Hajime Shishido

Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer's disease.

Several pathological and epidemiological studies have demonstrated a possible relationship between traumatic brain injury (TBI) and Alzheimers disease (AD). However, the exact contribution of TBI to AD onset and progression is unclear. Hence, we examined AD-related histopathological changes and cognitive impairment after TBI in triple transgenic (3×Tg)-AD model mice. Five- to seven-month-old 3×Tg-AD model mice were subjected to either TBI by the weight-drop method or a sham treatment. In the 3×Tg-AD mice subjected to TBI, the spatial learning was not significantly different 7 days after TBI compared to that of the sham-treated 3×Tg-AD mice. However, 28 days after TBI, the 3×Tg-AD mice exhibited significantly lower spatial learning than the sham-treated 3×Tg-AD mice. Correspondingly, while a few amyloid-β (Aβ) plaques were observed in both sham-treated and TBI-treated 3×Tg-AD mouse hippocampus 7 days after TBI, the Aβ deposition was significantly greater in 3×Tg-AD mice 28 days after TBI. Thus, we demonstrated that TBI induced a significant increase in hippocampal Aβ deposition 28 days after TBI compared to that of the control animals, which was associated with worse spatial learning ability in 3×Tg-AD mice. The present study suggests that TBI could be a risk factor for accelerated AD progression, particularly when genetic and hereditary predispositions are involved.

Blood Glucose Variability A Strong Independent Predictor of Neurological Outcomes in Aneurysmal Subarachnoid Hemorrhage

Purpose: In patients with aneurysmal subarachnoid hemorrhage (SAH), increased glucose variability (GV) is associated with increased mortality and cerebral infarction; however, there are no reports demonstrating an association between GV and neurological outcome. This study investigated whether GV had an independent effect on neurological outcomes in patients with SAH in the intensive care unit. Materials and Methods: Consecutive adult patients hospitalized with SAH between January 1, 2009, and May 31, 2015 (N = 122) were retrospectively reviewed. Univariate/multivariate analyses were performed to identify independent predictors of poor neurological outcome. Patients were divided according to the mean glucose level (80-139 vs 140-200 mg/dL) and further subdivided using quartiles (Q) of the standard deviation (SD, representing variability) of the glucose level (Q1, Q2 + 3, and Q4). Results: Unfavorable neurological outcomes occurred in 44.2% of the patients. On multiple regression analysis, age, Hunt and Kosnik grade, SD of glucose (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.17; P < .01), and minimum blood glucose level (OR, 0.95; 95% CI, 0.91-0.99; P < .01) were significantly associated with unfavorable neurological outcomes. Both groups (mean glucose levels: 80-139 and 140-200 mg/dL groups) had increasing unfavorable neurological outcomes with increasing SD of glucose (Q1, 15.0%; Q2 + 3, 40.0%; Q4, 52.4% and Q1, 44.4%; Q2 + 3, 50%; Q4, 88.9% in the 80-139 and 140-200 mg/dL groups, respectively). Patients with minimum glucose of <90 mg/dL comprised >50% of unfavorable neurological outcome. Conclusion: Increased GV was an independent predictor of unfavorable neurological outcomes in patients with SAH.

Serial blood lactate measurements and its prognostic significance in intensive care unit management of aneurysmal subarachnoid hemorrhage patients

Purpose: This study assesses the behavior of serial blood lactate measurements during intensive care unit (ICU) stay to identify prognostic factors of unfavorable neurological outcomes (UO) in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods: We retrospectively reviewed all patients who were consecutively hospitalized with SAH between 2009 and 2016. Arterial blood lactate levels were routinely obtained on admission and every 6 h in the ICU. Univariate/multivariate analyses were performed to identify independent predictors of UO (modified Rankin scale of 3–6 upon hospital discharge). Results: There were 145 patients with 46% of UO. Initially, increased lactate levels reached maximum levels during the first 24 h and then decreased to within the normal range. Then, the levels slightly increased again to within the normal range for the next 24 h, especially in UO. On multiple regression analysis, lactate levels measured at 24 h, and 48 h after admission were strong predictors of UO. Lactate level measured at 48 h after admission demonstrated the greatest accuracy and the highest specificity (area under the curve, 0.716; sensitivity, 40%; specificity, 92.1%). Conclusions: The lactate level at 48 h after admission was the most accurate predictor of UO with a high specificity in SAH patients. HIGHLIGHTSIn the unfavorable outcome group, initially increased lactate levels decreased to within the normal range for the first 24 h. Then, lactate levels slightly increased again to within the normal range for the next 24 h.The blood lactate level at each time point was greater in the unfavorable neurological outcome group than the favorable neurological outcome group.The lactate level at 48 h after admission was the most accurate predictor of unfavorable neurological outcomes in SAH patients.

Successful treatment of non-convulsive status epilepticus diagnosed using bedside monitoring by a combination of amplitude-integrated and two-channel simplified electroencephalography

A 66‐year‐old man developed disturbed consciousness and right hemiparesis with transient convulsions in the right arm. Bedside monitoring using a combination of amplitude‐integrated electroencephalography and two‐channel simplified electroencephalography revealed intermittent episodes of 1–3 Hz δ waves lasting for approximately 5 min, consistent with non‐convulsive status epilepticus. Fosphenytoin (22.5 mg/kg/day) and levetiracetam (1,000 mg) prevented right arm convulsions but did not restore consciousness. The two‐channel simplified electroencephalography also showed an intermittent periodic δ wave pattern in the Fp1‐C3 channel. Conventional electroencephalography revealed a polymorphic δ activity that was abolished by 2.5 mg diazepam, thus confirming the diagnosis of non‐convulsive status epilepticus.

Association between dexmedetomidine use and neurological outcomes in aneurysmal subarachnoid hemorrhage patients: A retrospective observational study

Purpose: Recent studies in animal subarachnoid hemorrhage (SAH) models have reported that dexmedetomidine (DEX) use demonstrates significantly better neurological outcomes. This study aimed to evaluate whether DEX use is associated with favorable neurological outcomes (FO) in SAH patients. Materials and methods: We retrospectively reviewed all SAH patients between 2009 and 2017. We calculated the total dosage of DEX administered for the first 24 h after admission. All patients were classified into no use, low dosage, and standard dosage group. Multivariate analysis was performed to clarify the association between DEX use and FO (modified Ranking Scale score of 0–2 at hospital discharge). Results: There were 161 patients with 55.3% of FO. On univariate analysis, there were significant differences with regard to age, Hunt and Kosnik (H&K) grade, and DEX use. Multivariate analysis showed that age, H&K grade, and low dosage DEX (rather than no use) (odds ratio (OR) 3.17; 95% confidence interval (CI), 1.24–8.53; p = 0.02) were significantly associated with FO. However, standard dosage DEX was not a significant factor (OR, 0.75; 95% CI, 0.25–2.16; p = 0.59). Conclusions: Low dosage DEX during the first 24 h after admission was associated with FO in SAH patients. HighlightsLow dosage dexmedetomidine was associated with favorable neurological outcomes.Low dosage dexmedetomidine showed rapid clearance of blood lactate levels.The incidence of adverse events increased with the increased use of dexmedetomidine.

Invasive group B streptococcal infection in a patient with post splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension

BACKGROUND Splenectomy in patients with liver cirrhosis (LC) is expected to become more common owing to its efficacy on portal hemodynamics. In this report we describe an alarming case of group B streptococcus (GBS) infection after splenectomy in a patient with LC. METHODS A 72-year-old woman with a history of LC was admitted to our emergency department because of respiratory failure. The patient had received left lateral segmentectomy of the liver and splenectomy three months before admission. Pulmonary examination revealed significant wheezing during inspiration and expiration, but no crackles and stridor. Chest radiography and CT showed no infiltrates. A presumptive diagnosis of bronchial asthma caused by upper respiratory infection was made. Four days after admission, GBS infection was confirmed by blood culture and penicillin G was administered. Antibiotics were given intravenously for a total of 12 days. RESULTS The patient was discharged on the 12th day after admission. CONCLUSIONS Although efficacy of splenectomy in patients with LC has been reported, immune status should be evaluated for a longer period. Patients who have undergone splenectomy are highly susceptible to bacteria; moreover, LC itself is an independent risk factor for mortality in patients with sepsis. Since prophylaxis against GBS has not been established, immediate action should be taken. Emergency physicians should be aware of invasive GBS infection in the context of the critical risk factors related to splenectomy and LC, particularly the expected increase of splenectomy performed in LC patients.

Data on amyloid precursor protein accumulation, spontaneous physical activity, and motor learning after traumatic brain injury in the triple-transgenic mouse model of Alzheimer׳s disease

This data article contains supporting information regarding the research article entitled “Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer׳s disease” (H. Shishido, Y. Kishimoto, N. Kawai, Y. Toyota, M. Ueno, T. Kubota, Y. Kirino, T. Tamiya, 2016) [1]. Triple-transgenic (3×Tg)-Alzheimer׳s disease (AD) model mice exhibited significantly poorer spatial learning than sham-treated 3×Tg-AD mice 28 days after traumatic brain injury (TBI). Correspondingly, amyloid-β (Aβ) deposition within the hippocampus was significantly greater in 3×Tg-AD mice 28 days after TBI. However, data regarding the short-term and long-term influences of TBI on amyloid precursor protein (APP) accumulation in AD model mice remain limited. Furthermore, there is little data showing whether physical activity and motor learning are affected by TBI in AD model mice. Here, we provide immunocytochemistry data confirming that TBI induces significant increases in APP accumulation in 3×Tg-AD mice at both 7 days and 28 days after TBI. Furthermore, 3×Tg-AD model mice exhibit a reduced ability to acquire conditioned responses (CRs) during delay eyeblink conditioning compared to sham-treated 3×Tg-AD model mice 28 days after TBI. However, physical activity and motor performance are not significantly changed in TBI-treated 3×Tg-AD model mice.

739: ASSOCIATION BETWEEN DEXMEDETOMIDINE USE AND NEUROLOGIC OUTCOME IN SUBARACHNOID HEMORRHAGE PATIENTS

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: Dexmedetomidine (DEX) is being increasingly accepted as a sedative drug option in patients requiring neurocritical care. Although recent studies in animal subarachnoid hemorrhage (SAH) models have reported that DEX use demonstrates significantly better neurological outcomes, the association between DEX use and neurological outcomes in SAH patients has not been examined. Therefore, the present study aimed to evaluate whether DEX use is associated with better neurological outcomes in SAH patients. Methods: We retrospectively reviewed all SAH patients aged 18 years or older who were hospitalized at Kagawa University Hospital between January 1, 2009 and March 31, 2017. We calculated the total dosage of DEX administered for the first 24 h after admission as the area under the DEX dosage-time curve. All patients were classified as follows: no use group (average dosage = 0 μg/kg/h), low dosage group (0.01–0.20 μg/kg/h), and standard dosage group (> 0.20 μg/kg/h). The primary outcome was a favorable neurological outcome at hospital discharge, defined as a modified Ranking Scale score of 0–2. The association between DEX use and favorable neurological outcomes was evaluated using multivariate logistic regression analysis. Secondary outcomes included the association between the use of DEX use and incidence of adverse events (both hypotension and bradycardia). Results: Favorable neurological outcomes were observed in 55.3% of 161 included patients. On performing univariate analysis, there were significant differences with regard to age, Hunt and Kosnik grade, and DEX use. Multivariate logistic regression analysis showed that age, Hunt and Kosnik grade, and low dosage DEX (rather than no use) (odds ratio (OR) 3.17; 95% confidence interval (CI), 1.24–8.53; p = 0.02) were significantly associated with favorable neurological outcomes. However, standard dosage DEX (rather than no use) was not a significant factor (OR, 0.75; 95% CI, 0.25–2.16; p = 0.59). The incidence of adverse events increased with the increased use of DEX (Cochran–Armitage trend test, p = 0.03). Conclusions: Low dosage DEX during the first 24 h after admission was associated with favorable neurological outcomes in SAH patients. Randomized controlled trials are needed to further determine whether DEX use can improve neurological outcomes.

Clinical characteristics of non‐convulsive status epilepticus diagnosed by simplified continuous electroencephalogram monitoring at an emergency intensive care unit

The present study aimed to elucidate the clinical characteristics of non‐convulsive status epilepticus (NCSE) in patients with altered mental status (AMS).

762: ASSOCIATION OF GLUCOSE VARIABILITY WITH NEUROLOGIC OUTCOMES IN ANEURYSMAL SUBARACHNOID HEMORRHAGE

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) optimum cerebral perfusion pressure value (CPPOpt) to be targeted in brain injured patients. The standard CPPOpt algorithm fails to calculate a value in a significant amount of the time. We present an alternative algorithm, implemented in the CHART-ADAPT (www.chartadapt.org) project, and compare the absolute values and reliability to the standard algorithm. Methods: Waveform resolution intracranial pressure and cerebral perfusion pressure values were recorded from 20 patients admitted to the neurological intensive care unit (NICU). The CPPOpt calculated using the standard method uses binning of PRx values over a CPP range and subsequent data reduction steps to enable the squared polynomial fit. Our alternative algorithm uses a simple generalised additive model (GAM) to find the CPP value associated with the minimum PRx value. Both algorithms were used to provide a CPPOpt value using a moving four hour window over the first 24 hours of NICU admission for each patient. We then compared the output of the algorithms by a linear mixed effects model. The model used per subject random effects to account for the paired nature of the data, as well as a compound symmetry correlation structure to cope with the repeated measures in time. Results: The standard model was able to provide a CPPOpt value to target for 62.5% of the first 24 hours on NICU. Our alternative algorithm was able to provide a CPPOpt value for 100% of the time. There was a non-significant effect (p = 0.74) of algorithm on the calculated CPPOpt values. Conclusions: Using our alternative algorithm we were more reliably able to calculate a CPPOpt to target in brain injured patients. These values were not statistically different from the values calculated using the standard method, indicating interchangeability of the methodologies. Further clinical studies are required to determine which of these methods is more suitable for future use to contribute to the management of brain injured patients.