Takahiro Himeno

Seizures after intracerebral hemorrhage; risk factor, recurrence, efficacy of antiepileptic drug

OBJECTIVE This study aimed to determine the risk factors for recurrent post stroke seizure (PSS) and the efficacy of anti-epileptic drugs (AED) in patients having intracerebral hemorrhage (ICH) with initial seizure. METHODS/SUBJECTS A total of 1920 consecutive patients with ICH from 2004 to 2012 were investigated retrospectively. The relationships among the baseline clinical and radiological data, administration of AED, and incidence of initial and recurrent PSS were evaluated using multiple logistic regression analysis. RESULTS Seizures occurred in 127 (6.6%) of the 1920 patients, displaying statistically significant relationships with cortical involvement of a cerebral lesion (P<0.001), non-hypertensive ICH (P<0.001), younger age (P<0.001), and severe neurological deficits (P<0.001). Early (4.3%) and late seizure (2.3%) had no significant relationship with the development of recurrent PSS. Larger volume of hematoma was the only independent factor associated with recurrence of PSS (OR 1.03; 95% CI 1.00-1.05; P=0.027). A Kaplan Meier survival analysis revealed that AED treatment had a poor association with recurrence of PSS (P=0.750). CONCLUSIONS Larger volume of hematoma was predictive of recurrence of PSS. AED therapy had poor association with preventing the recurrence of PSS.

Contrast-less stent placement for vertebral artery origin stenosis.

We performed stent placement under intravascular ultrasound (IVUS), without the use of contrast medium, in a male patient in his 70s who had vertebral artery origin stenosis and decreased renal function. Satisfactory dilatation was achieved without complications, and the patient remained asymptomatic at 2 years of follow-up. We now report the details of this procedure. Stent placement under IVUS guidance may be useful in patients in whom contrast medium is contraindicated.

Ischemic Stroke Mortality Is More Strongly Associated with Anemia on Admission Than with Underweight Status

BACKGROUND Underweight patients have recently been reported as a group with a high risk of poststroke death. Anemia also increases mortality rates in stroke patients. However, the causal associations between body weight and anemia resulting in stroke-related death remain unclear. We examined the association of weight status and hemoglobin levels with 3-month mortality after ischemic stroke. METHODS The study enrolled all consecutive patients with acute ischemic stroke and no history of stroke admitted to our hospital between January 2010 and December 2013. The patients were categorized into 4 body mass index (BMI) categories (underweight, normal-weight, overweight, and obese). Anemia was evaluated according to the World Health Organization criteria (men, <13 g/dL; women, <12 g/dL). RESULTS A total of 1733 acute ischemic stroke patients (149 underweight, BMI < 18.5 kg/m2; 1076 normal-weight, BMI = 18.5-24.9 kg/m2; 436 overweight, BMI = 25-29.9 kg/m2; and 72 obese, BMI > 30 kg/m2) were included. Death within 3 months occurred in 65 patients (underweight, 10.1%; normal-weight, 3.4%; overweight, 2.3%; and obese, 5.6%). Compared to nonanemic patients, those with anemia (n = 329, 19.0%) had lower BMI (21.8 kg/m2 versus 23.7 kg/m2, P <.001) and higher mortality rates (9.1% versus 2.5%, P <.001). Underweight status was associated with 3-month mortality after adjusting for age, sex, comorbidities, and initial stroke severity. However, in the models that included laboratory findings, it was anemia status (odds ratio, 2.81; 95% confidence interval, 1.46-5.43), not underweight status, that was independently associated with 3-month mortality. CONCLUSION Anemia on admission was associated with stroke mortality independent of underweight status.

Acute ischemic stroke associated with nephrotic syndrome: Incidence and significance — Retrospective cohort study

We report 10 cases with arterial ischemic stroke (AIS) with nephrotic syndrome (NS), and clarified its incidence and clinical characteristics. The patients having albumin less than 3.0 g/dl and serum cholesterol greater than 250 mg/dl at the same time were retrospectively screened from 11,161 cases of stroke. Furthermore, the patients of AIS showing heavy proteinuria were selected. The 10 cases were diagnosed as AIS with NS. Its incidence was 0.09% of all kinds of stroke and 0.12% of AIS. Their subtypes were 6 large-artery atherosclerosis, 3 small-vessel occlusion, and 1 cardioembolism. We carried out a retrospective cohort study to assess the association between NS and atherosclerosis progression in AIS patients. Seven AIS patients with NS due to diabetic nephropathy (cases; NS group) were compared with patients with AIS and diabetes mellitus (DM) without NS (control group). Control group subjects were matched in a 2:1 ratio to cases by age, sex, use of medications for DM, and hemoglobin A1c (HbA1c) level. The NS group had high cerebral artery atherosclerosis scores, especially in the anterior circulation. The NS group demonstrated atherosclerosis of the internal carotid and lower extremity arteries, although there were no statistical differences between the two groups. Study subjects had high serum fibrinogen and D-dimer levels, suggesting that AIS patients with NS have a greater degree of hypercoagulability than AIS patients without NS.

Ability of the Ankle Brachial Index and Brachial-Ankle Pulse Wave Velocity to Predict the 3-Month Outcome in Patients with Non-Cardioembolic Stroke

Aim: Both the ankle brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are surrogates for atherosclerosis. In this study, we aimed to evaluate the ability of ABI and baPWV to predict stroke outcome in patients with first-ever non-cardioembolic stroke. Methods: This study included consecutive patients with first-ever non-cardioembolic stroke admitted within 1 week after onset to Ota Memorial Hospital between January 2011 and December 2013. Baseline characteristics and National Institutes of Health stroke scale scores at admission were noted. ABI and baPWV were evaluated within 5 days of admission. The patients were categorized according to ABI (cut-off 0.9) and baPWV (cut-off 1870 cm/s) determined using the receiver operation curve for poor outcome. Clinical outcomes were defined based on the modified Rankin scale (mRS) scores 3 months after stroke onset as good (0 and 1) or poor (2–6). Results: A total of 861 patients were available for evaluation. ABI < 0.9 and baPWV > 1870 cm/s were associated with poor outcome in the univariate analysis (p < 0.001 and p < 0.001, respectively). After adjusting for factors that showed differences between groups, ABI < 0.9 was associated with poor outcome. Among patients with ABI ≥ 0.9, higher baPWV showed a slight association with poor outcome after adjustment [odds ratio 1.46 (95% CI 0.95–2.27)]. Conclusion: Our study suggests that the stroke outcome can be predicted using ABI and to an extent using baPWV when ABI ≥ 0.9 in patients with non-cardioembolic stroke.

Hydrophilic-interaction liquid chromatography-tandem mass spectrometric determination of erythrocyte 5-phosphoribosyl 1-pyrophosphate in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency.

Mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT) cause Lesch-Nyhan disease (LND) and its variants (LNV). Due to the technical problems for measuring the HPRT activity in vitro, discordances between the residual HPRT activity and the clinical severity were found. 5-Phosphoribosyl 1-pyrophosphate (PRPP) is a substrate for HPRT. Since increased PRPP concentrations were observed in erythrocytes from patients with LND and LNV, we have turned our attention to erythrocyte PRPP as a biomarker for the phenotype classification. In the present work, a method for determination of PRPP concentration in erythrocyte was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM). Packed erythrocyte samples were deproteinized by heating and the supernatants were injected into the LC-MS/MS system. All measurement results showed good precision with RSD <6%. PRPP concentrations of nine normal male subjects, four male patents with LND and six male patients with LNV were compared. The PRPP concentrations in erythrocyte from patients with LND were markedly increased compared with those from normal subjects, and those from patients with LNV were also increased but the degree was smaller than those with LND. The increase pattern of PRPP concentration in erythrocyte from patients with HPRT deficiency was consistent with the respective phenotypes and was correlated with the disease severity. PRPP concentration was suggested to give us supportive information for the diagnosis and the phenotype classification of LND and LNV.

Reversible cerebral vasoconstriction syndrome: a clinical study of 11 cases

This study reports eleven cases of reversible cerebral vasospasm syndrome (RCVS). Of the 11 patients, two were males and nine were females, with the average age of 47.9 ± 14.1 years. Many of these patients were young. The rates of severe, intractable and pulsative headache, generalized convulsions, and motor hemiparesis were 64%, 27%, and 36%, respectively. As complications of intracerebral lesions in the early stage of disease onset, convexal subarachnoid hemorrhage, lobar intracerebral hemorrhage, and posterior reversible encephalopathy syndrome were observed in 63%, 9%, and 45% of cases, respectively. Cerebral infarction occurred in 45% of cases at around 1-3 weeks after onset. Improvement of cerebral vasoconstriction was recognized in several cases from about the first month of onset. The post-partum period, migraine, transfusion, rapid amelioration for anemia, renal failure, bathing, and cerebrovascular dissection were suspected as disease triggers. Abnormally high blood pressure at onset was confirmed in 55% of cases. It is important to analyze the pathophysiology of RCVS associated with these triggers from the viewpoint of the breakdown of the blood-brain barrier.

Rapidly deteriorated lobar intracerebral hemorrhages: possible association of varicella zoster virus-vasculopathy

A 75-year-old man having dementia and lifestyle related diseases developed a lobar intracerebral hemorrhage (LICH) in the left parietal and a small cerebellar infarction in the left occipital lobe. Many micro bleeds (MB) due to cerebral amyloid angiopathy (CAA) in the subcortical areas and multiple vascular stenosis were also found by MRI and MRA. He developed herpes zoster in his buttocks on day 6 of hospitalization and complicated with varicella zoster virus (VZV) meningitis with positive for VZV-DNA in the cerebrospinal fluid. Subsequently, LICHs occurred in the left frontal lobe and in the right parietal lobe for a short period of time and died on the day 18. We speculated that the repeating hemorrhages was primarily caused by VZV vasculopathy and additionally the subcortical MBs increased the hemorrhagic risk. The relationship between VZV vasculopathy and CAA should be studied in the future.

Vascular Risk Factors and Internal Jugular Venous Flow in Transient Global Amnesia: A Study of 165 Japanese Patients

BACKGROUND The etiology of transient global amnesia (TGA) remains unclear. We studied the pathophysiology of TGA in 165 Japanese patients. SUBJECTS AND METHODS TGA was diagnosed in hospitalized patients from 2004 to 2015. We analyzed clinical characteristics, magnetic resonance imaging findings, and maximum intima-media thickness of the common carotid artery, and the reflux of internal jugular venous (IJV) flow by ultrasonography, and statistically compared patients with TGA with age-matched and sex-matched patients who have had a transient ischemic attack (TIA), small-vessel occlusion (SVO), and normal controls (each group, N = 165). RESULTS Patients with TGA showed lower prevalence of vascular risk factors than patients with TIA and SVO did. Eleven patients (6.7%) had 2 episodes of TAG, but specific clinical variables could not be recognized in these patients. The maximum intima-media thickness was significantly thinner in TGA (1.1 ± .7 mm) than in SVO (1.6 ± .9 mm; P = .001). The percentages of cases whose IJV flow reflux was increased by Valsalva maneuver showed no difference (P = .573) between TGA (26.0 %) and SVO (29.4%). MR diffusion-weighted imaging yielded small hyperintense signals in the hippocampus in 64 of 90 (71.1%) patients between 24 and 72 hours. Potential precipitating specific factors or events before the attacks could be recognized in 40 cases (24.2%) of 165 patients. CONCLUSION Arterial ischemia and IJV flow reflux might not contribute to TGA pathophysiology. The vulnerability of the hippocampus to physical or emotional stress might be suspected as an underlying mechanism in some patients with TGA.

Cerebral Venous Sinus Thrombosis: Incidence and Hyperhomocysteinemia as a Risk Factor in Japanese Patients

Background: Cerebral venous sinus thrombosis (CVT) occurs commonly in young female adults and is caused by various risk factors. Our aim was to determine the incidence, clinical characteristics, and risk factors of Japanese CVT patients. Patients and methods: We performed a retrospective study of CVT patients from January 2010 to June 2015. In the patients who had hyperhomocysteinemia, vitamin levels were measured. To define the clinical characteristics in patients with hyperhomocysteinemia, we statistically compared them to those patients with normal levels of homocysteine. Results: Sixteen patients (aged 54.6 ± 17.7 years; 13 men and 3 women) were included. The incidence of CVT was 0.23% among all types of strokes or 0.30% of acute ischemic strokes, which was lower than previously reported. The patients were characterized by advanced age, low frequency of headaches, and few female patients, especially female patients using oral contraceptives. The predisposing conditions included a notably high incidence of hyperhomocysteinemia (56.3%). They also included deficiencies of folate, vitamin B12, vitamin B6, or combined deficiencies. Marked hyperhomocysteinemia over 100 nmol/ml was noted in combined deficiencies. Conclusions: CVT in Japan commonly occurred in older males. The prevalence of hyperhomocysteinemia as a risk factor of CVT was high, and the main underlying disorders were folate and vitamin B12 or B6 deficiencies. This is clinically important, because these acquired risks can be corrected by supplementation therapy to prevent the recurrence of CVT.