Koji Tanaka

<bold>Background:</bold> Coronavirus Disease 2019 (COVID-19) has spread worldwide with collateral damage and therefore might affect the behavior of stroke patients with mild symptoms seeking medical attention. <bold>Methods:</bold> Patients with ischemic stroke who were admitted to hospitals within 7 days of onset were retrospectively registered. The clinical characteristics, including onset-to-door time (ODT), of patients with a transient ischemic attack (TIA)/mild stroke (National Institutes of Health Stroke Scale [NIHSS] score of ≤ 3 on admission) or moderate/severe stroke were compared between those admitted from April 2019 to March 2020 (pre-COVID-19 period) and from April to September 2020 (COVID-19 period). Multivariable regression analysis was performed to identify factors associated with the ODT. <bold>Results:</bold> Of 1,100 patients (732 men, median age, 73 years), 754 were admitted during the pre-COVID-19 period, and 346 were admitted during the COVID-19 period. The number and proportion of patients with TIA/minor stroke were 464 (61.5%) in the pre-COVID-19 period and 216 (62.4%) during the COVID-19 period. Among patients with TIA/mild stroke, the ODT was longer in patients admitted during the COVID-19 period compared with that of the pre-COVID-19 period (median 864 min vs. 508 min, <italic>p</italic> = 0.003). Multivariable analysis revealed the COVID-19 period of admission was associated with longer ODT (standardized partial regression coefficient 0.09, <italic>p</italic> = 0.003) after adjustment for age, sex, route of arrival, NIHSS score on admission, and the presence of hypertension, diabetes mellitus, and wake-up stroke. No significant change in the ODT was seen in patients with moderate/severe stroke. <bold>Conclusions:</bold> The COVID-19 epidemic might increase the ODT of patients with TIA/mild stroke.

<sec id="sec001"> <title>Background and purpose</title> The impact of the paraoxonase-1 (<italic>PON1</italic>) polymorphism, Q192R, on platelet inhibition in response to clopidogrel remains controversial. We aimed to investigate the association between carrier status of <italic>PON1</italic> Q192R and high platelet reactivity (HPR) with clopidogrel in patients undergoing elective neurointervention. </sec> <sec id="sec002"> <title>Methods</title> Post-clopidogrel platelet reactivity was measured using a VerifyNow^® P2Y12 assay in P2Y12 reaction units (PRU) for consecutive patients before the treatment. Genotype testing was performed for <italic>PON1</italic> Q192R and <italic>CYP2C19*2</italic> and <italic>*3</italic> (no function alleles), and <italic>*17</italic>. PRU was corrected on the basis of hematocrit. We investigated associations between factors including carrying ≥1 <italic>PON1</italic> 192R allele and HPR defined as original and corrected PRU ≥208. </sec> <sec id="sec003"> <title>Results</title> Of 475 patients (232 men, median age, 68 years), HPR by original and corrected PRU was observed in 259 and 199 patients (54.5% and 41.9%), respectively. Carriers of ≥1 <italic>PON1</italic> 192R allele more frequently had HPR by original and corrected PRU compared with non-carriers (91.5% vs 85.2%, P = 0.031 and 92.5% vs 85.9%, P = 0.026, respectively). In multivariate analyses, carrying ≥1 <italic>PON1</italic> 192R allele was associated with HPR by original (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.03–3.76) and corrected PRU (OR 2.34, 95% CI 1.21–4.74) after adjustment for age, sex, treatment with antihypertensive medications, hematocrit, platelet count, total cholesterol, and carrying ≥1 <italic>CYP2C19</italic> no function allele. </sec> <sec id="sec004"> <title>Conclusions</title> Carrying ≥1 <italic>PON1</italic> 192R allele is associated with HPR by original and corrected PRU with clopidogrel in patients undergoing elective neurointervention, although alternative results related to other genetic polymorphisms cannot be excluded. </sec>

<sec id="sec001"> <title>Objective</title> Periprocedural thromboembolic events are a serious complication associated with coil embolization of unruptured intracranial aneurysms. However, no established clinical rule for predicting thromboembolic events exists. This study aimed to clarify the significance of adding preoperative clopidogrel response value to clinical factors when predicting the occurrence of thromboembolic events during/after coil embolization and to develop a nomogram for thromboembolic event prediction. </sec> <sec id="sec002"> <title>Methods</title> In this prospective, single-center, cohort study, we included 345 patients undergoing elective coil embolization for unruptured intracranial aneurysm. Thromboembolic event was defined as the occurrence of intra-procedural thrombus formation and postprocedural symptomatic cerebral infarction within 7 days. We evaluated preoperative clopidogrel response and patients’ clinical information. We developed a patient-clinical-information model for thromboembolic event using multivariate analysis and compared its efficiency with that of patient-clinical-information plus preoperative clopidogrel response model. The predictive performances of the two models were assessed using area under the receiver-operating characteristic curve (AUC-ROC) with bootstrap method and compared using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). </sec> <sec id="sec003"> <title>Results</title> Twenty-eight patients experienced thromboembolic events. The clinical model included age, aneurysm location, aneurysm dome and neck size, and treatment technique. AUC-ROC for the clinical model improved from 0.707 to 0.779 after adding the clopidogrel response value. Significant intergroup differences were noted in NRI (0.617, 95% CI: 0.247–0.987, p &lt; .001) and IDI (0.068, 95% CI: 0.021–0.116, p = .005). </sec> <sec id="sec004"> <title>Conclusions</title> Evaluation of preoperative clopidogrel response in addition to clinical variables improves the prediction accuracy of thromboembolic event occurrence during/after coil embolization of unruptured intracranial aneurysm. </sec>

A 44-year-old male was admitted to our hospital because of sudden weakness and sensory loss in both legs following left scapular pain. He had a history of lower back pain but no vascular risk factors. Neurological examination on admission revealed flaccid paraplegia, a loss of both pinprick and vibratory sensations below the Th6 level, and bladder and rectal disturbances. Tendon reflexes were absent in both lower limbs. Diffusion-weighted imaging performed 5 hours after onset revealed an extensive high-intensity lesion at the Th2-6 spine levels, accompanied by a vague high intensity on T2-weighted images. CT angiography showed no abnormalities of the aorta or the artery of Adamkiewicz. Laboratory test results were normal and there was no evidence of coagulopathy. Autoantibodies, including anti-aquaporin-4 and anti-myelin oligodendrocyte glycoprotein antibodies, were negative. The cerebrospinal fluid test was normal. The lesion had expanded to the whole thoracic cord and was markedly swollen on T2-weighted imaging at 5 days after onset. Immunotherapies, including intravenous methylprednisolone pulse therapy and plasma exchange, were ineffective. Although there was no evidence of any source of embolism, we found degenerative calcified changes in the fibrocartilage of the intervertebral discs, with Schmorl's nodes in the thoracic spines. We clinically diagnosed the patient with spinal cord infarction caused by fibrocartilaginous embolism. He developed deep vein thrombosis and was treated with edoxaban. His neurological symptoms did not improve during 55 days of hospitalization. In a case with sudden-onset myelopathy, fibrocartilaginous embolism should be considered.

<title>Abstract</title>The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used for the assessment of early ischemic changes (EICs) before thrombolysis. However, for symptomatic intracerebral hemorrhage (sICH) following intravenous recombinant tissue plasminogen activator (rt-PA), the prediction abilities of CT-ASPECTS, diffusion-weighted imaging (DWI)-ASPECTS, and DWI-ASPECTS including EICs in deep white matter (DWI-ASPECTS + W) are unclear. We investigated associations between each score and sICH following intravenous rt-PA. Data from consecutive patients who received intravenous rt-PA for acute ischemic stroke from 2005 to 2015 in four hospitals were retrospectively screened. We included data from patients who had undergone both CT and magnetic resonance imaging before thrombolysis and without evidence of posterior circulation stroke. We analyzed the ability of CT-ASPECTS, DWI-ASPECTS, and DWI-ASPECTS + W to predict sICH, accompanied by an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥ 4 within the initial 36 h. Of 455 patients (273 men, median 75 years old), sICH occurred in 15 patients (3.3%). Receiver operating characteristics curve analysis showed that the optimal cut-offs of CT-ASPECTS, DWI-ASPECTS, and DWI-ASPECTS + W for predicting sICH were ≤ 9 (sensitivity 60.0%, specificity 59.8%, c-statistic 0.625), ≤ 6 (sensitivity 53.3%, specificity 80.9%, c-statistic 0.718), and ≤ 8 (sensitivity 86.7%, specificity 55.9%, c-statistic 0.756), respectively. A DWI-ASPECTS + W of ≤ 8 was independently associated with sICH (odds ratio 5.21, 95% confidence interval 1.30–35.31) after adjustment for pretreatment with antithrombotic agents, pretreatment NIHSS score, and large artery occlusions. DWI-ASPECTS + W predicted sICH in patients with acute anterior circulation stroke receiving intravenous rt-PA.

<title>Abstract</title>Early neurological deterioration (END) following intravenous recombinant tissue plasminogen activator (rt-PA) treatment is a serious clinical event that can be caused by hemorrhagic or ischemic insult. We investigated the differences in predictive factors for END due to hemorrhagic and END due to ischemic insults. Consecutive patients from four hospitals who received 0.6 mg/kg intravenous rt-PA for acute ischemic stroke were retrospectively recruited. END was defined as a National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points within 24 h compared with baseline. END was classified into those due to hemorrhagic (END_h) or ischemic (END_i) insult based on computed tomography (CT) or magnetic resonance imaging. Risk factors associated with END_h and END_i were investigated by comparison with non-END cases. A total of 744 patients (452 men, median 75 years old) were included. END was observed in 79 patients (10.6%), including 22 END_h (3.0%) and 57 END_i (7.7%), which occurred within a median of 7 h after treatment. Multivariate analyses showed that higher pretreatment NIHSS score (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.00–1.13) and pretreatment with antiplatelets (OR 2.84, 95% CI 1.08–7.72) were associated with END_h. Extensive early ischemic change (Alberta Stroke Program Early CT Score ≤ 7 on CT or ≤ 6 on diffusion-weighted imaging; OR 2.80, 95% CI 1.36–5.64) and large artery occlusions (OR 3.09, 95% CI 1.53–6.57) were associated with END_i. Distinct factors were predictive for the END subtypes. These findings could help develop preventative measures for END in patients with the identified risk factors.

Background and Purpose: In the acute phase of ischemia-reperfusion, hypoperfusion associated with ischemia and reperfusion in microvascular regions and disruption of the blood-brain barrier (BBB) contribute to post-ischemic brain injury. We aimed to clarify whether brain injury following transient middle cerebral artery occlusion (tMCAO) is ameliorated in Transient receptor potential vanilloid 4 knockout (Trpv4-/- ) mice. Methods: tMCAO was induced in wild-type (WT) and Trpv4-/- mice aged 8-10 weeks. Ischemia-induced lesion volume was evaluated by 2,3,5-triphenyltetrazolium chloride staining at 24 h post-tMCAO. Tissue water content and Evans blue leakage in the ipsilateral hemisphere and a neurological score were evaluated at 48 h post-tMCAO. Transmission electron microscopy (TEM) was performed to assess the morphological changes in microvasculature in the ischemic lesions at 6 h post-tMCAO. Results: Compared with WT mice, Trpv4-/- mice showed reduced ischemia-induced lesion volume and reduced water content and Evans blue leakage in the ipsilateral hemisphere alongside milder neurological symptoms. The loss of zonula occludens-1 and occludin proteins in the ipsilateral hemisphere was attenuated in Trpv4-/- mice. TEM revealed that parenchymal microvessels in the ischemic lesion were compressed and narrowed by the swollen endfeet of astrocytes in WT mice, but these effects were markedly ameliorated in Trpv4-/- mice. Conclusion: The present results demonstrate that TRPV4 contributes to post-ischemic brain injury. The preserved microcirculation and BBB function shortly after reperfusion are the key neuroprotective roles of TRPV4 inhibition, which represents a promising target for the treatment of acute ischemic stroke.

BACKGROUND: A transient visual symptom (TVS) is a clinical manifestation of transient ischemic attack (TIA). The aim of this study was to investigate differences in clinical characteristics among subtypes of TVS using multicenter TIA registry data. MATERIALS AND METHODS: Patients with TIA visiting within 7 days of onset were prospectively enrolled from 57 hospitals between June 2011 and December 2013. Clinical characteristics were compared between patients with 3 major subtypes of TVS (transient monocular blindness [TMB], homonymous lateral hemianopia [HLH], and diplopia). RESULTS: Of 1365 patients, 106 (7.8%) had TVS, including 40 TMB (38%), 34 HLH (32%), 17 diplopia (16%), and 15 others/unknown (14%). Ninety-one patients with 1 of the 3 major subtypes of TVS were included. Symptoms persisted on arrival in 12 (13%) patients. Isolated TVS was significantly more common in TMB than in HLH and diplopia (88%, 62%, and 0%, respectively; P < .001). Duration of symptoms was shorter in patients with TMB than those with HLH (P = .004). The ABCD2 score was significantly lower in patients with TMB compared with those with HLH and diplopia (median 2 [interquartile range 2-3] versus 3 [2-4] and 4 [2-5], respectively; P = .005). Symptomatic extracranial internal carotid artery stenosis or occlusion was seen in 14 (16%) patients, and was more frequent in TMB than in HLH and diplopia (28%, 9%, and 0%, respectively; P = .015). CONCLUSIONS: TVS was an uncommon symptom in our TIA multicenter cohort. Some differences in clinical characteristics were found among subtypes of TVS.

BACKGROUND: End-diastolic ratio, calculated by the side-to-side ratio of end-diastolic flow velocities of the common carotid arteries, is an indicator for large artery intracranial occlusive disease. However, the diagnostic ability of end-diastolic ratios derived from different measurement conditions is unclear. METHODS: End-diastolic ratios were measured twice by single carotid duplex ultrasonography. End-diastolic ratio1st was calculated from separate end-diastolic flow velocities measured during routine assessment. End-diastolic ratio2nd was calculated almost simultaneously without head rotation. For each end-diastolic ratio, the measurement conditions and prediction ability for occlusions of the internal carotid artery or proximal portion of the middle cerebral artery using an established cutoff of 1.4 or greater were compared. RESULTS: Two hundred thirty-three patients (147 men, median 67 years) were registered, with available intracranial artery information in 158 patients (67.8%) and occlusions detected in 7 patients (4.4%). End-diastolic ratio1st was significantly higher than end-diastolic ratio2nd (median 1.21 versus 1.08, P < .001). Compared with end-diastolic ratio1st, end-diastolic ratio2nd had a significantly shorter time interval (median 709 versus 28 seconds, P < .001) and smaller pulse rate difference (1.54 ± 5.10 versus .25 ± 4.63 beats per minute, P = .004). To predict occlusions, the sensitivity, specificity, and overall accuracy for end-diastolic ratio1st of 1.4 or greater were 85.7%, 70.9%, and 71.5%, respectively, and for end-diastolic ratio2nd of 1.4 or greater were 85.7%, 98.0%, and 97.5%, respectively. End-diastolic ratio2nd had better specificity and overall accuracy than end-diastolic ratio1st (P < .001). CONCLUSIONS: End-diastolic ratio varies with measurement conditions. Combined end-diastolic flow velocities measurement may improve diagnostic ability for large artery intracranial occlusive disease.

BACKGROUND: Symptoms of transient ischemic attack (TIA) persist on arrival and subsequently resolve in some patients admitted to hospitals early after onset. Differences in clinical characteristics between patients with acute TIA whose symptoms do and do not persist on arrival remain unclear. METHODS: We retrospectively extracted data of consecutive TIA patients with an onset-to-door time (ODT) of 24 hours or less and without a history of stroke from a multicenter TIA database. Clinical characteristics were compared between patients with and without persisting symptoms on arrival. RESULTS: Two hundred sixty-six patients (158 men, 68.0 ± 12.9 years) were included. Of the total number of patients, 105 (39.5%) had persisting symptoms with a mean National Institutes of Health Stroke Scale score of 2.4 (median, 1.0). Patients with persisting symptoms were more likely to have sensory disorder, ambulance-transported admission, long-duration TIA (≥60 minutes), and shorter ODT than those without. Multivariate analysis showed that sensory disorder (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.35-4.77), ambulance-transported admission (OR 1.80, 95% CI 1.00-3.28), and long-duration TIA (OR 3.96, 95% CI 2.12-7.71) were positively associated and that an ODT of more than 12 hours (OR .18, 95% CI .04-.63) was inversely associated with the presence ofpersisting symptoms. Patients with persisting symptoms were more likely to be examined by a stroke physician at first (69% versus 57%, P = .049) and then hospitalized in a stroke unit (59% versus 43%, P = .010). CONCLUSION: Clinical manifestations and management after admission might differ between patients with acute TIA whose symptoms do and do not persist on arrival.

Background and Purpose: Transient ischemic attack (TIA) is a high risk of subsequent ischemic stroke. We have reported one case receiving intravenous recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke occurring during hospitalization for TIA. We analyzed other consecutive patients receiving rt-PA for acute ischemic stroke occurring during hospitalization for TIA. Methods: We reviewed four cases (2 males and 2 females, aged from 74 to 89 years) from our facility's rt-PA database between October 2005 and December 2013. Results: The ABCD2 score of preceding TIA ranged from 4 to 6. Three of the four patients had atrial fibrillation and major artery occlusion on admission and/or time of the occurrence of subsequent ischemic stroke. Diffusion weighted imaging (DWI) on admission revealed a hyperintense lesion in the left medial thalamus in one patient. Elapsed time from the index TIA to the time of occurrence of ischemic stroke ranged from 2 hours to 3 days. The National Institutes of Health Stroke Scale score at the onset of ischemic stroke ranged from 7 to 30. The onset-to-treatment time of rt-PA was 33, 33, 160, and 170 minutes, respectively. Modified Rankin Scale score at 90 days was 0 in 2 patients and 5 in one patient. The other one patient could not be followed up. Conclusions: Patients with TIA being at high risk for subsequent ischemic stroke should be immediately hospitalized. To avoid delay in timely treatment including acute revascularization therapy, occurrence of subsequent ischemic stroke should be always kept in mind.

<sec><title>Background</title> Atrial fibrillation impairs left atrial appendage function and the thrombus formation in the left atrial appendage is a major cause of cardioembolic stroke. </sec><sec><title>Aims</title> To evaluate the association between the volume of the left atrial appendage measured by real-time three-dimensional transesophageal echocardiography and presence of paroxysmal atrial fibrillation in patients with cerebral infarction or transient ischemic attack. </sec><sec><title>Methods</title> Real-time three-dimensional transesophageal echocardiography was performed to measure left atrial appendage end-diastolic and end-systolic volumes to calculate left atrial appendage ejection fraction. Patients with normal sinus rhythm at the time of real-time three-dimensional transesophageal echocardiography were divided into groups with and without paroxysmal atrial fibrillation. Volumetric data were corrected with the body surface area. </sec><sec><title>Results</title> Of 146 patients registered, 102 (29 women, 72·2 ± 10·7 years) were normal sinus rhythm at the examination. In 23 patients with paroxysmal atrial fibrillation, left atrial appendage end-diastolic volume (4·78 ± 3·00 ml/m² vs. 3·14 ± 2·04 ml/m², P = 0·003) and end-systolic volume (3·10 ± 2·47 ml/m² vs. 1·39 ± 1·56 ml/m², P &lt; 0·001) were larger and left atrial appendage ejection fraction (37·3 ±19·1% vs. 57·1 ± 17·5%, P &lt; 0·001) was lower than in the other 79 patients without paroxysmal atrial fibrillation. The optimal cutoff for left atrial appendage peak flow velocity to predict paroxysmal atrial fibrillation was 39·0 cm/s (sensitivity, 54·6%; specificity, 89·7%; c-statistic, 0·762). The cutoffs for left atrial appendage end-diastolic volume, end-systolic volume, and ejection fraction were 4·52 ml/m² (sensitivity, 47·8%; specificity, 82·3%; c-statistic, 0·694), 1·26 ml/m² (sensitivity, 91·3%; specificity, 60·3%; c-statistic, 0·806), and 47·9% (sensitivity, 78·3%; specificity, 74·7%; c-statistic, 0·774), respectively. In multivariate analysis, all these parameters were independently associated with paroxysmal atrial fibrillation after adjusting for sex, age, diabetes mellitus, and previous stroke. </sec><sec><title>Conclusions</title> Left atrial appendage volumetric analysis by real-time three-dimensional transesophageal echocardiography is a promising method for detecting paroxysmal atrial fibrillation in acute cerebral infarction or transient ischemic attack. </sec>

BACKGROUND: Transient monocular blindness (TMB) is associated with a transient ischemic attack (TIA). The purpose of this study was to investigate the features of TMB in the Japanese population using data from a multicenter retrospective study of TIA. METHODS: The subjects were consecutive TIA patients admitted to 13 stroke centers within 7 days after symptom onset. We compared clinical characteristics of patients with TMB and those without TMB who had other symptoms of cerebral TIA. RESULTS: A total of 464 patients were registered between January 2008 and December 2009, and 444 patients (283 men, mean age: 68.5 years) were included in the analysis. Thirteen patients (2.9%) presented with TMB. Patients with TMB were less likely to arrive at the specialized stroke center quickly than those without TMB (P = .013). Stenotic lesions in the extracranial internal carotid artery were more common in patients with TMB (33.3% versus 9.1%, P = .022). CONCLUSIONS: TMB was not common in our TIA inpatients. This study suggests that patients with TMB should immediately undergo a diagnostic workup, including brain and vessel imaging, and cardiac evaluation, as is performed in patients with other cerebral TIA symptoms. A larger, prospective cohort is needed to confirm the risks and outcomes of patients with TMB in the Japanese population.

Our objective is to present a case of fatal multiple systemic emboli after intravenous thrombolysis for cardioembolic stroke. A 64-year-old woman with atrial fibrillation was admitted for evaluation of sudden consciousness disturbance, right hemiplegia, and aphasia. Diffusion-weighted imaging showed no early ischemic changes of the brain, and magnetic resonance angiography (MRA) showed occlusion of the left middle cerebral artery (MCA). One hour after initiation of 0.6 mg/kg of intravenous alteplase, the MCA was partially recanalized. Her symptoms disappeared the following day. We began intravenous heparin for secondary prevention of cardioembolic stroke. However, on the third day (52 hours after thrombolysis), she suddenly developed a coma and left hemiplegia. MRA showed acute occlusion of the right internal carotid artery (ICA). She developed acute kidney injury and sudden shock and then died of fatal cardiorespiratory arrest on the fourth day. Autopsy revealed occlusion of the mitral valve orifice by a spherical fresh red thrombus that led from the left atrial appendage. Acute embolic infarcts were identified in the spleen and right kidney, the latter secondary to occlusion of the right renal artery with fresh red thrombus. Intravenous thrombolysis and subsequent anticoagulation therapy may destabilize pre-existing intracardiac thrombus, potentially leading to recurrent stroke, multiple systemic embolisms, and the fatal "hole-in-one" effect.

We herein report two autopsy cases of severe cardioembolic stroke with oscillating thrombi in the bilateral extracranial internal carotid arteries (ICAs) demonstrated on carotid ultrasonography performed on admission. An autopsy study of Case 1 conducted on the third hospital day revealed no thrombi, while that of Case 2 conducted on the 42nd hospital day revealed red thrombi in the extracranial ICAs. Our postmortem studies confirm that oscillating thrombi may be seen in the region of blood stasis caused by occlusion of the distal portion of the ICA, thus reflecting a pre-state of thrombus formation.<br>

We report the case of a 62-year-old man with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO). He developed gait disturbance at 54 years of age, muscle weakness at 56 years, and difficulty hearing at 58 years. His brother had muscle weakness in both legs from age 20 years, and was diagnosed with Charcot-Marie-Tooth disease because he had muscle weakness of the four extremities, decreased CMAP and SNAP amplitudes on peripheral nerve conduction tests, and loss of large myelinated fibers and onion-bulb formations on sural nerve biopsy. His brother died aged 46 years, but no accurate cause of death was identified. Neurological examination of the present patient revealed bilateral ptosis, external ophthalmoparesis, dysarthria, dysphagia, sensorineural hearing loss, mild weakness and atrophy of proximal muscles in all four limbs, severe sensory ataxia, and disturbance of deep sensation in his legs. He showed elevation of lactate and pyruvate levels in cerebrospinal fluid and serum. An aerobic exercise test disclosed a marked increase in lactate and pyruvate levels in serum. On nerve conduction study, amplitudes of CMAP and SNAP, and F wave-evoked frequency were decreased. Needle electromyography showed chronic neurogenic patterns with fibrillation potentials in the extremity muscles. Head MRI demonstrated T2 prolonged lesions in the bilateral basal ganglia, while brain MRS revealed a small lactate peak. Biopsy of his left lateral vastus muscle showed ragged-red fibers and group atrophy, and some muscle fibers had decreased cytochrome c activity. Left sural nerve biopsy revealed a marked loss of large myelinated fibers, and some onion-bulb formations. Genetic testing disclosed a large mtDNA deletion in the biopsied muscle. Among nuclear genes, we found point mutations in ANT-1 (exon 1 c.105G>A, 5' untranslated region) and POLG-1 (exon 4, c.1218G>A, p. and exon 23 c.3920C>T, p.A1217V). We diagnosed SANDO. This is the first case of SANDO with large mitochondrial DNA deletions in Japanese.

An 85 year-old woman with hypertension and dyslipidemia was admitted with visual impairment, left hemiparesis, and sensory disturbance. A systolic bruit was not audible in her neck or supraclavicular fossa. Magnetic resonance imaging revealed a fresh infarct in the right occipital lobe and magnetic resonance angiography (MRA) showed occlusion of the right posterior cerebral artery (PCA). Carotid ultrasonography showed no stenotic lesions. We performed transesophageal echocardiography (TEE) and found a mobile lesion in the origin of the innominate artery. After several days, we performed real-time three-dimensional (3D) TEE for further evaluation. We found that the mobile lesion was stringy with a length of 2.7 cm and moving in a circle around the point of adhesion. We could also detect the lesion by ultrasonography with a sector probe from the superior thoracic aperture. The lesion could not be detected by cervical MRA or computed tomography angiography.<br>The patient had no cardiogenic embolic source such as atrial fibrillation or a right to left shunt. There was no abnormal vascular form of dissection or aneurysm. We considered the mobile thrombogenic lesion to have originated from a ruptured atherosclerotic plaque with thrombus.<br>3D TEE may be a useful method for real-time three-dimensional evaluation of a mobile lesion located in the innominate artery or aortic arch, which is often difficult to evaluate by other methods.

A 77-year-old woman suffering from chronic bronchial asthma and chronic atrial fibrillation who had had a previous ischemic stroke presented to our emergency unit with gait disturbance. She had new-onset truncal ataxia, right hemiparesis, and right sensory disturbance related to the previous stroke. Her lower legs were slightly swollen and had a reddened appearance. Her medical history included mitral valve replacement because of severe mitral valve regurgitation. Her white blood cell count was 8600/μL, mainly consisting of eosinophils (4480/μL; 52.1%). Serum nonspecific immunoglobulin E was elevated to 1600 IU/mL (normal range <170 IU/mL). She was taking warfarin for secondary stroke prevention, and on admission her prothrombin time international normalized ratio was 3.06. Diffusion-weighted magnetic resonance imaging revealed a fresh infarct in the right cerebellum. No stenosis or occlusion was shown in the cervicocephalic arteries on magnetic resonance angiography or carotid ultrasound. No emboligenic diseases, except for atrial fibrillation, were identified. On day 3, an extensive itchy, purpuric rash appeared on her lower limbs. The rash remitted and recurred spontaneously for several weeks. A skin biopsy specimen of the purpuric lesions revealed massive eosinophilic infiltration of the dermis and eosinophilic vasculitis involving small vessels. We diagnosed the patient with Churg-Strauss syndrome (CSS). Skin lesions and eosinophilia disappeared after oral corticosteroid therapy. In this case, cerebellar infarction occurred with purpuric rash despite well-controlled anticoagulation. Patients with CSS may suffer from ischemic stroke when the condition of CSS deteriorates.

Hereditary hemorrhagic telangiectasia (HHT) is characterized by systemic vascular diseases mainly shown as arterio-visnous fistula (AVF). Here, we presented a 29-year-old woman with HHT complicated with migraine with aura (MWA) and vertigo. At the age of twelve years, she developed migraine with visual aura. At that time, migraine attacks were seen three times a year. At the age of 29 years, she also developed speech disturbance as migraine aura. At the ages of 20 and 29 years, she repeatedly suffered from positional vertigo attacks for a month. Physical examination revealed dilation of the capillary vessels at tongue, soft palate, and nasal mucosa and AVFs were located in the upper cervical cord, parietal lobe, and bilateral lungs. These clinical findings were consistent with the diagnostic criteria of HHT. Embolization of pulmonary AVF decreased the frequency of migraine attacks during 2-year follow-up after the embolization. The frequency of migraine in patients with HHT is higher than that of general population as well as the prevalence of vertigo. Therefore, MWA and vertigo presented in the patient with HHT suggests that there is a common pathological mechanism of dysfunction of endothelial cells and R-L shunt, among HHT, MWA, and vertigo.

A 66-year old hypertensive man having a prostate cancer was admitted to our hospital with sudden onset right hemiparesis. On admission, he showed left hemiplegia, hypesthesia, right limb ataxia, and dysarthria. The NIHSS score was 16. Diffusion weighted magnetic resonance imaging showed an acute infarct in the middle pons and magnetic resonance angiography (MRA) revealed basilar artery (BA) occlusion. Carotid Doppler ultrasonography showed distal occlusion pattern of the bilateral vertebral artery. He was treated with intravenous rt-PA at 116 minutes after symptom onset. One hour later, his symptom was not improved and BA was still occluded on follow-up MRA. Therefore, we performed mechanical thrombectomy with Merci(®) Retrieval System. At 323 minutes after onset, BA was successfully recanalized and NIHSS score decreased to 4 without hemorrhagic complication. Medication of oral warfarin was started on day 19 because paroxysmal atrial fibrillation was detected by electrocardiogram. The retrieved thrombus was pathologically diagnosed as a organizing mixed thrombus probable cardiac origin. On day 27, he was discharged home without any neurological deficit. Additional thrombectomy with Merci(®) Retrieval System is a promising treatment strategy for BA occlusion which is resistant to intravenous rt-PA thrombolysis.

A 66-year－old man was admitted with dizziness, and suffering from hypertension, hyperlipidemia, brain hemorrhage, and brain infarction. There was a difference in blood pressure between the right arm (77/61 mmHg) and the left (120/60 mmHg) , and the pulse of the right radial artery was markedly diminished. A systolic bruit was audible in the right supraclavicular fossa. Doppler ultrasonography demonstrated a "post-stenotic pattern" in the right vertebral artery (VA) and right common carotid artery (CCA) , characterized by diminished peak systolic flow velocity. We then performed aortic arch angiography and confirmed the presence of severe innominate artery stenosis. The stenosis was successfully treated by balloon angioplasty and stenting. After the treatment, the pulse of the right radial artery became easily palpable, the post－stenotic pattern by Doppler ultrasonography normalized, and the blood pressures in the bilateral arms equalized. When Doppler ultrasonography indicates a post－stenotic pattern in the right VA and the right CCA, stenosis of the innominate artery and occlusion of the left VA should be investigated.

A 75 year-old female transported to hospital by heli-ambulance presented with disturbance of consciousness. She had been treated for hypertension, chronic atrial fibrillation, and chronic heart failure with an angiotensin converting enzyme (ACE) inhibitor (imidapril 10 mg/day). Examination on admission showed roving eye movement and right hemiparesis. NIHSS score was 35. Head magnetic resonance imaging (MRI) showed a fresh infarction in the left middle cerebral artery (MCA) territory. Magnetic resonance angiography showed the left MCA as defective downstream of the M2 portion. She was treated with 0.6 mg/kg intravenous alteplase at 103 minutes after onset. Shortly after recombinant human tissue-type plasminogen activator (rt-PA) thrombolysis, we found lingual swelling and she was intravenously treated with 500 mg of methylprednisolone. Her disturbance of consciousness and right hemiparesis improved (NIHSS score 16), but after 17 hours, her consciousness disturbance worsened again. Head MRI demonstrated a relapse of a brain infarction in the right MCA territory. Lingual angioedema completely disappeared after 36 hours. When a patient taking an ACE inhibitor is treated with intravenous rt-PA, it appears necessary to ascertain any orolingual angioedema, which can be difficult to find when limited to the tongue.

We report a patient with top of the basilar syndrome associated with persistent primitive hypoglossal artery (PPHA). A 94-year-old female was transported by ambulance because of disturbance of consciousness. She was in a deep coma. Her eyes were fixed in the middle position without pupillary light reaction. NIHSS score was 40. Head MRI demonstrated fresh infarction in the bilateral midbrain, cerebral peduncle, and thalamus. MRA demonstrated that the PPHA arose from the right internal carotid artery and formed the basilar artery (BA). BA was occluded in the end. Three-dimensional CT angiography after 4 days showed hypoplasia of the left vertebral artery and aplasia of the bilateral posterior communicating artery and the right vertebral artery. BA was recanalized, but the patient showed no improvement in symptoms. Because the development of collateral blood circulation was defective, top of the basilar syndrome may become severe in a patient with PPHA.