[Difficulties in distinguishing abnormal intensities associated with convulsion from tumor on MRI: a case report].

A 48-year-old man was admitted to our department with generalized convulsive seizures followed by recurrent partial clonic convulsions in the left face and arm. Convulsions stopped temporarily after administration of diazepam, fosphenytoin, and levetiracetam. However, frequent partial seizures occurred repeatedly and general anesthesia was required to control seizures. Diffusion-weighted and T2-weighted images revealed a high-intensity lesion in the right frontal lobe. A tumor-like area in the white matter showed high intensity on T2-weighted images with ring enhancement on gadolinium-enhanced T1-weighted images. An area of frontal cortex near the tumor was also enhanced. Brain surgery was performed for the purposes of diagnosis, seizure control and tumor resection. Histological findings demonstrated oligodendroglioma in the ring-enhancing area, but not in the frontal cortex. This fact indicated that contrast enhancement of the frontal cortex was caused by status epilepticus. It is important to recognize that status epilepticus could cause contrast enhancement on magnetic resonance imaging.

[A case of bilateral cervical internal carotid artery dissection following herpes zoster of the trigeminal nerve].

A 62 year-old man, who was taking prednisolone for nephrotic syndrome, was diagnosed with herpes zoster of the trigeminal nerve and treated with oral valacyclovir. One month later, he reported pain from the right side of the head and vomiting. MRI revealed an acute infarction in the right frontal lobe and dissection of the internal carotid artery of the right cervix. Trauma or other potential triggers were not observed. In consideration of the preceding condition of varicella zoster virus infection, acyclovir was administered in addition to unfractionated heparin, but an intramural hematoma emerged in the left internal carotid artery. Furthermore, evidence showing progression of these lesions was found. On the fifth day, prednisolone was increased to 1 mg/kg/day, and progression of vascular lesions was not observed. This case may prove valuable because it suggests a relationship between cervical artery dissection and herpes zoster.

[Case of an elderly patient with community acquired bacterial meningitis due to extended spectrum ß lactamase producing Escherichia coli].

Community acquired bacterial meningitis due to extended spectrum ß lactamase-producing Escherichia coli is very rare. We report the case of a 72-year-old woman being treated for longstanding diabetes mellitus. She developed lower back pain accompanied by elevated body temperature, and was transported to the emergency unit in our hospital five days later because of impaired consciousness. An abdominal plane CT showed acute pyelonephritis and a brain MRI showed inflammatory exudate in the posterior horn of her bilateral ventricles. A lumbar puncture was performed, and examination of the cerebrospinal fluid revealed a marked elevation in her cell count (polymorphonuclear leukocytes dominant) that we diagnosed as bacterial meningitis. Initially, she was treated with intravenous meropenem, ceftriaxon, and vancomycin. Extended spectrum ß lactamase-producing Escherichia coli were then detected in her urinary and blood cultures, and the antibiotics were changed to intravenous meropenem, gentamicin, and intrathecal gentamicin. Her clinical symptoms improved, but her inflammatory reaction was prolonged and we detected spondylitis. She was then treated with levofloxacin, and the inflammatory reaction improved. Extended spectrum ß lactamase-producing Escherichia coli should be taken into consideration as a cause of community acquired bacterial meningitis.

Ulcerated plaques in the aortic arch contribute to symptomatic multiple brain infarction.

BACKGROUND: The configuration of aortic plaque appears to be as important as its thickness when it acts as an embolic source to the brain. The frequency and clinical predictors of ulcerated plaque at the aortic arch identified using transoesophageal echocardiography (TOE) in patients with stroke were determined, and the association between the ulcer and recent ischaemic stroke, particularly multiple brain infarcts, which appear to indicate embolic stroke, was examined. METHODS: Aortic and cardiac embolic sources were evaluated using TOE in 360 patients with fresh ischaemic stroke proven by diffusion-weighted MRI, including 210 patients with a single infarct and 150 with multiple infarcts, as well as in 101 non-stroke control patients. An ulcer was defined as a crater on the plaque ≥2.0 mm in depth and width. RESULTS: An ulcerated plaque was identified in 10.6% of patients with stroke versus 2.0% of non-stroke patients, showing a 5.11-fold higher frequency in patients with stroke (95% CI 1.51 to 31.96) after adjustment for age and sex. After multivariate adjustment for clinical and ultrasonographic features, multiple-infarct patients had a 7.61-fold higher risk (95% CI 1.99 to 50.43) of having an ulcer than control patients and a 3.32-fold higher risk (95% CI 1.61 to 7.18) of having an ulcer than single-infarct patients. Diabetes mellitus and drinking habit were independently related to the presence of ulcerated plaque in patients with stroke. CONCLUSIONS: Ulcerated plaque in the aortic arch was associated with the development of ischaemic stroke, especially multiple brain infarcts, probably involving, at least in part, an embolic mechanism.

Atheromatous plaques at the origin of the left subclavian artery in patients with ischemic stroke.

BACKGROUND: Atheromatous plaques of the aortic arch that extend to the origin of its branches may cause stroke. The frequency and clinical implications of plaque at the origin of the left subclavian artery (LSCA) in patients with recent ischemic stroke were investigated. METHODS: We studied 347 consecutive patients (223 men, 69 +/- 12 years) who developed symptomatic ischemic stroke and underwent transesophageal echocardiography (TEE). RESULTS: The origin of the LSCA was identified in 303 of 347 patients (87.3%). Plaque > or =1.0 mm was detected in 108 of the 303 patients (35.6%), ranging between 1.0 and 6.1 mm (median, 2.5 mm). Patients having thicker plaque (> or =2.5 mm) were older (p = 0.012) and more commonly took antiplatelets prior to stroke (p = 0.038) than patients with no plaque and those with thinner plaque (<2.5 mm). Of the aortic arch findings detected on TEE, maximum intima-media thickness (IMT) was the highest (p < 0.001) in patients with thicker plaque, and large plaque (> or =4.0 mm) (p = 0.017), ulcerative plaques (p < 0.001), and spontaneous echo contrasts (p = 0.001) were identified most commonly in patients with thicker plaque. The frequency of infarcts involving the posterior circulation was similar among the three groups. After multivariate adjustment, maximum IMT of the aortic arch was independently related to thicker plaque at the LSCA origin (OR = 1.24, 95% CI = 1.03-1.51, p = 0.024, per 1-mm increase). CONCLUSIONS: Atheromatous plaque at the origin of the LSCA was present in approximately one third of patients with a recent ischemic stroke. High IMT at the aortic arch was independently related to the presence of thick plaque at the LSCA origin. The present study does not support the concept that plaque at the LSCA origin may be associated with posterior circulation infarction.

Tortuous carotid artery lumens in Takayasu's arteritis.

We report a 68-year-old woman who was incidentally diagnosed as having an occlusion in the right internal carotid artery on magnetic resonance angiography. On ultrasound, the right common carotid artery showed narrow and tortuous lumens, which suggest the uneven thickening of the arterial wall in the nonactive stage of Takayasu's arteritis. Although macaroni-like diffuse and circumferential thickening of the arterial wall is a known ultrasonographic finding of Takayasu's arteritis, the tortuous sign also appears to be characteristic as an ultrasonographic finding of the healed arteritis in aged patients.

Cardiac papillary fibroelastoma as a cause of embolic stroke: ultrasound and histopathological characteristics.

Although a cardiac papillary fibroelastoma is a benign cardiac tumor, it can cause severe embolic complications. A 51-year-old man presented with an ischemic stroke in the right middle cerebral artery territory. Transesophageal echocardiography revealed a small mobile tumor on the mitral valve as the only detectable source of emboli to the brain. On histology, the tumor was diagnosed as a papillary fibroelastoma. In this paper, the detailed characteristics of the tumor on ultrasound and histopathology are documented. In patients with cryptogenic stroke, transesophageal echocardiography should be done to rule out such an unusual emboligenic heart disease.

Genetic variations of CYP2C9 in 724 Japanese individuals and their impact on the antihypertensive effects of losartan.

CYP2C9, a drug-metabolizing enzyme, converts the angiotensin II receptor blocker losartan to its active form, which is responsible for its antihypertensive effect. We resequenced CYP2C9 in 724 Japanese individuals, including 39 hypertensive patients under treatment with losartan. Of two novel missense mutations identified, the Arg132Gln variant showed a fivefold lower intrinsic clearance toward diclofenac when expressed in a baculovirus-insect cell system, while the Arg335Gln variant had no substantial effect. Several known missense variations were also found, and approximately 7% of the Japanese individuals (53 out of 724) carried one of the deleterious alleles (CYP2C9*3, *13, *14, *30, and Arg132Gln) as heterozygotes. After 3 months of losartan treatment, systolic blood pressure was not lowered in two patients with CYP2C9* 1/*30, suggesting that they exhibited impaired in vivo CYP2C9 activity. CYP2C9*30 might be associated with a diminished response to the antihypertensive effects of losartan.

Asystole caused by vegetation and abscess of right ventricle attached to a tip of pacemaker lead.

A 69-year-old man with pacemaker was referred to our center for cerebral infarction. He had a high fever for 10 days during his hospitalization. Pacing failures deteriorating to asystole were observed responsible for bacterial vegetation around the tip of the pacemaker lead, which is rare but important for the cause of pacing failure.

Heart and vessel pathology underlying brain infarction in 142 stroke patients.

OBJECTIVE: This study was designed to determine the histopathological characteristics of cardiac and vascular lesions responsible for various subtypes of ischemic stroke. METHODS: Postmortem pathological examination was performed on 142 patients who died within 30 days of the onset of ischemic stroke in the National Cardiovascular Center, Osaka, Japan. RESULTS: The numbers of cases with autopsy-proven diagnoses of atherothrombotic, cardioembolic, and lacunar strokes, ischemic stroke of other determined causes, and ischemic stroke of undetermined cause were 17, 107, 2, 12, and 4, respectively. Thrombi that developed at the culprit plaques of the cerebral arteries were responsible for atherothrombotic stroke. In 70% of the cases with cardioembolic stroke, the presence of thrombi as potential embolic sources were confirmed in the heart or, in some cases, in the venous circulation of patients with patent foramen ovale and tetralogy of Fallot. INTERPRETATION: In most atherothrombotic strokes, fibrin- and platelet-rich thrombi of various thicknesses develop at the culprit plaques of the cerebral arteries, which are finally occluded with fibrin- and red-cell-rich thrombi (red thrombi). In most cardioembolic strokes, red thrombi generated in the heart or peripheral veins are dislodged to embolize the cerebral arteries.

Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients.

The dose required for the anticoagulant effect of warfarin exhibits large inter-individual variations. This study sought to determine the contribution of four genes, vitamin K epoxide reductase (VKORC1), gamma-glutamyl carboxylase (GGCX), calumenin (CALU), and cytochrome P450 2C9 (CYP2C9) to the warfarin maintenance dose required in Japanese patients following ischemic stroke. We recruited 93 patients on stable anticoagulation with a target International Normalized Ratio (INR) of 1.6-2.6. We genotyped eleven representative single nucleotide polymorphisms (SNPs) in the three genes involved in vitamin K cycle and the 42613A>C SNP in CYP2C9, known as CYP2C93, and then examined an association of these genotypes with warfarin maintenance doses (mean+/-SD=2.96+/-1.06 mg/day). We found an association of effective warfarin dose with the -1639G>A (p=0.004) and 3730G>A genotypes (p=0.006) in VKORC1, the 8016G>A genotype in GGCX (p=0.022), and the 42613A>C genotype in CYP2C9 (p=0.015). The model using the multiple regression analysis including age, sex, weight, and three genetic polymorphisms accounted for 33.3% of total variations in warfarin dose. The contribution to inter-individual variation in warfarin dose was 5.9% for VKORC1 -1639G>A, 5.2% for CYP2C9 42613A>C, and 4.6% for GGCX 8016G>A. In addition to polymorphisms in VKORC1 and CYP2C9, we identified GGCX 8016G>A, resulting in the missense mutation R325Q, as a genetic determinant of warfarin maintenance dose in Japanese patients.

Polymorphisms in vitamin K-dependent gamma-carboxylation-related genes influence interindividual variability in plasma protein C and protein S activities in the general population.

gamma-Glutamyl carboxylation, a reaction essential for the activity of vitamin K-dependent proteins, requires the concerted actions of gamma-glutamyl carboxylase (GGCX), vitamin K 2, 3-epoxide reductase complex 1 (VKORC1), and the chaperone calumenin (CALU). We evaluated the contribution of genetic polymorphisms in VKORC1, GGCX, and CALU to interindividual variation in the activities of plasma protein C and protein S. We sequenced these 3 genes in 96 Japanese individuals and geno-typed 9 representative single-nucleotide polymorphisms in 3655 Japanese individuals representative of the general population. The mean activity of protein C in women bearing the GG genotype of GGCX 8016G>A (130.8% +/- 1.5%, n = 156) was significantly greater (P = .002) than that of individuals with either the AG (126.8% +/- 0.7%, n = 728) or the AA (125.4% +/- 0.6%, n = 881) genotype, after adjusting for confounding factors. The GGCX 8016G>A change leads to the substitution of Gin for Arg at amino acid residue 325 (Arg 325 Gln). This effect was comparable to that of a previously defined polymorphism in the protein C promoter. Mean protein S activity was influenced by the VKORC1 3730G>A and CALU 20943T>A genotypes, after adjusting for confounding factors. Thus, polymorphisms in genes involved in the vitamin K-dependent gamma-carboxylation reaction influence interindividual variation in the activities of protein C and protein S in the general population.

Moderate atheroma of the aortic arch and the risk of stroke.

BACKGROUND AND PURPOSE: Severe atheroma >or=4 or 5 mm of the aortic arch is a risk factor for stroke. We investigated the most predictive characteristics of arch atheroma, including maximal plaque thickness, for subsequent cardiovascular events, and also examined whether moderate atheroma<4 mm is a risk of cerebral emboli. METHODS: The maximal plaque thickness (MPT) and plaque morphologies of the aortic arch were evaluated by transesophageal echocardiography in 236 patients with ischemic stroke. We assessed the relationship between the incidence of cardiovascular events, recurrent stroke or myocardial infarction, and the characteristics of the atheroma. We also investigated the thickness of atheroma in patients with known causes of stroke (n=148) and in patients with undetermined causes (n=19). RESULTS: Cardiovascular events occurred in 47 patients in the follow-up period with a mean of 3.5 years. MPT was a significant risk factor of the cardiovascular events, although plaque morphologies were not. For the receiver operator characteristics curve analysis, the suitable cutoff point of MPT associated with the cardiovascular events was 3.5 mm. Patients with MPT >or=3.5 mm had a higher risk of cardiovascular events than did those with MPT<3.5 mm. In addition, aortic atheroma with MPT >or=3.5 mm was more frequently observed in patients with undetermined causes of stroke than those with known causes at 68 vs. 39% (p=0.024). CONCLUSIONS: MPT >or=3.5 mm is the best predictor of subsequent cardiovascular events and a possible cause of embolic stroke.

Is stroke a paradoxical embolism in patients with patent foramen ovale?

OBJECTIVE: Purpose was to assess the stroke mechanism in patients with patent foramen ovale (PFO). METHODS: We reviewed the medical records of 111 stroke patients with PFO and sinus rhythm (PFO-S group), 25 with PFO and atrial fibrillation (AF) (PFO-AF group) and 67 with AF but not PFO (AF group), who had received contrast transesophageal echocardiography. The clinical and neuroradiological findings were then compared among the three groups. Deep vein thrombosis was investigated in 93 patients with PFO. We determined the number of patients with definite paradoxical embolism who met three criteria: deep vein thrombosis, neuroradiological features indicating embolic stroke, and the absence of other sources of emboli. We also evaluated those with probable paradoxical embolism who met two of the three criteria. RESULTS: The PFO-S group more frequently exhibited hypercholesterolemia (p<0.0001) and lesions limited to the posterior circulation (p<0.0004), and less frequently exhibited large or cortical lesions in the anterior circulation (p=0.0008, p<0.0001, respectively), than the PFO-AF and AF groups. In the PFO-S and PFO-AF groups, other sources of emboli such as a cardiac source of emboli, cerebral artery stenosis > or =50%, or complicated atheroma in the aortic arch were identified in 72 cases (52.9%). In the 93 patients with examination for deep vein thrombosis, the definite and probable criteria of paradoxical embolism were fulfilled only in three (3.2%) and 33 cases (35.5%), respectively. CONCLUSION: In stroke patients with PFO, not only paradoxical brain embolism through the PFO but also other causes of stroke may contribute to the development of stroke.

Right-to-left shunt evaluated at the aortic arch by contrast-enhanced transesophageal echocardiography.

OBJECTIVE: The right-to-left shunt (RLS) is diagnosed by contrast-enhanced transesophageal echocardiographic monitoring of the bilateral atria (cTEE-BA). However, the procedure is often disturbed by nonsmoke spontaneous individual contrast (NSSIC) with fast motion, which appears in the left atrium after respiratory maneuvers without administration of a contrast medium and moves past in several seconds. We attempted to perform cTEE monitoring of the aortic arch (cTEE-AA) for evaluation of the RLS and compared the findings with those of cTEE-BA. METHODS: Both cTEE-BA and cTEE-AA were performed in 168 patients with ischemic stroke (133 men and 35 women; mean age +/- SD, 62.0 +/- 14.4 years). The frequency of NSSIC in the left atrium was compared with that in the aortic arch during the respiratory maneuver. When contrast much brighter than the NSSIC was visualized in the left atrium and the aortic arch during the respiratory maneuver with administration of the contrast medium, we considered the RLS to be positive in the cTEE-BA and cTEE-AA, respectively. Findings were then compared between the 2 examinations. RESULTS: Nonsmoke spontaneous individual contrast was more frequently observed in the left atrium than the aortic arch (61.3% versus 14.9%; chi2 test, P < .0001). The RLS was positive in 34 patients in the cTEE-BA and in 39 patients in the cTEE-AA. The sensitivity and specificity of the cTEE-AA for the cTEE-BA were 100% and 96.3%, respectively. CONCLUSIONS: The cTEE-AA may be an alternative method for detection of an RLS, especially in patients with a large amount of NSSIC in the left atrium.

[Stroke recurrence in patients with brain embolism and patent foramen ovale--association with deep vein thrombosis detected by ultrasonography].

Paradoxical embolism through a patent foramen ovale (PFO) is a recognized cause of stroke, but its prognosis is not well known. The aim of our study is to evaluate differences in risk factors, recurrent stroke subtypes and effects of various preventive therapies between PFO associated stroke patients with and without deep vein thrombosis (DVT). A total of 63 patients who had an embolic stroke with a PFO within 3 months from stroke onset were enrolled. Venous ultrasonography, which was performed in all the patients, revealed DVT in 26 patients (41%). Venous thrombosis was confined to the isolated calf veins in 24 of 26 cases (92%). For prevention of stroke recurrence, warfarin was administrated in 32 patients, antiplatelet therapy was given in 21 patients, and combination of warfarin and antiplatelet therapy was chosen in 10 patients. Three patients with DVT and three other patients without DVT had recurrent ischemic events during a mean follow-up period of 14.6 months. In all the 3 patients without DVT, complicated aortic arch lesions were also observed, and 2 of them had lacunar infarcts. In all the three patients with DVT recurrent embolic stroke or TIA occurred in spite of anticoagulant therapy. Their INR values at the time of recurrence were all below 1.7, and 2 of them were associated with atrial septal aneurysm (ASA). Association with PFO, ASA, and DVT may be a substantial risk factor for recurrent stroke. Higher INR value in anticoagulation may be recommended for such patients to prevent stroke recurrence.

Aortic arch atherosclerotic lesions and the recurrence of ischemic stroke.

BACKGROUND AND PURPOSE: Aortic arch atherosclerotic lesions are often associated with embolic brain infarction. We investigated the relationship between stroke recurrence and the characteristics of aortic arch atherosclerotic lesions. METHODS: Among 487 stroke patients who underwent transesophageal echocardiography, 283 patients with brain embolism diagnosed without significant occlusive lesions (> or =50%) in their cerebral arteries were included in this study. We measured the intima-media thickness (IMT) and evaluated the extension and mobility of the aortic arch atherosclerotic lesions. During a mean follow-up period of 3.4 years, we investigated the relationship between stroke recurrence and the various characteristics of the aortic arch atherosclerotic lesions. RESULTS: An IMT > or =4.0 mm was found in 67 patients (25.3%). In 51 of these patients, the aortic lesions extended to the origin of the branches of the arch. Recurrences of cerebral ischemic events were found in 32 patients (recurrence group) and not in the other 251 (nonrecurrence group). Aortic atheroma > or =4.0 mm (41% versus 22%), aortic atheroma extending to the branches (63% versus 39%), and both (38% versus 16%) were more frequently seen in the recurrence group than in the nonrecurrence group (P<0.05, P<0.1, P<0.01, respectively). After adjustment for age and the presence of hypertension, an aortic atheroma that was > or =4.0 mm as well as extending to the branches was found to be an independent predictor of ischemic stroke recurrence (hazard ratio=2.42, P<0.05). CONCLUSIONS: Stroke recurrence is associated with the severity of the atheroma (IMT > or =4.0 mm) and plaque extension to the branches.