Differential regulation of TRP channel gene and protein expression by intervertebral disc degeneration and back pain.

Intervertebral disc (IVD) degeneration and consequent low back pain (LBP) are common and costly pathological processes that require improved treatment strategies. Transient Receptor Potential (TRP) channels constitute a family of multimodal ion channels that have recently emerged as contributors to disc pathologies and were thus proposed as potential therapeutic targets, although limited data on their presence and function in the IVD exist. The purpose of this study was to determine the mRNA and protein expression of TRP channels in non-degenerated and degenerated human IVD tissue (with different pain intensity and chronicity) using gene array, conventional qPCR and immunohistochemistry. We could demonstrate that 26 out of 28 currently known TRP channels are expressed in the IVD on the mRNA level, thereby revealing novel therapeutic candidates from the TRPC, TRPM and TRPML subfamilies. TRPC6, TRPM2 and TRPML1 displayed enhanced gene and protein expression in degenerated IVDs as compared to non-degenerated IVDs. Additionally, the gene expression of TRPC6 and TRPML1 was influenced by the IVD degeneration grade. Pain intensity and/or chronicity influenced the gene and/or protein expression of TRPC6, TRPM2 and TRML1. Interestingly, decreased gene expression of TRPM2 was observed in patients treated with steroids. This study supports the importance of TRP channels in IVD homeostasis and pathology and their possible application as pharmacological targets for the treatment of IVD degeneration and LBP. However, the exact function and activation of the highlighted TRP channels will have to be determined in future studies.

[Significantly shorter anesthesia time for surgery of the lumbar spine : process analytical comparison of spinal anesthesia and intubation narcosis]. / Signifikant kürzere Anästhesiezeit bei lumbaler Wirbelsäulenchirurgie : Prozessanalytischer Vergleich von Spinalanästhesie und Intubationsnarkose.

INTRODUCTION: Most surgery of the lumbar spine is performed with the patient under general anesthesia (GA); however, qualitative benefits of spinal anesthesia (SA) have been reported. The goal of this study was to compare time efficiency between these two anesthesia methods in lumbar spine surgery. To test the hypothesis that the use of SA leads to significant time saving compared to GA for lumbar spine surgery, key points in the preoperative, intraoperative and postoperative anesthesiology care times were analyzed. The focus was on anesthesia time excluding surgery time. MATERIALS AND METHODS: Electronically based data of 473 anesthesia procedures (368 SA, 105 GA) for lumbar spine interventions performed in the prone position (i. e. decompression, discectomy and transpedicular instrumentation) were analyzed retrospectively. Patient population data including gender, age, American Society of Anesthesiologists (ASA) classification and body mass index (BMI) were analyzed. The focus was on the documented perioperative key time points which are defined as follows: (1) induction, (2) positioning (turning into prone position), (3) scrubbing and covering, (4) surgery time (knife to skin closure), (5) closing (end of surgery until leaving operating room) and (6) handing over to recovery. Differences in the amount of time for each perioperative period were calculated for SA and GA. RESULTS: In 7 out of the 368 SA patients SA failed and had to be converted to GA. There were no significant differences in BMI, ASA prevalence and gender between SA and GA patients but SA patients were significantly older (median 61.7 ± 15.4 years) than GA patients (median 56.1 ± 14.6 years). However, SA required significantly less time for induction (SA: 17.7 ± 7.0 min, GA: 21.6 ± 7.2 min), preoperative preparation (SA: 9.7 ± 3.6 min, GA: 13.3 ± 5.4 min) and closing period (SA: 4.9 ± 1.1 min, GA: 15.3 ± 5.7 min) compared to GA. Total anesthesia time with exclusion of the surgery time revealed a significant time reduction using SA of 19 min (95 % confidence interval: range 13.6-24.4 min, median in SA: 56.7 min, median in GA: 75.7 min, p < 0.0001). CONCLUSIONS: This study showed that in lumbar spine surgery 19 min of anesthesia time can be saved using SA compared to GA which could have an impact on economic aspects. Gender, BMI and ASA had no statistically detectable influence on the choice between the two anesthesia methods. The fact that time-intensive complex instrumentation is mainly performed in younger patients may explain why GA patients were younger than SA patients.

Post-traumatic inflammation following spinal cord injury.

Inflammatory reaction following a spinal cord injury (SCI) contributes substantially to secondary effects, with both beneficial and devastating effects. This review summarizes the current knowledge concerning the structural features (vascular, cellular, and biochemical events) of SCI and gives an overview of the regulation of post-traumatic inflammation.

Protective effects of oral creatine supplementation on spinal cord injury in rats.

STUDY DESIGN: To evaluate a potential protective effect of increased creatine levels in spinal cord injury (SCI) in an animal model. OBJECTIVES: Acute SCI initiates a series of cellular and molecular events in the injured tissue leading to further damage in the surrounding area. This secondary damage is partly due to ischemia and a fatal intracellular loss of energy. Phospho-creatine in conjunction with the creatine kinase isoenzyme system acts as a potent intracellular energy buffer. Oral creatine supplementation has been shown to elevate the phospho-creatine content in brain and muscle tissue, leading to neuroprotective effects and increased muscle performance. SETTING: Zurich, Switzerland. METHODS: Twenty adult rats were fed for 4 weeks with or without creatine supplemented nutrition before undergoing a moderate spinal cord contusion. RESULTS: Following an initial complete hindlimb paralysis, rats of both groups substantially recovered within 1 week. However, creatine fed animals scored 2.8 points better than the controls in the BBB open field locomotor score (11.9 and 9.1 points respectively after 1 week; P=0.035, and 13 points compared to 11.4 after 2 weeks). The histological examination 2 weeks after SCI revealed that in all rats a cavity had developed which was comparable in size between the groups. In creatine fed rats, however, a significantly smaller amount of scar tissue surrounding the cavity was found. CONCLUSIONS: Thus creatine treatment seems to reduce the spread of secondary injury. Our results favour a pretreatment of patients with creatine for neuroprotection in cases of elective intramedullary spinal surgery. Further studies are needed to evaluate the benefit of immediate creatine administration in case of acute spinal cord or brain injury.

Intramedullary spinal cord tumours: a clinical outcome and radiological follow-up study.

PRINCIPLES: Intramedullary spinal cord tumours are rare. The long-term results depend on their varying natural histories and the surgical approach. Less extensive tumour resection avoids greater postoperative neurological impairment without a negative impact on postoperative outcome. METHODS: Twenty-seven patients who underwent a total of 34 surgical interventions (including 7 reoperations) were clinically and radiologically reinvestigated. Histology revealed 19 glial, 4 nonglial and 4 miscellaneous tumours. RESULTS: Postoperative long-term clinical follow-up (mean 62 months postoperatively) in 25 patients revealed functional improvement in 2 cases, stable conditions in 17 and deterioration in 6. Although there was residual tumour on MRI in 19 of the 22 patients reexamined, stable radiological studies were seen in 15 cases. Despite the high percentage of partial resections or biopsies, good long-term clinical results were found in 19 patients (70%). CONCLUSION: The long-term outcome depends on tumour biology and the type of surgery. For low-grade astrocytomas we propose partial resection without incurring the risk of major postoperative neurological deficits, with semi-annual and, after 5 years, annual follow-up. Despite the fact that ependymomas are amenable to complete surgical resection, this was achieved in only one of six cases in this series. Postoperative MRI follow-up of intramedullary tumours must be protracted, as most of these tumours are slow-growing. An increase in the extent and intensity of contrast enhancement of the tumours was defined as tumour recurrence or progressive tumour growth.

[Bilateral glomus tumors with a blood pressure regulation disorder due to baroreceptor dysfunction]. / Bilaterale Glomustumoren mit Blutdruckregulationsstörung durch Barorezeptordysfunktion.

HISTORY AND CLINICAL FINDINGS: A 73-year-old woman was admitted because of vertigo of recent onset with a tendency to fall down and progressive hearing impairment with tinnitus over the last 2 years. Neurological examination also revealed right recurrent nerve paresis, facial hemispasm and lingual atrophy, pointing to a lesion involving cranial nerves VII, VIII, IX, X and XII. She was found to have spontaneous nystagmus to the left, due to peripheral vestibular function deficit, without otoscopic abnormalities. She was in atrial fibrillation with a blood pressure of 140/80 mm Hg. The suspected cause was a hormonally active glomus jugulare tumour with intermittent hypertension and involvement of several cranial nerves. INVESTIGATIONS: Repeatedly measured plasma and urinary catecholamine concentration was normal. Neuroradiology showed a contrast-rich lesion close to the jugular vein and the hypoglossal nerve, as well as a tumour in the left retromandibular fossa with displacement of the left internal carotid artery. The suspected cause of these findings was a neurologically asymptomatic left carotid body tumour with multiple cranial nerve deficits (VII, VIII, IX and XII) due to their compression at the base of the skull. No abnormal catecholamine activity could be demonstrated. TREATMENT AND COURSE: After complete excision of the right carotid body there were no further hypertensive crises. Later on the left carotid body tumour was embolised because it had continued to grow. CONCLUSION: The repeated hypertensive crises were probably caused by absent blood pressure regulation, the result of destruction of the afferent fibres. This destruction was due to compression of the hypoglossal nerve by the right jugular glomus, at the same time as the contralateral carotid body had been destroyed by tumour.

Cavernous angioma of the cerebellopontine angle.

Cavernous angiomas are vascular malformations that are seldom found in the cerebellopontine angle or in the internal auditory canal. We report the case of a 51-year-old man suffering from a rapidly progressive hearing loss, tinnitus and minor unsteadiness. Neurootological examination showed a canal paresis of 91% on the right side. The subsequent neuroradiological examination with magnetic resonance imaging revealed a tumour of the cerebellopontine angle with intracanalicular extension. The observed intensities on T1-, T2- and gadolinium-enhanced sequences suggested the diagnosis of a vestibular schwannoma. Intraoperatively, a reddish tumour was found and histological examination revealed a cavernous angioma. Even though extensive diagnostic procedures were performed, the correct diagnosis could not be established preoperatively.

Idiopathic dural herniation of the thoracic spinal cord.

Symptomatic anterior or anterolateral dural herniation of the spinal cord is rare, and not uncommonly misdiagnosed, both clinically and radiologically. We present four patients with a radiological diagnosis of herniation of the thoracic spinal cord, and review the current literature. All affected patients have been adults, typically presenting with long-standing, unexplained sensory symptoms and eventually developing a Brown-Séquard syndrome, with or without motor changes. Herniation occurs in the upper or midthoracic region, between the T2 and T8 levels.