Johann Fontana

Vagal stimulation in brain dead donor rats decreases chronic allograft nephropathy in recipients

BACKGROUND Although it has been shown that a vagus nerve stimulation of brain dead (BD) donors leads to an improvement of renal function in recipients in an acute allograft rejection model, its influence on chronic allograft nephropathy is still unknown. In the present study, we assessed the influence of donor vagus nerve stimulation on survival, renal function and histology in a chronic allograft model. METHODS Brain death was induced in Fisher rats, and electro-stimulation of the vagus nerve was applied in one group (BD + vagus) during the whole course of BD (6 h). Unstimulated BD Fisher donor rats served as controls. Allogeneic Lewis rats were used as recipients and no immunosuppressive medication was administered. Blood and urine samples were collected every second week. Banff classification was assessed from harvested allografts. RESULTS Vagal stimulation of BD donors resulted in an improved survival of recipients. Long-term renal function was significantly better in these recipients as reflected by improved creatinine clearance. Banff classification revealed significantly reduced vasculopathy and less tubulopathy in the BD + vagus group. CONCLUSIONS In conclusion, our data demonstrate a long-lasting beneficial effect of vagus nerve stimulation in BD donors on the renal transplantation outcome. Hence, activation of the cholinergic anti-inflammatory pathway in BD donors may represent a novel therapeutic modality to reduce chronic allograft nephropathy without any side effects for the recipient.

Surgical Management of Basilar Artery Laceration Caused by Transorbital Penetrating Injury: Case Report

Transorbital penetrating injuries are rare and present with a heterogeneity of intracranial injury patterns that require individualized therapeutic procedures. In this report, we describe the case of a distal basilar artery laceration in a 16-month-old boy caused by accidental transorbital penetration with a pencil. Surgical removal of the pencil was performed, but hemostasis could only be achieved by clipping the impaired vessel. Adequate diagnostics and an individualized surgical strategy are necessary to deal with these life-threatening injuries.

Impairment of Dynamic Pressure Autoregulation Precedes Clinical Deterioration after Aneurysmal Subarachnoid Hemorrhage

This study was designed to evaluate the potential of the dynamic autoregulation index (ARI) to serve as an early warning system for an imminent clinical deterioration after subarachnoid hemorrhage (SAH).

N-Octanoyl Dopamine Treatment of Endothelial Cells Induces the Unfolded Protein Response and Results in Hypometabolism and Tolerance to Hypothermia

Aim N-acyl dopamines (NADD) are gaining attention in the field of inflammatory and neurological disorders. Due to their hydrophobicity, NADD may have access to the endoplasmic reticulum (ER). We therefore investigated if NADD induce the unfolded protein response (UPR) and if this in turn influences cell behaviour. Methods Genome wide gene expression profiling, confirmatory qPCR and reporter assays were employed on human umbilical vein endothelial cells (HUVEC) to validate induction of UPR target genes and UPR sensor activation by N-octanoyl dopamine (NOD). Intracellular ATP, apoptosis and induction of thermotolerance were used as functional parameters to assess adaptation of HUVEC. Results NOD, but not dopamine dose dependently induces the UPR. This was also found for other synthetic NADD. Induction of the UPR was dependent on the redox activity of NADD and was not caused by selective activation of a particular UPR sensor. UPR induction did not result in cell apoptosis, yet NOD strongly impaired cell proliferation by attenuation of cells in the S-G2/M phase. Long-term treatment of HUVEC with low NOD concentration showed decreased intracellular ATP concentration paralleled with activation of AMPK. These cells were significantly more resistant to cold inflicted injury. Conclusions We provide for the first time evidence that NADD induce the UPR in vitro. It remains to be assessed if UPR induction is causally associated with hypometabolism and thermotolerance. Further pharmacokinetic studies are warranted to address if the NADD concentrations used in vitro can be obtained in vivo and if this in turn shows therapeutic efficacy.

Occurrence of discal and non-discal changes after sequestrectomy alone versus sequestrectomy and implantation of an anulus closure device

Sequestrectomy alone represents a procedure for the treatment of lumbar disc herniation. For selected cases, an anulus closure device (ACD) can be implanted which may result in lower reoperation rates. However, comparative magnetic resonance imaging (MRI) changes and their clinical relevance of both procedures are unclear and have not been reported so far. Clinical and MRI data of patients after limited discectomy with ACD implantation (group ACD; N=45) and patients after sequestrectomy alone (group S; N=40) with primary lumbar disc herniation were compared retrospectively. Pain intensity on the visual analogue pain scale (VAS), oswestry disability index (ODI) or the patient satisfaction index (PSI) were collected. Disc signal intensity, Modic type changes, endplate reactions, anular tears and reherniations were investigated using MRI before and <18months postoperative. Morphologic changes were correlated with clinical outcome. There was no difference in VAS back, VAS leg or ODI/PSI after the operation although group S showed significantly more reherniations in MRI. The overall rate of repeated surgery at the same level was similar with a trend in favour of the ACD group (P=0.729). Significantly more patients of the ACD group experienced endplate erosions after surgery (P<0.001). Both groups experienced progression of disc signal intensity, Modic type changes, and anular tears with most MRI signs being without clinical relevance. ACD implantation is associated with a significantly lower reherniation rate in MRI but showed a significantly higher rate of endplate erosions. The structural changes do not appear to be clinically relevant.

The spontaneous arterial blood pressure rise after aneurysmal subarachnoid hemorrhage - a biphasic phenomenon.

OBJECTIVES A spontaneous blood pressure (BP) rise is frequently observed after aneurysmal subarachnoid hemorrhage (aSAH). The current study was designed to characterize the time course of this BP rise and its relation to clinical and radiological parameters. METHODS The diastolic (DBP), mean (MAP), and systolic (SBP) BP values were determined in 61 aSAH patients from day 0 to 9. The patients initial status was evaluated by the world federation of neurological surgeons scale and the Hijdra scale. The clinical outcome was quantified by the modified Rankin Scale, the Glasgow Outcome Scale Extended, and the National Institute of Health Stroke Scale. The degree of proximal and global vasospasm was calculated by comparison of the baseline angiography on day 0 and the control angiography on day 8. Furthermore, the influence of propofol and norepinephrine application was analyzed. RESULTS DBP, MAP, and SBP demonstrated an early rise in all patients from day 2 till 5 (p<0.001) and remained hypertensive until day 9. No significant correlation could be detected between this early BP rise and most clinical and radiological variables. From day 8 onwards, a divergence of the SBP courses was detected between patients with severe vs. non-severe global vasospasm. There was a secondary, norepinephrine independent SBP rise in patients with severe global vasospasm that significantly correlated with the initial Hijdra-scale and an unfavorable clinical outcome. CONCLUSIONS The results demonstrate a biphasic BP course with a uniform early BP rise in all patients and an additional delayed SBP rise in patients with severe global vasospasm.

The Preinterventional Psychiatric History as a Major Predictor for a Reduced Quality of Life After Treatment of Unruptured Intracranial Aneurysms

BACKGROUND A significantly increased rate of positive preinterventional psychiatric histories in the unruptured aneurysm collective was demonstrated previously. The current study was designed to analyze the influence of the preinterventional psychiatric status on the outcome after treatment of unruptured intracranial aneurysms. METHODS Patients treated due to meningioma World Health Organization °I and unruptured intracranial aneurysms in 2 German neurosurgical centers between 2007 and 2013 were screened for exclusion criteria including malignant/chronic diseases, recurrence of the tumor/aneurysm, and neurologic deficits among others. The preinterventional psychiatric histories and the rates of postinterventional headaches, sleeping disorders, symptoms of chronic fatigue syndrome, and quality of life (QOL) were determined by questionnaires that were mailed to the patients in a printed version. RESULTS A total of 58 M patients and 45 iA patients who met the inclusion criteria returned the questionnaires; 10 M (17.2%) and 17 iA patients (37.8%) had a positive psychiatric history. The overall Incidental aneurysm collective demonstrated significantly lower overall QOL scores (P = 0.003) and significant greater rates of chronic fatigue syndrome (P = 0.009) compared with the M collective. After we excluded all patients with positive pre-interventional psychiatric histories, those differences were no longer reproducible. Subjectively, the patients did not realize any significant changes in their QOL after successful aneurysm treatment. CONCLUSIONS The results of the current study demonstrate the importance of taking the preinterventional psychiatric history into considerations when evaluating the outcome after unruptured aneurysm treatment. The unfavorable outcome of the aneurysm group seems to be caused by factors that are not related the aneurysm diagnosis or treatment itself.

Smart Trepanation System: Preclinical Analysis of Safety, Efficiency, and User Satisfaction

BACKGROUND/OBJECTIVE To reduce the risk of dural tears during craniotomies and the associated complications, we developed the Smart Trepanation System (STS) that provides an image- and sensor-based automatic control of the cutting depth of a manually guided soft tissue preserving saw. This article presents the results of an initial user-centered evaluation. METHODS Interactive usability tests with six neurosurgeons were conducted. Resection time and accuracy were recorded in a standardized laboratory setting and compared with a standard craniotome. User satisfaction and subjective workload were assessed using the National Aeronautics and Space Administration Task Load Index scale and a questionnaire regarding intuitiveness, fault tolerance, learnability, and user satisfaction. RESULTS The mean resection time after getting used to the STS was 36.4 ± 9.2 second longer than with the conventional craniotome. All task load indexes except for the temporal demand were rated higher when using the STS, but all were rated smaller than 3 and thus classified as only a small extra task load. The questionnaire showed that the system is not only feasible but also accepted by surgeons and that the user interaction seems to be designed as intuitive, fault tolerant, and easy to learn. CONCLUSION Although the conventional craniotome seems to perform a trepanation faster and with less workload, the advantage of performing a dura-preserving trepanation with significantly smaller cutting gaps outweighs those disadvantages. For validation of those promising in vitro results, further studies have to be conducted in a fresh human cadaver model or in a clinical setting.

The neglected need for psychological intervention in patients suffering from incidentally discovered intracranial aneurysms.

OBJECTIVES Previous studies demonstrated a conspicuously elevated rate of psychiatric disorders in patients with incidental intracranial aneurysms. This study was designed to analyze the impact of this observation on the post-interventional rates of PTSD, depressions and anxiety disorders in this collective. METHODS Physically unaffected iA patients with an unremarkable medical history were included in this two center study. Pre-interventional psychiatric histories, rates of post-interventional depressions, subjective trauma, PTSD, and pre-interventional fears were determined by questionnaires (Beck Depression Inventory (BDI), Impact of Event Scale (IES), civilian Post-traumatic-Stress-Disorder (PTSD) Check List (PCL-C)). Benign meningioma (M) patients served as controls. RESULTS 58 M and 45 iA patients were enrolled. Significantly higher rates of PTSD, elevated trauma scores, and moderate/severe depressions (PTSD: p=0.0017; IES: p=0.0038; BDI: p=0.0301) were demonstrated in the iA collective. After excluding patients with a positive pre-interventional psychiatric history those differences were not reproducible. 70% of the iA patients reported an improvement of their unspecific pre-interventional symptoms, while 30% would have rated a psychological consultation as helpful. CONCLUSION The data identifies the early psychological consultation as a relevant and by affected patients accepted treatment modification when trying to improve the outcome after treatment of incidental aneurysms.

The pre-interventional psychiatric history - an underestimated confounder in benign intracranial lesions studies.

OBJECTIVES The current study was designed to analyze the influence of a positive pre-interventional psychiatric history on the quality of life (QOL) after successful treatment of benign intracranial extra-cerebral lesions. METHODS Patients treated due to meningioma WHO I or unruptured intracranial aneurysms in two German neurosurgical centers between 2007 and 2013 were screened for exclusion criteria including malignant/chronic diseases, recurrence of the tumor/aneurysm and neurological deficits among others. 131 patients who met the criteria of an objectively unaffected health status were included. The pre-interventional psychiatric histories and the rates of post-interventional headaches, sleeping disorders, symptoms of chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD) and QOL were determined by questionnaires which were mailed to the patients. RESULTS 103 patients returned the questionnaires. Despite the objectively unaffected health status, the patients with a positive pre-interventional psychiatric history demonstrated a post-interventionally significantly lower QOL (p=0.002), a significantly higher Pittsburgh Sleep Quality Index sum score (p=0.009), as well as significantly higher rates of symptoms of a chronic fatigue syndrome (p=0.003) and PTSD (p=0.024), compared to the patient collective with a negative pre-interventional psychiatric status. CONCLUSION The results of the current study demonstrate the importance of taking the pre-interventional psychiatric history as a significant and independent confounder into consideration when evaluating the outcome after treatment of benign intracranial extra-cerebral lesions. A pre-interventional psychiatric screening and an early psychological intervention might help to improve the overall outcome after successful treatment of such lesions.