[A case of cryptogenic new-onset refractory status epilepticus (NORSE) in which cerebrospinal fluid IL-6 was elevated with increased seizure frequency early in the disease: a case report].

A 25-year-old male presented with clonic seizures three days following a fever. The patient developed status epilepticus and required mechanical ventilation and intravenous anesthesia. The patient's epileptic seizures persisted despite administering intravenous anesthesia and multiple anti-epileptic drugs. The clinical presentation in this case, without pre-existing relevant neurological disorder and an active structural, toxic, or metabolic cause in the acute phase, was compatible with new-onset refractory status epilepticus (NORSE). After immunotherapy, including intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulin therapy, the epileptic discharge on electroencephalogram (EEG) decreased gradually, and mechanical ventilation was discontinued. Neversless the final outcome was poor. The patient's condition was finally diagnosed as cryptogenic NORSE. The IL-6 levels in the cerebrospinal fluid showed a significant increase between day 6 and 11 after onset, during which time there was a rapid escalation in seizure frequency on EEG. Considering this, IL-6 may be involved in the process of seizure exacerbation.

Association between Living Conditions and the Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults.

Objective In recent decades, living conditions have changed drastically. However, there are few data regarding the interaction between living conditions and the risk of ischemic stroke (IS) in young adults. The present study explored the association between living conditions or marital status and the risk factors, etiology, and outcome of IS in young adults. Methods We prospectively enrolled patients with incident IS who were 20-49 years old from 37 clinical stroke centers. We collected the demographic data, living conditions, marital status, vascular risk factors, disease etiology, treatment, and outcomes at discharge. A comparison group was established using the official statistics of Japan. We categorized patients into the two groups based on living conditions: solitary group and cohabiting group. Clinical characteristics were then compared between living conditions. Results In total, 303 patients were enrolled (224 men; median age at the onset: 44 years old). Significant factors associated with the incidence of IS were as follows: solitary status, body mass index >30 kg/m2, current smoking, heavy alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia. Furthermore, in the solitary group, the proportions of men, unmarried individuals, and current smokers were significantly higher than in the cohabiting group. In addition, poor outcomes (modified Rankin Scale ≥4) of IS were more common in the solitary group than in the cohabiting group. Conclusion Our study showed that not only conventional vascular risk factors but also living conditions, especially living alone while unmarried, were independent risk factors for IS in young adults.

Characteristics of Ischemic Versus Hemorrhagic Stroke in Patients Receiving Oral Anticoagulants: Results of the PASTA Study.

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p>0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p<0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p<0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

A novel COL4A1 variant associated with recurrent epistaxis and glioblastoma.

COL4A1-related disorders are characterized by a higher incidence of cerebral hemorrhage than other hereditary cerebral small vessel diseases. Accumulating data have shown broad phenotypic variations, and extracerebral hemorrhages have been linked to these disorders. Moreover, the coexistence of neural tumors has been described. Here, we report a Japanese family with a novel COL4A1 variant, including a patient with recurrent epistaxis and glioblastoma.

Risk factors, etiology, and outcome of ischemic stroke in young adults: A Japanese multicenter prospective study.

PURPOSE: This study aimed to evaluate the risk factors, etiology, and outcomes of ischemic stroke (IS) in Japanese young adults. METHODS: This was a prospective multicenter study. We enrolled patients aged 16 to 55 years with IS within seven days of the onset of symptoms. We assessed the demographic data, risk factors, stroke etiology, and outcome at discharge. The clinical characteristics were compared between sexes and among age groups. RESULTS: We prospectively enrolled 519 patients (median age, 48 years: 139 females). The mean National Institute of Health Stroke Scale score was 3.6 ± 0.2. The most common risk factors were hypertension (HT) (55%), dyslipidemia (DL) (47%), and current smoking (42%). Body mass index, incidence of current smoking, and heavy alcohol consumption were higher in males. The prevalence of current smoking, HT, DL, and diabetes mellitus increased with aging. The most common etiologic subgroup of IS was small vessel disease (145/510, 28%). Intracranial arterial dissection (IAD) was the most common among the other determined causes (56/115, 49%). The outcome at discharge was relatively good (mRS 0-1, 71.7%); however, poor outcome (mRS ≥ 4) was observed at an incidence of 9.5%. CONCLUSIONS: Most young adults with IS had modifiable risk factors, of which prevalence increased with age. This emphasizes lifestyle improvement to prevent IS in the young population. Furthermore, we indicated that the incidence rate of IAD was high among the other determined causes.

Predictors of neurologic deterioration in patients with small-vessel occlusion and infarcts in the territory of perforating arteries.

BACKGROUND: It is difficult to predict neurologic deterioration in patients with small-vessel occlusion (SVO), that is, small infarcts in the territory of cerebral perforating arteries. METHODS: We reviewed 110 patients with SVO who were admitted to our hospital. We divided them into groups with (n = 32, group 1) and without deterioration (n = 78, group 2) and evaluated their medical records, risk factors, magnetic resonance imaging findings, grade of periventricular hyperintensity (PVH), maximum diameter of the infarct area, and the number of slices showing infarcts on diffusion-weighted images (DWI). RESULTS: Our study population consisted of 110 patients (71 males and 39 females; mean age 69.2 years): 32 (29%) did and 78 (71%) did not suffer deterioration. By univariate analysis, the age, current smoking, history of stroke, maximum diameter of the infarcted area, number of DWI slices with infarcts, frequency of PVH, and PVH grade based on Fazekas classification differed significantly between the 2 groups. By multivariate analysis, conventional risk factors other than PVH and history of stroke were not associated with neurologic deterioration (PVH grade ≥ 2 versus PVH grade ≤ 1, odds ratio 6.72, P = .006; with stroke versus without stroke, odds ratio .21, P = .049). We also found that higher the PVH grade, the worse the National Institutes of Health Stroke Scale score at the time of discharge. CONCLUSIONS: PVH and without history of stroke are independently associated with neurologic deterioration in patients with SVO.

Increasing and persistent DWI changes in a patient with hereditary diffuse leukoencephalopathy with spheroids.

We report a case with genetically confirmed hereditary diffuse leukoencephalopathy with spheroids with distinctive MRI features. A 52-year-old woman with a family history of juvenile dementia presented with an 18-month history of progressive cognitive decline. Longitudinal magnetic resonance imaging studies of the brain revealed increasing and persistent white matter hyperintensities on diffusion-weighted images. Linear high intensity signal along axonal fibers arisen from the cerebral cortex was also shown. Finding of subcortical calcifications was noted on brain CT scan. Sequence analysis of CSF1R showed a novel missense mutation c.2467C>T (p.Ala823Val). Persistent and increasing diffusion on magnetic resonance image, presumably reflecting intramyelinic oedema in regions of neurodegeneration, is a distinctive feature observed in this case. The presence of this unique finding can be a diagnostic clue in the early stage of the disease.

[A case of cerebral air embolism developed during pleural lavage].

We report a patient with cerebral air embolism in whom we could perform serial brain magnetic resonance images (MRIs). A 78-year-old man was admitted to our hospital because of recurrent empyema after surgery for esophageal cancer. He suddenly demonstrated left hemiparesis in the middle of pleural lavage. After about 30 minutes from onset, the computed tomography (CT) revealed multiple air-isodense spots in the right hemisphere of the brain. After about 2 hours from onset, many hypointense spots in the right hemisphere were revealed on T2*-weighted image (T2*WI). These findings suggested cerebral air embolism. He didn't receive hyperbaric oxygen therapy because he had status epilepticus. The hypointense spots on the T2*WI became smaller and spread after 7 hours from onset and almost disappeared after 53 days. It is important to recognize that cerebral arterial air embolism is similar to multiple microbleeds and cerebral arteriovenous fistula in hypointense spots on the T2*WI.

Predictors of aortic complicated lesions in stroke patients.

Aortic complicated lesions (ACLs) should be associated with cerebral infarction. Our aim was to develop a simple clinical scale (ACL scale) to predict the presence of ACL. Consecutive stroke patients undergoing transesophageal echocardiogram (TEE) examination were prospectively enrolled. We defined ACL as the presence of >4 mm wall thickness, ulceration or mobile plaque in aortic arch. We also examined carotid intima-media thickness (IMT), ankle-brachial index (ABI) and brachial-ankle pulse-wave velocity (baPWV). We compared the clinical characteristics of patients with ACL (ACL group) and without ACL (non-ACL group), and devised a new ACL scale to predict the presence of ACL. In all, 165 patients (male 108, age 66.9 years) were enrolled and of these, 38% had ACL. The patients of the ACL group were older than those of the non-ACL group (73.0+/-10.2 vs. 63.1+/-13.6 years, P=0.001). Peripheral artery disease (PAD) was more frequent in the ACL group (18 vs. 4%, P=0.004). IMT was thicker in ACL group than in the non-ACL group (1.29+/-0.74 vs. 1.11+/-0.79 mm, P=0.002), and baPWV was higher in the ACL group (2164.2+/-643.2 vs. 1833.7+/-492.9 cm s(-1), P=0.001). We used three variables for determining the ACL scale score; (1) age >70, (2) presence of PAD and (3) smoking. The frequencies of ACL associated with ACL scale scores were as follows: 6% of patients with ACL scale score 0, 40% with score 1, 58% with score 2 and 100% with score 3. The ACL scale can predict the presence of aortic complicated lesions.

Heart failure may be associated with the onset of ischemic stroke with atrial fibrillation: a brain natriuretic peptide study.

BACKGROUND AND PURPOSE: Congestive heart failure is a risk factor for ischemic stroke. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. We hypothesized that heart failure was associated with the onset of ischemic stroke patients with atrial fibrillation (AF). METHODS: Between June 2006 and December 2007, we prospectively enrolled consecutive acute ischemic stroke patients with AF within 24 h of onset. Plasma BNP was measured twice, on admission and on days 28 or at discharge. As a control, we measured plasma BNP of chronic phase of stroke outpatients with AF. We investigated whether plasma BNP was elevated in the acute phase of stroke. RESULTS: One hundred and nine patients (58 females; mean age, 76.3 years) were enrolled in the present study. Mean+/-SD of NIHSS score on admission and mRS score at discharge were 12.6+/-8.3 and 3.7+/-1.8, respectively. The interval from stroke onset to plasma BNP measurement on admission was 6.8+/-6.3 h. Moreover, follow up BNP was measured at mean of 26+/-9 days after stroke onset. The plasma BNP level in the acute phase of stroke was significantly higher than that of the subacute phase of stroke (median (interquartile range, IQR) 299.0 (176.8-469.5) vs. 149.5 (68.1-347.0) pg/ml, p<0.001). There was no significant difference in plasma BNP level between the subacute phase of stroke and control group (median (IQR) 149.5 (68.1-347.0) vs. 165.0 (64.6-224.0) pg/ml, p=0.543). CONCLUSION: Plasma BNP was elevated in the acute phase of stroke. Heart failure may be associated with the onset of ischemic stroke patients with AF.

Prevalence of atrial fibrillation in community-dwelling Japanese aged 40 years or older in Japan: analysis of 41,436 non-employee residents in Kurashiki-city.

BACKGROUND: A community-based study was conducted to estimate the prevalence of atrial fibrillation (AF) in Japanese adults aged >or=40 years in Kurashiki-city and to examine associated risk factors. METHODS AND RESULTS: Adult residents (>or=40-year-old) were examined in the Kurashiki-city Annual Medical Survey (KAMS) provided by the Kurashiki-city Public Health Center from May to December 2006. KAMS consisted of medical interviews, physical examination, blood testing and electrocardiography to assess the presence of AF. All participants were divided into AF and non-AF groups, their clinical characteristics compared, and the risk factors associated with AF investigated. Of 246,246 adult residents, 41,436 (age: 72.1+/-11.3 years; 13,963 men) underwent the KAMS. Estimated overall prevalence of AF was 1.6%. Multivariate analysis demonstrated that AF was independently associated with cardiac disease (odds ratio (OR), 9.00; 95% confidence interval (CI), 7.65-10.6; p<0.001), chronic kidney disease (OR, 1.76; 95%CI, 1.49-2.07; p<0.001), male sex (OR, 1.59; 95%CI, 1.34-1.85; p<0.001), and diabetes mellitus (OR, 1.46; 95%CI, 1.20-1.78; p<0.001). Hypercholesterolemia was highly associated with the absence of AF (OR, 0.54; 95%CI, 0.45-0.64, p<0.001). CONCLUSIONS: Prevalence of AF in Japan is approximately 1.6%, lower than that in Western populations. Male sex, and cardiac and chronic kidney diseases are associated with the presence of AF.

[Case of hemodynamic brain infarction diagnosed by transcranial Doppler].

A 64 year-old man was admitted to our hospital because of left leg weakness after a lot of alcohol drink. On admission, his blood pressure was 96/43 mmHg, and heart rate was 97 beats/min and regular. His laboratory data showed severe anemia, and Hb was 5.0 g/dl due to bleeding from gastric cancer. His clinical condition indicated pre-shock and we began to give him a blood transfusion immediately after admission. His neurological findings on admission were mild consciousness disturbance without aphasia, left unilateral spatial neglect, and mild monoparesis on left leg. Brain diffusion-weighted magnetic resonance images demonstrated the small hyper-intense lesions in the borderzone area between the anterior cerebral artery and the middle cerebral artery (MCA). MR angiography showed the occlusion of the right internal carotid artery (ICA) and the right MCA was fully supplied through anterior communicating artery from the left ICA. Transcranial Doppler (TCD) revealed the blunted waveform with low-resistance in the right MCA, but normal flow wave in the left MCA. We diagnosed him as having a hemodynamic brain infarction based on MRI and TCD findings. On day 5, severe anemia and pre-shock improved to Hb 8.2 g/dl and 148/78 mmHg, respectively. According to elevation of blood pressure, his neurological findings normalized. Follow-up TCD revealed that the abnormal waveform in the right MCA changed to normal. Finally we considered the stroke mechanism of this case as hemodynamic stroke based on TCD findings. Serial TCD examinations are useful to identify the hemodynamic mechanism of stroke in such case.

[Case of methotrexate encephalopathy: findings on diffusion tensor image and correlation with clinical outcome].

Methotrexate (MTX) is a major cause of treatment-related acute neurotoxicity. We report on clinical and imaging findings of reversibly restricted diffusion in a patient with transient encephalopathy after high dose MTX therapy for osteosarcoma. During the chemotherapy, a 19-year-old man was introduced for the evaluation of consciousness disturbance. Neurological examination revealed confusion, inability of speak at the onset On next day, there were still difficulties in swallowing and phonation, and furthermore deep tendon reflexes were hyperactive in bilateral lower limbs with positive Babinski responses bilaterally. By the 6th day, findings at neurological examination were completely normal. Initial imaging on presentation was performed using MRI. Diffusion weighted MRI clearly indicated areas of restricted diffusion within both centrum semiovale. These abnormalities were confirmed by the diffusion tensor (DT) technique (ADC and FA map). The follow-up MRI examinations using same protocol showed resolution of the ADC and FA abnormalities but increasing T2-signal changes. Neither contrast enhancement nor atrophy was encountered. Early detection of MTX white matter injury by DT image has the potential to alert the oncologist and neurologist to this event and provide a technique by which treatment of neurotoxicity can be monitored.

[A case of hyperglycemic neuropathy with possible dysfunction of axonal excitability].

A 66-year-old woman with SLE who recently started oral steroid was admitted to our hospital because of subacute numbness of the bilateral legs and gait disturbance, despite of the stable symptoms of SLE and its serology. Blood tests revealed hyperglycemia. Nerve conduction study showed decreased nerve conduction velocities consistent with demyelinative neuropathy. On initiation of insulin to control hyperglycemia, conduction velocities were rapidly increased in one week, suggesting hyperglycemic neuropathy. The rapid improvement of the conduction velocities was argued against mechanical "demyelination", rather suggesting axonal dysfunction, possibly associated with impaired function of Na(+)-K(+)-ATPase in hyperglycemic state.