS, and ASPECTS-time score with clinical outcome. ASPECTS-time score was calculated as follows: [11 - ASPECTS] × [ORT (h)]. RESULTS: Rates of good outcome for patients with ASPECTS-time scores of tertile values, scores 5.67 or less, scores greater than 5.67 to 10.40 or less, and scores greater than 10.40, were 66.7%, 56.4%, and 33.3%, respectively (P < .05). Ordinal logistic regression analysis showed that the ASPECTS-time score (per category increase) was an independent predictor for better outcome (common odds ratio: .374; 95% confidence interval: .150-0.930; P < .05). CONCLUSIONS: A lower ASPECTS-time score may predict better clinical outcomes after endovascular treatment.

National Institutes of Health Stroke Scale-Time Score Predicts Outcome after Endovascular Therapy in Acute Ischemic Stroke: A Retrospective Single-Center Study.

BACKGROUND: Outcomes after successful endovascular therapy in acute ischemic stroke are associated with onset-to-reperfusion time (ORT) and the National Institutes of Health Stroke Scale (NIHSS) score. In intravenous recombinant tissue plasminogen activator therapy, the NIHSS-time score, calculated by multiplying onset-to-treatment time with the NIHSS score, has been shown to predict clinical outcomes. In this study, we assessed whether a similar combination of the ORT and the NIHSS score can be applied to predict the outcomes after endovascular therapy. METHODS: We retrospectively reviewed the charts of 128 consecutive ischemic stroke patients with successful reperfusion after endovascular therapy. We analyzed the association of the ORT, the NIHSS score, and the NIHSS-time score with good outcome (modified Rankin Scale score ≤ 2 at 3 months). RESULTS: Good outcome rates for patients with NIHSS-time scores of 84.7 or lower, scores higher than 84.7 up to 127.5 or lower, and scores higher than 127.5 were 72.1%, 44.2%, and 14.3%, respectively (P < .01). Multivariate logistic regression analysis revealed that the NIHSS-time score was an independent predictor of good outcomes (odds ratio, .372; 95% confidence interval, .175-.789) after adjusting for age, sex, internal carotid artery occlusion, plasma glucose level, ORT, and NIHSS score. CONCLUSIONS: The NIHSS-time score can predict good clinical outcomes after endovascular treatment.

Triple balloon protection technique using the mo.ma ultra with the carotid GuardWire for carotid stenting: technical note.

BACKGROUND: We describe the "triple balloon protection technique" (TBPT) using the Mo.Ma Ultra in combination with the Carotid GuardWire during carotid artery stenting (CAS). This technique is expected to prevent distal embolism to the internal and external carotid arteries, and is suitable for East Asians in whom the origin of the superior thyroid artery is lower than that in Caucasians. METHODS: From December 2012 to May 2013, 11 patients underwent CAS using TBPT in our center. RESULTS: Procedural success was achieved in all patients. Complete flow blockade by angiography could not be obtained in 8 patients (72.7%) by proximal occlusion using the Mo.Ma Ultra only. Complete angiographic flow blockade was obtained in all patients by TBPT. No major adverse cardiovascular events, including stroke, myocardial infarction, or death because of any cause, occurred within 30 days. CONCLUSIONS: The use of TBPT for CAS may be effective for preventing distal embolisms, especially for East Asians.

A case of Adult-onset Acute Flaccid Myelitis Accompanied by Rhombencephalitis which First Presented with Prominent Psychiatric Symptoms and Dysautonomia Mimicking Anti-N-methyl-d-aspartate Receptor Encephalitis.

A 44-year-old woman with a subacute onset of an altered mental status, urinary retention, and fluctuating blood pressure was initially diagnosed with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, meeting the criteria of Graus et al. Cardiac arrest occurred, which required pacemaker placement. She subsequently showed profound flaccid limb paralysis, with magnetic resonance imaging demonstrating focal necrotic lesions localized in the anterior horn of the longitudinal segments of the spinal cord and in the pontine tegmentum. Enteroviruses or autoimmune encephalitis-associated autoantibodies were not detected. We herein report a case of acute flaccid myelitis with profound psychiatric symptoms and dysautonomia, resembling NMDAR encephalitis.

An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke.

BACKGROUND: Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism. METHODS: We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age. RESULTS: Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p < 0.001) and higher extent of NETosis (p = 0.006). Restricted mean survival time analysis revealed that older thrombi were associated with longer puncture-to-reperfusion times (difference: 15.6 minutes longer for older thrombi, p = 0.002). This association remained significant even after adjustment for erythrocyte content and the extent of NETosis (adjusted difference: 10.8 minutes, 95% confidence interval [CI]: 0.6-21.1 minutes, p = 0.039). Compared with fresh thrombi, older thrombi required more device passes before reperfusion (p < 0.001) and were associated with poorer functional outcomes (adjusted common odds ratio: 0.49; 95% CI: 0.24-0.99). CONCLUSION: An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.

Cyclo-oxygenase-2 -765G > C promoter variants are associated with lower carotid plaque echogenicity in Japanese.

BACKGROUND AND PURPOSE: Recent studies revealed that inflammation contributes to plaque instability. Cyclo-oxygenase (COX)-2 is one of the key enzymes in plaque inflammation. We examined the relation between a polymorphism in the COX-2 gene and carotid plaque echogenicity in patients with high risk of cerebrovascular disease to evaluate the involvement of COX-2 in plaque instability. METHODS: The study comprised 469 individuals with carotid atherosclerotic plaques. We quantified the echogenicity of the largest plaque in each participant by integrated backscatter analysis. The -765G > C variant of the COX-2 gene was genotyped by restriction enzyme fragment length polymorphism analysis. Urinary 6-keto prostaglandin F(1)(alpha) levels and flow-mediated dilation were measured in 25 participants from the -765GC genotype group and 25 matched participants from the -765GG genotype group. RESULTS: The carotid plaque echogenicity in the variant genotype group (n = 44) was lower than that in the -765GG genotype group (n = 425, p = 0.017). The association remained significant when we controlled for atherosclerotic risk factors, plaque thickness and serum levels of interleukin-6 (p = 0.027). The level of urinary 6-keto prostaglandin F(1)(alpha) and flow-mediated dilation in the variant genotype group was significantly lower than that in the -765GG genotype group. CONCLUSIONS: The -765G > C variant of COX-2 was associated with reduced carotid plaque echogenicity in Japanese. Diminished COX-2 activity in the endothelium may contribute to plaque instability.

Statin therapy increases carotid plaque echogenicity in hypercholesterolemic patients.

Stabilization of carotid artery plaques by pharmacologic intervention is a promising strategy for the prevention of ischemic stroke. In this study, we examined the effect of 12 months of statin therapy on carotid plaque echogenicity. This study included 81 hypercholesterolemic patients with carotid atherosclerotic plaques. Echogenicity of the largest plaque in each patient was evaluated by ultrasound with integrated backscatter analysis. All patients underwent dietary modification. Forty patients were treated with simvastatin (10 mg/day, n = 24) or atorvastatin (5 mg/day, n = 16) according to the choice by each attending physician. Carotid plaques were monitored by measuring plaque thickness and echogenicity during a 12-month follow-up period. Levels of serum high-sensitivity CRP (hs-CRP), interleukin (IL)-6 and IL-18 were determined in all patients. Total cholesterol, triglyceride, hs-CRP and IL-18 were significantly decreased after 12 months of statin therapy. The change in IL-6 level was not significant. Significant increases in echogenicity of carotid plaques and decreases in plaque thickness were noted after statin therapy. In the 41 patients without statin therapy, carotid plaque echogenicity, plaque thickness and serum levels of inflammatory markers were not significantly altered. Our results suggest that statin therapy in hypercholesterolemic patients for 12 months increases carotid plaque echogenicity and decreases plaque thickness, in addition to lowering serum levels of lipids and inflammatory markers.

Multiple small hemorrhagic infarcts in cerebral air embolism: a case report.

BACKGROUND: Cerebral air embolism is a rare cause of cerebral infarction. In cerebral air embolism, T2 star-weighted imaging shows numerous spotty hypointense signals. Previous reports have suggested that these signals represent air in the brain and are gradually diminished and absorbed. We experienced two cases of cerebral air embolism, and in one of them, we conducted an autopsy. CASE PRESENTATION: Case 1 was a 76-year-old Japanese man with lung cancer and emphysema. A spasmodic cough induced massive cerebral and cardiac air embolisms and the patient died because of cerebral herniation. T2 star-weighted imaging of brain magnetic resonance imaging showed multiple spotty low signals. Brain autopsy showed numerous spotty hemorrhagic infarcts in the area of T2 star-weighted imaging signals. Case 2 was an 85-year-old Japanese man with emphysema who suffered from acute stroke. Similar spotty T2 star-weighted imaging signals were observed and remained unchanged 2 months after the onset. CONCLUSIONS: These findings indicate that T2 star-weighted imaging in cerebral air embolism partially represents micro-hemorrhagic infarction caused by air bubbles that have migrated into the brain.

Associations of serum IL-18 levels with carotid intima-media thickness.

OBJECTIVE: Elevated circulating levels of IL-18 can predict future coronary heart disease. Although IL-18 is thought to play a crucial role in atherosclerosis, whether circulating IL-18 levels are associated with the severity of atherosclerosis remains to be determined. With the use of B-mode ultrasound, this study examines the relationships of serum IL-18 levels with carotid intima-media thickness (IMT) as a reflector for systemic atherosclerosis. METHODS AND RESULTS: The study comprised 366 patients without histories of cardiovascular accidents. Severity of carotid atherosclerosis was evaluated by the mean max IMT, ie, mean of the maximal wall thickness at 12 carotid segments. Serum IL-18, IL-6, and high-sensitive C-reactive protein (hs-CRP) levels were determined in all patients. Log-transformed IL-18 concentrations were positively correlated with IMT (r=0.36, P<0.001), and the association remained significant (beta=0.20, P<0.001) when controlling for traditional atherosclerotic risk factors, IL-6 and hs-CRP levels. Also, IMT was greater in the highest and the middle tertile of IL-18 levels than in the lowest tertile. CONCLUSIONS: Higher serum IL-18 levels appear to be associated with greater carotid IMT, suggesting the link between IL-18 and atherosclerosis.

Relations of serum high-sensitivity C-reactive protein and interleukin-6 levels with silent brain infarction.

BACKGROUND AND PURPOSE: Small silent brain infarction (SBI) is often found on magnetic resonance (MR) images of apparently healthy individuals at cardiovascular risk. Particularly, small SBI found in subcortical white matter, basal ganglia, or thalamus is thought to be caused by cerebral small vessel disease. Although several lines of evidence suggest a role of inflammatory processes in atherothrombotic vascular events, their involvement in SBI remains to be determined. This study examines the associations between serum inflammatory markers and SBI as a manifestation of cerebral small vessel disease. METHODS: One hundred ninety-four patients without histories of cardiovascular accidents were prospectively enrolled for this study. All patients underwent brain MR imaging and carotid ultrasonography, and patients with SBI diagnosed underwent further MR angiography. As common inflammatory markers, serum levels of high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were evaluated. RESULTS: SBIs were found in 40 patients, and all of those were located in subcortical and infratentorial area, without MR angiographic evidence for obstructive lesions in proximal cerebral arteries. Mean hsCRP and IL-6 levels were higher in patients with SBI than in those without. Also, higher levels of both hsCRP (odds ratio [OR], 1.85 per standard deviation [SD] increase) and IL-6 (OR, 2.00/SD increase) were associated with higher likelihood for SBI. Moreover, the associations were only slightly attenuated when adjusting traditional cardiovascular risk factors and carotid IMT. CONCLUSIONS: Higher levels of hsCRP and IL-6 appear to be associated with small SBI, suggesting a role of inflammatory processes in cerebral small vessel disease.

Imaging of distal internal carotid artery by ultrasonography with a 3.5-MHz convex probe.

BACKGROUND AND PURPOSE: Conventionally, carotid ultrasonography has been performed with a 7.5-MHz linear probe to evaluate the extracranial internal carotid artery (ICA). However, usually only the carotid bulb or proximal portion of the ICA can be evaluated. We attempted to evaluate the distal extracranial ICA with a 3.5-MHz convex probe. METHODS: The subjects were 17 consecutive patients with ICAs free of occlusive disease and 3 other patients with distal extracranial ICA stenosis. Using a 7.5-MHz linear probe and a 3.5-MHz convex probe, we performed long-axis B-mode imaging of the ICAs to evaluate the distance between the distal limit of visualized ICA and the bifurcation of the common carotid artery. RESULTS: The distal limit of the ICA, visualized with a 7.5- or a 3.5-MHz probe, was 31+/-11 or 57+/-8 mm distal to the common carotid artery bifurcation, respectively. In the 3 patients with distal extracranial ICA stenosis, the lesion could be successfully diagnosed with only the 3.5-MHz probe. CONCLUSIONS: This form of carotid imaging is feasible and may be potentially useful in the evaluation of carotid disease.

Association of plasma homocysteine concentration with atherosclerotic carotid plaques and lacunar infarction.

BACKGROUND AND PURPOSE: Higher plasma total homocysteine (tHcy) levels have been associated with carotid atherosclerosis and cerebral infarction in whites. However, data regarding such associations are limited for Asians. This study examined associations between tHcy levels and severity of carotid atherosclerosis in Japanese subjects. Additionally, because lacunar infarction is the most prevalent type of ischemic stroke in Japan, we also investigated its associations with tHcy levels. METHODS: The subjects were 152 Japanese patients (age, 66.2+/-11.0 years) at our hospital. Using ultrasound, we evaluated severity of carotid atherosclerosis by plaque score, which is defined by the sum of all plaque (intima-media thickness > or =1.1 mm) height in bilateral carotid arteries. In 112 of 152 patients, the existence of lacunar infarction was evaluated on brain MRI scans. RESULTS: A moderate linear association was found between tHcy levels and plaque score (r=0.48, P<0.0001). Moreover, tHcy level was associated with plaque score (beta=0.26, P<0.001) independently of traditional atherosclerotic risk factors. In logistic regression analyses, each 1-micromol/L-higher tHcy level was associated with a 1.37-fold-higher [95% confidence interval (CI), 1.19 to 1.58] likelihood for lacunar infarction, increasing the likelihood by 1.22-fold (95% CI, 1.04 to 1.43) independently of traditional atherosclerotic risk factors. CONCLUSIONS: Higher tHcy levels appear to have associations with increased severity of carotid atherosclerotic plaques and prevalent lacunar infarction in the Japanese. Larger prospective studies are necessary to establish whether higher tHcy levels serve as a harbinger for insidious carotid and cerebrovascular diseases.

Prognostic value of subacute crossed cerebellar diaschisis: single-photon emission CT study in patients with middle cerebral artery territory infarct.

BACKGROUND AND PURPOSE: Although chronic-stage crossed cerebellar diaschisis (CCD) is reported to be associated with the neurologic state or clinical improvement after infarct, the prognostic value of early-stage CCD remains controversial. Our aim was to determine whether measurements of CCD in the acute and subacute stages obtained at single-photon emission CT (SPECT) facilitate the prediction of stroke outcome. METHODS: The pattern of cerebral blood flow changes after the occurrence of acute middle cerebral artery ischemia with severe cortical symptoms was examined by using technetium 99m-hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) SPECT. Fifteen patients (mean age, 73 years +/- 8 [SD]) with unilateral ischemia were examined in the early subacute stage (10 days +/- 5). In 11 patients, SPECT was performed in both the acute (16 hours +/- 10) and subacute stages. From the total counts obtained from each cerebellar hemisphere, the asymmetry index (AI) was calculated as follows: [(value in unaffected hemisphere--value in affected hemisphere)/value in unaffected hemisphere] x 100. Clinical outcome (at 60 days) was assessed by means of the Scandinavian Stroke Scale (SSS) and Barthel Index (BI). RESULTS: AIs in the acute stage and clinical outcome (ie, SSS and BI scores) showed no significant correlation, but the severity of AI in the early subacute stage correlated significantly with both the final SSS (r = -0.69; P <.01) and BI scores (r = -0.82; P <.01). CONCLUSION: Cerebellar hypoperfusion detected at (99m)Tc-HMPAO SPECT in the early subacute stage in patients with supratentorial infarct indicates a worse clinical outcome.

[Reversible hepatic myelopathy: a case report].

We report a case of reversible hepatic myelopathy. A 42-year-old female patient with 3-year history of alcoholic liver cirrhosis developed spastic gait, hyperreflexia and mild somatosensory disturbance in her lower extremities. The increased level of serum ammonia and the deficits of N30 and P38 in the tibial somatosensory evoked potentials (SEP) in conjunction with exclusion of the other known causes of myelopathy supported the diagnosis of her hepatic myelopathy. The ammonia lowering therapy by the oral administration of lactulose successfully improved the spastic gait accompanied with the emergence of N30 and P38 in the tibial SEP. Although liver transplantation was known to be the only therapy for hepatic myelopathy in the literatures, our case showed that the ammonia lowering therapy can be effective for the early stage of hepatic myelopathy.

Silent cerebral infarction is associated with incident stroke and TIA independent of carotid intima-media thickness.

BACKGROUND: Both silent cerebral infarction (SCI) and carotid intima-media thickness (IMT) are associated with future stroke. We evaluated whether SCI could be a predictor for incident stroke independent of carotid IMT in high-risk patients. METHODS: We performed a prospective cohort study among 282 outpatients who had one or more atherosclerotic risk factors but without a history of cardiovascular disease. We conducted cranial MRI and measured carotid IMT at baseline, and then evaluated the risks of incident stroke and transient ischemic attacks (TIA) using Cox proportional hazards models. RESULTS: SCI was present in 67 patients (23.7%) at baseline. During 4.1 years of follow-up, stroke and TIA occurred in 8 patients (2.8%). The incidence of stroke/TIA was 22.3 per 1,000 person-years in those with SCI compared with 2.2 per 1,000 person-years in those without SCI. Both SCI and carotid IMT at baseline were associated with incident stroke/TIA events after adjustment for age, sex, and traditional vascular risk factors. The predictive value of SCI remained significant even after adjustment for carotid IMT (HR 8.56; 1.72-42.55). CONCLUSION: SCI, similar to carotid IMT, is an independent predictor of stroke and TIA in high-risk patients.

Relation between interleukin-6 level and subclinical intracranial large-artery atherosclerosis.

BACKGROUND: The levels of systemic inflammatory markers have been shown to predict future cardiovascular events, but whether they are associated with intracranial large-artery atherosclerosis is uncertain. We investigated the relation between the level of inflammatory markers interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) and subclinical intracranial large-artery atherosclerosis in patients with risk factors for atherosclerosis. METHODS: Magnetic resonance angiography (MRA) was performed in 226 Japanese patients age range, 45-87 years without a history of cerebrovascular disease. Serum IL-6 and hsCRP and conventional risk factors for atherosclerosis were assessed. RESULTS: Forty-six patients (20.4%) were found by MRA to have one or more intracranial steno-occlusive lesions. Mean IL-6 levels were higher in patients with intracranial large-artery atherosclerosis than in those without. In addition, patients in the highest IL-6 tertile had higher unadjusted odds ratio (OR) for intracranial large-artery atherosclerosis than that of those in the lowest tertile (OR 3.25, 95% CI; 1.42-7.39). These associations were only slightly attenuated upon adjustment for conventional atherosclerotic risk factors and carotid intima-media thickness. CONCLUSIONS: Increased levels of IL-6 appear to be associated with intracranial large-artery disease, suggesting a role for the inflammatory process in atherosclerosis of intracranial large arteries.