Meningoencephalomyelitis Caused by Brucella Canis: A Case Report and Literature Review.

Human brucellosis, one of the most common zoonoses worldwide, is rare in Japan. Brucella canis is the specific pathogen of human brucellosis carried by dogs. According to an epidemiological study of B. canis infection in Japan, B. canis is the specific pathogen of human brucellosis in dogs. We herein report a rare case of meningoencephalomyelitis caused by B. canis in a 68-year-old Japanese man. Neurobrucellosis was diagnosed based on a serum tube agglutination test and abnormal cerebrospinal fluid findings. The patient was started on targeted treatment with a combination of doxycycline and streptomycin. Although extremely rare, neurobrucellosis should be considered in patients with a fever of unknown origin and unexplained neurological symptoms.

[A case of recurrent non embolic stroke with non-fluent aphasia due to polycythemia vera].

A 79-year-old woman was admitted to our hospital with a diagnosis of acute noncardioembolic stroke on division of the left middle cerebral artery with non-fluent aphasia. Although she was treated with dual antiplatelet therapy of aspirin and clopidogrel at first, she suffered a second stroke with enlargement of the same stroke lesion and worsening aphasia symptoms. There were only 46 days between the initial onset and recurrent stroke event.She had been diagnosed with polycythemia vera (PV) based on an increase in the blood cell count and a JAK2 mutation. The administration of hydroxyurea was effective for normalizing the blood cell count and preventing stroke recurrence. Cerebral infarction with or without any risk factors accompanied by an elevated blood cell count with a hematocrit value >45% can be PV, so it is necessary to start cytoreductive therapy as soon as possible in such cases.

Multiscale Entropy of Resting-State Functional Magnetic Resonance Imaging Differentiates Progressive Supranuclear Palsy and Multiple System Atrophy.

Distinguishing progressive supranuclear palsy (PSP) from multiple system atrophy (MSA) in the early clinical stages is challenging; few sensitive and specific biomarkers are available for their differential diagnosis. Resting-state functional magnetic resonance imaging (rs-fMRI) is used to study the fluctuations in blood oxygen level-dependent (BOLD) signals at rest, which provides evidence for aberrant brain functional networks in neurodegenerative diseases. We aimed to examine whether rs-fMRI data could differentiate between PSP and MSA via a multiscale entropy (MSE) analysis of BOLD signals, which estimates the complexity of temporal fluctuations in brain activity. We recruited 14 and 18 patients with PSP and MSA, respectively, who underwent neuropsychological tests and rs-fMRI. PSP patients demonstrated greater cognitive function impairments, particularly in the frontal executive function. The bilateral prefrontal cortex revealed lower entropy BOLD signal values in multiple time scales for PSP, compared to the values observed in MSA patients; however, the functional connectivity of the representative brain networks was comparable between the diseases. The reduced complexity of BOLD signals in the prefrontal cortex was associated with frontal dysfunction. Thus, an MSE analysis of rs-fMRI could differentiate between PSP and MSA, and the reduced complexity of BOLD signals could be associated with cognitive impairment.

Retrospective Analysis of Argatroban in 353 Patients with Acute Noncardioembolic Stroke.

BACKGROUND: Argatroban is a thrombin inhibitor agent for acute noncardioembolic ischemic stroke in Japan. We studied the prognosis in patients with acute stroke treated by argatroban in comparison with the control group with ozagrel in our hospital. SUBJECTS AND METHODS: A total of 513 patients with acute noncardioembolic ischemic stroke were enrolled retrospectively from our hospital database. Of all patients with stroke, 353 were administered with argatroban. The other 160 control patients were administered with ozagrel. The patients were examined as to their stroke types, the neurological severity according to the National Institutes of Health Stroke Scale (NIHSS), and clinical outcomes on discharge were determined according to the modified Rankin Scale (mRS). RESULTS: A total of 353 patients with acute noncardioembolic stroke, including 138 with lacunar infarction (LIs) and 215 with atherothrombotic infarction (ATI) showed functional recovery by argatroban, but the effectiveness of argatroban was not superior to ozagrel therapy defined by the control group. A total of 255 patients with ATI who were treated with both argatroban and ozagrel showed improvement by 1 point. We could not find any significant difference between argatroban and ozagrel in the 2 stroke subtypes, LI and ATI. We also found that combination therapy of argatroban and edaravone was not superior to argatroban monotherapy in clinical outcome. CONCLUSIONS: Argatroban therapy was not superior to control with ozagrel therapy in acute noncardioembolic ischemic stroke, including LI and ATI, regardless of the use of edaravone.

Metabolic syndrome is associated with incidence of deep cerebral microbleeds.

Metabolic syndrome (MetS) has been associated with silent brain lesions; however, there are no data on the relationship between MetS and the incidence of cerebral microbleeds (CMBs) in Asian populations. The aim of this study was to evaluate the longitudinal association between MetS and incidence of CMBs in the Japanese population. We performed a prospective cohort study involving 684 Japanese participants (mean age, 61.7 years) with a mean 6.5 ± 3.4 years follow-up. All participants underwent 1.5 T magnetic resonance imaging, and CMBs were classified by their locations. Logistic regression analyses were performed to examine the relationship of MetS and its components with the incidence of CMBs. MetS was observed in 7.5% of the study population. Forty-nine (7.2%) subjects (36 had new deep or infratentorial CMBs, 13 had new strictly lobar CMBs) developed new CMBs during the follow-up period. In multivariable analysis, MetS was significantly associated with the incidence of deep or infratentorial CMBs (odds ratio, 4.03; 95% confidence interval, 1.72-9.41), and the elevated blood pressure component was most robustly associated with the incidence of deep or infratentorial CMBs (odds ratio, 5.16; 95% confidence interval, 2.02-13.2). Increased body mass index was also associated with incidence of deep or infratentorial CMBs (odds ratio, 2.45; 95% confidence interval, 1.06-5.67). The present study showed that MetS predicts incidence of CMBs in the deep brain regions and high blood pressure is the most important among the MetS components.

Analysis of Recurrent Stroke Volume and Prognosis between Warfarin and Four Non-Vitamin K Antagonist Oral Anticoagulants' Administration for Secondary Prevention of Stroke.

OBJECTIVE: We investigated recurrent stroke volume with nonvalvular atrial fibrillation (NVAF) patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) about clinical backgrounds and number of recurrent stroke. METHODS: We administered 4 NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban in 101 postcardioembolic strokes with NVAF. In a retrospective study, we measured recurrent stroke volume with magnetic resonance imaging volumetric software and compared them between 10 vitamin K anticoagulant (VKA: warfarin) cases and 13 NOAC cases under anticoagulant therapy. RESULTS: Of 101 cases, 31 were started with a VKA and switched to NOACs after 10 recurrent strokes. Other 70 cases were directly started with NOACs and 13 cases with NOACs as first anticoagulants had recurrent stroke. The frequency of recurrent stroke during anticoagulant therapy is not different between the VKA group and the 3 NOACs group. Recurrent stroke volume is significantly larger in the VKA group (26.4 cm3) than in the NOACs group (1.2 cm3). CONCLUSIONS: Secondary prevention with NOACs after stroke might be more beneficial than a VKA by reducing recurrent infarct volume.

Serum Lipid Fractions and Cerebral Microbleeds in a Healthy Japanese Population.

BACKGROUND: Cerebral microbleeds (CMBs) are associated with focal hemosiderin deposits and represent a form of cerebral small vessel disease. To date, indefinite and inconsistent reports are available regarding the association between serum lipid fractions and CMBs. In addition, these previous studies did not include Asian populations, who may have a higher risk of cerebral hemorrhage. The purpose of this study was to examine the associations between serum lipid fractions and CMBs in healthy Japanese subjects. METHODS: We performed a cross-sectional study involving 4,024 neurologically normal Japanese subjects (mean age 61.6 years). All the participants underwent 1.5-Tesla magnetic resonance imaging scan, and CMBs were classified into 3 groups based on their locations. The concentrations of lipid fractions were categorized into quartiles and the association between the lipid fractions and CMBs were investigated using logistic regression analysis. RESULTS: CMBs were observed in 164 (4.1%) of participants. Of these participants with CMBs, 33 (20.1%) had lobar CMBs and 91 (55.5%) had deep CMBs. Subjects with deep CMBs had lower total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels. After adjusting for confounding factors, lower TC and HDL-C levels were still associated with the presence of deep CMBs (OR for the highest vs. the lowest quartiles of TC and HDL-C was 2.28 [95% CI 1.05-4.94], and 1.93 [95% CI 1.02-3.65], respectively). The presence of subcortical infarcts and periventricular hyperintensities was more frequently observed in deep CMBs, whereas white matter hyperintensities were more frequently observed in lobar CMBs. CONCLUSIONS: Our results suggest that low serum TC and HDL-C levels are closely associated with deep CMBs.

The Effectiveness of Repetitive Transcranial Magnetic Stimulation for Poststroke Apathy Is Associated with Improved Interhemispheric Functional Connectivity.

Poststroke apathy is relatively common and has negative effects on the functional recovery of the patient; however, few reports have demonstrated the existence of effective treatments for poststroke apathy. Here, we describe a case of poststroke apathy that was successfully treated with repetitive transcranial magnetic stimulation (rTMS). Using resting-state functional magnetic resonance imaging, we detected improved interhemispheric functional connectivity that was correlated with the patient's recovery from poststroke apathy. Our case suggests that rTMS can improve the transfer of information through the corpus callosum, which is crucial for helping patients recover from poststroke apathy.

A Prospective Study of Asymptomatic Intracranial Atherosclerotic Stenosis in Neurologically Normal Volunteers in a Japanese Cohort.

Atherosclerotic stenosis of major intracranial arteries is a leading cause of ischemic stroke in Asia. However, the long-term prognosis of asymptomatic intracranial atherosclerotic stenosis (ICAS) in healthy volunteers has not been fully examined. Here, we conducted a longitudinal study to examine the prognosis of healthy volunteers with asymptomatic ICAS and to determine the risk factors for ICAS, including asymptomatic brain parenchymal lesions. We studied 2,807 healthy Japanese volunteers with no history of stroke (mean age, 62.0 years). They were followed for a mean interval of 64.5 months. The degree of ICAS and the presence of asymptomatic brain lesions were assessed by using magnetic resonance imaging. Asymptomatic ICAS was detected in 166 volunteers (5.9%) at the initial examination. Moderate and mild stenoses were observed in 1.5 and 4.4% of patients, respectively. Significant risk factors for ICAS were older age and a history of hypertension and/or dyslipidemia. During follow-up, ischemic stroke developed in 32 volunteers. Seven strokes occurred in the ICAS group, whose stroke incidence rate was higher than that in the non-ICAS group (0.78 vs. 0.18% per year). According to a Cox regression analysis, asymptomatic ICAS was an independent risk factor for future ischemic stroke after adjustment for age. Furthermore, after asymptomatic brain lesions were taken into account, ICAS was still a significant risk factor for stroke onset. In conclusion, even mild to moderate asymptomatic ICAS was a significant risk factor for future stroke, independent of asymptomatic brain lesions, in a healthy Japanese population. Mild to moderate ICAS might be a therapeutic target for stroke prevention.

Association of mild kidney dysfunction with silent brain lesions in neurologically normal subjects.

BACKGROUND: Chronic kidney disease (CKD) has been closely associated with stroke. Although a large number of studies reported the relationship between CKD and different types of asymptomatic brain lesions, few comprehensive analyses have been performed for all types of silent brain lesions. METHODS: We performed a cross-sectional study involving 1,937 neurologically normal subjects (mean age 59.4 years). Mild CKD was defined as an estimated glomerular filtration rate between 30 and 60 ml/min/1.73 m(2) or positive proteinuria. RESULTS: The prevalence of mild CKD was 8.7%. Univariate analysis revealed an association between CKD and all silent brain lesions, including silent brain infarction, periventricular hyperintensity, subcortical white matter lesion, and microbleeds, in addition to hypertension and diabetes mellitus after adjusting for age and sex. In binary logistic regression analysis, the presence of CKD was a significant risk factor for all types of silent brain lesions, independent of other risk factors. CONCLUSIONS: These results suggest that mild CKD is independently associated with all types of silent brain lesions, even in neurologically normal subjects.

Primary brain abscess caused by Nocardia otitidiscaviarum.

Diagnosing primary cerebral nocardiosis is difficult. This case report describes a 79-year-old immunocompetent Japanese woman with a primary brain abscess caused by Nocardia otitidiscaviarum (IFM 11321) and reviews the findings of 11 previous patients with N. otitidiscaviarum-induced brain abscesses. Four patients survived, including ours. Beta-lactams were not effective in our patient, and the diagnosis required a pathologic analysis of the surgical specimen. Sulfamethoxazole/trimethoprim (ST) was administered to the patient. On antibiotic susceptibility testing, N. otitidiscaviarum (IFM11321) was found to be resistant to amoxicillin-clavulanic acid, ceftriaxone, cefotaxime, cefepime, imipenem and clarithromycin, but sensitive to amikacin, gentamicin, ST and linezolid. Antimicrobial susceptibility patterns differ among Nocardia species, making species identification important for treatment. Patients with suspected Nocardia infection should therefore be treated empirically with ST and/or amikacin and considered for surgical management.

Effects of omeprazole on sleep disturbance: randomized multicenter double-blind placebo-controlled trial.

OBJECTIVES: Gastroesophageal reflux is considered to cause sleep disturbance, whereas proton pump inhibitor (PPI) administration is reported to improve insomnia associated with gastroesophageal reflux disease (GERD). The majority of patients with gastroesophageal reflux are asymptomatic and a significant number with erosive esophagitis are also reported to be asymptomatic. We examined whether PPI administration has a therapeutic effect for improving insomnia in patients without reflux symptoms in the same manner as patients with reflux symptoms. METHODS: We performed a randomized multicenter double-blind placebo-controlled trial using 176 patients with insomnia regardless of the presence of reflux symptoms. The patients were divided into those administered omeprazole (20 mg) or a placebo for 14 days. Four self-reporting questionnaires, QOLRAD-J (Japanese translation of Quality of Life in Reflux and Dyspepsia), Pittsburg Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and a sleep diary, were used for evaluating GERD-related quality of life (QOL) and sleep disturbance. RESULTS: We evaluated 171 patients with insomnia, of whom 69 had typical reflux symptoms. Omeprazole statistically significantly improved GERD-related QOL from 30.8±0.7 to 33.0±0.5 (P<0.01) (QOLRAD-J, total) and from 6.0±0.2 to 6.6±0.1 (P<0.01) (QOLRAD-J, sleep-related) when administrated to patients with reflux symptoms. Omeprazole also improved insomnia significantly better than the placebo in patients with reflux symptoms; PSQI, from 9.3±0.5 to 7.9±0.5 (P<0.01) and sleep diary, from 2.1±0.1 to 1.8±0.1 (P<0.01). On the other hand, the therapeutic effects of omeprazole and the placebo were not different in patients without reflux symptoms. CONCLUSIONS: Our results showed that PPI administration is effective only for insomnia in patients with reflux symptoms.

Validation of a new mass screening tool for cognitive impairment: Cognitive Assessment for Dementia, iPad version.

BACKGROUND: We have developed a new screening test for dementia that runs on an iPad and can be used for mass screening, known as the Cognitive Assessment for Dementia, iPad version (CADi). The CADi consists of items involving immediate recognition memory for three words, semantic memory, categorization of six objects, subtraction, backward repetition of digits, cube rotation, pyramid rotation, trail making A, trail making B, and delayed recognition memory for three words. The present study examined the reliability and validity of the CADi. METHODS: CADi evaluations were conducted for patients with dementia, healthy subjects selected from a brain checkup system, and community-dwelling elderly people participating in health checkups. RESULTS: CADi scores were lower for dementia patients than for healthy elderly individuals and correlated significantly with Mini-Mental State Examination scores. Cronbach's alpha values for the CADi were acceptable (over 0.7), and test-retest reliability was confirmed via a significant correlation between scores separated by a one-year interval. CONCLUSION: These results suggest that the CADi is a useful tool for mass screening of dementia in Japanese populations.

Gastroesophageal reflux during enteral feeding in stroke patients: a 24-hour esophageal pH-monitoring study.

BACKGROUND: Patients who are unable to eat or drink after stroke may receive percutaneous endoscopic gastrostomy (PEG) or nasogastric tube feeding. Although the most common serious complication is well known to be aspiration pneumonia, the role of gastroesophageal reflux (GER) has not been fully assessed. The aim of this study was to examine, by means of 24-hour esophageal pH monitoring, whether GER is related to aspiration pneumonia and whether the size and laterality of brain lesions influence GER. METHODS: Sixteen stroke patients were examined using a Degitrapper pH400 (Medtronic Japan Co., Tokyo, Japan) and Zinetics 24ME multiuse pH catheter (Medtronic). All patients had stroke lesions in the territory of the left or right middle cerebral artery that were confirmed by magnetic resonance imaging (MRI) and were receiving PEG or nasogastric feeding. Stroke volume was measured with MRIcron software. RESULTS: Nine patients (56%) were diagnosed with GER, and 10 (63%) developed aspiration pneumonia after enteral feeding. The rate of aspiration pneumonia was significantly higher in patients with GER (88.9%) than in those without GER (42.9%; P = .04). Patients with left hemispheric lesions had a significantly higher incidence of acid reflex than those with right lesions (116 ± 105 vs 13 ± 17; P = .04). There were no significant differences in total time of acid reflux or mean pH value between patients with left and right hemispheric lesions. The lesion volume had no significant effect on any of 3 indices of GER. CONCLUSIONS: GER is associated with aspiration pneumonia and occurs more often in patients with stroke lesions in the left hemisphere.

Microbleeds are associated with subsequent hemorrhagic and ischemic stroke in healthy elderly individuals.

BACKGROUND AND PURPOSE: Cerebral microbleeds (MBs) are frequently detected in patients with stroke, especially those who experience intracerebral hemorrhage. However, the clinical significance of MBs in subjects without cerebrovascular disease is still unclear. We performed a prospective study to determine whether the presence of MBs provides useful prognostic information in healthy elderly individuals. METHODS: We tracked 2102 subjects (mean age, 62.1 years) over a mean interval of 3.6 years after they voluntarily participated in the brain checkup system at the Shimane Institute of Health Science. An initial assessment was performed to document the presence of MBs and silent ischemic brain lesions and to map the location of the MBs. During the follow-up period, we obtained information about stroke events that occurred in each subject. RESULTS: MBs were detected in 93 of the 2102 subjects (4.4%). Strokes occurred in 44 subjects (2.1%) during the follow-up period. They were significantly more common among subjects with MBs. Age and hypertension were independent risk factors for MBs. The presence of MBs was more strongly associated with a deep brain hemorrhage (hazard ratio, 50.2; 95% CI, 16.7 to 150.9) than ischemic stroke (hazard ratio, 4.48; 95% CI, 2.20 to 12.2). All hemorrhagic strokes occurred in deep brain regions, and they were associated with MBs located in the deep brain region. CONCLUSIONS: This longitudinal study demonstrated that the presence of MBs can be used to predict hemorrhagic and ischemic stroke, even in healthy elderly individuals.

Post-stroke apathy and hypoperfusion in basal ganglia: SPECT study.

BACKGROUND: Although apathy has been reported as one of the neuropsychiatric symptoms following stroke, there are few studies on regional cerebral blood flow (rCBF) in stroke patients with apathy. The present study compared rCBF between apathetic and non-apathetic patients after stroke. METHODS: We recruited 102 patients with cerebral infarction within 1 month after stroke and performed neuropsychiatric assessments that included the apathy scale. rCBF was quantitatively measured using N-isopropyl-p-(123)I-iodoamphetamine single-photon emission computed tomography. RESULTS: Thirty-seven patients (36%) had apathy. The apathetic group showed lower cognitive function and a higher depressive state than the non-apathetic group. rCBF in the basal ganglia was reduced for the apathetic group compared with the non-apathetic group. Furthermore, lesions in the left basal ganglia were associated with hypoperfusion in bilateral basal ganglia and the presence of apathy. CONCLUSION: These findings demonstrate that apathy is a frequent symptom among stroke patients and that hypoperfusion caused by basal ganglia lesions may contribute to post-stroke apathy.

Successful treatment of post-stroke apathy by the dopamine receptor agonist ropinirole.

Dopamine D2/3 receptor agonists have been widely used to treat motor symptoms in Parkinson's disease and are also reported to improve cognitive and emotional disturbances. Here we describe a patient who developed severe apathy after cerebral infarction in the prefrontal cortex. After administration of ropinirole, his verbal output and spontaneity in daily life was improved remarkably. This improvement was associated with increased blood flow in the prefrontal cortex and basal ganglia. We suggest that ropinirole may be a treatment option for deficits in motivated behavior after prefrontal damage.