How to apply case reports in clinical practice using surrogate models via example of the trigeminocardiac reflex.

Case reports are an increasing source of evidence in clinical medicine. Until a few years ago, such case reports were emerged into systematic reviews and nowadays they are often fitted to the development of clinical (thinking) models. We describe this modern progress of knowledge creation by the example of the trigeminocardiac reflex that was first described in 1999 by a case series and was developed over the cause-and-effect relationship, triangulation to systematic reviews and finally to thinking models. Therefore, this editorial not only underlines the increasing and outstanding importance of (unique) case reports in current science, but also in current clinical decision-making and therefore also that of specific journals like the Journal of Medical Case Reports.

Molecular imaging of potential bone metastasis from differentiated thyroid cancer: a case report.

INTRODUCTION: Molecular imaging of the spine is a rarely used diagnostic method for which only a few case reports exist in the literature. Here, to the best of our knowledge we present the first case of a combination of molecular imaging by single photon emission computer tomography and positron emission tomography used in post-operative spinal diagnostic assessment. CASE PRESENTATION: We present the case of a 50-year-old Caucasian woman experiencing progressive spinal cord compression caused by a vertebral metastasis of a less well differentiated thyroid cancer. Following tumor resection and vertebral stabilization, total thyroidectomy was performed revealing follicular thyroid carcinoma pT2 pNxM1 (lung, bone). During follow-up our patient underwent five radioiodine therapy procedures (5.3 to 5.7 GBq each) over a two-year period. Post-therapeutic I-131 scans showed decreasing uptake in multiple Pulmonary metastases. However, following an initial decrease, stimulated thyroglobulin remained at pathologically increased levels, indicating further neoplastic activity. F18 Fludeoxyglucose positron emission tomography, which was performed in parallel, showed remaining hypermetabolism in the lungs but no hypermetabolism of the spinal lesions correlating with the stable neurological examinations. While on single photon emission computer tomography images Pulmonary hyperfixation of I-131 disappeared (most likely indicating dedifferentiation), there was persistent spinal hyperfixation at the operated level and even higher fixation at the spinal process of L3. Based on the negative results of the spinal F18 fludeoxyglucose positron emission tomography, a decision was made not to operate again on the spine since our patient was completely asymptomatic and the neurological risk seemed to be too high. During further follow-up our patient remained neurologically stable. CONCLUSIONS: Molecular imaging by F18 fludeoxyglucose positron emission tomography helps to exclude metabolically active spinal metastases and to spare further risky surgery.

Usefulness of case reports to improve medical knowledge regarding trigemino-cardiac reflex in skull base surgery.

We describe the discovery of the trigemino-cardiac reflex by Schaller in 1999 and the continued improvement of the knowledge about the trigemino-cardiac reflex involved in neurosurgery, especially in skull base surgery, during the past several years. The achieved medical progress could be gained only by the practical experience described by different case reports and later case series that have been published in several principal scientific journals. Additionally, we explain the scientific as well as clinical importance of the communication of the case reports on TCR. Special reference has been given to the validity of the case reports for new phenomena in clinical medicine.

Trigeminocardiac reflex, bilateral sagittal split ramus osteotomy, Gow-Gates block: a randomized controlled clinical trial.

PURPOSE: The behavior of trigeminocardiac reflex (TCR) during maxillofacial surgeries has not yet been sufficiently studied and knowledge of its behavior is limited to some case reports. The present study aimed to assess the occurrence of TCR in bilateral sagittal split ramus osteotomy and to determine the possible effect of Gow-Gates block on its incidence. MATERIALS AND METHODS: Twenty candidates for bilateral sagittal split ramus osteotomy (included were American Society of Anesthesiologists I Class III patients with a prognathism of 3 to 5 mm) were given routine general anesthesia after at least 12 hours of fasting. All patients received Gow-Gates mandibular nerve block on 1 random side (case ramus; the other side was used as the control) after induction of general anesthesia before surgery. Pulse rate was recorded at baseline, soft tissue cutting, bone cutting, sagittal splitting, setback manipulation, and recovery. Mean pulse rate values were compared statistically using t test for the 2 sides in patients. RESULTS: No statistically significant differences were found between the blocked and control sides except during ramus sagittal splitting and setback manipulation (P < .0001), when a significantly decreased pulse rate was recorded for the control ramus compared with the blocked ramus. CONCLUSIONS: The present study provides further evidence for the complex neurophysiologic mechanism and probable prevention of peripheral TCR. The results of the present study should be further validated through future studies but already provide strong evidence that peripheral and central TCR may act differently based on slightly different pathways.

Trigemino-cardiac reflex and antecedent transient ischemic attacks.

OBJECTIVES: The trigemino-cardiac reflex (TCR) is a brainstem reflex that has gained enormous interest in recent years and was initially described by Schaller and coworkers as a centrally inducible reflex during skull-base surgery. In the meantime, parts of its functional consequences have been described. Here, we present a study that gives special reference to preventive factors of the TCR and investigates the hypothesis linking preceding transient ischemic attacks (TIAs) to the occurrence of TCR. METHODS: We retrospectively reviewed 338 consecutive patients with the histological diagnosis of a pituitary adenoma, who were operated on from 2000 to 2006 in the Neurosurgery department of the University of Gottingen in Germany. Depending on the occurrence of intraoperative TCR, patients were divided into TCR and non-TCR groups. In 19 of these patients (6%), we found the intraoperative occurrence of the TCR. The patient characteristics between the two subgroups were comparable. RESULTS: There was a statistically significant difference between the subgroups of precedent TIA (TCR: 11% vs non-TCR: 4%) versus nonprecedent TIA (TCR: 89% vs non-TCR: 96%) regarding the intraoperative occurrence of the TCR (chi(2): p < 0.01). CONCLUSION: A precedent TIA less than 6 weeks before operation represents a significant risk factor for subsequent intraoperative occurrence of the TCR. Our data may indicate, for the first time, the existence of an oxygen-conserving reflex not only in animals but also in humans. Its neuroprotective effect in the context of the TCR is discussed.

Molecular imaging of brain tumors personal experience and review of the literature.

Non-invasive energy metabolism measurements in brain tumors in vivo are now performed widely as molecular imaging by positron emission tomography. This capability has developed from a large number of basic and clinical science investigations that have cross fertilized one another. Apart from precise anatomical localization and quantification, the most intriguing advantage of such imaging is the opportunity to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Most importantly, molecular imaging represents a key-technology in translational research, helping to develop experimental protocols that may later be applied to human patients. Common clinical indications for molecular imaging of primary brain tumors therefore contain (i) primary brain tumor diagnosis, (ii) identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), and (iii) prediction of treatment response by measurement of tumor perfusion, or ischemia. The key-question remains whether the magnitude of biochemical alterations demonstrated by molecular imaging reveals prognostic value with respect to survival. Molecular imaging may identify early disease and differentiate benign from malignant lesions. Moreover, an early identification of treatment effectiveness could influence patient management by providing objective criteria for evaluation of therapeutic strategies for primary brain tumors. Specially, its novel potential to visualize metabolism and signal transduction to gene expression is used in reporter gene assays to trace the location and temporal level of expression of therapeutic and endogenous genes. The authors present here illustrative data of PET imaging: the thymidine kinase gene expression in experimentally transplanted F98 gliomas in cat brain indicates, that [(18)F]FHBG visualizes cells expressing TK-GFP gene in transduced gliomas as well as quantities and localizes transduced HSV-1-TK expression if the blood brain barrier is disrupted. The higher uptake of [(18)F]FLT in the wild-type compared to the transduced type may demonstrate the different doubling time of both tumor tissues suggesting different cytosolic thymidine kinase activity. Molecular imaging probes are developed to image the function of targets without disturbing them or as drug in oder to modify the target's function. This is transfer of gene therapy's experimental knowledge into clinical applications. Molecular imaging closes the gap between in vitro to in vivo integrative biology of disease.

Strategies for molecular imaging dementia and neurodegenerative diseases.

Dementia represents a heterogeneous term that has evolved to describe the behavioral syndromes associated with a variety of clinical and neuropathological changes during continuing degenerative disease of the brain. As such, there lacks a clear consensus regarding the neuropsychological and other constituent characteristics associated with various cerebrovascular changes in this disease process. But increasing this knowledge has given more insights into memory deterioration in patients suffering from Alzheimer's disease and other subtypes of dementia. The author reviews current knowledge of the physiological coupling between cerebral blood flow and metabolism in the light of state-of-the-art-imaging methods and its changes in dementia with special reference to Alzheimer's disease. Different imaging techniques are discussed with respect to their visualizing effect of biochemical, cellular, and/or structural changes in dementia. The pathophysiology of dementia in advanced age is becoming increasingly understood by revealing the underlying basis of neuropsychological changes with current imaging techniques, genetic and pathological features, which suggests that alterations of (neuro) vascular regulatory mechanisms may lead to brain dysfunction and disease. The current view is that cerebrovascular deregulation is seen as a contributor to cerebrovascular pathologies, such as stroke, but also to neurodegenerative conditions, such as Alzheimer's disease. The better understanding of these (patho) physiological mechanisms may open an approach to new interventional strategies in dementia to enhance neurovascular repair and to protect neurovascular coupling.

Pathophysiological changes of the gastrointestinal tract in ischemic stroke.

OBJECTIVE: Dysphagia is common after stroke and represents a marker of poor prognosis. After ischemic stroke, dysphagia represents only one part of the clinical spectrum of changes in the gastrointestinal (GI) tract and includes GI hemorrhage, delayed GI emptying, and colorectal dysfunction. State-of-the-art imaging techniques have started to revolutionize to study the cortical and brainstem control of these GI symptoms. It has become increasingly obvious that GI alterations after stroke are complex and its recovery following stroke is even more so. METHODS: In this review, an electronic database research was performed in MEDLINE, EMBASE, and the COCHRANE database using the terms stroke, dysphagia, GI motility, or cortical reorganization; an extensive manual searching was additionally conducted. RESULTS: Cerebral ischemia may lead to an interruption of the axis between central nervous system and GI system. This altered interrelation between the central nervous system and the GI system may cause, among other things, mainly dysphagia, GI dysmotility, and GI hemorrhage. The consecutive clinical symptoms can often be directly attributed to specific cerebral ischemic lesions involving the brain stem as well as certain cortical and subcortical structures. However, in some cases the pathophysiological mechanisms leading to GI symptoms are incompletely understood. Recent improvement of imaging techniques, especially in functional imaging, has lead to new insights of the central control of the GI tract, suggesting that its cortical and medullar organization is multifocal, and bilateral with handness-independent hemispheric dominance. CONCLUSIONS: Following stroke, patients may have swallowing impairment and other changes of the GI tract that could affect nutritional and hydration status and that lead to aspiration pneumonia. Impaired nutritional status is associated with reduced functional improvement, increased complication rates, and prolonged hospital stays.

Neuroprotection in primary brain tumors: sense or nonsense?

Primary brain tumors are generally difficult to treat because of the unique location of the lesions. In addition, normal brain structures are often destroyed by the growing neoplasm. Even with effective therapy to surgically resect and destroy the neoplastic tissues, the brain is sometimes still injured, which can leave the patient in a debilitated state. The hemodynamic and metabolic state of such peritumoral brain tissue is not yet well understood, and there are only a small number of experimental hypotheses of its reaction and changes to the growing primary brain tumor. In addition, primary brain tumors may be influenced by certain anticancer drugs, which cause oxidative stress and consecutive cell death, or by gamma-irradiation. Currently, no established diagnostic methods exist to demonstrate and/or quantify the metabolic condition of the peritumoral tissue. The therapeutic strategy for possible pharmacological neuroprotection should, in the future, still be related to metabolic parameters, as well as in the peritumor tissue to treat primary brain tumors without risk to sensitive normal tissue. To achieve this aim, there has been particular emphasis on the biological behavior of primary brain tumors and peritumor tissue, as well as the potential correlation among them. Thus, priority should be given to identifying more target antigens in primary brain tumors and defining those cells present in the brain parenchyma that are essential to maintain a neuroprotective effect. However, at this time, the postinjury enhancement of neurogenesis appears to offer the best hope for long-lasting functional recovery following surgery of primary brain tumors.

Piezoelectric bone surgery: a revolutionary technique for minimally invasive surgery in cranial base and spinal surgery? Technical note.

OBJECTIVE: Piezoelectric surgery represents an innovative, ultrasonic surgery technique for performing a safe and effective osteotomy or osteoplasty that contrasts with the traditional hard and soft tissue management methods with rotating instruments. METHODS: Because of its physical and mechanical properties, the definitive clinical advantage of piezoelectric bone surgery with regard to precision cutting lies in the sparing of vital neurovascular bundles or general soft tissue and better visualization of the surgical field, thus suggesting its great safety. Piezoelectric bone surgery has been previously described only in oral and maxillofacial operative procedures in adults. RESULTS: Five children between the age of 6 and 84 months were operated on for craniosynostosis, tethered cord, and an extraconal intraorbital tumor. The usefulness of piezoelectric bone surgery during neurosurgical procedures is presented for these cases. This technique is especially recommended when there are anatomic difficulties because of poor intraoperative visibility or the presence of delicate anatomic structures. CONCLUSION: The present preliminary report (comprising illustrative case reports) demonstrates and introduces for the first time the utility of piezoelectric bone surgery in cranial base and spinal surgery in children. Until now, there has been no documented neurosurgical experience of this technique even in adults.