Diagnostic value of transcranial doppler to predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage : To predict delayed cerebral ischemia.

BACKGROUND: Transcranial Doppler (TCD) is a technique to assess blood flow velocity in the cerebral arteries. TCD is frequently used to monitor aneurysmal subarachnoid hemorrhage (aSAH) patients. This study compares TCD-criteria for vasospasm and its association with Delayed Cerebral Ischemia (DCI). An overall score based on flow velocities of various intracranial arteries was developed and evaluated. METHODS: A retrospective diagnostic accuracy study was conducted between 1998 and 2017 with 621 patients included. Mean flow velocity (MFV) of the cerebral artery was measured between 2-5 days and between 6-9 days after ictus. Cutoff values from the literature, new cutoff values, and a new composite score (Combined Severity Score) were used to predict DCI. Sensitivity, specificity, and area under the curve (AUC) were determined, and logistic regression analysis was performed. RESULTS: The Combined Severity Score showed an AUC 0.64 (95%CI 0.56-.71) at days 2-5, with sensitivity 0.53 and specificity 0.74. The Combined Severity Score had an adjusted Odds Ratio of 3.41 (95CI 1.86-6.32) for DCI. MCA-measurements yielded the highest AUC to detect DCI at day 2-5: AUC 0.65 (95%CI 0.58-0.73). Optimal cutoff MFV of 83 cm/s for MCA resulted in sensitivity 0.73 and specificity 0.50 at days 2-5. CONCLUSION: TCD-monitoring of aSAH patients may be a valuable strategy for DCI risk stratification. Lower cutoff values can be used in the early phase after the ictus (day 2-5) than are commonly used now. The Combined Severity Score incorporating all major cerebral arteries may provide a meaningful contribution to interpreting TCD measurements.

The Diagnostic Value of Near-Infrared Spectroscopy to Predict Delayed Cerebral Ischemia and Unfavorable Outcome After Subarachnoid Hemorrhage.

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a noninvasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data are available on NIRS regional cerebral tissue oxygen saturation (rSO2) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO2 values in patients with nontraumatic SAH with the occurrence of DCI and functional outcome at 2 months. In addition, the predictive value of NIRS rSO2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, World Federation of Neurosurgical Societies after REsuscitation). METHODS: In this study, the rSO2 distribution of patients with and without DCI after SAH was compared. The optimal cutoff points to predict DCI and outcome were assessed, and its predictive value was compared with the SAFIRE grade. RESULTS: Of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve of 0.77 (95% confidence interval 0.62-0.92; P = 0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an area under the curve of 0.86 (95% confidence interval 0.74-0.98; P = 0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO2 score is complementary to the SAFIRE grade. CONCLUSIONS: NIRS rSO2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH.

Validation of a cerebral hemodynamic model with personalized calibration in patients with aneurysmal subarachnoid hemorrhage.

This study aims to validate a numerical model developed for assessing personalized circle of Willis (CoW) hemodynamics under pathological conditions. Based on 66 computed tomography angiography images, investigations were obtained from 43 acute aneurysmal subarachnoid hemorrhage (aSAH) patients from a local neurovascular center. The mean flow velocity of each artery in the CoW measured using transcranial Doppler (TCD) and simulated by the numerical model was obtained for comparison. The intraclass correlation coefficient (ICC) over all cerebral arteries for TCD and the numerical model was 0.88 (N = 561; 95% CI 0.84-0.90). In a subgroup of patients who had developed delayed cerebral ischemia (DCI), the ICC had decreased to 0.72 but remained constant with respect to changes in blood pressure, Fisher grade, and location of ruptured aneurysm. Our numerical model showed good agreement with TCD in assessing the flow velocity in the CoW of patients with aSAH. In conclusion, the proposed model can satisfactorily reproduce the cerebral hemodynamics under aSAH conditions by personalizing the numerical model with TCD measurements. Clinical trial registration: [http://www.trialregister.nl/], identifier [NL8114].

The predictive value of the CTA Vasospasm Score on delayed cerebral ischaemia and functional outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Delayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage. METHODS: The CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI-DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut-off scores. Inter-rater reliability was evaluated by Cohen's kappa coefficient. RESULTS: This study included 59 patients. CI-DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI-)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI-DCI 0.89 (95% confidence interval [CI] 0.79-0.99), DCI 0.68 (95% CI 0.50-0.87) and functional outcome 0.74 (95% CI 0.57-0.91). Cohen's kappa between the two raters was moderate to substantial (0.57-0.63). CONCLUSIONS: This study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI-)DCI and unfavorable outcome.

Transcranial Doppler Versus CT-Angiography for Detection of Cerebral Vasospasm in Relation to Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Prospective Single-Center Cohort Study: The Transcranial doppler and CT-angiography for Investigating Cerebral vasospasm in Subarachnoid hemorrhage (TACTICS) study.

Cerebral vasospasm in the first 2 weeks after aneurysmal subarachnoid hemorrhage is recognized as a major predictor of delayed cerebral ischemia. The routine screening for cerebral vasospasm with either transcranial Doppler or CT angiography has been advocated, although its diagnostic value has not yet been determined. Our study investigated the diagnostic accuracy of detecting vasospasm by transcranial Doppler and CT angiography for the prediction of delayed cerebral ischemia and functional outcome. Additionally, agreement between transcranial Doppler and CT angiography was determined. DESIGN: Prospective diagnostic accuracy study. SETTINGS: Neurocritical care unit and neurosurgical ward at a tertiary academic medical center. PATIENTS: Between 2013 and 2016, 59 consenting patients were included. INTERVENTION: Patients undergo both transcranial Doppler and CT angiography for detection of cerebral vasospasm on days 5 and 10 after aneurysmal subarachnoid hemorrhage. Delayed cerebral ischemia was defined as secondary neurologic deterioration, not explained otherwise. Unfavorable outcome was defined modified Rankin Scale > 2 at 6 months. MEASUREMENTS AND MAIN RESULTS: On transcranial Doppler, cerebral vasospasm was observed in 26 patients (45%). On CT angiography, vasospasm was observed in 54 patients (95%). The agreement between transcranial Doppler and CT angiography was 0.47. Delayed cerebral ischemia occurred in 16 patients (27%); unfavorable outcome in 12 patients (20%). Transcranial Doppler predicted delayed cerebral ischemia with a sensitivity of 0.44 (day 5) and 0.50 (day 10), with a specificity of 0.67 (day 5) and 0.57 (day 10). CT angiography predicted delayed cerebral ischemia with a sensitivity of 0.81 (day 5 and 10) and with a specificity of 0.070 (day 5) and 0.00 (day 10). The highest accuracy for predicting unfavorable outcome was on day 5 (0.61 for transcranial Doppler vs 0.27 for CT angiography). CONCLUSION: The diagnostic accuracy of both CT angiography and transcranial Doppler for detection of cerebral vasospasm as well as prediction of delayed cerebral ischemia and functional outcome is limited. The agreement between CT angiography and transcranial Doppler is low.

Quantified tracking and monitoring of diazepam treated socially housed cynomolgus monkeys.

Quantitative assessment of behavioural patterns is frequently used in rodent toxicity studies, however only limited approaches are available for monkeys. Often qualitative behavioural scoring using functional observation batteries (FOBs) is performed, with difficulties like poor reproducibility or lack of sensitivity. In this study, we investigated whether quantitative behavioural monitoring can be applied to group-housed cynomolgus monkeys. Video-tracking EthoVision® XT system and special analysis software were used to evaluate diazepam (i.v. 1mg/kg) related behavioural changes in group-housed animals. Recordings were made predose and at the anticipated time of maximum drug exposure (T(max)). General parameters such as distance travelled and velocity did not reveal the known sedative effects of diazepam. However, inspection of the automatically generated track images indicated that diazepam-treated animals had more a meandering movement pattern suggesting that diazepam induced a loss of balance which was regained by corrective movements. Therefore, parameters revealing specific aspects of the meandering movement pattern such as velocity profiles and turn angles have been analyzed and revealed an increase in the curvature and in the number of directional changes of the movement path.

Treatment of central nervous system tuberculosis infections and neurological complications of tuberculosis treatment.

Tuberculosis (TB) with central nervous system (CNS) manifestation is a form of TB with a high mortality and morbidity. Tuberculous meningitis (TM) is the most common form of CNS-TB. Although diagnosis of CNS-TB can be challenging, early treatment of CNS-TB is related to a better outcome. If CNS-TB is suspected, even though the clinical picture is not specific, it should be immediately treated. For the treatment of CNS-TB, knowledge of the penetration across the blood-brain barrier of the various antituberculosis agents used in TB treatment is important. These will be described here in order to serve as a guide in choosing a treatment for CNS-TB. Corticosteroids have an evidence-based value in the treatment of TM and so are recommended. As for thalidomide use in CNS-TB, sound evidence is still lacking. We will also include a description of the adverse neurotoxic effects of the various other agents including their psychiatric, ototoxic and ophthalmic adverse effects.

Leg kinematics and kinetics in landing from a single-leg hop for distance. A comparison between dominant and non-dominant leg.

BACKGROUND: Anterior cruciate ligament (ACL) deficiency can be a major problem for athletes and subsequent reconstruction of the ACL may be indicated if a conservative regimen has failed. After ACL reconstruction signs of abnormality in the use of the leg remain for a long time. It is expected that the landing after a single-leg hop for distance (horizontal hop) might give insight in the differences in kinematics and kinetics between uninjured legs and ACL-reconstructed legs. Before the ACL-reconstructed leg can be compared with the contralateral leg, knowledge of differences between legs of uninjured subjects is needed. METHODS: Kinematic and kinetic variables of both legs were measured with an optoelectronic system and a force plate and calculated by inverse dynamics. The dominant leg (the leg with biggest horizontal hop distance) and the contralateral leg of nine uninjured subjects were compared. FINDINGS: No significant differences were found in most of the kinematic and kinetic variables between dominant leg and contralateral leg of uninjured subjects. Only hop distance and hip extension angles differed significantly. INTERPRETATION: This study suggests that there are no important differences between dominant leg and contralateral leg in healthy subjects. As a consequence, the uninvolved leg of ACL-reconstructed patients can be used as a reference. The observed variables of this study can be used as a reference of normal values and normal differences between legs in healthy subjects.

Reduced 5-HT1A- and GABAB receptor function in dorsal raphé neurons upon chronic fluoxetine treatment of socially stressed rats.

Autoinhibitory serotonin 1A receptors (5-HT(1A)) in dorsal raphé nucleus (DRN) have been implicated in chronic depression and in actions of selective serotonin reuptake inhibitors (SSRI). Due to experimental limitations, it was never studied at single-cell level whether changes in 5-HT(1A) receptor functionality occur in depression and during SSRI treatment. Here we address this question in a social stress paradigm in rats that mimics anhedonia, a core symptom of depression. We used whole cell patch-clamp recordings of 5-HT- and baclophen-induced G-protein-coupled inwardly rectifying potassium (GIRK) currents as a measure of 5-HT(1A)- and GABA(B) receptor functionality. 5-HT(1A)- and GABA(B) receptor-mediated GIRK-currents were not affected in socially stressed rats, suggesting that there was no abnormal (auto)inhibition in the DRN on social stress. However, chronic fluoxetine treatment of socially stressed rats restored anticipatory behavior and reduced the responsiveness of 5-HT(1A) receptor-mediated GIRK currents. Because GABA(B) receptor-induced GIRK responses were also suppressed, fluoxetine does not appear to desensitize 5-HT(1A) receptors but rather one of the downstream components shared with GABA(B) receptors. This fluoxetine effect on GIRK currents was also present in healthy animals and was independent of the animal's "depressed" state. Thus our data show that symptoms of depression after social stress are not paralleled by changes in 5-HT(1A) receptor signaling in DRN neurons, but SSRI treatment can alleviate these behavioral symptoms while acting strongly on the 5-HT(1A) receptor signaling pathway.

Characteristics of wet work in the cleaning industry.

Wet work is the main cause of occupational contact dermatitis in the cleaning industry. Dermatologists and occupational physicians need to base their primary and secondary prevention for workers in the cleaning industry on the characteristics of wet work exposures. We quantified the burden of wet work in professional office cleaning activities with a continuous standardized observation by trained observers of 41 office cleaners. Duration and frequency of wet work exposure and of different cleaning activities were assessed. Wet work made up 50% of such cleaning work. Within a typical 3-hr shift, a mean frequency of 68 episodes of wet work was observed, which classifies office cleaning as wet work. Skin exposure to irritants was markedly different among cleaners who did the same cleaning activities. Reduction in skin irritation can be achieved by training the workers. Because this group of workers, who have a low level of education, has a high risk of developing irritant hand dermatitis, a special effort on training and instruction should be made. A reduction of exposure can be achieved by: using gloves more often; using gloves for a shorter period of time; using gloves while doing activities that otherwise cause the skin to be in contact with water and cleaning substances and washing hands with water only, reserving soap for when the hands are visibly dirty.

Skin protection in nursing work: promoting the use of gloves and hand alcohol.

Nursing has been identified as a wet-work occupation, with a high prevalence of occupational irritant contact dermatitis. Reduction of exposure to skin irritants contributes to the prevention of occupational skin disease in nurses. The role of the use of soap and water, hand alcohol and gloves in prevention programmes is discussed. 2 additional measures for reducing exposure to skin irritants are postulated: use of hand alcohol instead of soap and water in disinfection procedures when the hands are not visibly dirty; use of gloves in wet activities such as patient washing to prevent the hands from becoming wet and visibly dirty. We investigated the effectiveness of these recommendations in a model. Mean daily wet-work exposure during nursing work was modelled: regular model. We also modelled exposure to skin irritants in combination with the implementation of these recommendations: prevention model. The hands of healthy volunteers were exposed to the regular or the prevention model over 3 weeks for 5 days a week. The change in transepidermal water loss (TEWL) on the back of the hands was measured after 3 weeks of exposure to these wet-work simulations. An increase in TEWL occurred with the regular model, while mean TEWL decreased in the prevention model. Skin irritation from occlusion by gloves appeared to be more pronounced in the regular model compared to the prevention model. The results of this study justify the conclusion that in nursing work, hand alcohol is the preferred disinfectant. Although the prevention model implies increased occlusive exposure, this has no additional irritant effect, probably because of the absence of soap exposure.

Defeat followed by individual housing results in long-term impaired reward- and cognition-related behaviours in rats.

In contrast to the well-documented acute effects on behavioural sensitivity, chronic effects that persist for weeks or even months after the cessation of the stressor received relatively little attention. This study aimed at the long-term effects of a severe stressor, i.e. social defeat followed by individual housing. Defeated and subsequently individually housed animals displayed impaired social memory, decreased social interaction and diminished anticipation for a sucrose solution for up until a period of 3 months after defeat. Remarkably, social housing counteracted the defeat-induced effects. The impaired capability to anticipate for a reward was discussed in relation to anhedonia, an important symptom of human depression. Moreover, the disturbed memory, the chronic nature of the effects, and the therapeutic effects of social housing, suggest that the defeat model may serve as a potential model for human psychopathology.