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Ischemic stroke is the leading cause of morbidity and mortality with a significant health burden worldwide and few treatment options. Among the short- and long-term effects of ischemic stroke is the cardiovascular sympathetic autonomic dysfunction, presented in part as the by-product of the ischemic damage to the noradrenergic centers of the brain. Unlike high levels in the plasma, the brain may face suboptimal levels of norepinephrine (NE), with adverse effects on the clinical and functional outcomes of ischemic stroke. The intravenous administration of NE and other sympathomimetic agents, in an attempt to increase cerebral perfusion pressure, often aggravates the ischemia-induced rise in blood pressure (BP) with life-threatening consequences for stroke patients, the majority of whom present with hypertension at the time of admission. Unlike the systemic administration, the central administration of NE reduces BP while exerting anti-inflammatory and neuroprotective effects. These characteristics of centrally administered NE, combined with the short latency of response, make it an ideal candidate for use in the acute phase of stroke, followed by the use of centrally acting noradrenergic agonists, such as NE reuptake inhibitors and B2-adrenergic receptor agonists for stroke rehabilitation. In addition, a number of nonpharmacological strategies, such as transcutaneous vagus nerve stimulation (tVNS) and trigeminal nerve stimulation (TNS), have the potential to enhance the central noradrenergic functional activities and improve stroke clinical outcomes. Many factors could influence the efficacy of the noradrenergic treatment in stroke patients. These factors include the type of the noradrenergic agent; the dose, frequency, and duration of administration; the timing of administration in relation to the acute event; and the site and characteristics of the ischemic lesions. Having this knowledge, combined with the better understanding of the regulation of noradrenergic receptors in different parts of the brain, would pave the path for the successful use of the centrally acting noradrenergic agents in the management of ischemic stroke. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to assess external and internal selenium exposure and potential biological effects in employees working in a selenium-processing plant. Methods: Twenty male employees of a selenium-processing plant (exposed) and 20 age-matched male individuals without occupational selenium exposure (controls) participated in the study. Exposure to selenium at the workplace was determined by personal air sampling. Internal exposure was assessed by measuring total selenium concentration in plasma after a workshift and after holidays as well as by measuring the selenium concentration in urine before and after shift and after holidays. The activity of glutathione peroxidase (GPx) in blood and the prothrombin time were determined as biological effect parameters. Results: The exposure to selenium in the workplace air ranged from 8 to 950 µg/m and exceeded in a large part current occupational exposure limits. The selenium levels in plasma samples of the exposed ranged from 49 to 182 µg/L during exposure and were significantly higher than the plasma levels observed after holidays as well as in the control group. The selenium concentration in pre- and post-shift urine samples did not differ significantly, and the average urinary selenium levels of the employees (18-1,104 µg/g creatinine) were significantly higher than those measured after holidays or determined in controls. Both the concentration of selenium in plasma and in urine did not correlate with the current external exposure of the employees at the workplace. However, we found a strong and significant association between the two biomonitoring parameters. In spite of the considerable high external exposure to elemental selenium, we did not find any effect on the GPx activity in blood as well as on the prothrombin time. Conclusions: Both the selenium levels in plasma and urine may be used as biological monitoring parameters for the assessment of chronic occupational exposure to selenium. Nevertheless, the toxicokinetics of the urinary excretion of selenium remain still unclear and require further investigations. Moreover, our findings emphasise the necessity of a re-evaluation of occupational exposure limits for elemental selenium and inorganic selenium compounds. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 transsphenoidal surgery and to describe possible pre-dispositional 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 afterTCR 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. [ABSTRACT FROM AUTHOR]

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 previonsly [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 occured 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 expierenced 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. [ABSTRACT FROM AUTHOR]

Fractures of the anterior skull base, because of the region’s anatomical relationships, are readily complicated by neurological damage to the brain or cranial nerves. This review highlights the use of a subcranial approach in the operative treatment of injuries of the anterior skull base and compares it to the more traditional neurosurgical transcranial approach. The extended anterior subcranial approach takes advantage of the specific features of injuries in this region and allows direct access to the central anterior cranial base in order to repair fractures, close CSF fistulae and relieve of optic nerve compression. It avoids extensive frontal lobe manipulation. The success of the approach in achieving the aims of surgery with low morbidity is reviewed. [ABSTRACT FROM AUTHOR]

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The trigemino-cardiac reflex (TCR) 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. 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. This afferent pathway continues along the short internuncial nerve fibers in the reticular formatio to connect with the efferent pathway in the motor nucleus of the vagus nerve. Clinically, the trigeminocardiac reflex has been reported to occur during craniofacial surgery, balloon-compression rhizolysis of the trigeminal ganglion, and tumor resection in the cerebellopontine angle.Apart from the few clinical reports, the physiological function of this brainstemreflex has not yet been fully explored. From experimental findings, it may be suggested that the trigemino-cardiac reflex represents an expression of a central neurogenic reflex leading to rapid cerebrovascular vasodilatation generated from excitation of oxygensensitive neurons in the rostral ventrolateral medulla oblongata. By this physiological response, the adjustments of the systemic and cerebral circulations are initiated to divert blood to the brain or to increase blood flow within it.As it is generally accepted that the diving reflex and ischemic tolerance appear to involve at least partially similar physiological mechanisms, the existence of such endogenous neuroprotective strategies may extend the actually known clinical appearance of the TCR and include the prevention of other potentially brain injury states as well. This may be in line with the suggestion that the TCR is a physiological, but not a pathophysiological entity. [ABSTRACT FROM AUTHOR]

Segmental instability represents one of several different factors that may cause or contribute to the failed back surgery syndrome after lumbar microdiscectomy. As segmental lumbar instability poses diagnostic problems by lack of clear radiological and clinical criteria, only little is known about the occurrence of this phenomenon following primary microdiscectomy. Retrospectively, the records of 2,353 patients were reviewed according to postoperative symptomatic segmental single-level instability after lumbar microdiscectomy between 1989 and 1997. Progressive neurological deficits increased (mean of 24 months; SD: 12, range 1–70) after the initial surgical procedure in 12 patients. The mean age of the four men and eight women was 43 years (SD: 6, range 40–77). The main symptoms and signs of secondary neurological deterioration were radicular pain in 9 of 12 patients, increased motor weakness in 6 of 12 patients and sensory deficits in 4 of 12 patients. All 12 symptomatic patients had radiological evidence of segmental changes correlating with the clinical symptoms and signs. All but one patient showed a decrease in the disc height greater than 30% at the time of posterior spondylodesis compared with the preoperative images before lumbar microdiscectomy. All patients underwent secondary laminectomy and posterior lumbar sponylodesis. Postoperatively, pain improved in 8 of 9 patients, motor weakness in 3 of 6 patients, and sensory deficits in 2 of 4 patients. During the follow-up period of 72±7 months, one patient required a third operation to alleviate spinal stenosis at the upper end of the laminectomy. Patients with secondary segmental instability following microdiscectomy were mainly in their 40s. Postoperative narrowing of the intervertebral space following lumbar microdiscectomy is correlated to the degree of intervertebral disc resection. It can therefore be concluded that (1) patients in their 40s are prone to postoperative narrowing of the intervertebral disc space and hence subsequent intervertebral instability and (2) that a small extent of intervertebral disc resection and preservation of the “segmental frame” may be beneficial in those patients. The present study demonstrated for the first time that the degree of extensive operative techniques in microdiscectomy increased the risk of subsequent segmental instability. In addition, narrowing of the intervertebral space of more than 30% represents a clear radiological sign of segmental instability. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1–2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed. [ABSTRACT FROM AUTHOR]

Summary¶Objective. The purpose of the study was to measure the effects of increased inspired oxygen on patients suffering severe head injury and consequent influences on the correlations between CPP and brain tissue oxygen (PtiO2) and the effects on brain microdialysate glucose and lactate. Methods. In a prospective, observational study 20 patients suffering severe head injury (GCS≤8) were studied between January 2000 and December 2001. Each patient received an intraparenchymal ICP device and an oxygen sensor and, in 17 patients brain microdialysis was performed at the cortical-subcortical junction. A 6 h 100% oxygen challenge (FIO2 1.0) (Period A) was performed as early as possible in the first 24 hours after injury and compared with a similar 6 hour period following the challenge (Period B). Statistics were performed using the linear correlation analysis, one sample t-test, as well as the Lorentzian peak correlation analysis. Results. FIO2 was positively correlated with PtiO2 (p<0.0001) over the whole study period. PtiO2 was significantly higher (p<0.001) during Period A compared to Period B. CPP was positively correlated with PtiO2 (p<0.001) during the whole study. PtiO2 peaked at a CPP value of 78 mmHg performing a Lorentzian peak correlation analysis of all patients over the whole study. During Period A the brain microdialysate lactate was significantly lower (p=0.015) compared with Period B. However the brain microdialysate glucose remained unchanged. Conclusion. PtiO2 is significantly positively correlated with FIO2, meaning that PtiO2 can be improved by the simple manipulation of increasing FIO2 and ABGAO2. PtiO2 is positively correlated with CPP, peaking at a CPP value of 78 mmHg. Brain microdialysate lactate can be lowered by increasing PtiO2 values, as observed during the oxygen challenge, whereas microdialysate glucose is unchanged during this procedure. Extension of the oxygen challenge time and measurement of the intermediate energy metabolite pyruvate may clarify the metabolic effects of the intervention. Prospective comparative studies, including analysis of outcome on a larger multicenter basis, are necessary to assess the long term clinical benefits of this procedure. [ABSTRACT FROM AUTHOR]

Neurons can be preconditioned by various procedures to resist ischemic events. The preconditioning mechanism induced is characterized by a brief episode of ischemia that renders the brain more resistant against subsequent longer ischemic events. This ischemic tolerance has been shown in numerous experimental models of cerebral ischemia. The basic molecular mechanisms of ischemic tolerance are largely unknown. During the induction phase N-methyl-O-aspartate and adenosine receptors and, possibly, oxygen free radicals and conservation of energy metabolism are required. Protein kinases, transcription factors, and immediate early genes appear to transduce the signal into a tolerant response. Although the mechanism of ischemic tolerance remains uncertain, its discovery provides the focus for further understanding of the mechanism of endogenous neuroprotection and the potential of novel therapeutic strategies for neuroprotection. Such neuroprotective strategies may extend beyond ischemic tolerance to include other brain injury states as well. [ABSTRACT FROM AUTHOR]

Objective. Meningiomas represent the second most common type of neoplasm of the cerebellopontine angle (cpa). Their relationship to critical neural or vascular structures of the cpa is variable and they present with different signs and symptoms. Materials and Methods. A retrosigmoid craniotomy was performed in 31 cpa-meningiomas from January 1981 to February 1997. The mean age of the 25 women (81%) and the 6 men (19%) was 53±13 years. According to their location within the posterior fossa and with special reference to the internal auditory canal (IAC), they were classified in 17 cases (55%) as retromeatal (posterior to the iac) and in 14 cases (45%) as premeatal (anterior to the iac). Results. The retromeatal group showed a significantly larger tumour size (21±15 vs 29±20 mm) and the diagnosis was made later ($2.7±3.2 vs 1.1±0.9 years) compared to premeatally located meningiomas. Before the operation, a reduction of the facial nerve function (64% vs 0%) and hearing function (100% vs 25%) was present significantly more often in premeatal meningiomas. The clinical appearance of the retromeatal group was dominated by cerebellar symptoms (44% vs 0%). Both preoperative and postoperative impairment of facial nerve and auditory function prevailed in the premeatal group. Conclusion. The topological classification of CPA-meningiomas according to their location anterior or posterior to the ICA is important, because the clinical presentation, the surgical strategy to be applied, and the functional outcome of critical neural structures differ between the two subtypes. Our results provide substantial evidence for the paradoxical observation that premeatal meningiomas have a significantly worse postoperative functional outcome compared to retromeatal meningiomas although premeatal meningiomas become symptomatic earlier and at smaller sizes. [ABSTRACT FROM AUTHOR]

Pre-operative and postoperative auditory function was reviewed retrospectively in 98 patients with vestibular schwannomas. According to their hormonal status, women were categorized as 'premenopausal' and 'postmenopausal'. Before surgery, 48% of the women (65% premenopausal) and 16% of the men presented with sudden hearing loss. The degree of autitory function before operation was similar for women and men. Preservation of preoperative hearing was possible for 41% of the women (21% premenopausal) and 59% of the men. Further details of the surgery and the results of histopathological examination were also compared for women and men. Our results support substantial evidence that hearing preservation after surgery of vestibular schwannoma is easier to accomplish for men than for women. The finding of significantly more sudden hearing loss in premenopausal women may suggest a hormonal influence on tumour growth, which may also be partially responsible for the difference in hearing prognosis between women and men. [ABSTRACT FROM AUTHOR]

The article reflects on the treatment in the trigemino-cardiac reflex in skull base surgery. It highlights that the trigemino-cardiac reflex is a sudden onset of parasympathetic dysrhythmia or other related problems during stimulation of the sensory trigeminal nerves that send neuronal signals while forming an afferent pathway of the reflex arc.

A letter to the editor is presented in response to the article on preventing trigemino-cardiac reflex (TCR).

A letter to the editor which discussed trigemino-cardiac reflex (TCR) during skull base surgery is presented .

A letter to the editor is presented in response to the article "The Michel Benoist and Robert Mulholland Yearly European Spine Journal Review" by Robert Mulholland in the December 2005 issue of the "European Spine Journal."

A letter to the editor is presented in response to a letter by A. Gharabaghi, M.A. Acioly de Souse and M. Tatagiba about detection and prevention of the trigeminocardiac reflex during skull base surgery which appeared in a previous issue of the journal.