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.

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.

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.

Molecular imaging of brain tumors: a bridge between clinical and molecular medicine?

As the research on cellular changes has shed invaluable light on the pathophysiology and biochemistry of brain tumors, clinical and experimental use of molecular imaging methods is expanding and allows quantitative assessment. The term molecular imaging is defined as the in vivo characterization and measurement of biologic processes at the cellular and molecular level. Molecular imaging sets forth to probe the molecular abnormalities that are the basis of disease rather than to visualize the end effects of these molecular alterations and, therefore, provides different additional biochemical or molecular information about primary brain tumors compared to histological methods "classical" neuroradiological diagnostic studies. Common clinical indications for molecular imaging contain primary brain tumor diagnosis and identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), prediction of treatment response by measurement of tumor perfusion, or ischemia. The interesting key question remains not only whether the magnitude of biochemical alterations demonstrated by molecular imaging reveals prognostic value with respect to survival, but also whether it identifies early disease and differentiates benign from malignant lesions. Moreover, an early identification of treatment success or failure by molecular imaging could significantly influence patient management by providing more objective decision criteria for evaluation of specific therapeutic strategies. Specially, as molecular imaging represents a novel technology for visualizing metabolism and signal transduction to gene expression, reporter gene assays are used to trace the location and temporal level of expression of therapeutic and endogenous genes. Molecular imaging probes and drugs are being developed to image the function of targets without disturbing them and in mass amounts to modify the target's function as a drug. Molecular imaging helps to close the gap between in vitro and in vivo integrative biology of disease.

Influence of age on stroke and preconditioning-induced ischemic tolerance in the brain.

Ischemic brain damage occurs through all age subgroups, ranging from the newborn to the elderly, but with predominance in more aged brains either in animals or in humans. The present understanding of the pathophysiological mechanisms of ischemic brain damage suggests that, despite different age and its consecutive changed molecular behavior to ischemic states, there is a common underlying cascade of events. But, there exists an age-dependent influence on stroke of which the few existing experimental data are complex: the immature brain is, in fact, less resistant to hypoxic-ischemic brain damage than its adult counterpart. The intermediate age subgroup is more tolerant to hypoxic-ischemic brain damage than either very young or more mature ages. In addition, the neuroprotective mechanism of ischemic preconditioning is also influenced by this different molecular behavior to cerebral ischemia within the different age subgroups. The authors put these findings from experimental or clinical studies into the context of the current knowledge of ischemic preconditioning of the brain and discuss their relevance for experimental and clinical research. From the present data, it seems that neuroprotection of preconditioned brain in different age subgroup is not the result of any difference in the extent of the underlying cascade of ischemic events but rather the result of different sensitivity to ischemic preconditioning in different age subgroups.