[Interventional pain management, indications and results]

When conservative treatment modalities provide inadequate relief, interventional techniques play an important role in the management of chronic pain patients. They are performed in diagnostic or therapeutic intention (or both) and either directly target the pain generating anatomic structure (e.g. intraarticular joint injections) or the neural structures which are thought to mediate the experience of pain (e.g. facet joint nerve blocks, spinal cord stimulation). In order to enhance precision and patient safety, these interventions are performed with image guidance; of which fluoroscopy is the most commonly used technique. CT- or Ultrasound-guided techniques are also performed. This article is an overview of the indications and results of the most commonly performed interventional techniques used in chronic pain treatment with focus on spinal interventional procedures.

Breathing adapted radiotherapy: a 4D gating software for lung cancer

Purpose Physiological respiratory motion of tumors growing in the lung can be corrected with respiratory gating when treated with radiotherapy (RT). The optimal respiratory phase for beam-on may be assessed with a respiratory phase optimizer (RPO), a 4D image processing software developed with this purpose. Methods and Materials Fourteen patients with lung cancer were included in the study. Every patient underwent a 4D-CT providing ten datasets of ten phases of the respiratory cycle (0-100% of the cycle). We defined two morphological parameters for comparison of 4D-CT images in different respiratory phases: tumor-volume to lung-volume ratio and tumor-to-spinal cord distance. The RPO automatized the calculations (200 per patient) of these parameters for each phase of the respiratory cycle allowing to determine the optimal interval for RT. Results Lower lobe lung tumors not attached to the diaphragm presented with the largest motion with breathing. Maximum inspiration was considered the optimal phase for treatment in 4 patients (28.6%). In 7 patients (50%), however, the RPO showed a most favorable volumetric and spatial configuration in phases other than maximum inspiration. In 2 cases (14.4%) the RPO showed no benefit from gating. This tool was not conclusive in only one case. Conclusions The RPO software presented in this study can help to determine the optimal respiratory phase for gated RT based on a few simple morphological parameters. Easy to apply in daily routine, it may be a useful tool for selecting patients who might benefit from breathing adapted RT.

Unique paleopathology in a pre-Columbian mummy remnant from Southern Peru--severe cervical rotation trauma with subluxation of the axis as cause of death

We describe the multidisciplinary findings in a pre-Columbian mummy head from Southern Peru (Cahuachi, Nazca civilisation, radiocarbon dating between 120 and 750 AD) of a mature male individual (40-60 years) with the first two vertebrae attached in pathological position. Accordingly, the atlanto-axial transition (C1/C2) was significantly rotated and dislocated at 38° angle associated with a bulging brownish mass that considerably reduced the spinal canal by circa 60%. Using surface microscopy, endoscopy, high-resolution multi-slice computer tomography, paleohistology and immunohistochemistry, we identified an extensive epidural hematoma of the upper cervical spinal canal-extending into the skull cavity-obviously due to a rupture of the left vertebral artery at its transition between atlas and skull base. There were no signs of fractures of the skull or vertebrae. Histological and immunohistochemical examinations clearly identified dura, brain residues and densely packed corpuscular elements that proved to represent fresh epidural hematoma. Subsequent biochemical analysis provided no evidence for pre-mortal cocaine consumption. Stable isotope analysis, however, revealed significant and repeated changes in the nutrition during his last 9 months, suggesting high mobility. Finally, the significant narrowing of the rotational atlanto-axial dislocation and the epidural hematoma probably caused compression of the spinal cord and the medulla oblongata with subsequent respiratory arrest. In conclusion, we suggest that the man died within a short period of time (probably few minutes) in an upright position with the head rotated rapidly to the right side. In paleopathologic literature, trauma to the upper cervical spine has as yet only very rarely been described, and dislocation of the vertebral bodies has not been presented.

[Tremorgenic syndrome in a cattle herd after feeding silage contaminated with A. clavatus];;Tremorgenes Syndrom in einem Rinderbestand nach Verfütterung einer mit A. clavatus befallenen Silage

The clinical signs, pathological and laboratory findings of cattle suffering from a tremorgenic syndrome are described. Animals on a farm with a total of 22 cows, 18 heifers and 9 calves were fed mouldy grass and spent malt-grain silage. Five heifers were affected with muscular tremor, hyperexcitability and hypersensitivity. They were ataxic or in sternal recumbency, while their appetite remained normal. Haematology and blood chemistry in two heifers as well as cerebrospinal fluid from one sick animal were unremarkable. The pathological examination of one animal brought no macroscopic changes to light. Histological examination, however, revealed the degeneration of motor neurones in the midbrain, brain stem and spinal cord. Analysis of a silage sample provided evidence of the presence of Aspergillus clavatus, a mould capable of producing neurotoxic tremorgenic mycotoxins. Epidemiology, clinical findings, pathology and microbiological examination suggest that the five cattle were suffering from neuromycotoxicosis.

Effects of isoflurane upon minimum alveolar concentration and cerebral cortex depression in pigs and goats: an interspecies comparison

This study compared the effects of isoflurane in pigs (n=10 Yorkshire-Landrace cross) and dairy goats (n=10) by evaluation of electroencephalographic (EEG) burst suppression thresholds (BST) in the cerebral cortex and minimum alveolar concentration (MAC) values in the spinal cord. The study also investigated whether individual MAC values can predict the effects of isoflurane on the cerebral cortex. MAC values and BST/MAC ratios were significantly different between species. Inhibition of movement by isoflurane may be less effective in pigs than in goats. No significant correlation was found between individual MAC and BST values, indicating that in single animals the individual MAC poorly reflects the cerebrocortical depressant effect of isoflurane in pigs and goats.

Comparison of brain PrPd distribution in ovine BSE and scrapie

Scrapie and bovine spongiform encephalopathy (BSE) are both prion diseases affecting ruminants, and these diseases do not share the same public health concerns. Surveillance of the BSE agent in small ruminants has been a great challenge, and the recent identification of diverse prion diseases in ruminants has led to the development of new methods for strain typing. In our study, using immunohistochemistry (IHC), we assessed the distribution of PrP(d) in the brains of 2 experimentally BSE-infected sheep with the ARQ/ARQ genotype. Distribution of PrP(d) in the brain, from the spinal cord to the frontal cortex, was remarkably similar in the 2 sheep despite different inoculation routes and incubation periods. Comparatively, overall PrP(d) brain distribution, evaluated by IHC, in 19 scrapie cases with the ARQ/ARQ, ARQ/VRQ, and VRQ/VRQ genotypes, in some cases showed similarities to the experimentally BSE-infected sheep. There was no exclusive neuroanatomical site with a characteristic and specific PrP(d) type of accumulation induced by the BSE agent. However, a detailed analysis of the topography, types, and intensity of PrP(d) deposits in the frontal cortex, striatum, piriform cortex, hippocampus, mesencephalon, and cerebellum allowed the BSE-affected sheep group to be distinguished from the 19 scrapie cases analyzed in our study. These results strengthen and emphasize the potential interest of PrP(d) brain mapping to help in identifying prion strains in small ruminants.

Cyber medicine enables remote neuromonitoring during aortic surgery

This study assessed the feasibility and effectiveness of remote neuromonitoring as an adjunct to spinal cord protection during surgical repair of descending thoracic aortic aneurysms and thoracoabdominal aortic aneurysms.

TRPM4 channels in the cardiovascular system: physiology, pathophysiology, and pharmacology

The transient receptor potential channel (TRP) family comprises at least 28 genes in the human genome. These channels are widely expressed in many different tissues, including those of the cardiovascular system. The transient receptor potential channel melastatin 4 (TRPM4) is a Ca(2+)-activated non-specific cationic channel, which is impermeable to Ca(2+). TRPM4 is expressed in many cells of the cardiovascular system, such as cardiac cells of the conduction pathway and arterial and venous smooth muscle cells. This review article summarizes the recently described roles of TRPM4 in normal physiology and in various disease states. Genetic variants in the human gene TRPM4 have been linked to several cardiac conduction disorders. TRPM4 has also been proposed to play a crucial role in secondary hemorrhage following spinal cord injuries. Spontaneously hypertensive rats with cardiac hypertrophy were shown to over-express the cardiac TRPM4 channel. Recent studies suggest that TRPM4 plays an important role in cardiovascular physiology and disease, even if most of the molecular and cellular mechanisms have yet to be elucidated. We conclude this review article with a brief overview of the compounds that have been shown to either inhibit or activate TRPM4 under experimental conditions. Based on recent findings, the TRPM4 channel can be proposed as a future target for the pharmacological treatment of cardiovascular disorders, such as hypertension and cardiac arrhythmias.

The anatomical and cellular basis of immune surveillance in the central nervous system

The central nervous system (CNS) comprises the brain, spinal cord, optic nerves and retina, and contains post-mitotic, delicate cells. As the rigid coverings of the CNS render swelling dangerous and destructive, inflammatory reactions must be carefully controlled in CNS tissues. Nevertheless, effector immune responses that protect the host during CNS infection still occur in the CNS. Here, we describe the anatomical and cellular basis of immune surveillance in the CNS, and explain how this shapes the unique immunology of these tissues. The Review focuses principally on insights gained from the study of autoimmune responses in the CNS and to a lesser extent on models of infectious disease. Furthermore, we propose a new model to explain how antigen-specific T cell responses occur in the CNS.

Molecular mechanisms involved in T cell migration across the blood-brain barrier

In the healthy individuum lymphocyte traffic into the central nervous system (CNS) is very low and tightly controlled by the highly specialized blood-brain barrier (BBB). In contrast, under inflammatory conditions of the CNS such as in multiple sclerosis or in its animal model experimental autoimmune encephalomyelitis (EAE) circulating lymphocytes and monocytes/macrophages readily cross the BBB and gain access to the CNS leading to edema, inflammation and demyelination. Interaction of circulating leukocytes with the endothelium of the blood-spinal cord and blood-brain barrier therefore is a critical step in the pathogenesis of inflammatory diseases of the CNS. Leukocyte/endothelial interactions are mediated by adhesion molecules and chemokines and their respective chemokine receptors. We have developed a novel spinal cord window preparation, which enables us to directly visualize CNS white matter microcirculation by intravital fluorescence videomicroscopy. Applying this technique of intravital fluorescence videomicroscopy we could provide direct in vivo evidence that encephalitogenic T cell blasts interact with the spinal cord white matter microvasculature without rolling and that alpha4-integrin mediates the G-protein independent capture and subsequently the G-protein dependent adhesion strengthening of T cell blasts to microvascular VCAM-1. LFA-1 was found to neither mediate the G-protein independent capture nor the G- protein dependent initial adhesion strengthening of encephalitogenic T cell blasts within spinal cord microvessel, but was rather involved in T cell extravasation across the vascular wall into the spinal cord parenchyme. Our observation that G-protein mediated signalling is required to promote adhesion strengthening of encephalitogenic T cells on BBB endothelium in vivo suggested the involvement of chemokines in this process. We found functional expression of the lymphoid chemokines CCL19/ELC and CCL21/SLC in CNS venules surrounded by inflammatory cells in brain and spinal cord sections of mice afflicted with EAE suggesting that the lymphoid chemokines CCL19 and CCL21 besides regulating lymphocyte homing to secondary lymphoid tissue might be involved in T lymphocyte migration into the immuneprivileged CNS during immunosurveillance and chronic inflammation. Here, I summarize our current knowledge on the sequence of traffic signals involved in T lymphocyte recruitment across the healthy and inflamed blood-brain and blood-spinal cord barrier based on our in vitro and in vivo investigations.

The LPS receptor, CD14, in experimental autoimmune encephalomyelitis and multiple sclerosis

Innate immune receptors are crucial for defense against microorganisms. Recently, a cross-talk between innate and adaptive immunity has been considered. Here, we provide first evidence for a role of the key innate immune receptor, LPS receptor (CD14) in pathophysiology of experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. Indicating a functional importance in vivo, we show that CD14 deficiency increased clinical symptoms in active experimental autoimmune encephalomyelitis. Consistent with these observations, CD14 deficient mice exhibited a markedly enhanced infiltration of monocytes and neutrophils in brain and spinal cord. Moreover, we observed an increased immunoreactivity of CD14 in biopsy and post mortem brain tissues of multiple sclerosis patients compared to age-matched controls. Thus, the key innate immune receptor, CD14, may be of pathophysiological relevance in experimental autoimmune encephalomyelitis and multiple sclerosis.

Canine neurological diseases in a referral hospital population between 1989 and 2000 in Switzerland

OBJECTIVES: To merge clinical information from partly overlapping medical record databases of the Small Animal Teaching Hospital of the Vetsuisse Faculty, University of Berne. To describe the frequencies and localisations of neurological diseases in dogs, as well as their age, gender, breed and geographical distributions. METHODS: In this retrospective study, a new database, with specific variables and a diagnosis key list 'VITAMIN D', was created and defined. A total of 4497 dogs (average of 375 per year) with a well-documented neurological disease were included in the study. A key list for the diagnoses was developed and applied to either the presumptive or the clinical and neurohistopathological diagnosis, with a serial number, a code for localisation and a code for differential diagnoses. RESULTS: Approximately 1159 dogs (26 per cent) had a neurohistopathological diagnosis confirmed, 1431 (32 per cent) had a clinical diagnosis confirmed and 1491 (33 per cent) had a presumptive diagnosis. The most frequent breeds were mixed-breed dogs (577 of 4497, 13 per cent), followed by German shepherd dogs (466 of 4497, 10 per cent). The most common localisations were the forebrain (908 of 4497, 20 per cent) and the spinal cord at the thoracolumbar area (840 of 4497, 19 per cent). Most dogs were diagnosed with degenerative diseases (38 per cent), followed by inflammatory/infectious diseases (14 per cent). The highest number of submissions originated from geographic regions around the referral hospital and from regions with higher human population densities. CLINICAL SIGNIFICANCE: By defining closed-list fields and allocating all data to the corresponding fields, a standardised database that can be used for further studies was generated. The analysis of this study gives examples of the possible uses of a standardised database.

Daily controlled physiotherapy increases survival time in dogs with suspected degenerative myelopathy

The purposes of the study reported here were to evaluate the signalment and clinical presentation in 50 dogs with degenerative myelopathy, to evaluate whether mean survival time was significantly affected by various means of physiotherapy performed in 22 dogs, and to determine whether neurologic status, anatomic localization, or age at onset had an influence on survival time in dogs that received physiotherapy. We found a significant (P < .05) breed predisposition for the German Shepherd Dog, Kuvasz, Hovawart, and Bernese Mountain Dog. Mean age at diagnosis was 9.1 years, and both sexes were affected equally. The anatomic localization of the lesion was spinal cord segment T3-L3 in 56% (n = 28) and L3-S3 in 44% (n = 22) of the dogs. Animals that received intensive (n = 9) physiotherapy had longer (P < .05) survival time (mean 255 days), compared with that for animals with moderate (n = 6; mean 130 days) or no (n = 7; mean 55 days) physiotherapy. In addition, our results indicate that affected dogs which received physiotherapy remained ambulatory longer than did animals that did not receive physical treatment.

Immunohistochemical screening for viral agents in cheetahs (Acinonyx jubatus) with myelopathy

Numerous cases of acute-onset progressive ataxia, hindlimb paresis and paralysis of unknown aetiology occurred during 1993 to 2003 in cheetahs (Acinonyx jubatus) within the European Endangered Species Programme (eep). This study describes the immunohistochemical investigation of a possible viral aetiology of the "cheetah myelopathy". Antibodies to feline herpesvirus type 1, canine distemper virus, canine parvovirus and Borna disease virus were applied to formalin-fixed and paraffin-embedded brain and spinal cord sections from 25 affected cheetahs aged between three-and-a-half months and 13 years. Using the avidin-biotin complex technique, none of the antibodies gave positive immunosignals in either the brain or the spinal cord tissue.

Hepatic encephalomyelopathy in a calf with congenital portosystemic shunt (CPSS)

A 4-month-old female Holstein Friesian calf was referred to the Veterinary Teaching Hospital, University of Berne, Switzerland for evaluation of ataxia, weakness, apathy and stunted growth. Clinical examination revealed generalized ataxia, propioceptive deficits, decreased menace response and sensibility. Postmortem examination did not reveal macroscopic changes of major organs. Histologically, the brain and the spinal cord lesions were characterized by polymicrocavitation, preferentially affecting the white matter fibers at the junction of grey and white matter and by the presence of Alzheimer type II cells. The liver revealed lesions consistent with a congenital portosystemic shunt, characterized by increased numbers of arteriolar profiles and hypoplasia to absence of portal veins. The pathological investigations along with the animal history and clinical signs indicated a hepatic encephalomyelopathy due to a congenital portosystemic shunt.