Focal Spinal Cord Lesions Research Articles

Brainstem lesions are associated with diffuse spinal cord involvement in early multiple sclerosis

BackgroundEarly infratentorial and focal spinal cord lesions on magnetic resonance imaging (MRI) are associated with a higher risk of long-term disability in patients with multiple sclerosis (MS). The role of diffuse spinal cord lesions remains less understood. The purpose of this study was to evaluate focal and especially diffuse spinal cord lesions in patients with early relapsing-remitting MS and their association with intracranial lesion topography, global and regional brain volume, and spinal cord volume.MethodsWe investigated 58 MS patients with short disease duration (< 5 years) from a large academic MS center and 58 healthy controls matched for age and sex. Brain, spinal cord, and intracranial lesion volumes were compared among patients with- and without diffuse spinal cord lesions and controls. Binary logistic regression models were used to analyse the association between the volume and topology of intracranial lesions and the presence of focal and diffuse spinal cord lesions.ResultsWe found spinal cord involvement in 75% of the patients (43/58), including diffuse changes in 41.4% (24/58). Patients with diffuse spinal cord changes exhibited higher volumes of brainstem lesion volume (p = 0.008). The presence of at least one brainstem lesion was associated with a higher probability of the presence of diffuse spinal cord lesions (odds ratio 47.1; 95% confidence interval 6.9–321.6 p < 0.001) as opposed to focal spinal cord lesions (odds ratio 0.22; p = 0.320). Patients with diffuse spinal cord lesions had a lower thalamus volume compared to patients without diffuse spinal cord lesions (p = 0.007) or healthy controls (p = 0.002).ConclusionsDiffuse spinal cord lesions are associated with the presence of brainstem lesions and with a lower volume of the thalamus. This association was not found in patients with focal spinal cord lesions. If confirmed, thalamic atrophy in patients with diffuse lesions could increase our knowledge on the worse prognosis in patients with infratentorial and SC lesions.

Idiopathic longitudinally extensive myelitis: a brief historical excursion (review) and own clinical observation

Background: Idiopathic longitudinally extensive transverse myelitis is defined as a focal spinal cord lesion that involves three or more segments of the spinal cord as shown by neuroimaging, and results in a profound disability. The clinical picture of a patient with idiopathic longitudinally advanced transverse myelitis is often dramatic and may consist of paraparesis or tetraparesis, sensory disturbances, and pelvic dysfunction. Idiopathic longitudinally advanced transverse myelitis is a common manifestation of the neuromyelitis optica spectrum disorders, but can also occur in various other autoimmune and inflammatory diseases of the CNS, such as multiple sclerosis, sarcoidosis, or Sjogrens syndrome, or in infectious diseases involving the CNS. It is less likely to occur in isolation, as the only manifestation of a demyelinating disease of the nervous system of an unknown etiology (idiopathic myelitis).&#x0D; Clinical case description: The clinical observation presented in the article demonstrates the difficulties of establishing a nosological diagnosis in the case of a monophasic course of TM in the absence of other autoimmune and infectious diseases of the central nervous system. The patient with idiopathic longitudinally distributed TM had no visual disturbances and no antibodies to aquaporin 4 and to myelin oligodendrocyte glycoprotein (MOG-IgG) with twice repeated tests.&#x0D; Conclusion: In this regard, it is important to dynamically monitor the clinical manifestations and MRI signs in patients with an isolated lesion of a demyelinating nature in the form of longitudinally extensive transverse myelitis.

Eosinophilic Meningomyelitis Probably Associated with Toxoplasmosis in a Cat

Background: The cerebrospinal fluid (CSF) of healthy cats presents up to 5 cells/µL, with predominance of mononuclear cells and the presence of more than 1% eosinophils is rare and should always be considered an abnormal finding. There is no consensus on the term eosinophilic pleocytosis, as it is used to indicate the presence of more than 10 eosinophils/µL or more than 10% of the total neutrophils. The increase in eosinophils in the CSF may result from infectious, inflammatory, neoplastic and idiopathic diseases. The objective of this paper is to report a case of marked pleocytosis in CSF, with 84% eosinophils, probably due to toxoplasmosis, in a cat with paraparesis and diffuse spinal pain.Case: A mixed breed female cat, neutered, adult and domiciled in a rural area was presented due to gait abnormalities in the pelvic limbs that started one day before presentation. The general physical examination was unremarkable. On neurological examination it was observed asymmetric deficit of postural reactions in pelvic limbs, patellar reflex normal to increased and pain elicited on palpation of the thoracic and lumbar spine. Based on these findings, the neurological syndrome was classified as thoracolumbar, but with diffuse pain, and the main differential diagnoses were inflammatory/infectious and neoplastic diseases. The leukogram showed eosinophilia and the serum biochemistry showed no significant changes. Serological assays for feline immunodeficiency virus and feline leukemia virus were negative. Analysis of cerebrospinal fluid (CSF) identified marked pleocytosis with 84% eosinophils and increase in protein concentration. Myelography showed no compressive or expansive changes. Fungal culture for CSF cryptococcosis was negative. Serum immunofluorescence antibody titer for Toxoplasma gondii (IgG) was 1:256. There was a marked improvement after treatment with sulfametoxazole/trimethoprim and pyrimethamine and after 3 weeks of treatment, there was almost complete recovery of neurological signs and after 9 months the cat was neurologically normal.Discussion: The most common causes of acute-onset thoracolumbar spinal cord syndrome in cats, with diffuse pain on spinal palpation, are meningomyelitis of inflammatory/infectious origin, such as feline infectious peritonitis (FIP) and neoplasms such as lymphoma. Other meningomyelitis of inflammatory origin, such as infectious and immune-mediated meningomyelitis of unknown origin are considered uncommon in cats. Although the clinical, systemic and neurological signs of FIP and toxoplasmosis may have similarities, in the present case FIP was not considered responsible for the observed signs, as the evolution of the case and the analysis of the CSF tend to be different. The peripheral eosinophilia, the cytological analysis of the CSF, characterized by marked eosinophilic pleocytosis, associated with a positive titer for toxoplasmosis, good response to treatment and improvement in the neurological condition, with survival for more than 9 months after treatment, rules out the possibility of FIP. Neurological signs observed in the absence of systemic signs are more common in cases of protozoan reactivation, which probably occurred in the present case. The possibility of toxoplasmosis in the patient in this report was reinforced by the fact that the animal came from a rural area. Eosinophilia of CSF is most commonly associated with parasitic infections, although it can be caused by a variety of infectious agents, but in the cat of the present report, the marked eosinophilic pleocytosis was likely due to toxoplasmosis, which is a rare occurrence in this specie. In conclusion, toxoplasmosis should be considered in the differential diagnosis of focal spinal cord lesions in cats. The identification of laboratory findings as well as the appropriate therapy favored the good evolution of the condition.Keywords: eosinophilic pleocytosis, feline, Toxoplasma gondii, cerebrospinal fluid.Descritores: pleocitose eosinofílica, felino, Toxoplasma gondii, líquido cerebroespinhal.

Thoracolumbar meningeal fibrosis in pugs.

BackgroundThoracolumbar myelopathies associated with spinal cord and vertebral column lesions, with a similar clinical phenotype, but different underlying etiologies, occur in pugs.ObjectivesTo further characterize the clinical and neuropathological characteristics of pugs with longstanding thoracolumbar myelopathy.AnimalsThirty client‐owned pure‐bred pugs with a history of more than a month of ataxia and paresis of the pelvic limbs, suggesting a myelopathy localized to the thoracolumbar spinal cord, were included in the study.MethodsProspective clinicopathological study. Included pugs underwent a complete neurological examination and gross and histopathologic postmortem studies with focus on the spinal cord. Computed tomography (n = 18), magnetic resonance imaging (n = 17), and cerebrospinal fluid analysis (n = 27) were performed before or immediately after death.ResultsTwenty male and 10 female pugs had a median age at clinical onset of 84 months (interquartile range, 66‐96). Affected pugs presented with a progressive clinical course and 80% were incontinent. There was circumferential meningeal fibrosis with concomitant focal, malacic, destruction of the neuroparenchyma in the thoracolumbar spinal cord in 24/30 pugs. Vertebral lesions accompanied the focal spinal cord lesion, and there was lympho‐histiocytic inflammation associated or not to the parenchymal lesion in 43% of the pugs.Conclusions and Clinical ImportanceMeningeal fibrosis with associated focal spinal cord destruction and neighboring vertebral column lesions were common findings in pugs with long‐standing thoracolumbar myelopathy.

Current questions of multiple sclerosis: the secunder progressive form of the disease

Recent data suggest that long-term worsening is common in relapsing-remitting multiple sclerosis patients and is largely independent of relapses or new lesion formation on brain MRI. The current definition of secunder progressive multiple sclerosis is worsening of disability independent of relapses over at least 6-month interval. Early focal inflammatory disease activity and spinal cord lesion are predictors of very-long term disease outcomes in relapse - onset multiple sclerosis. The potential of PET imaging to visualize hidden inflammation in MS brain in vivo is an important contribution for better understanding the progression of the disease. Therefore, PET imaging is a promising tool in detecting the conversion from relapsing remitting multiple sclerosis to secunder progressive form of multiple sclerosis. Furthermore, neuro-axonal damage is the pathological substrate of permanent disability in different neurological disorders including multiple sclerosis. The neurofilament proteins have promise in this context because their levels rise upon neuro-axonal damage not only in the cerebrospinal fluid but also in blood. Patients with increased serum levels of neurofilament at baseline, independent of other clinical and MRI variables, experience significantly more brain and spinal cord volume loss over 2 years and 5 years of follow-up. The kynurenine-pathway abnormalities may be associated with the swich from early-mild stage multiple sclerosis to debilitating progressive forms of the disease. Analysis of these metabolites in serum may have application as multiple sclerosis disease biomarkers. Free radical action has been suggested as a causal factor in the illness. Increased free radical production and consumption of the scavenger molecules were found during the active phase of the disease. Based on the clinical findings (EXPAND Study) and pathomechanism of the disease siponimod is approved by the US Food and Drug Administration for the treatment of relapsing remitting forms of multiple sclerosis, to include secunder progressive multiple sclerosis with active disease, relapsing-remitting multiple sclerosis and clinically isolated syndrome.

Anatomy and function of the vertebral column lymphatic network in mice

Cranial lymphatic vessels (LVs) are involved in the transport of fluids, macromolecules and central nervous system (CNS) immune responses. Little information about spinal LVs is available, because these delicate structures are embedded within vertebral tissues and difficult to visualize using traditional histology. Here we show an extended vertebral column LV network using three-dimensional imaging of decalcified iDISCO+-clarified spine segments. Vertebral LVs connect to peripheral sensory and sympathetic ganglia and form metameric vertebral circuits connecting to lymph nodes and the thoracic duct. They drain the epidural space and the dura mater around the spinal cord and associate with leukocytes. Vertebral LVs remodel extensively after spinal cord injury and VEGF-C-induced vertebral lymphangiogenesis exacerbates the inflammatory responses, T cell infiltration and demyelination following focal spinal cord lesion. Therefore, vertebral LVs add to skull meningeal LVs as gatekeepers of CNS immunity and may be potential targets to improve the maintenance and repair of spinal tissues.

Early imaging predictors of long-term outcomes in relapse-onset multiple sclerosis.

The clinical course of relapse-onset multiple sclerosis is highly variable. Demographic factors, clinical features and global brain T2 lesion load have limited value in counselling individual patients. We investigated early MRI predictors of key long-term outcomes including secondary progressive multiple sclerosis, physical disability and cognitive performance, 15 years after a clinically isolated syndrome. A cohort of patients with clinically isolated syndrome (n = 178) was prospectively recruited within 3 months of clinical disease onset and studied with MRI scans of the brain and spinal cord at study entry (baseline) and after 1 and 3 years. MRI measures at each time point included: supratentorial, infratentorial, spinal cord and gadolinium-enhancing lesion number, brain and spinal cord volumetric measures. The patients were followed-up clinically after ∼15 years to determine disease course, and disability was assessed using the Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test. Multivariable logistic regression and multivariable linear regression models identified independent MRI predictors of secondary progressive multiple sclerosis and Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test, respectively. After 15 years, 166 (93%) patients were assessed clinically: 119 (72%) had multiple sclerosis [94 (57%) relapsing-remitting, 25 (15%) secondary progressive], 45 (27%) remained clinically isolated syndrome and two (1%) developed other disorders. Physical disability was overall low in the multiple sclerosis patients (median Expanded Disability Status Scale 2, range 0-10); 71% were untreated. Baseline gadolinium-enhancing (odds ratio 3.16, P < 0.01) and spinal cord lesions (odds ratio 4.71, P < 0.01) were independently associated with secondary progressive multiple sclerosis at 15 years. When considering 1- and 3-year MRI variables, baseline gadolinium-enhancing lesions remained significant and new spinal cord lesions over time were associated with secondary progressive multiple sclerosis. Baseline gadolinium-enhancing (β = 1.32, P < 0.01) and spinal cord lesions (β = 1.53, P < 0.01) showed a consistent association with Expanded Disability Status Scale at 15 years. Baseline gadolinium-enhancing lesions was also associated with performance on the Paced Auditory Serial Addition Test (β = - 0.79, P < 0.01) and Symbol Digit Modalities Test (β = -0.70, P = 0.02) at 15 years. Our findings suggest that early focal inflammatory disease activity and spinal cord lesions are predictors of very long-term disease outcomes in relapse-onset multiple sclerosis. Established MRI measures, available in routine clinical practice, may be useful in counselling patients with early multiple sclerosis about long-term prognosis, and personalizing treatment plans.

CNS myelination and remyelination depend on fatty acid synthesis by oligodendrocytes.

Oligodendrocytes (OLs) support neurons and signal transmission in the central nervous system (CNS) by enwrapping axons with myelin, a lipid-rich membrane structure. We addressed the significance of fatty acid (FA) synthesis in OLs by depleting FA synthase (FASN) from OL progenitor cells (OPCs) in transgenic mice. While we detected no effects in proliferation and differentiation along the postnatal OL lineage, we found that FASN is essential for accurate myelination, including myelin growth. Increasing dietary lipid intake could partially compensate for the FASN deficiency. Furthermore, FASN contributes to correct myelin lipid composition and stability of myelinated axons. Moreover, we depleted FASN specifically in adult OPCs to examine its relevance for remyelination. Applying lysolecithin-induced focal demyelinating spinal cord lesions, we found that FA synthesis is essential to sustain adult OPC-derived OLs and efficient remyelination. We conclude that FA synthesis in OLs plays key roles in CNS myelination and remyelination.

Transient depression of pelvic limb reflexes in dogs with acute focal thoracolumbar myelopathy.

OBJECTIVE To determine the prevalence of depressed pelvic limb reflexes and changes in those reflexes over time in dogs with acute thoracolumbar myelopathy. DESIGN Prospective study. ANIMALS 34 dogs. PROCEDURES Dogs with acute pelvic limb paralysis caused by acute noncompressive nucleus pulposus extrusion (ANNPE), fibrocartilaginous embolism (FCE), or compressive intervertebral disk herniation (IVDH) within the T3-L3 spinal cord segments were enrolled in the study. Dogs with depressed or absent pelvic limb withdrawal reflexes as determined by 2 examiners were classified as affected and underwent additional testing to rule out multifocal lesions. Pelvic limb reflexes of affected dogs were reassessed every 12 hours until they returned to normal. Neurologic examinations were performed at 4 and 8 weeks after initial examination for some dogs. RESULTS Compressive IVDH, ANNPE, and FCE were diagnosed in 30, 1, and 3 dogs, respectively. Nine (5 with compressive IVDH and all 4 with FCE or ANNPE) of 34 (26%) dogs were classified as affected. Patellar reflexes were depressed in 2 of 9 affected dogs. The median time required for withdrawal reflexes to return to normal was 60 hours (range, 12 to 156 hours). Onset duration of paralysis was negatively associated with the odds of a dog being classified as affected. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dogs with focal thoracolumbar spinal cord lesions, especially those with peracute onset of paralysis, can develop transient depression of pelvic limb reflexes. Awareness of this phenomenon is important for veterinarians to accurately localize lesions and develop appropriate diagnostic plans and prognoses.

Evaluation of Focal Cervical Spinal Cord Lesions in Multiple Sclerosis: Comparison of White Matter-Suppressed T1 Inversion Recovery Sequence versus Conventional STIR and Proton Density-Weighted Turbo Spin-Echo Sequences.

Conventional MR imaging of the cervical spinal cord in MS is challenged by numerous artifacts and interreader variability in lesion counts. This study compares the relatively novel WM-suppressed T1 inversion recovery sequence with STIR and proton density-weighted TSE sequences in the evaluation of cervical cord lesions in patients with MS. Retrospective blinded analysis of cervical cord MR imaging examinations of 50 patients with MS was performed by 2 neuroradiologists. In each patient, the number of focal lesions and overall lesion conspicuity were measured in the STIR/proton density-weighted TSE and WM-suppressed T1 inversion recovery sequence groups. Independent side-by-side comparison was performed to categorize the discrepant lesions as either "definite" or "spurious." Lesion contrast ratio and edge sharpness were independently calculated in each sequence. Substantial interreader agreement was noted on the WM-suppressed T1 inversion recovery sequence (κ = 0.82) compared with STIR/proton density-weighted TSE (κ = 0.52). Average lesion conspicuity was better on the WM-suppressed T1 inversion recovery sequence (conspicuity of 3.1/5.0 versus 3.7/5.0, P < .01, in the WM-suppressed T1 inversion recovery sequence versus STIR/proton density-weighted TSE, respectively). Spurious lesions were more common on STIR/proton density-weighted TSE than on the WM-suppressed T1 inversion recovery sequence (23 and 30 versus 3 and 4 by readers 1 and 2, respectively; P < .01). More "definite" lesions were missed on STIR/proton density-weighted TSE compared with the WM-suppressed T1 inversion recovery sequence (37 and 38 versus 3 and 6 by readers 1 and 2, respectively). Lesion contrast ratio and edge sharpness were highest on the WM-suppressed T1 inversion recovery sequence. There is better interreader consistency in the lesion count on the WM-suppressed T1 inversion recovery sequence compared with STIR/proton density-weighted TSE sequences. The focal cord lesions are visualized with better conspicuity due to better contrast ratio and edge sharpness. There are fewer spurious lesions on the WM-suppressed T1 inversion recovery sequence compared with STIR/proton density-weighted TSE. The WM-suppressed T1 inversion recovery sequence could potentially be substituted for either STIR or proton density-weighted TSE sequences in routine clinical protocols.

Grey matter involvement by focal cervical spinal cord lesions is associated with progressive multiple sclerosis

Background: The in vivo relationship of spinal cord lesion features with clinical course and function in multiple sclerosis (MS) is poorly defined. Objective: The objective of this paper is to investigate the associations of spinal cord lesion features on MRI with MS subgroup and disability. Methods: We recruited 120 people: 25 clinically isolated syndrome, 35 relapsing–remitting (RR), 30 secondary progressive (SP), and 30 primary progressive (PP) MS. Disability was measured using the Expanded Disability Status Scale. We performed 3T axial cervical cord MRI, using 3D-fast-field-echo and phase-sensitive-inversion-recovery sequences. Both focal lesions and diffuse abnormalities were recorded. Focal lesions were classified according to the number of white matter (WM) columns involved and whether they extended to grey matter (GM). Results: The proportion of patients with focal lesions involving at least two WM columns and extending to GM was higher in SPMS than in RRMS (p = 0.03) and PPMS (p = 0.015). Diffuse abnormalities were more common in both PPMS and SPMS, compared with RRMS (OR 6.1 (p = 0.002) and 5.7 (p = 0.003), respectively). The number of lesions per patient involving both the lateral column and extending to GM was independently associated with disability (p < 0.001). Conclusions: More extensive focal cord lesions, extension of lesions to GM, and diffuse abnormalities are associated with progressive MS and disability.

MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis

The spinal cord is a clinically important site that is affected by pathological changes in most patients with multiple sclerosis; however, imaging of the spinal cord with conventional MRI can be difficult. Improvements in MRI provide a major advantage for spinal cord imaging, with better signal-to-noise ratio and improved spatial resolution. Through the use of multiplanar MRI, identification of diffuse and focal changes in the whole spinal cord is now routinely possible. Corroborated by related histopathological analyses, several new techniques, such as magnetisation transfer, diffusion tension imaging, functional MRI, and proton magnetic resonance spectroscopy, can detect non-focal, spinal cord pathological changes in patients with multiple sclerosis. Additionally, functional MRI can reveal changes in the response pattern to sensory stimulation in patients with multiple sclerosis. Through use of these techniques, findings of cord atrophy, intrinsic cord damage, and adaptation are shown to occur largely independently of focal spinal cord lesion load, which emphasises their relevance in depiction of the true burden of disease. Combinations of magnetisation transfer ratio or diffusion tension imaging indices with cord atrophy markers seem to be the most robust and meaningful biomarkers to monitor disease evolution in early multiple sclerosis.

Cervical spinal intradural arachnoid cysts in related, young pugs

Seven related young pugs were diagnosed with cervical spinal intradural arachnoid cysts by magnetic resonance imaging (n = 6) and myelography (n = 1). All dogs were presented with skin abrasions on their thoracic limbs and non-painful neurological deficits, indicating a C1-T2 myelopathy. In all six dogs examined by magnetic resonance imaging not only the spinal arachnoid cyst but also a concomitant, most likely secondary, syringohydromyelia was confirmed. Pedigree analysis suggested a genetic predisposition for spinal arachnoid cysts in this family of pugs. Generalised proprioceptive deficits more pronounced in the thoracic limbs suggesting a focal cervical spinal cord lesion, with concomitant skin abrasions on the dorsal aspect of the thoracic limbs in a young pug, should alert veterinarians to the possibility of cervical spinal arachnoid cysts.

Focal spinal cord lesions in children: A practical approach to differential diagnosis

Focal spinal cord lesions in children: A practical approach to differential diagnosis

Assessing the value of spinal cord lesions in predicting development of multiple sclerosis in patients with clinically isolated syndromes

The purpose of this study was to determine the value of spinal cord lesions as a predictive factor for conversion in clinically isolated syndrome (CIS) patients. Patients with CIS and without immunomodulatory treatment were prospectively included. Age at onset, sex, clinical syndrome at onset, oligoclonal bands, and presence, number and location of lesions on brain and spinal MRI were analyzed. Conversion to multiple sclerosis (MS) was the primary endpoint. Cox regression was used to compare outcomes between groups. A total of 75 patients were included: 53 (71%) women, mean age at onset 32.7 years (SD ± 7.5), mean follow-up time 72.5 months (SD ± 9; range 17-104 months). There were 11 (14.6%) patients with one focal spinal cord lesion, while 13 (17%) patients had two or more spinal cord lesions at the first scan during the onset of the disease. Of the 23 patients (30.6%) who converted to clinically definite MS (CDMS), 2 had a normal spinal cord MRI, 8 patients had one spinal cord lesion, and 13 had more than one lesion on MRI (p < 0.001). In multivariable analyses, one focal spinal cord lesion was significantly associated with increased risk of conversion to MS (p = 0.01, HR 3.5, CI 95% 2.1-6.9), while the presence of two or more focal spinal cord lesions was independently associated with a higher risk of conversion to MS (p < 0.001, HR 5.9, CI 95% 3.2-10.8). CIS patients with an abnormal baseline spinal cord MRI have a higher risk for developing clinically definite MS, independent of brain lesions as well as the presence of cerebrospinal fluid oligoclonal banding (OSF-OB) .

Transmembrane tumour necrosis factor is neuroprotective and regulates experimental autoimmune encephalomyelitis via neuronal nuclear factor-κB

Tumour necrosis factor mediates chronic inflammatory pathologies including those affecting the central nervous system, but non-selective tumour necrosis factor inhibitors exacerbate multiple sclerosis. In addition, TNF receptor SF1A, which encodes one of the tumour necrosis factor receptors, has recently been identified as a multiple sclerosis susceptibility locus in genome-wide association studies in large patient cohorts. These clinical data have emphasized the need for a better understanding of the beneficial effects of tumour necrosis factor during central nervous system inflammation. In this study, we present evidence that the soluble and transmembrane forms of tumour necrosis factor exert opposing deleterious and beneficial effects, respectively, in a multiple sclerosis model. We compared the effects, in experimental autoimmune encephalomyelitis, of selectively inhibiting soluble tumour necrosis factor, and of both soluble and transmembrane tumour necrosis factor. Blocking the action of soluble tumour necrosis factor, but not of soluble tumour necrosis factor and transmembrane tumour necrosis factor, protected mice against the clinical symptoms of experimental autoimmune encephalomyelitis. Therapeutic benefit was independent of changes in antigen-specific immune responses and focal inflammatory spinal cord lesions, but was associated with reduced overall central nervous system immunoreactivity, increased expression of neuroprotective molecules, and was dependent upon the activity of neuronal nuclear factor-κB, a downstream mediator of neuroprotective tumour necrosis factor/tumour necrosis factor receptor signalling, because mice lacking IκB kinase β in glutamatergic neurons were not protected by soluble tumour necrosis factor blockade. Furthermore, blocking the action of soluble tumour necrosis factor, but not of soluble tumour necrosis factor and transmembrane tumour necrosis factor, protected neurons in astrocyte-neuron co-cultures against glucose deprivation, an in vitro neurodegeneration model relevant for multiple sclerosis, and this was dependent upon contact between the two cell types. Our results show that soluble tumour necrosis factor promotes central nervous system inflammation, while transmembrane tumour necrosis factor is neuroprotective, and suggest that selective inhibition of soluble tumour necrosis factor may provide a new way forward for the treatment of multiple sclerosis and possibly other inflammatory central nervous system disorders.

Reliability, Sensitivity, Specificity and Safety of Computed Tomography-guided Percutaneous Vertebral Biopsies

Purpose This is a retrospective study of the role played by computed tomography (CT)-guided percutaneous vertebral biopsy (PVB) in the study of focal spinal cord lesions. The aim was to analyze sample size sufficiency, adequacy of the biopsy, sensitivity and specificity of the diagnosis and last but not least the safety of the procedure. Materials and methods Inclusion criteria: diagnostic presumption of neoplasm or infection, focal spinal cord lesion, performance of a CT-guided PVB (ELSCINT 2400 Elect scanner purchased in 1993) and clinical/radiological followup for at least one year post puncture. Between February 1993 and February 2001 (8 years) CT-guided PVB was carried out in 236 consecutive patients, 14 of whom were rejected for various reasons (n = 222). Mean age was 57.9 years (range:6-8);119 were male (54%) and 103 female (46%). Location: 82% thoracolumbar spine, 11% sacrum and 7% cervical spine. Results Sensitivity: 86%, specificity: 100%, positive predictive value: 100%, negative predictive value: 14.3%, diagnostic accuracy: 84.2%. Histological material was obtained for 217 patients (98%); in 207 of these (93%) the material was adequate for diagnosis and in 5 (2.2%) assessment was impossible. In 187 patients (84.2%) the final diagnosis matched the result of PVB and in 30 (13.5%) this was not the case. In 5 patients (2,2%) no diagnosis was reached.The most frequent diagnoses were vertebral metastasis (69 patients, 31%) and culture-positive infection (51 patients, 23%). In 150 cases (68%) PVB turned out to be the key diagnostic factor. None of the 222 patients had a major or severe complication resulting from PVB. Minor complications were of two kinds: a) patient-related (4 vagal reactions, one subcutaneous hematoma and an allergic reaction, and b) technique-related (3 instances of needle breakage, with extraction being possible in all cases). A telephone-call based post-puncture pain evaluation was conducted in 40 consecutive patients at 24-48 hours. No significant repercussions were reported. Conclusion CT-scan guided PVB is a reliable, sensitive, specific and safe technique for diagnosing focal spinal cord lesions.

Lyme Disease Mimicking Central Nervous System Lymphoma

A 33-year-old male presented with a complaint of intermittently blurred vision and right facial weakness. MRI of the brain and orbits revealed numerous cranial nerve abnormalities. There were no focal brain or spinal cord lesions. Cerebral spinal fluid flow cytometry revealed a monoclonal population of B-lymphoid cells. No other evidence of disease was found. Serum Lyme antibody was reported to be IgM positive. Therapy with ceftriaxone, was followed by improvement in his symptoms. Although flow cytometry is a useful tool in distinguishing malignancy from inflammatory disorders it does not always establish the diagnosis of malignancy by itself.

Fecal incontinence and spinal cord abnormalities in seven dogs

Seven dogs with fecal incontinence and abnormal gaits were evaluated. Fecal incontinence was characterized as defecation of normal stools without posturing. Duration of clinical signs prior to evaluation ranged from 5 months to 3 years. Five dogs had upper motor neuron (UMN) paraparesis, and 2 dogs had UMN tetraparesis. With magnetic resonance imaging, spinal cord abnormalities primarily involving the dorsal aspect of the spinal cord were identified in all dogs. Five dogs had focal abnormalities, and 2 dogs had diffuse abnormalities of the spinal cord. Of the dogs with focal spinal cord lesions, 4 had cystic spinal cord abnormalities and 1 had a meningioma. Surgery was performed on all dogs with focal lesions; 4 of the 5 dogs had resolution of fecal incontinence after surgery. Results in these dogs suggest that fecal incontinence can be associated with spinal cord abnormalities and, depending on the characteristics of the lesion, can resolve after surgical treatment of the abnormality.

Antibody-mediated CNS demyelination II. Focal spinal cord lesions induced by implantation of an IgM antisulfatide-secreting hybridoma.

We showed previously that spinal cord implants of hybridoma cells (O1) that secrete an IgM antigalactocerebroside cause focal multiple-sclerosis-like plaques of demyelination followed by remyelination to form "shadow plaques" (Rosenbluth et al., 1999). The antibody in that case was directed against a glycolipid present in mature oligodendrocytes and myelin but not in precursor cells. We now report the effects of implanting a different hybridoma (O4) that secretes IgM antibodies directed against sulfatide, a constituent not only of mature myelin and oligodendrocytes but also of late precursor cells, in order to determine whether this hybridoma too would generate focal demyelination and would, in addition, block remyelination. Our results show that focal plaques of demyelination indeed appear after O4 implantation, and that remyelination does occur, but only in cases where the hybridoma cells have degenerated, probably through host rejection. The occurrence of remyelination suggests that oligodendrocyte precursor cells are capable of migrating in rapidly from adjacent areas or that early precursors, not yet expressing sulfatide, remain undamaged within the lesions. In cases where intact hybridoma cells persist at lesion sites, remyelination does not occur. Failure of remyelination in this model thus appears to result from the continuing presence of antimyelin antibodies rather than from depletion of oligodendrocyte precursors.