Yasuhisa Akaiwa

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 dentified, 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.

Adult-onset leukoencephalopathy with vanishing white matter with a missense mutation in EIF2B5

We report of a woman aged 52 years born to consanguineous parents and seeking treatment for progressive dementia and delusion. Neurologic examination revealed dementia and emotional instability, indifference, and confabulation. There was also mild spasticity of the bilateral lower limbs. MRI revealed diffuse white matter hyperintensity on T2-weighted images accompanied by hypointense areas on fluid-attenuated inversion recovery images. A homozygous missense mutation was identified in EIF2B5.

High frequency of calcification in basal ganglia on brain computed tomography images in Japanese older adults

To investigate the frequency of calcification in the basal ganglia and the dentate nuclei in the cerebellum, and compare the difference in age and area, we examined the brain computed tomography (CT) images of all patients in two representative university hospitals in Japan.

Isolated Trochlear Nerve Palsy in CREST Syndrome

Introduction Trochlear nerve palsy is a common cause of vertical diplopia and anomalous head position. Although trochlear nerve palsy is most commonly congenital or secondary to head injury, the etiologies of acquired trochlear nerve palsies remain undetermined in approximately one third of patients [1, 2]. Here, we report the case of a patient with histologically confirmed CREST syndrome who developed trochlear nerve palsy, which has rarely been described in association with CREST syndrome.

Usefulness of Acceleration Time for Internal Carotid Artery Origin Stenosis

Calcification of the internal carotid artery (ICA) hinders accurate evaluation of the stenosis by conventional ultrasonography due to acoustic shadow. We examined the relationship between acceleration time (AcT) and ICA origin stenosis. One hundred thrity seven samples (266 vessels) that enforced duplex ultrasonography in our hospital were targeted. The results have shown that there is a significant relationship between AcT and stenosis. AcT of more than 110 msec suggests that the stenosis is more than 60% by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method. AcT is thought to be useful for the diagnosis of ICA stenosis with calcification. (English Translation of J Jpn Coll Angiol 2011; 51: 365-371).

Spontaneous Middle Cerebral Artery Dissection Demonstrated by High-Resolution T1-Weighted 3D Image

Case Report A 39-year-old, right-handed man was admitted to our hospital because of sudden onset of right hemiparesis and aphasia. His medical history included atopic dermatitis, and included no episodes of trauma. He was alert on admission; however, his speech and comprehension were impaired, and was assessed a National Institutes of Health Stroke Scale score of 15. Brain computed tomography showed obscuration of the lentiform nucleus on the left side. Computed tomography angiography (CTA) demonstrated an occlusion of the left MCA at the horizontal segment. Laboratory examination yielded unremarkable results. Administration of intravenous recombinant tissue plasminogen activator (IV rtPA) was started at 164 min after symptom onset (alteplase, 0.6 mg/ kg). However, no neurological improvement was observed. Transcranial color-coded flow velocity measurements demonstrated reperfusion of the left MCA just after IV rt-PA administration, and 1.5T MRI detected an acute infarction in the left putamen, insular cortex, and corona radiata ( fig. 1 a). Magnetic resonance angiography results could not be evaluated because of motion artifacts. On day 4, CTA showed dilatation of the left MCA ( fig. 1 b) and the double lumen sign ( fig. 1 c), on the basis of which spontaneous MCAD was strongly suggested. However, atherothrombic occlusion, while unlikely given the circumstances, could not be completely ruled out at the time, since the fat-saturated T1-weighted imaging [4] needed to make an unambiguous diagnosis of MCAD was not performed. On day 17, fast spoiled gradient-echo images Spontaneous cervicocephalic arterial dissection is an uncommon cause of stroke [1] . Segments of the middle cerebral artery (MCA) are rarely involved, and the incidence of MCA dissection (MCAD) is reported to be 4% of the spontaneous cervicocephalic arterial dissections in Japan [2] . A previous report suggests that magnetic resonance imaging (MRI) may be useful for detecting intracranial vertebrobasilar artery dissection [3] , although the applicability in MCAD patients is unknown. Here, we report a patient who had MCAD with characteristic lesions, which was demonstrated by high-resolution T1-weighted 3D images obtained using a 3-tesla MRI (3T MRI) system. Published online: October 12, 2013

High Incidence of Deep Vein Thrombosis in the Perioperative Period of Neurosurgical Patients

INTRODUCTION A prospective study was designed to elucidate incidence and predictors of deep venous thrombosis (DVT) in patients undergoing craniotomies. MATERIALS AND METHODS Ninety-two patients who underwent craniotomies received pre- and postoperative venous ultrasonography and/or contrast-enhanced spiral computed tomography for diagnosis of DVT. The primary endpoint was DVT occurrence. Serial levels of serum D-dimer, soluble fibrin, and thrombin-antithrombin complex (TAT) were analyzed. RESULTS Twenty-four of 92 patients (26.1%) had DVT, of whom 10 (41.7%) were diagnosed preoperatively. In patients with preoperative DVT, age, incidence of decreased performance status and leg paresis, levels of D-dimer, soluble fibrin, and TAT were significantly greater. In patients with postoperative DVT, length of surgery, incidence of decreased postoperative performance status, levels of D-dimer on postoperative days (POD) 3, 7, and 14, and TAT on POD7 were significantly greater. Patients with postoperative DVT had elevated D-dimer levels on POD 7 compared with POD 3. The D-dimer cutoff of 2.65 μg/mL at POD 7 could be used to identify DVT with 85.7% sensitivity and 72.3% specificity. A cutoff of 5.25 μg/mL at POD 7 yielded a specificity of 96.9%. Decreased performance status and elevated D-dimer were independent predictors for preoperative DVT, prolonged operation time, and elevated D-dimer on POD 7 for postoperative DVT. CONCLUSIONS DVT frequently was observed in patients before and after undergoing craniotomies. Patients with decreased performance status should be preoperatively screened for DVT by checking D-dimer levels. Elevated D-dimer levels on POD 7 compared with POD 3 and D-dimer levels greater than 2.65 μg/mL at POD7 suggest the presence of DVT.

Apparent diffusion coefficient reduction might be a predictor of poor outcome in patients with posterior reversible encephalopathy syndrome

It is thought that posterior reversible encephalopathy syndrome (PRES) is both clinically and radiologically reversible. However, its reversible nature has been challenged based on reports of permanent neurological impairments. The factors that predict the development of irreversible neurological impairment are still unclear. In the present study, we investigated clinical manifestations, laboratory findings, and neuroradiological images to identify predictors of functional outcomes in PRES. We investigated 23 PRES patients. Apparent diffusion coefficient (ADC) reduction was observed in 4 patients in the poor outcome group, whereas no patients presented ADC reduction in the favourable outcome group (p<0.01). Further studies are warranted to evaluate the association between ADC reduction and functional outcome after PRES.

Blood biomarkers associated with neurological deterioration in patients with acute penetrating artery territory infarction: A multicenter prospective observational study:

Background and purpose Neurological deterioration in acute penetrating artery territory infarction is unpredictable and associated with unfavorable clinical outcomes. The aim of this prospective study was to clarify the cause of neurological worsening and predict clinical outcomes using blood biomarkers. Methods Eight Japanese stroke centers participated. Blood samples were obtained within 24 h (the first sampling) and on day 7 in hospital (the second sampling) in patients with penetrating artery territory infarction, arriving within two days of stroke onset. Symptomatic worsening was defined as a minimum increase of one point on the National Institutes of Health Stroke Scale. Poor outcome was defined as a modified Rankin Scale score of ≥3 at 90 days after ictus. Results Of the 89 patients, 25 (28%) had symptomatic worsening, and 25 (28%) had a poor outcome. Although tumor necrosis factor-alpha, high-sensitivity C-reactive protein levels were significantly increased in both groups at the second sampling, soluble lectin-like oxidized low-density lipoprotein receptor-1, CD40 ligand, and pro-adrenomedullin levels were significantly increased and ADAMTS13 activity was decreased in symptomatic worsening patients (p < 0.05 for all). After multivariate adjustment, a low number of CD34+ cells at the first sampling was an independent predictor of poor outcome (odds ratio, 0.20; 95% confidence interval, 0.04–0.74, p = 0.011, per 1 cell/µl increase). Conclusions Blood biomarkers associated with atherosclerotic processes seem to be an indication for symptomatic worsening, and the number of CD34+ cells may help to predict three-month functional outcome in patients with penetrating artery territory infarction.

Visualization of the Intimal Flap in Intracranial Arterial Dissection Using High-Resolution 3T MRI.

Presence of an intimal flap is a critical imaging finding in diagnosing intracranial artery dissection (ICAD). Recent reports showed that high‐resolution magnetic resonance imaging (MRI) was better at identifying intimal flaps as compared with routine MRI techniques used in clinical settings. However, no current standardized sequence for high‐resolution MRI without gadolinium enhancement produces images of satisfactory quality with clinically tolerable scanning times. This study evaluated a nonenhanced high‐resolution fast spin echo (HR‐FSE) MRI sequence for visualizing intimal flaps in patients with ICAD.