Jan F. Cornelius

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.

Oxygen-conserving reflexes of the brain: the current molecular knowledge

The trigemino‐cardiac reflex (TCR) may be classified as a sub‐phenomenon in the group of the so‐called ‘oxygen‐conserving reflexes’. Within seconds after the initiation of such a reflex, there is neither 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 and gives substantial evidence that the TCR is an oxygen‐conserving reflex. This system, which mediates 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 centre appears to be dedicated to reflexively transduce a neuronal signal into cerebral vasodilatation and synchronization of electrocortical activity. Sympathetic excitation is mediated by cortical‐spinal projection to spinal pre‐ganglionic sympathetic neurons whereas bradycardia is mediated via projections to cardiovagal motor medullary neurons. The integrated reflex response serves to redistribute blood from viscera to brain in response to a challenge to cerebral metabolism, but seems also to initiate a preconditioning mechanism. Better and more detailed knowledge of the cascades, transmitters and molecules engaged in such endogenous (neuro) protection may provide new insights into novel therapeutic options for a range of disorders characterized by neuronal death and into cortical organization of the brain.

Bow-hunter’s syndrome caused by dynamic vertebral artery stenosis at the cranio-cervical junction—a management algorithm based on a systematic review and a clinical series

Bow hunters syndrome (BHS) is defined as symptomatic, vertebro-basilar insufficiency caused by mechanical occlusion of the vertebral artery (VA) at the atlanto-axial level during head rotation. In the literature, about 40 cases have been reported. However, due to the rarity of this pathology, there are no guidelines for diagnosis and treatment. Conservative, surgical, and endovascular concepts have been proposed. In order to work out an algorithm, we performed a systematic review of the literature and a retrospective analysis of patients, which have been treated in our institutions over the last decade. The clinical series was comprised of five patients. The symptoms ranged from transient vertigo to posterior circulation stroke. Diagnosis was established by dynamic angiography. In all patients, the VA was decompressed; one patient required additional fusion. The clinical and radiological results were good, and the treatment-related morbidity was low. The literature review demonstrated that Bow hunters syndrome is a rare pathology but associated with a pathognomonic and serious clinical presentation. The gold standard of diagnosis is dynamic angiography, and patients were well managed with tailored vertebral artery decompression. By this management, clinical and radiological results were excellent and the treatment-related morbidity was low.

Transnasal endoscopic odontoidectomy after occipito-cervical fusion during the same operative setting—technical note

Recently, a purely transnasal endoscopic approach (TNEA) for decompression of the anterior cranio-cervical junction has been described. At present, there is only a limited number of patients having been operated on in a few specialized centers. The possibilities, safety, and limits of this approach are still under investigation. The relationship between TNEA and occipito-cervical fusion, especially, which may typically be considered in this kind of pathologies, should be further elucidated. So far, the feasibility of TNEA after previous occipito-cervical fusion has only been reported for a single case. In that case, there was a posterior atlanto-axial subluxation and basilar invagination. In the present paper, another example of a surgical procedure of TNEA after previous posterior fusion during the same operative setting is given. It differs from the other case concerning the pathophysiology. In fact, here, there was anterior atlanto-axial subluxation and no basilar invagination. The possibilities and limits of this novel approach are thoroughly discussed. Special interest is given to the problem of CCJ instability and previous occipito-cervical fusion. Technical hints and pitfalls are described in detail.

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.

Ischemic tolerance in stroke treatment

Although outcome after stroke treatment has significantly improved over the last 30 years, there has been no revolutionary breakthrough. Among different combined approaches, systemic thrombolysis in combination with neuroprotection became a favorite research target. Recent studies suggest that transient ischemic attacks may represent a clinical model of such ischemic tolerance; thus, a new focus on this research has emerged. In this review, we show the parallels between ischemia and neuroprotection and discuss the potential therapeutic options that may be opened by this new molecular knowledge.

Treatment of acute ischemic stroke: role of ischemic tolerance in intravenous and endovascular therapies

At present, the most effective breakthrough in the treatment of cerebral ischemia is the successful establishment of systemic thrombolysis and, currently, it is the only US FDA-approved therapy [1,2]. Recently, intravenous and endovascular treatment modalities have gained much attention because of the European Cooperative Acute Stroke Study (ECASS), which concluded that an extension of the therapeutic window could be established for patients with acute ischemic stroke treated with intravenous alteplase (recombinant tissue plasminogen activator [rtPA]) up to 4.5 h after initial onset of symptoms, which may be beneficial [3]. This concept is, of course, not entirely new, but is now confirmed by a prospective, double-blinded randomized study. In practical terms, however, the main problem remains, since only a minor proportion of all stroke patients can profit from such intravenous and endovascular treatment options [4]. Further compounding this type of intervention is the risk of symptomatic intracerebral hemorrhage, which seems to be increased with rtPA treatment, particularly in patients treated between 5 and 6 h after onset [4]. Therefore, the sole extension of the time window with the rtPA treatment does not appear to be beneficial. These facts clearly indicate that increasing our knowledge on the cellular and molecular mechanisms leading to ischemia-related cell damage, combined with strategies based on thrombolysis, might lead us to supplementary therapies that may arise from the field of endogenous neuroprotection. This approach appears promising and may lead to the development of new additional treatments/drugs [5,6].

Evaluation of hemodynamic changes after extracranial-intracranial bypass using dynamic perfusion CT imaging with acetazolamide challenge

Objective: Since the failure of the extracranial-intracranial (EC-IC) bypass study and COSS study in showing the usefulness of cerebral revascularization to decrease stroke risk in patients with chronic cerebrovascular insufficiency great effort was made to identify a subgroup of high-risk patients [for full text, please go to the a.m. URL]

Endoscopic Resection for Ethmoid Adenocarcinomas and Olfactory Neuroblastomas Involving the Anterior Skull Base

Objectives: The treatment of ethmoid malignant tumors combines a surgical combined approach with radiotherapy, at the cost of significant morbidity. Compared with the gold standard of craniofacial resection, the minimally invasive endoscopic resection may provide satisfactory results. The aim of this work is twofold: (1) to evaluate the quality of tumoral resection in the case of endoscopic anterior skull base resection and (2) to measure the morbidity of this technique. Patients and Methods: From 2000 to 2008, selected cases of patients presenting with ethmoid adenocarcinomas or olfactory neuroblastomas underwent surgery performed through an exclusive transnasal endoscopic approach with unilateral or bilateral removal of the anterior skull base. They were all preoperatively evaluated by CT scan and MRI, and then followed with repeated MRI. The study focused on analysis of the surgical margins and local control and on morbidity of the combined treatment. Results: Sixteen patients (11 with ethmoid adenocarcinoma and 5 with neuroblastoma) were operated on through a purely endoscopic approach with skull base removal; 12 of the cases also involved resection of the dura mater. The cribriform plate was invaded in 6 cases (37.5%), although it was not suspected from imaging data in 3 cases (sensitivity 50%). The only perioperative complication was 1 subdural hematoma, which was looked after. After radiotherapy, there was 1 case of encephalocele, which required a subfrontal approach, and 1 case of extended frontal brain radionecrosis. Local control was good except for 1 case with fulminant progression along the V nerve. One case is alive with metastases. Conclusion: Compared with craniofacial resection, these early results point out a minimal morbidity with dural resection. The rate of unsuspected invasion of the cribriform plate underlines the need for extensive resection. As far as local control is concerned, results require validation with long-term follow-up.

Cervical nerve root decompression by lateral approach as salvage operation after failed anterior transdiscal surgery: technical case report

Cervical nerve root compression caused by disco-osteophytic changes is classically operated by anterior transdiscal approach with disc replacement. If compression persists or recurs, reoperation via the same surgical route may be difficult, because of scar tissue and/or implants. An alternative approach may be necessary. We recommend the lateral cervical approach (retrojugular) as salvage operation in such cases. We report a patient with cervical nerve root compression operated by anterior transdiscal approach with plate and bone graft. As some compression persisted clinically and radiologically, the patient was re-operated via a lateral approach. The surgical access was free of scar tissue. The arthrodesis could be left intact and did not prevent effective nerve root decompression. The patient became asymptomatic. The lateral cervical approach (retrojugular) as reported here, is an excellent alternative pathway if reoperation after anterior transdiscal surgery with disc replacement becomes necessary.