Nora Sandu

The trigemino-cardiac reflex: An update of the current knowledge

The trigemino-cardiac reflex (TCR) is clinically defined as the sudden onset of parasympathetic activity, sympathetic hypotension, apnea, or gastric hypermotility during central or peripheral stimulation of any of the sensory branches of the trigeminal nerve. Clinically, the TCR has been reported to occur during craniofacial surgery, manipulation of the trigeminal nerve/ganglion and during surgery for lesion in the cerebellopontine angle, cavernous sinus, and the pituitary fossa. Apart from the few clinical reports, the physiologic function of this brainstem reflex has not yet been fully explored. The manifestation of the TCR can vary from bradycardia and hypotension to asystole. From the experimental findings, the TCR represents an expression of a central reflex leading to rapid cerebrovascular vasodilatation generated from excitation of oxygen-sensitive neurons in the rostral ventro-lateral medulla oblongata. By this physiologic response, the systemic and cerebral circulations may be adjusted in a way that augments cerebral perfusion. This review summarizes the current state of knowledge about TCR.

Management of the trigeminocardiac reflex: facts and own experience.

The trigeminocardiac reflex (TCR) is defined as the sudden onset of parasympathetic dysrhythmia, sympathetic hypotension, apnea, or gastric hyper-motility during stimulation of any of the sensory branches of the trigeminal nerve. The proposed mechanism for the development of TCR is--the sensory nerve endings of the trigeminal nerve send neuronal signals via the Gasserian ganglion to the sensory nucleus of the trigeminal nerve, forming the afferent pathway of the reflex arc. It has been demonstrated that the TCR may occur with mechanical stimulation of all the branches of the trigeminal nerve anywhere along its course (central or peripheral). The reaction subsides with cessation of the stimulus. But, some patients may develop severe bradycardia, asystole, and arterial hypotension which require intervention. The risk factors already known to increase the incidence of TCR include: Hypercapnia; hypoxemia; light general anesthesia; age (more pronounced in children); the nature of the provoking stimulus (stimulus strength and duration); and drugs: Potent narcotic agents (sufentanil and alfentanil); beta-blockers; and calcium channel blockers. Because of the lack of full understanding of the TCR physiology, the current treatment options for patients with TCR include: (i) risk factor identification and modification; (ii) prophylactic measures; and (iii) administration of vagolytic agents or sympathomimetics.

A new predisposing factor for trigemino-cardiac reflex during subdural empyema drainage: a case report.

IntroductionThe trigemino-cardiac reflex is defined as the sudden onset of parasympathetic dysrhythmia, sympathetic hypotension, apnea, or gastric hypermotility during stimulation of any of the sensory branches of the trigeminal nerve. Clinically, trigemino-cardiac reflex has been reported to occur during neurosurgical skull-base surgery. Apart from the few clinical reports, the physiological function of this brainstem reflex has not yet been fully explored. Little is known regarding any predisposing factors related to the intraoperative occurrence of this reflex.Case presentationWe report the case of a 70-year-old Caucasian man who demonstrated a clearly expressed form of trigemino-cardiac reflex with severe bradycardia requiring intervention that was recorded during surgical removal of a large subdural empyema.ConclusionTo the best of our knowledge, this is the first report of an intracranial infection leading to perioperative trigemino-cardiac reflex. We therefore add a new predisposing factor for trigemino-cardiac reflex to the existing literature. Possible mechanisms are discussed in the light of the relevant literature.

New Molecular Knowledge Towards the Trigemino-Cardiac Reflex as a Cerebral Oxygen-Conserving Reflex

The trigemino-cardiac reflex (TCR) represents the most powerful of the autonomous reflexes and is a subphenomenon in the group of the so-called “oxygen-conserving reflexes”. Within seconds after the initiation of such a reflex, there is a powerful and differentiated activation of the sympathetic system with subsequent elevation in regional cerebral blood flow (CBF), with no changes in the cerebral metabolic rate of oxygen (CMRO2) or in the cerebral metabolic rate of glucose (CMRglc). Such an increase in regional CBF without a change of CMRO2 or CMRglc provides the brain with oxygen rapidly and efficiently. Features of the reflex have been discovered during skull base surgery, mediating reflex protection projects via currently undefined pathways from the rostral ventrolateral medulla oblongata to the upper brainstem and/or thalamus, which finally engage a small population of neurons in the cortex. This cortical center appears to be dedicated to transduce a neuronal signal reflexively into cerebral vasodilatation and synchronization of electrocortical activity; a fact that seems to be unique among autonomous reflexes. Sympathetic excitation is mediated by cortical-spinal projection to spinal preganglionic sympathetic neurons, whereas bradycardia is mediated via projections to cardiovagal motor medullary neurons. The integrated reflex response serves to redistribute blood from viscera to the brain in response to a challenge to cerebral metabolism, but seems also to initiate a preconditioning mechanism. Previous studies showed a great variability in the human TCR response, in special to external stimuli and individual factors. The TCR gives, therefore, not only new insights into novel therapeutic options for a range of disorders characterized by neuronal death, but also into the cortical and molecular organization of the brain.

The trigemino-cardiac reflex in adults: own experience

The trigemino-cardiac reflex The trigemino-cardiac reflex (TCR) has previously been described in the literature as a reflexive response composed of bradycardia, hypotension and gastric hypermotility seen upon mechanical stimulation anywhere in the distribution of the trigeminal nerve [1–5]. Based on the initial rabbit neurostimulation experiments of Kumada et al. in 1977 [6], TCR was first observed by Schaller et al. in 1999 during neurosurgical operations [5]. By systematic observation, the incidence of the TCR during neurosurgical procedures around the trigeminal nerve was shown to be approximately 10–18%, independently of the surgeon who operated or the approach that was used [3,7–12]. In their key works, Schaller et al. first defined TCR in detail, and their observations are at present generally accepted [3,5,13–15].

Current molecular imaging of spinal tumors in clinical practice.

Energy metabolism measurements in spinal cord tumors, as well as In osseous spinal tumors/metastasis in vivo, are rarely performed only with molecular imaging (MI) by positron emission tomography (PET). This imaging modality developed from a small number of basic clinical science investigations followed by subsequent work that influenced and enhanced the research of others. Apart from precise anatomical localization by coregistration of morphological imaging and quantification, the most intriguing advantage of this imaging is the opportunity to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Most importantly, MI represents one of the key technologies in translational molecular neuroscience research, helping to develop experimental protocols that may later be applied to human patients. PET may help monitor a patient at the vertebral level after surgery and during adjuvant treatment for recurrent or progressive disease. Common clinical indications for MI of primary or secondary CNS spinal tumors are: (i) tumor diagnosis, (ii) identification of the metabolically active tumor compartments (differentiation of viable tumor tissue from necrosis) and (iii) prediction of treatment response by measurement of tumor perfusion or ischemia. While spinal PET has been used under specific circumstances, a question remains as to whether the magnitude of biochemical alterations observed by MI in CNS tumors in general (specifically spinal tumors) can reveal any prognostic value with respect to survival. MI may be able to better identify early disease and to differentiate benign from malignant lesions than more traditional methods. Moreover, an adequate identification of treatment effectiveness may influence patient management. MI probes could be developed to image the function of targets without disturbing them or as treatment to modify the target’s function. MI therefore closes the gap between in vitro and in vivo integrative biology of disease. At the spinal level, MI may help to detect progression or recurrence of metastatic disease after surgical treatment. In cases of nonsurgical treatments such as chemo-, hormone- or radiotherapy, it may better assess biological efficiency than conventional imaging modalities coupled with blood tumor markers. In fact, PET provides a unique possibility to correlate topography and specific metabolic activity, but it requires additional clinical and experimental experience and research to find new indications for primary or secondary spinal tumors.

Cerebral Hemodynamic Changes during the Trigeminocardiac Reflex: Description of a New Animal Model Protocol

The trigeminocardiac reflex (TCR) is a well-known brainstem reflex, first described in skull base and neurosurgery by the senior author in 1999, leading to reflex apnea, bradycardia, and changes of mean arterial pressure. There seem to be differences between peripheral and central stimulation of the TCR, and there is a lack of clear data about the cerebral hemodynamic changes during the TCR. However, the research of this reflex principally focused on clinical cases for peripheral and central stimulation during the last years, and on rabbits for peripheral stimulation several decades ago, so there was a need for an animal model that allows us to use the current state-of-the-art imaging methods. The new animal model protocol as introduced by the authors gives, for the first time, deep insights into the cerebral hemodynamic changes during the TCR and gives substantial evidence whether the TCR represents an oxygen-conserving reflex or not.

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 targets function. This is transfer of gene therapys experimental knowledge into clinical applications. Molecular imaging closes the gap between in vitro to in vivo integrative biology of disease.

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 (χ2: 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.

Trigemino-cardiac reflex during chronic subdural haematoma removal: report of chemical initiation of dural sensitization.

The paper presents a new risk factor for the trigemino-cardiac reflex and goes deep into the reflexs physiology.