Shuichiro Neshige

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.

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.

[Reversible changes on MR images in a patient with metronidazole-induced encephalopathy].

A 66-year-old woman was diagnosed with a brain abscess. The abscess was drained by sterotactic catheter insertion. She was administered metronidazole at a dose of 2 g/day. On the 30th day of treatment, she had nausea that gradually progressed. On the 45th day, she developed a disturbance of consciousness and was admitted to our department. She was in stuporous state, and had slight vestibular and cerebellar dysfunctions. Diffusion-weighted and FLAIR brain MR images showed bilateral symmetrical high signals in the splenium of the corpus callosum (SCC), cerebellar dentate nucleus, and inferior colliculus. The apparent diffusion coefficient (ADC) map was reduced in the SCC, but not in the other locations. The peak of lactate on MR spectroscopy was increased in the SCC. The clinical presentation and image changes of the patient were thought to be most consistent with metronidazole toxicity. Metronidazole was discontinued, and her condition improved rapidly. She was discharged 14 days later. The lesions in her cerebellar dentate nucleus and inferior colliculus, suspected to be vasogenic edema, had disappeared 5 to 10 days later, whereas the lesion in the SCC, which gradually diminishing, could still be faintly detected 40 days later, which corresponded to our suspicion of cytotoxic edema.

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.

Cerebral venous sinus thrombosis associated with hyperhomocysteinemia due to combined deficiencies of folate and vitamin B12

A 63-year-old man was admitted to our hospital because of convulsive seizures. Radiological examinations revealed cerebral venous sinus thrombosis in the anterior part of the superior sagittal sinus. He had marked hyperhomocysteinemia (93.5 nmol/ml) due to combined deficiencies of folate and vitamin B12. He was T/T homozygous for methylene tetrahydrofolate reductase C677T polymorphism. He received a supplement therapy of vitamins. First, he was administered folate orally. After 3 months, the serum level of homocysteine decreased to 22.6 nmol/ml (an 86% reduction), but was still above the normal level. Next, an additional supplement therapy of vitamin B12 lowered the homocysteine level to normal (12.3 nmol/ml) after 4 months. These results showed that the increase of homocysteine levels in this patient was mainly caused by the deficiency of folate. Additionally, acquired risk factors like vitamin deficiencies increased the level of serum homocysteine to almost 100 nmol/ml.

Acute encephalopathy due to angel’s trumpet intoxication: A case report and literature review

We report two cases (a married couple) of intoxication due to angels trumpet ingestion. Case 1: A 71-year-old woman was found lying unconscious on the sofa at home and was brought to our hospital by ambulance. She showed mydriatic anisocoria, and an intracerebral lesion was suspected. However, the brain magnetic resonance imaging showed no abnormal lesion and acute encephalopathy of unknown cause was diagnosed. Case 2: A 68-year-old man (husband of the patient of Case 1) showed alteration of consciousness with agitation and was admitted to our hospital on the next day. He also had slight mydriasis. As his manifestations were similar to those of his wife, we studied their medical history again. We found that they mistook the roots of angels trumpet for burdock and cooked and ate them. This intoxication causes characteristic encephalopathy with altered consciousness and mydriasis. In the case of anisocoria or mild mydriasis, the diagnosis is difficult sometimes. The intoxication occurred within a family; this was a clue to the correct diagnosis. Severe cases exhibit pyramidal signs and symptoms or convulsion, and deaths have been reported. Angels trumpet intoxication is an important neurological emergency.

Metabolic abnormalities associated with homozygosity for the 677C>T mutation in the methylenetetrahydrofolate reductase gene.

(臨床神経 2016;56:358-359) 拝復 私どもの論文「葉酸,ビタミン B12複合欠乏による著明な 高ホモシステイン血症を呈した脳静脈洞血栓症」に関して荒 井元美先生から貴重なご意見を頂き誠にありがとうございま した .Corresponding authorから返信させていただきます. 私どもの論文は脳静脈洞血栓症のリスク因子としてのホモシ ステイン(Hcy)が中心的論点であり,また短報であるため 字数制限があり,舌足らずだったことをご理解いただきたい と思います. まず,メチレンテトラヒドロ葉酸還元酵素(MTHFR)遺 伝子 677C>T変異ホモ接合体については,この遺伝子異常が 単なる遺伝子多型でなく酵素欠損症と考えるべきとの指摘に 関して,この遺伝子異常で酵素が熱不安定になり活性低下す ることは我々も熟知しております .そのため血中 Hcy濃度 が約 20%高くなり,人種的にこの比率が異なり,日本人では 野生型遺伝子をホモに持つ C/Cが 60~70%で変異型ホモの T/Tが約 10%であるなども含め,現在投稿中の論文(高 Hcy を伴った脳静脈洞血栓症 9症例のまとめ)に考察しておりま す.酵素活性が低下する機序は,まさに先生のご指摘どおり で,一部の先天性酵素欠損症と共通の機序として異論はあり ませんが,一般的にはこの異常は遺伝子多型として取り扱わ れています.我々の論文が掲載された同じ臨床神経 2016年 2 月号にも,偶然同じ遺伝子異常の論文が,「遺伝子多型 (C677T)を認めた脳血管性パーキンソニズム」として掲載さ れています. 私達は葉酸測定を外注依頼しますが,一般臨床ではこの方 法でしか葉酸値を把握することはできません.葉酸-Hcy-メ チオニンサイクルの活動状態を把握するためにはHcy値がバ イオマーカーともいえます.MTHFR欠損症(異常症)では 葉酸は低値でも欠乏症ではないとのご指摘ですが,我々の患 者さん,先生の呈示された患者さんもそうですが,葉酸を投 与することで,Hcyは確実に低下しておりますので,その個 体においては葉酸は欠乏状態であると言えるのではないで しょうか.要は,その人において必要な量に達しているか否 かで,必要量に達していないのであればその患者さんにとっ ては欠乏状態といえるのだと思います.先生からの letterで 教えていただいた,Zittanの論文は私は未読でしたので,読 ませていただき大変興味ある論文でした.以前から,葉酸代 謝とビタミンB12の代謝が密接に関連することはよく知られ た事実です.欠乏症の類似性を生化学的に説明する機序とし て「メチルトラップ仮説」が知られていますが,まだ完全に は解明されていないこれからの課題も多くあります .葉酸 欠乏に関しては,一般的には葉酸欠乏は,緑黄色野菜,豆類, 穀類などの摂取不足や腸管吸収障害による摂食障害,薬剤(抗 てんかん薬など),アルコール摂取など多くの要因が影響しま す .この患者さんは野菜嫌いで大量飲酒者です.豆や穀類 などのシリアルに関しては摂取不足かの判断は難しく,吸収 障害があるか否かも検討しておりません.論文中には偏食で ある点のみ記載しました. 葉酸の補充に関して,葉酸の補充を先に行うとビタミン Reply from the Author

Brain Natriuretic Peptide and Particular Left Ventricle Segment Asynergy Associated with Cardioembolic Stroke from Old Myocardial Infarction

BACKGROUND It is important to determine the usage of anticoagulants by defining the actual risk of cardioembolic stroke in patients with old myocardial infarction. In the present study, we aimed to more precisely evaluate the risks of each segment associated with cardioembolic stroke using a 16-segment model. The usage of the plasma brain natriuretic peptide (BNP) associated with cardioembolic stroke was also evaluated in comparison with a left ventricle ejection fraction less than 40%. METHODS There were a total of 190 ischemic stroke patients who had premorbid myocardial infarction. The study included a total of 143 ischemic stroke patients with old myocardial infarction who were available for evaluation and excluded patients with atrial fibrillation or acute myocardial infarction. Their left ventricle wall motion abnormality and the level of plasma BNP at their admission were analyzed. RESULTS Hypertension and a plasma BNP level of 206.9 pg/mL or higher, determined from the receiver operating characteristic curve, were independently associated with cardioembolic stroke (χ(2) = 35.6, R(2) = .30, P < .001). Adjusting for these factors, statistically independent high risk was observed at the basal-inferior, basal-inferolateral, mid-anterior, mid-anteroseptal, apical-anterior, and apical-septal left ventricles. CONCLUSION High plasma BNP levels and left ventricular wall motion abnormalities in the segments perfused with left anterior descending coronary artery or right coronary artery show a high risk for cardioembolic stroke in patients with old myocardial infarction. Considering these factors, it could be possible to more precisely define the risk of cardioembolic stroke and to perform appropriate antithrombotic treatments in old myocardial infarction patients.

[Riluzole-induced interstitial pneumonia in a case with amyotrophic lateral sclerosis].

A 74-year-old woman was clinically diagnosed with possible amyotrophic lateral sclerosis (ALS) and was administered 100 mg/day of riluzole. After 2 months, she developed dyspnea and experienced gradual difficulty walking. Chest computed tomography revealed ground-glass opacity and consolidation in the lower lobes of both the lungs, thereby suggesting a diagnosis of interstitial pneumonia. Because the condition was suspected to be drug-induced, riluzole administration was discontinued and steroid (methylprednisolone) pulse therapy (1,000 mg/day, 3 days) was started. Her symptoms and radiological findings improved immediately. At 16 months later, she wanted to take riluzole again. She had the similar interstitial pneumonia on the 4(th) day of the re-administration. Drug (riluzole)-induced lymphocyte stimulation tests (DLST) were negative two times. The symptoms of interstitial pneumonia, a rare adverse effect of riluzole, are very similar to worsening symptoms of ALS; therefore, patients with ALS receiving riluzole therapy should be carefully monitored.