The incidence and predictors of antibiotic-associated encephalopathy: a multicenter hospital-based study.

This study aimed to evaluate the incidence and likelihood of antibiotic-associated encephalopathy (AAE), comparing rates among the classes of antibiotics in monotherapy or in combination therapy. We also investigated the associations between the incidence of AAE and the glomerular filtration rate (GFR) and electroencephalogram features. Consecutive admissions that used any kind of antibiotics to treat infectious diseases were identified from six hospitals. We classified antibiotics according to three distinct pathophysiologic mechanisms and clinical subtypes. We searched for the incidence of AAE as the primary outcome. A total of 97,433 admission cases among 56,038 patients was identified. Cases that received type 1 antibiotics had significantly more frequent AAE compared to those that received type 2 antibiotics (adjusted odds ratio [OR], 2.62; 95% confidence interval [CI] 1.15-5.95; P = 0.021). Combined use of type 1 + 2 antibiotics was associated with a significantly higher incidence of AAE compared to the use of type 2 antibiotics alone (adjusted OR, 3.44; 95% CI 1.49-7.93; P = 0.004). Groups with GFR < 60 mL/min/1.73 m2 had significantly higher incidence rates of AAE compared to those with GFRs ≥ 90 mL/min/1.73 m2 among cases that received type 1 + 2 antibiotics. Detection of spike-and-wave or sharp-and-wave patterns on electroencephalogram was significantly more common in the combination therapy group. Combination use of antibiotics was associated with a higher incidence of AAE compared to monotherapy. The incidence of AAE significantly increased as renal function decreased, and epileptiform discharges were more likely to be detected in cases receiving combined antibiotics.

Clinical manifestation and imaging characteristics of transient global amnesia: patent foramen ovale as an underlying factor.

Transient global amnesia is not rare, but its etiology remains unknown. Cerebral ischemia is a suspected cause because high signal intensity is observed on diffusion-weighted brain magnetic resonance imaging; however, previous studies have not established it as a cause. Of the 128 patients (114 females) enrolled in this study, 82 (64.6%) experienced extreme stress before transient global amnesia. The number of female patients with patent foramen ovale was more than that of males. The patent foramen ovale-positive group had fewer vascular risk factors and fewer old ischemic lesions on fluid-attenuated inversion recovery magnetic resonance imaging than the patent foramen ovale-negative group. Brain magnetic resonance imaging confirmed that high signal intensity was more likely to be detected on the initial diffusion-weighted imaging when there was an old lesion detected by fluid-attenuated inversion recovery. Furthermore, a longer period from symptom onset to brain magnetic resonance imaging was associated with a positive initial diffusion-weighted imaging result. It is difficult to attribute one underlying mechanism to all the transient global amnesia cases. This study confirmed that transient global amnesia patients with patent foramen ovale had lesser vascular risk factors and showed fewer old lesions on fluid-attenuated inversion recovery magnetic resonance imaging than those without. These results suggest that transient global amnesia may be caused by a paradoxical embolus rather than ischemia due to traditional vascular risk factors in patients with patent foramen ovale.

Cognitive decline according to amyloid uptake in patients with poststroke cognitive impairment.

BACKGROUND AND PURPOSE: Poststroke cognitive impairment (PSCI) is common, but the impact of ß-amyloid (Aß) on PSCI is uncertain. The proposed study will investigate amyloid pathology in participants with PSCI and how differently their cognition progress according to the amyloid pathology. METHODS: This multicenter study was designed to be prospective and observational based on a projected cohort size of 196 participants with either newly developed cognitive impairment, or rapidly aggravated CI, within 3 months after acute cerebral infarction. They will undergo 18F-flutemetamol positron emission tomography at baseline and will be categorized as either amyloid-positive (A+) or amyloid-negative (A-) by visual rating. The primary outcome measures will be based on Korean Mini-Mental State Examination changes (baseline to 12 months) between the A+ and A- groups. The secondary outcome measures will be the dementia-conversion rate and changes in the Korean version of the Montreal Cognitive Assessment (baseline to 12 months) between the A+ and A- groups. CONCLUSIONS: This study will provide a broadened perspective on the impact of Aß on the cause and outcomes of PSCI in clinical practice. Identifying amyloid pathology in patients with PSCI will help select patients who need more focused treatments such as acetylcholinesterase inhibitors. TRIAL REGISTRATION: Clinical Research Information Service identifier: KCT0005086.

Syncope after Influenza Virus Infection.

Influenza is an epidemical acute respiratory disease caused by viral infection. Several complications in the respiratory tract, such as pneumonia can occur. However, rare but serious neurological complications are also observed. Here, we described the prevalence, characteristics and suggestive pathomechanism of syncope after influenza infection season. Of 2.2% of patients diagnosed as influenza experienced syncope. None of the patients had severe cough, low blood pressure (BP) or dehydration. Patients suffered with frequent dizziness before syncope. Patient with long duration of loss of consciousness was more observed in those with high fever or positive orthostatic BP drop.

Clinical significance of the internal carotid artery angle in ischemic stroke.

The carotid artery plays a major role in stroke aetiology and is a good indicator of atherosclerosis. However, the clinical significance of internal carotid artery (ICA) anatomy remains unclear in patients with ischaemic stroke. This study examined the relationship between ICA angle and risk of ischaemic stroke. ICA angles of patients with acute ischaemic stroke were retrospectively compared with those of control patients between March 2014 and July 2014. Controls consisted of those with headaches but without ischaemic stroke. In both groups, ICA angles were measured using Maximum Intensity Projection images from computed tomography angiography, and the relationship between ICA angle and risk of ischaemic stroke was analysed. Of 128 screened patients with acute ischaemic stroke, 27 were enrolled, and 29 with headache were enrolled as controls. No differences were found in baseline characteristics between the two groups, but intracranial stenosis was more frequent in patients with stroke than in controls. Bilateral ICA angles were significantly larger in patients with stroke than in controls. Multiple logistic regression models showed that the right ICA angle was associated with risk of ischaemic stroke. Measuring the ICA angle may help assess the risk of ischaemic stroke.

Cervical myelitis presenting as occipital neuralgia.

AIM: Occipital neuralgia is a common form of headache that is characterized by paroxysmal severe lancinating pain in the occipital nerve distribution. METHODS: The exact pathophysiology is still not fully understood and occipital neuralgia often develops spontaneously. There are no specific guidelines for evaluation of patients with occipital neuralgia. RESULT: Cervical spine, spinal cord and posterior neck muscle lesions can induce occipital neuralgia. Brain and spine imaging may be necessary in some cases, according to the nature of the headache or response to treatment. DISCUSSION: We report a case of cervical myelitis presenting as occipital neuralgia.

Cardiac Vulnerability to Cerebrogenic Stress as a Possible Cause of Troponin Elevation in Stroke.

BACKGROUND: Troponin elevation with electrocardiography changes is not uncommon in patients with acute ischemic stroke; however, it is still unclear whether the mechanism of these changes is due to cardiac problems or neurally mediated myocytic damage. Thus, we investigated cardiac and neurological predictors of troponin elevation in those patients. METHODS AND RESULTS: We retrospectively analyzed medical data of the prospectively registered ischemic stroke patients on stroke registry who were admitted and underwent a serum cardiac troponin I and 12-lead electrocardiography within 24 hours of symptom onset. However, patients with well-known troponin-elevating comorbidities were excluded from the analysis. Among 1404 ischemic stroke patients, 121 (8.7%) had elevated troponin, which was defined as more than 0.04 mg/mL. Multivariable analysis identified electrocardiography abnormalities such as QTc-prolongation (odds ratio [OR]: 1.52, 95% CI: 1.02-2.28), left ventricular hypertrophy (OR: 2.14, 95% CI 1.43-3.19), Q-wave (OR: 2.53, 95% CI: 1.48-4.32), and ST elevation (OR: 2.74, 95% CI: 1.12-6.72) as cardiac variables associated with troponin elevation, and higher National Institutes of Health Stroke Scale score (OR: 1.04, 95% CI: 1.01-1.07) and insular cortical lesions (OR: 2.78, 95% CI: 1.85-4.19) as neurological variables associated with troponin elevation. Incidence of troponin elevation as well as QTc-prolongation was increased further in combination with cardiac and neurological factors. CONCLUSIONS: Certain cardiac and neurological conditions in acute ischemic stroke may contribute to troponin elevation. The proposed concept of cardiac vulnerability to cerebrogenic stress can be a practical interpretation of troponin elevation and electrocardiography abnormalities in stroke patients.

Impact of Provoking Risk Factors on the Prognosis of Cerebral Venous Thrombosis in Korean Patients.

BACKGROUND AND PURPOSE: Little is known about the relationships between provoking risk factors, prognosis, and optimal duration of anticoagulation in patients with cerebral venous thrombosis (CVT), especially in Asians. We aimed to investigate whether the prognosis and required duration of anticoagulation in CVT patients differ according to the provoking risk factors. METHODS: Prospectively recorded data from a tertiary medical center in South Korea were retrospectively reviewed. CVTs were categorized into three groups: unprovoked, those with possibly resolved provoking factors (PR), and those with persistent provoking factors (PP). The baseline characteristics, treatment, and prognosis of patients in these three groups were analyzed. RESULTS: From 2000 to 2015, 61 patients presented with CVT: 19 (31.1%) unprovoked, 11 (18.0%) with PR, and 31 (50.9%) with PP. The patients in our cohort had a slight female predominance and lower frequency of oral contraceptive use compared to Western cohorts. Median follow-up and duration of anticoagulation were 35 and 8 months, respectively. Despite the similarities in baseline characteristics, deaths (n=3; P=0.256) and recurrences (n=7; P=0.020) were observed only in the PP group. The median intervals to death and recurrence were 9 and 13 months, respectively. Death was associated with underlying disease activity, not with CVT progression. Recurrences in the PP group were associated with lack of anticoagulation (P=0.012). CONCLUSIONS: Although the prognosis of CVT is generally benign in Koreans, recurrence and death were observed in patients with persistent risk factors, suggesting their need for long-term treatment with anticoagulants.

Emotional disturbance in CADASIL: its impact on quality of life and caregiver burden.

BACKGROUND AND PURPOSE: Recurrent strokes and cognitive dysfunction are the major symptoms of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, emotional disturbances in CADASIL patients are incompletely understood. The aim of this study was to investigate emotional disturbances in CADASIL and their impact on the patients' quality of life (QOL) and caregiver burden. METHODS: From 54 patients who were diagnosed as CADASIL between January 2000 and August 2012 in the Asan Medical Center, Seoul, Korea, 23 patients were enrolled in this study. The Montgomery-Asberg Depression Rating Scale was used for the assessment of depressive emotional disturbances (DED). For nondepressive emotional disturbances (NDED), the criteria of Kim and Choi-Kwon [Neurology 2000;54:1805-1810] were used for emotional incontinence (excessive/inappropriate expression of laughing or crying), and the modified Spielberger Trait Anger Scale was used for anger proneness (excessive/inappropriate expression of anger). Patients' QOL and caregiver burden were assessed with stroke-specific emotional QOL and the Sense of Competence Questionnaire (SCQ), respectively. Functional disability was assessed by the modified Rankin scale (mRS), and white matter ischemic changes and microbleeds were analyzed using brain magnetic resonance images. RESULTS: Twelve patients (52.2%) had various emotional disturbances including DED (n=10, 43.5%) and NDED (n=7, 30.4%). The presence of any emotional disturbances was associated with thalamic (p=0.012) and cortical (p=0.037) microbleeds, mRS (p=0.001), cognitive impairment (p=0.002), patients' low QOL (p=0.009) and increased caregiver burden (p=0.002). DED was associated with multiple (≥10) microbleeds (p=0.039), cognitive impairment (p=0.030) and mRS (p=0.030), and negatively influenced all domains of patients' QOL and caregiver burden. NDED was associated with cortical microbleeds (p=0.017) and mRS (p=0.014). Unlike DED, NDED was not associated with patients' poor QOL, except for thinking domain, but was significantly related to total SCQ and subscales 1 and 2 of SCQ (p=0.012). CONCLUSIONS: More than half the CADASIL patients had emotional disturbances, either DED or NDED. Both are associated with patients' poor QOL and increased caregiver burden, the former more markedly than the latter. Considering that CADASIL is a progressive disease with deteriorating patients' QOL, physicians have to pay more attention to emotional problems in CADASIL patients. Treatment strategies should be investigated in this regard to improve patients' QOL and reduce caregiver burden.

Complementarity between (18)F-FDG PET/CT and Ultrasonography or Angiography in Carotid Plaque Characterization.

BACKGROUND AND PURPOSE: To estimate clinical roles of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) versus angiography and ultrasonography in carotid plaque characterization. METHODS: We characterized two groups of patients with recently (<1 month) symptomatic (n=14; age=71.8±8.6 years, mean±SD) or chronic (n=13, age=68.9±9.0 years) carotid stenosis using a battery of imaging tests: diffusion magnetic resonance (MR) imaging, MR or transfemoral angiography, duplex ultrasonography (DUS), and carotid FDG-PET/computed tomography. RESULTS: The degree of angiographic stenosis was greater in patients with recently symptomatic carotid plaques (67.5±21.5%) than in patients with chronic carotid plaques (32.4±26.8%, p=0.001). Despite the significant difference in the degree of stenosis, lesional maximum standardized uptake values (maxSUVs) on the carotid FDG-PET did not differ between the recently symptomatic (1.56±0.53) and chronic (1.56±0.34, p=0.65) stenosis groups. However, lesional-to-contralesional maxSUV ratios were higher in the recently symptomatic stenosis group (113±17%) than in the chronic stenosis group (98±10%, p=0.017). The grayscale median value of the lesional DUS echodensities was lower in the recently symptomatic stenosis group (28.2±10.0, n=9) than in the chronic stenosis group (53.9±14.0, n=8; p=0.001). Overall, there were no significant correlations between angiographic stenosis, DUS echodensity, and FDG-PET maxSUV. Case/subgroup analyses suggested complementarity between imaging modalities. CONCLUSIONS: There were both correspondences and discrepancies between the carotid FDG-PET images and DUS or angiography data. Further studies are required to determine whether FDG-PET could improve the clinical management of carotid stenosis.

NINJ2 SNP may affect the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions.

BACKGROUND: To investigate if single nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 would be associated with earlier-onset (vs. late-onset) first-ever ischemic stroke and increase silent cerebrovascular lesions prior to the manifestation of the stroke. METHODS: We prospectively enrolled 164 patients (67.6 ± 12.9 years, 92 men) admitted with first-ever ischemic strokes. All patients underwent genotyping of rs11833579 and rs12425791 as well as systemic investigations including magnetic resonance (MR) imaging and other vascular workup. Stroke-related MR lesions were registered on a brain-template-set using a custom-built software package 'Image_QNA': high-signal-intensity ischemic lesions on diffusion, T2-weighted, or fluid attenuation inversion recovery (FLAIR) MR images, and low signal intensity hemorrhagic lesions on gradient-echo MR images. RESULTS: The rs11833579 A/A or G/A genotype was independently associated with the first-ever ischemic stroke before the age 59 vs. 59 or over, after adjusting for cardiovascular risk factors and prior medication of antiplatelet or anticoagulant drugs, increasing the risk by about 2.5 fold. In the quantitative MR lesion maps from age-sex matched subgroups (n = 124 or 126), there was no difference between the patients with the rs11833579 A/A or G/A genotype and those with the G/G genotype. Unexpectedly, the extent of leukoaraiosis on FLAIR-MR images tended to be smaller in the corona radiata and centrum semiovale of the patients with the rs12425791 A/A or G/A genotype than in those with the G/G genotype (P = 0.052). Neither the rs11833579 nor the rs12425791 genotype significantly affected initial stroke severity; however the latter was associated with relatively low modified Rankin scale scores at 1 year after stroke. CONCLUSIONS: The rs11833579 A/A or G/A genotype may bring forward the onset age of first-ever ischemic stroke without increasing silent cerebrovascular lesions prior to the stroke. Further studies are required to confirm our preliminary findings.

A new image-based stroke registry containing quantitative magnetic resonance imaging data.

BACKGROUND: Conventional stroke registries contain alphanumeric text-based data on the clinical status of stroke patients, but this format captures imaging data in a very limited form. There is a need for a new type of stroke registry to capture both text- and image-based data. METHODS AND RESULTS: We designed a next-generation stroke registry containing quantitative magnetic resonance imaging (MRI) data, 'DUIH_SRegI', developed a supporting software package, 'Image_QNA', and performed experiments to assess the feasibility and utility of the system. Image_QNA enabled the mapping of stroke-related lesions on MR onto a standard brain template and the storage of this extracted imaging data in a visual database. Interuser and intrauser variability of the lesion mapping procedure was low. We compared the results from the semi automatic lesion registration using Image_QNA with automatic lesion registration using SPM5 (Statistical Parametric Mapping version 5), a well-regarded standard neuroscience software package, in terms of lesion location, size and shape, and found Image_QNA to be superior. We assessed the clinical usefulness of an image-based registry by studying 47 consecutive patients with first-ever lacunar infarcts in the corona radiata. We used the enriched dataset comprised of both image-based and alphanumeric databases to show that diffusion MR lesions overlapped in a more posterolateral brain location for patients with high NIH Stroke Scale scores (≥4) than for patients with low scores (≤3). In April 2009, we launched the first prospective image-based acute (≤1 week) stroke registry at our institution. The registered data include high signal intensity ischemic lesions on diffusion, T(2)-weighted, or fluid attenuation inversion recovery MRIs, and low signal intensity hemorrhagic lesions on gradient-echo MRIs. An interim analysis at 6 months showed that the time requirement for the lesion registration (183 consecutive patients, 3,226 MR slices with visible stroke-related lesions) was acceptable at about 1 h of labor per patient by a trained assistant with physician oversight. CONCLUSIONS: We have developed a novel image-based stroke registry, with database functions that allow the formulation and testing of intuitive, image-based hypotheses in a manner not easily achievable with conventional alphanumeric stroke registries.