Functional Outcome Changes in Surgery for Pituitary Adenomas After Intraoperative Occurrence of the Trigeminocardiac Reflex: First Description in a Retrospective Observational Study.

Trigeminocardiac reflex (TCR) represents now a nearly ubiquitary phenomenon in skull base surgery. Functional relevance of the intrainterventional TCR occurrence is hitherto only proven for vestibular schwannoma. In a retrospective observational study, 19 out of 338 (8%) enrolled adult patients demonstrated a TCR during transsphenoidal/transcranial surgery for pituitary adenomas. The 2 subgroups (TCR vs non-TCR) had similar patient's characteristics, risk factors, and histology. Preoperatively, there was a similar distribution of normal pituitary function in the TCR and non-TCR subgroups. In this TCR subgroup, there was a significant decrease of that normal pituitary function after operation (37%) compared to the non-TCR group (60%) (P < 0.03). The TCR subgroup therefore demonstrated a 3.15 times (95%CI 1.15-8.68) higher risk for non-normalizing of postoperative pituitary function compared with the non-TCR subgroup (P < 0.03). It is presented, for the first time, an impact of TCR on the functional hormonal outcome after pituitary surgery and strongly underline again the importance of the TCR in clinical daily practice. As a consequence, TCR should be considered as a negative prognostic factor of hormonal normalization after surgery for pituitary adenomas that should be included into routine practice.

Premature craniosynostosis--the role of skull base surgery in its correction. A surgical and radiological experience of 172 operated infants/children.

BACKGROUND: Most craniofacial abnormalities are non-syndromic craniosynostoses due to premature fusion of one or more craniofacial sutures. Functional impairment is caused either by a pathological growth pattern or increased intracranial pressure. The indications for surgery are to increase intracranial volume and to correct aesthetics. PATIENTS AND METHODS: We retrospectively reviewed 172 patients who had been operated on for premature craniosynostosis, including fronto-orbital advancement, from 1992 to 2002. Demographic data, clinical follow-up findings, and regular photo documentation were analyzed. RESULTS: After a mean follow-up of 6 years the overall outcome for those operated on within the first 6 months of life was satisfactory in 97%. The remaining 3% were reoperated at between 4 and 6 years of age. All cephalometric indices normalized postoperatively. Eight patients underwent SPECT studies which showed preoperative perfusion asymmetry corresponding to the fused sutures that were normalized following surgical decompression. No severe perioperative complications were seen. DISCUSSION: Cephalometric parameters represent an excellent method to compare the postoperative outcome. Standard skull base procedures need to be adapted carefully to the individual form of craniosynostosis to avoid an unfavourable result. Single Photon Emissin Computed Tomography (SPECT) studies give evidence that correction of single cranial suture synostosis allows for normalization of cerebral blood flow and should be performed within first 6-8 months of life.

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.

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.

Trigemino-cardiac reflex in humans initiated by peripheral stimulation during neurosurgical skull-base operations. Its first description.

BACKGROUND: The trigemino-cardiac reflex (TCR) is a well-recognised phenomenon (first described in skull base surgery by the authors in 1999) that consists of bradycardia, arterial hypotension, apnoea, and gastric hypermobility. TCR occurs during skull base surgery at or around structures that are innervated by any sensory branch of the trigeminal nerve. Thus far, it has not been shown that peripheral stimulation of a trigeminal nerve can also cause this reflex. METHODS: The TCR was defined as clinical hypotension with a drop in mean arterial blood pressure (MABP) and in heart rate (HR) of more than 20% compared to the baseline level and coinciding with the surgical manipulation at or around any branches of the trigeminal nerve. The anaesthesiological and the operative techniques that were used were standardised. CLINICAL FEATURES: We describe here a 29-year-old woman with an endocrinological and imaging-proved micro-prolactinoma in which a TCR with a decrease in "arterial blood pressure" (130/70 mmHg up to a 100/40 mmHg) and an accompanying decrease of the HR (70 beats/min to 50 beats/min) was seen during preparation of the nasal mucosa for a transsphenoidal approach under general anaesthesia, lasting a few seconds until normalisation. After immediate application of atropine, the surgical procedure and the post-operative course was uneventful. MANAGEMENT: We present the first report of peripheral stimulation of a sensory branch of the trigeminal nerve that leads to a TCR under general anaesthesia according to our strict criteria as defined in 1999. The present finding is therefore a key research development and gives substantial evidence that TCR is coincident enhancement of sympathetic and parasympathetic outflows to the heart, suggesting that genetic differences may affect the susceptibility for TCR.

Difference in functional outcome of ipsilateral tinnitus after intraoperative occurrence of the trigemino-cardiac reflex in surgery for vestibular schwannomas.

OBJECT: Surgical manipulation of the fifth cranial nerve in its intra- or extracranial course may lead to bradycardia or even asystole as well as arterial hypotension, a phenomenon described as the trigemino-cardiac reflex (TCR), first described by the authors previously [11]. The authors report here the impact of this reflex on post-operative ipsilateral tinnitus in patients undergoing vestibular schwannoma surgery. METHODS: Thirty six patients scheduled for vestibular schwannoma surgery were studied retrospectively for parameters influencing the post-operative ipsilateral tinnitus function. According to the occurrence of intra- operative TCR the patients were divided into a TCR-subgroup and a non-TCR subgroup. There was no difference in tumour size between these subgroups. RESULTS: The TCR occurred in 17% of the patients during vestibular schwannoma surgery and influenced the occurrence of post-operative ipsilateral tinnitus: the overall incidence of post-operative ipsilateral tinnitus was 22%. Sixty (60) percent of the patients in the TCR subgroup and 17% of those in the non-TCR subgroup experienced ipsilateral tinnitus postoperatively. There was no correlation between tinnitus and pre- or post-operative hearing function. CONCLUSION: Hypotension after intra-operative TCR is not only a negative prognostic factor for hearing preservation but also for ipsilateral tinnitus in patients undergoing vestibular schwannoma surgery. In combination with worse hearing function after intra-operative TCR, the present finding underlines the importance of the TCR during skull base surgery in relation to improved functional outcome.

[Trigeminocardiac reflex in pituitary surgery. A prospective pilot study]. / Trigeminokardialer Reflex bei Hypophysenoperationen. Eine prospektive Pilotstudie.

BACKGROUND: The trigeminocardiac reflex (TCR) is a relatively recently described brainstem reflex in the fields of neurosurgery which leads to a simultaneous drop in mean arterial pressure (MAP) and heart rate of at least 20% from baseline levels after stimulation of a sensible branch of the trigeminal nerve. PATIENTS AND METHODS: The purpose of this study was to register prospectively for the first time the rate of TCR during trans-sphenoidal surgery and to describe possible predispositional factors. This was examined by determining selected biomarkers thought to correlate with possible intraoperative ischemic events after occurrence of TCR and furthermore with neuroprotective mechanisms ("ischemic tolerance"). RESULTS: Three of the 40 patients included (7.5%) demonstrated intraoperative occurrence of TCR after exposure of the cavernous sinus. One (2.5%) demonstrated a TCR during preparation of the nasal mucosa. Permanent cardiovascular damage or unfavorable postoperative outcome through the appearance of TCR was not found. There was a trend to lower C-reactive protein levels after occurrence of TCR (32 mg/dl vs 14 mg/dl) following normal values before operations in all cases. Considering that no clinical clue of ischemia was detected, this could mean that some neuroprotective cascades are initiated. There was a correlation between tumor necrosis factor A and noradrenalin levels with the size (invasivity) of the pituitary adenoma. The administration of atropine was necessary in only one patient with intraoperative occurrence of TCR. CONCLUSION: On the basis of this study, it cannot be said to what extent neuroprotective mechanisms after TCR are activated, but a trend is still apparent. Considering the adverse effects and the reflex arc, prophylactic or therapeutic treatment with atropine is not justified.

Trigemino-cardiac reflex during transsphenoidal surgery for pituitary adenomas: methodological description of a prospective skull base study protocol.

A systematic clinical neuroscience protocol is described for the use to examine the trigemino-cardiac reflex (TCR) response in humans. Target neurosurgical conditions are operations that require manipulations around the peripheral and central part of the trigeminal nerve and its branches, e.g. the cerebellopontine angle or the sellar region. To assess the hemodynamic and cardiac responses of patients after TCR initiation, anesthetic monitoring has been applied. The TCR is defined as a drop of more than 20% of the heart rate and the mean arterial blood pressure compared with the baseline values before the stimulus and coinciding with the surgical manipulation at or around any branches of the trigeminal nerve. By help of illustrative cases, we present for the first time preliminary results regarding the differentiation of the TCR in a central and a peripheral induction during transsphenoidal surgery of pituitary adenomas. Based on these results, we can conclude that we have developed a battery of preoperative examination procedures based on event-related diagnostics that was useful to differentiate different subgroups of TCR during transsphenoidal surgery. The presented protocol can be performed directly pre-, intra- and postoperatively and applied for assessment of TCR even in patients with known risk factors.