The endocannabinoid system in canine Steroid-Responsive Meningitis-Arteritis and Intraspinal Spirocercosis.

Endocannabinoids (ECs) are involved in immunomodulation, neuroprotection and control of inflammation in the central nervous system (CNS). Activation of cannabinoid type 2 receptors (CB2) is known to diminish the release of pro-inflammatory factors and enhance the secretion of anti-inflammatory cytokines. Furthermore, the endocannabinoid 2-arachidonoyl glycerol (2-AG) has been proved to induce the migration of eosinophils in a CB2 receptor-dependent manner in peripheral blood and activate neutrophils independent of CB activation in humans. The aim of the current study was to investigate the influence of the endocannabinoid system in two different CNS inflammatory diseases of the dog, i.e. Steroid-Responsive Meningitis-Arteritis (SRMA) and Intraspinal Spirocercosis (IS). The two main endocannabinoids, anandamide (AEA) and 2-AG, were quantified by mass spectrometry in CSF and serum samples of dogs affected with Steroid- Responsive Meningitis-Arteritis in the acute phase (SRMA A), SRMA under treatment with prednisolone (SRMA Tr), intraspinal Spirocercosis and healthy dogs. Moreover, expression of the CB2 receptor was evaluated in inflammatory lesions of SRMA and IS and compared to healthy controls using immunohistochemistry (IHC). Dogs with SRMA A showed significantly higher concentrations of total AG and AEA in serum in comparison to healthy controls and in CSF compared to SRMA Tr (p<0.05). Furthermore, dogs with IS displayed the highest ECs concentrations in CSF, being significantly higher than in CSF samples of dogs with SRMA A (p<0.05). CSF samples that demonstrated an eosinophilic pleocytosis had the highest levels of ECs, exceeding those with neutrophilic pleocytosis, suggesting that ECs have a major effect on migration of eosinophils in the CSF. Furthermore, CB2 receptor expression was found in glial cells in the spinal cord of healthy dogs, whereas in dogs with SRMA and IS, CB2 was strongly expressed not only in glial cells but also on the cellular surface of infiltrating leukocytes (i.e. neutrophils, eosinophils, lymphocytes, plasma cells, and macrophages) at lesion sites. The present study revealed an upregulated endocannabinoid system in dogs with inflammatory CNS diseases, highlighting the endocannabinoid system as a potential target for treatment of inflammatory CNS diseases.

Intracranial hemorrhage after spine surgery.

OBJECT: The authors describe the largest case series of 8 patients with intracranial hemorrhage (ICH) after spinal surgery and identify associated pre-, intra-, and postoperative risk factors in relation to outcome. METHODS: The authors retrospectively reviewed the cases of 8 patients treated over 16 years at a single institution and also reviewed the existing literature and collected demographic, treatment, and outcome information from 33 unique cases of remote ICH after spinal surgery. RESULTS: The risk factors most correlated with ICH postoperatively were the presence of a CSF leak intraoperatively and the use of drains postoperatively with moderate hourly serosanguineous output in the early postoperative period. CONCLUSIONS: Intracranial hemorrhage is a rare complication of spinal surgery that is associated with CSF leakage and use of drains postoperatively, with moderate serosanguinous output. These associations do not justify a complete avoidance of drains in patients with CSF leakage but may guide the treating physician to keep in mind drain output and timing of drain removal, while noting any changes in neurological examination status in the meantime. Additionally, continued and worsening neurological symptoms after spinal surgery may warrant cranial imaging to rule out intracranial hemorrhage, usually within the first 24 hours after surgery. The presence of cerebellar hemorrhage and hydrocephalus indicated a trend toward worse outcome.

[Case of cerebrospinal fluid hypovolemia possibly due to acceleration of cerebrospinal fluid absorption].

The authors present a case of a 31-year-old man suffering from intractable cerebrospinal fluid hypovolemia (CSFH), in whom autologous epidural blood patch at the cervical, thoracolumbal, and sacral sites was not effective. Repeated radionuclide cisternography reproducibly demonstrated "early accumulation of radioactivity in the bladder", "cystic accumulation of radioactivity at the sacral site" and "less activity than expected over the cerebral convexities"; but computerized tomography myelography did not demonstrate CSF leakage but detected a sacral cyst. These repeated radionuclide cisternography findings suggested unusually rapid uptake of tracer by the circulation but did not always CSF leakage. The finding of strong accumulation of radioactivity in the sacral cyst might mean the opposite CSF flow against normal caudal-cranial flow. The formation of this abnormal cranial-caudal CSF flow could be produced with CSF leakage or abnormal absorption at the caudal site, where the cyst existed in the patient. Therefore, it is not unreasonable to suppose that the sacral cyst appeared to be responsible for development of CSFH in the patient. The possibility of acceleration of cerebrospinal fluid absorption in the sacral cyst was proposed for the cause of CSFH if CSF leakage was denied.

Lumbosacral cerebrospinal fluid volume in humans using three-dimensional magnetic resonance imaging.

BACKGROUND: The clinical response to spinal anesthesia is influenced by lumbosacral cerebrospinal fluid (CSF) volume, which is highly variable among patients. METHODS: Lumbosacral magnetic resonance images were obtained in 71 patients using a long echo time (TE = 198 msec), fast spin echo sequence with fat suppression. Three-dimensional images were created and lumbosacral CSF volume was estimated using a threshold-based region growing algorithm. RESULTS: A validation experiment using a water bath and cadaveric spinal cord demonstrated that the technique was accurate (1.4 +/- 0.4% difference between estimated and measured). The coefficient of variance was 0.42% among the three estimated CSF values per subject. The mean calculated volume was 35.8 +/- 10.9 mL with a range of 10.6-61.3 mL. Lumbosacral CSF volume was widely variable among patients and was inversely proportional to body mass index (r = -.276, P = 0.02). Mean calculated lumbosacral CSF volumes were smaller in the group of subjects that had radiographic diagnoses of spinal stenosis when compared with subjects with no diagnosis (mean difference -8.4 mL, 95% CI of the difference, -16.1 to -0.8 mL, P = 0.03) and were not different when compared with those with herniated disk disease (mean difference -6.4 mL, 95% CI of the difference -14.7 to 1.9 mL, P = 0.19). CONCLUSIONS: Application of this technique to clinical investigations may further enhance our understanding of spinal anesthesia.

Nosocomial spondylodiskitis with epidural abscess and CSF fistula cured with quinupristin/dalfopristin and linezolid.

Nosocomial infections after spinal surgery are relatively uncommon but potentially serious. The goal of diagnostic evaluation is to determine the extent of infection and identify the microorganism involved. Neuroimaging provides accurate information on correct topography, localization and propagation of the infection. Microbiological data are able to give aetiological causes. In this patient with severe, chronic polymicrobial spine infection with epidural abscess and CSF fistula due to multidrug-resistant organisms, the cure was achieved with long-term antimicrobial specific therapy with quinupristin-dalfopristin (50 days) and linezolid (100 days) with mild side effects. This positive result was due to combined medical and surgical treatment.

Elevated concentration of hyaluronan in the cerebrospinal fluid is a secondary marker of spinal disorders: hyaluronan in the cerebrospinal fluid in patients with spinal disorders.

BACKGROUND: Hyaluronan (HA) was measured in cerebrospinal fluid (CSF) to ascertain the clinical significance of this substance in patients with spinal disorders, a topic that, to the best of our knowledge, has not previously been studied. METHODS: We examined correlations of CSF HA concentration with age, sex, height, body weight, and spinal disorders. By using a sandwich-binding protein assay, HA was measured in CSF samples obtained from 500 patients aged 12 to 104 years who underwent lumbar spinal anesthesia for surgery, myelography, or CSF examination. These patients were classified into 3 groups: (1) a control group (306 patients with injury or benign tumor of the lower limbs); (2) a cervical disorders group (84 patients with cervical disc herniation, cervical spondylotic myelopathy, or ossification of the posterior longitudinal ligament); and (3) a lumbar disorders group (110 patients with lumbar disc herniation, lumbar spinal canal stenosis tethered cord syndrome, lumbar fracture, or spondylolytic spondylolisthesis). RESULTS: CSF HA concentration was found to be positively correlated with age, and was significantly higher in patients with cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, or lumbar spinal canal stenosis tumor than in the control group. CONCLUSIONS: CSF HA concentration might be a secondary marker for inflammation in patients with spinal disease.

Application of solid phase extraction and high-performance liquid chromatography to qualitative and quantitative analysis of nucleotides and nucleosides in human cerebrospinal fluid.

New method of qualitative and quantitative analysis of nucleotides in human cerebrospinal fluid (CSF), based on the combination of extraction of purines and pyrimidines to the solid phase (SPE) and high-performance liquid chromatography (HPLC), was proposed. Use of SPE and lyophilization of samples allowed for the first time to detect the presence of di- and triphosphonucleotides in human CSF. Concentration of those compounds varied from 0.003 to 5.0 microM. Differences in the nucleotide mixture composition in human CSF detected with the new method are coupled with the neurological disorders and might be a basis for an efficient diagnostic tool.

Analysis of chondrex (YKL-40, HC gp-39) in the cerebrospinal fluid of patients with spine disease.

STUDY DESIGN: The expression of chondrex (YKL-40, HC gp-39) was measured in the cerebrospinal fluid of from patients with spine diseases. OBJECTIVES: To quantify the levels of chondrex in human cerebrospinal fluid, and to clarify the nature of its expression. SUMMARY OF BACKGROUND DATA: Chondrex is a newly discovered 40-kDa glycoprotein identified originally in the whey secretions of nonlactating cows. It is secreted by a human osteosarcoma cell line, human articular cartilage chondrocytes, and human fibroblasts. However, the function of chondrex in chondrogenesis is unknown, and the expression of chondrex in human cerebrospinal fluid has never been reported. METHODS: The concentration of chondrex in human cerebrospinal fluid was measured by sandwich immunoassay with antihuman chondrex antibodies. Cerebrospinal fluid samples were collected from two groups of patients. Group 1, the control group, consisted of 34 trauma patients. Group 2 consisted of 130 patients with spine diseases: 29 with cervical spondylotic myelopathy, 30 with lumbar disc herniation, 35 with lumbar canal stenosis, and 36 with scoliosis. All values are expressed as the mean +/- standard deviation. RESULTS: The concentration of chondrex in Group 1 (control group) was 113.8 +/- 48.3 ng/mL. The concentrations of chondrex in Group 2 were 245.3 +/- 107.2 ng/mL in cervical myelopathy, 143.2 +/- 53.6 ng/mL in lumbar disc herniation, 241.5 +/- 77.2 ng/mL in lumbar canal stenosis, and 71.4 +/- 33.9 ng/mL in scoliosis. The concentrations of chondrex in cervical myelopathy, lumbar canal stenosis, and lumbar disc herniation were significantly higher than in the control group (P < 0.05). CONCLUSIONS: In this study, the chondrex concentration was high in spine diseases causing spinal stenosis. The authors believe that chondrex is expressed in cerebrospinal fluid as a result of damage or stress to the neural structure, and that it could be a new marker for spine diseases.

Concentration of nitric oxide (NO) in spinal fluid of chronic spinal disease.

We studied total nitric oxide (nitrite + nitrate) (NO) levels in cerebrospinal fluid (CSF) of chronic spinal diseases in nonsmokers (133 patients: 76 men and 57 women; mean age, 63 years; range, 15-92 years) by the Griess method to clarify the role of NO in different spinal diseases. The extent of compression in terms of numbers of disc level at the compressed spinal nerve and neurological evaluation were also assessed according to the Japanese Orthopaedic Association scores. The spinal diseases included cervical myelopathy and radiculopathy (cervical disease group), ossification of yellow ligament (thoracic disease group), and lumbar disc herniation, lumbar canal stenosis and lumbar spondylolisthesis (lumbar disease group). NO levels in the spinal disease groups (4.98+/-2.28 micromol/l: mean +/- SD) were significantly higher than that in the control group (2.53+/-0.94 micromol/l). An inverse correlation was detected between the elevated levels of NO and the grade of clinical symptoms in the cervical disorders. The number of disc level at the compressed spinal nerve was positively correlated with elevated NO levels in CSF in the cervical and lumbar disorder groups. These results indicate that nerve compression may elevate NO levels in CSF, and that NO concentration in the CSF might be a useful marker of damage to nervous system in spinal disorders.

Analysis of cartilage-derived retinoic acid-sensitive protein in cerebrospinal fluid From patients With spinal diseases.

STUDY DESIGN: The expression of cartilage-derived retinoic acid-sensitive protein (CD-RAP) was measured in cerebrospinal fluid from patients with spinal diseases. OBJECTIVES: To quantify the levels of CD-RAP in human cerebrospinal fluid and to clarify its character. SUMMARY OF BACKGROUND DATA: Cartilage-derived retinoic acid-sensitive protein is a newly discovered, secreted molecule that is expressed during the chondrogenesis phase of endochondral bone formation and in articular cartilage. In recent studies CD-RAP has been detected in the serum of patients with melanoma and breast cancer, and it has been used to monitor tumor activity. However, the function of CD-RAP is unknown, and the expression of CD-RAP in human cerebrospinal fluid has never been reported. METHODS: The concentration of CD-RAP in human cerebrospinal fluid was measured by enzyme-linked immunosorbent assay with antihuman CD-RAP antibodies. Cerebrospinal fluid samples were collected from two groups of patients. Group 1, the control group, consisted of 40 patients: 22 with trauma and 18 with gynecologic diseases. Group 2 consisted of 172 patients with spinal diseases: 5 with meningioma, 5 with neurinoma, 5 with arachnoid cyst, 30 with cervical spondylotic myelopathy, 35 with lumbar disc herniation, 56 with lumbar canal stenosis, and 36 with scoliosis. RESULTS: The concentration of CD-RAP in the control group was 16.5 +/- 8.3 ng/mL. The concentrations of CD-RAP in Group 2 were: 35.3 +/- 14.7 ng/mL in meningioma, 23.5 +/- 7.41 ng/mL in neurinoma, 26.0 +/- 22.2 ng/mL in arachnoid cyst, 41.7 +/- 22.3 ng/mL in cervical myelopathy, 27.8 +/- 14.7 ng/mL in lumbar disc herniation, 36.5 +/- 18.4 ng/mL in lumbar canal stenosis, and 13.4 +/- 7.48 ng/mL in scoliosis. The concentrations of CD-RAP in cervical myelopathy, lumbar canal stenosis, and lumbar disc herniation were significantly higher than in the control group (P < 0.001). CONCLUSIONS: The CD-RAP concentration was low in the control group, whereas it was significantly higher in spinal diseases that cause spinal stenosis. CD-RAP is expressed in cerebrospinal fluid as a result of damage to or stressing of neural structures and could be a marker for spinal diseases.

Cerebrospinal fluid nitric oxide metabolites in painful diseases.

To elucidate the involvement of NO in pain transmission in humans, we measured NO metabolites (nitrite/nitrate) in the CSF of patients with painful diseases using an NO analyzer based on the Griess method. The nitrite/nitrate levels in patients with degenerative lumbar disease (DLD), but not those with fracture or appendicitis, were significantly higher than those in an age-matched control group. The duration of pain in the DLD group was much longer than that in the fracture or appendicitis group. The nitrite/nitrate levels in the middle-aged and elderly DLD patients depended on the duration of pain. These data probably suggest that the duration of pain is critical for the elevation in nitrite/nitrate levels.

Soluble CD95 (Fas/APO-1) in malignant glioma: (no) implications for CD95-based immunotherapy?

CD95 targeting is a novel approach of immunotherapy for malignant glioma that might be antagonized by the release of soluble CD95 by the tumor cells. An alternatively spliced CD95 mRNA that encodes a secreted CD95 variant has been detected in glioma cell lines in vitro and in human tumors in vivo. Here, we report that the levels of soluble CD95 in the serum of malignant glioma patients do not differ from those of lumbar disk disease patients. Soluble CD95 was detected in the CSF in 2 of 20 malignant glioma patients by ELISA. Bioassay studies indicate that these low levels of soluble CD95 in the CSF of some patients with malignant glioma cells are unlikely to interfere with CD95-based immunotherapy of malignant gliomas in vivo.

Detection of immunoreactive parathyroid hormone-related protein in human cerebrospinal fluid.

Immunoreactive parathyroid hormone-related protein (PTH-rP) was measured in simultaneously obtained cerebrospinal fluid (CSF) and plasma from 51 patients suspected of suffering from a prolapsed intervertebral disc. Endocrine or psychiatric diseases were excluded. In addition, immunoreactive parathyroid hormone (PTH) in the CSF samples was measured. Both, PTH-rP and PTH were assayed by immunoradiometric assay. The results indicate the presence of both, PTH-rP and PTH in CSF. The following concentrations (mean values +/- SD) were found: PTH-rP (pmol/l) in CSF without pleocytosis (n = 17) 0.432 +/- 0.157, with pleocytosis (n = 34) 0.654 +/- 0.675; in plasma (pmol/l) 54.1 +/- 14.632; PTH (nmol/l) in CSF without pleocytosis (n = 17) 0.454 +/- 0.099, with pleocytosis (n = 34) 0.437 +/- 0.140, and in plasma 4.272 +/- 0.794. The concentrations of both, PTH-rP and PTH, in CSF with and without pleocytosis were not significantly different. No correlation was found between PTH-rP and PTH values. The present study demonstrated PTH-rP as a normal constituent in human CSF.

Effects of iodinated contrast agents in MR imaging.

PURPOSE: To investigate the effects of iodinated contrast agents in MRI. MATERIAL AND METHODS: Twenty patients were examined with MRI immediately, 8 and 24 h after lumbar myelography. Signal intensities and calculated T1- and T2-relaxation times of different iodinated contrast agents, a dilution row of iopamidol, and a mixture of CSF and iotrolan were compared with physiological saline solution using different T1- and T2-weighted sequences. 1H-spectroscopy was performed with several solutions containing iodine or other substances. RESULTS: A fluid-fluid level of the CSF existed in the lumbar dural sac in all patients immediately after lumbar myelography with a non-ionic iodinated contrast agent. Increased signal intensity on T1-weighted and decreased signal intensity on T2-weighted sequences was found for all contrast agents, as well as for the dilution row, compared with physiological saline solution. The structure of the side chains of the contrast agents is responsible for the T1- and T2-shortening effect. CONCLUSION: It is important to be aware of the effect of iodinated contrast agents in MRI. To avoid misinterpretation of atypical findings, MRI of the spine should not be performed earlier than 24 h after myelography.

Magnetic resonance imaging of spinal cord in multiple sclerosis by fluid-attenuated inversion recovery.

Magnetic resonance imaging examination of the upper spinal cord was done in sixteen adult patients with clinically definite multiple sclerosis (MS) by T2 weighted fluid attenuated inversion recovery (FLAIR) scanning in which the signal from cerebrospinal fluid was suppressed. These scans were compared with matched images obtained with conventional T1 and T2 weighted pulse sequences (including contrast enhancement). 6 lesions (five patients) were seen with the conventional scans and 37 lesions (fourteen patients) were seen with the FLAIR scans. The FLAIR sequence considerably improves the ability of MRI to demonstrate spinal involvement in MS.

High-resolution 1H NMR spectroscopy of cerebrospinal fluid in spinal diseases.

Twenty-nine patients with disk herniations, 7 patients with intraspinal tumors, 4 patients with multiple sclerosis and one patient with infection by borrelia have been studied by CT, myelography and/or MR. To gain information on the metabolism of central nervous system disease (CNS), and thus, to improve diagnosis the cerebrospinal fluid (CSF) was studied in all cases using high-resolution 1H NMR spectroscopy at 360 MHz. Seventeen metabolites could be identified in CSF in addition to the usual clinical chemical parameters. As compared to a control group discrimination of tumors from inflammation was possible by means of different metabolites and/or metabolite concentration. The CSF in disk herniations differed in the concentration of acetate from the control group. In CSF of tumors, multiple sclerosis and of infection by borrelia distinct differences in the concentrations of putrescine, citrate, valine, alpha-alanine, acetate, creatinine, glucose, beta-hydroxy-butyric acid, glutamine and creatine have been observed both as compared directly and in comparison to the control group. Thus, high-resolution 1H NMR spectroscopy of CSF gives speedy information on metabolism, since a variety of metabolites, usually examined only in different tests, can be studied in one single step. Thus, high-resolution 1H NMR spectroscopy supports imaging, especially MR, as morphological changes in diseases may be differentiated by means of different metabolite profiles. This assumption needs further confirmation on a prospective study with a larger patient population.

Clinical implications of acute cerebrospinal fluid changes following iophendylate myelography.

Clinical features and serial cerebrospinal fluid (CSF) samples of 50 patients who underwent myelography with iophendylate were studied. Forty two patients (84%) developed one or more features suggestive of meningism lasting for 2-4 days. There was significant rise in the average (mean) CSF counts from 9.81 in the premyelogram sample to 532.6 at the end of 24 hours (p less than 0.001). Both neutrophil and lymphocyte (p less than 000) count increased. At the end of one week, there was significant decrease of total cells in the CSF to 204 (p less than 0.001). Both, neutrophils and lymphocytes decreased. There was significant rise in total proteins in the 24 hours sample, but the fall at one week was not significant statistically. The sugar and chloride values did not change significantly. All CSF samples were negative for bacterial cultures. In conclusion, a significant proportion of the patients undergoing iophendylate myelography develop clinical features suggestive of meningeal irritation and change in the CSF fractions suggestive of meningitis: however these changes are transient and do not warrant institution of chemotherapy or steroids.