Neurofilament Light in CSF and Plasma Is a Marker of Neuronal Damage in HTLV-1-Associated Myelopathy and Correlates With Neuroinflammation.

BACKGROUND AND OBJECTIVES: To evaluate the usefulness of CSF and plasma neurofilament light (Nf-L) as a biomarker for human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM). METHODS: Nf-L, CXCL10, and neopterin were measured by ELISA in 83 CSF samples obtained from 49 individuals living with HTLV-1/2. Plasma Nf-L was also measured by single molecule array. Results were correlated with duration of disease, age, mobility, CSF cell counts, CSF protein, and HTLV-1 proviral load. RESULTS: Nf-L was detected in all CSF samples (median [range] = 575 [791.8-2,349] pg/mL) and positively correlated with markers of inflammation (CXCL10 (r = 0.733), neopterin (r = 0.499), cell count (r = 0.403), and protein levels (r = 0.693) in CSF; p < 0.0015). There was an inverse correlation between Nf-L and duration of disease (r = -0.584, p < 0.0001). Wheelchair-dependent patients had high concentrations of markers of inflammation and neuronal damage. Concentrations of CXCL10, neopterin, and Nf-L remained elevated in follow-up samples (mean follow-up 5.2 years). Nf-L in plasma correlated with concentration of Nf-L, neopterin, CXCL10, and protein in CSF. CONCLUSIONS: Nf-L in plasma and CSF has potential to be used as a biomarker of disease activity in HAM. Neuronal damage seems to be more intense early in disease but persists long term. Wheelchair-dependent patients have ongoing neuroinflammation.

Free light chains kappa can differentiate between myelitis and noninflammatory myelopathy.

OBJECTIVE: To test the hypothesis that the intrathecal synthesis of free light chain kappa (FLC-k) can be used as a CSF biomarker to differentiate patients with myelitis due to multiple sclerosis (MS), myelitis due to neuromyelitis optica spectrum disease (NMOSD), and noninflammatory myelopathy, we analyzed FLC-k in 26 patients with MS myelitis, 9 patients with NMOSD myelitis, and 14 patients with myelopathy. METHODS: This is a retrospective monocentric cohort study. FLC-k were analyzed using the nephelometric Siemens FLC-k kit in paired samples of CSF and sera. Intrathecal fraction (IF) of FLC-k was plotted in a FLC-k quotient diagram. RESULTS: Ninety-six percent of patients with MS myelitis had an intrathecal synthesis of FLC-k in comparison with 55.6% for NMOSD and 14.3% of patients with noninflammatory myelopathy. The locally synthesized absolute amount of FLC-k was significantly higher in patients with myelitis due to MS than in patients with NMOSD (p = 0.038) or noninflammatory myelopathy (p < 0.0001). The sensitivity of FLC-k synthesis to detect inflammation in patients with myelitis is 85.7%. Using a receiver operating characteristic analysis, FLC-k IF >78% can discriminate patients with myelitis due to MS and NMOSD with a sensitivity of 88.5% and a specificity of 88.9% CONCLUSIONS: With the hyperbolic reference range in quotient diagrams for FLC-k, it is possible to distinguish inflammatory myelitis from noninflammatory myelopathies. An FLC-k IF >78% can be a hint to suspect myelitis due to MS rather than NMOSD.

Clinical and MRI phenotypes of sarcoidosis-associated myelopathy.

OBJECTIVE: To determine the characteristic clinical and spinal MRI phenotypes of sarcoidosis-associated myelopathy (SAM), we analyzed a large cohort of patients with this disorder. METHODS: Patients diagnosed with SAM at a single center between 2000 and 2018 who met the established criteria for definite and probable neurosarcoidosis were included in a retrospective analysis to identify clinical profiles, CSF characteristics, and MRI lesion morphology. RESULTS: Of 62 included patients, 33 (53%) were male, and 30 (48%) were African American. SAM was the first clinical presentation of sarcoidosis in 49 patients (79%). Temporal profile of symptom evolution was chronic in 81%, with sensory symptoms most frequently reported (87%). CSF studies showed pleocytosis in 79% and CSF-restricted oligoclonal bands in 23% of samples tested. Four discrete patterns of lesion morphology were identified on spine MRI: longitudinally extensive myelitis (n = 28, 45%), short tumefactive myelitis (n = 14, 23%), spinal meningitis/meningoradiculitis (n = 14, 23%), and anterior myelitis associated with areas of disc degeneration (n = 6, 10%). Postgadolinium enhancement was seen in all but 1 patient during the acute phase. The most frequent enhancement pattern was dorsal subpial enhancement (n = 40), followed by meningeal/radicular enhancement (n = 23) and ventral subpial enhancement (n = 12). In 26 cases (42%), enhancement occurred at locations with coexisting structural changes (e.g., spondylosis). CONCLUSIONS: Recognition of the clinical features (chronically evolving myelopathy) and distinct MRI phenotypes (with enhancement in a subpial and/or meningeal pattern) seen in SAM can aid diagnosis of this disorder. Enhancement patterns suggest that SAM may have a predilection for areas of the spinal cord susceptible to mechanical stress.

Schistosomal Myeloradiculopathy - A case report.

The most common neurological impairments related to schistosomiasis involve the lower portions of the medulla and the cauda equina. A 22-year-old woman, with no history, signs, or symptoms of hepatointestinal schistosomiasis, presented with lumbar pain associated with acute paresthesia and paresis of the right lower limb. Spinal schistosomiasis was suspected based on the disease progression and radiological findings, and the diagnosis was confirmed after cerebrospinal fluid analysis. The authors emphasize this pathology as important as a differential diagnosis in similar clinical scenarios, especially in endemic areas, because both early diagnosis and treatment are essential to avoid permanent sequelae.

Characteristics of Spontaneous Spinal Cord Infarction and Proposed Diagnostic Criteria.

Importance: Spinal cord infarction (SCI) is often disabling, and the diagnosis can be challenging without an inciting event (eg, aortic surgery). Patients with a spontaneous SCI are often misdiagnosed as having transverse myelitis. Diagnostic criteria for SCI are lacking, hindering clinical care and research. Objective: To describe the characteristics of spontaneous SCI and propose diagnostic criteria. Design, Setting, and Participants: An institution-based search tool was used to identify patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1997 to December 2017 with a spontaneous SCI. Patients provided written consent to use their records for research. Participants were 18 years and older with a diagnosis of spontaneous SCI (n = 133), and controls were selected from a database of alternative myelopathy etiologies for validation of the proposed diagnostic criteria (n = 280). Main Outcomes and Measures: A descriptive analysis of SCI was performed and used to propose diagnostic criteria, and the criteria were validated. Results: Of 133 included patients with a spontaneous SCI, the median (interquartile range) age at presentation was 60 (52-69) years, and 101 (76%) had vascular risk factors. Rapid onset of severe deficits reaching nadir within 12 hours was typical (102 [77%]); some had a stuttering decline (31 [23%]). Sensory loss occurred in 126 patients (95%), selectively affecting pain/temperature in 49 (39%). Initial magnetic resonance imaging (MRI) spine results were normal in 30 patients (24%). Characteristic MRI T2-hyperintense patterns included owl eyes (82 [65%]) and pencil-like hyperintensity (50 [40%]); gadolinium enhancement (37 of 96 [39%]) was often linear and located in the anterior gray matter. Confirmatory MRI findings included diffusion-weighted imaging/apparent diffusion coefficient restriction (19 of 29 [67%]), adjacent dissection/occlusion (16 of 82 [20%]), and vertebral body infarction (11 [9%]). Cerebrospinal fluid showed mild inflammation in 7 of 89 patients (8%). Diagnostic criteria was proposed for definite, probable, and possible SCI of periprocedural and spontaneous onset. In the validation cohort (n = 280), 9 patients (3%) met criteria for possible SCI, and none met criteria for probable SCI. Conclusions and Relevance: This large series of spontaneous SCIs provides clinical, laboratory, and MRI clues to SCI diagnosis. The diagnostic criteria proposed here will aid clinicians in making the correct diagnosis and ideally improve future care for patients with SCI. The validation of these criteria supports their utility in the evaluation of acute myelopathy.

Schistosomal myeloradiculopathy - A case report

Abstract The most common neurological impairments related to schistosomiasis involve the lower portions of the medulla and the cauda equina. A 22-year-old woman, with no history, signs, or symptoms of hepatointestinal schistosomiasis, presented with lumbar pain associated with acute paresthesia and paresis of the right lower limb. Spinal schistosomiasis was suspected based on the disease progression and radiological findings, and the diagnosis was confirmed after cerebrospinal fluid analysis. The authors emphasize this pathology as important as a differential diagnosis in similar clinical scenarios, especially in endemic areas, because both early diagnosis and treatment are essential to avoid permanent sequelae.

Potential role of CSF cytokine profiles in discriminating infectious from non-infectious CNS disorders.

Current laboratory testing of cerebrospinal fluid (CSF) does not consistently discriminate between different central nervous system (CNS) disease states. Rapidly distinguishing CNS infections from other brain and spinal cord disorders that share a similar clinical presentation is critical. New approaches focusing on aspects of disease biology, such as immune response profiles that can have stimulus-specific attributes, may be helpful. We undertook this preliminary proof-of-concept study using multiplex ELISA to measure CSF cytokine levels in various CNS disorders (infections, autoimmune/demyelinating diseases, lymphomas, and gliomas) to determine the potential utility of cytokine patterns in differentiating CNS infections from other CNS diseases. Both agglomerative hierarchical clustering and mixture discriminant analyses revealed grouping of CNS disease types based on cytokine expression. To further investigate the ability of CSF cytokine levels to distinguish various CNS disease states, non-parametric statistical analysis was performed. Mann-Whitney test analysis demonstrated that CNS infections are characterized by significantly higher CSF lP-10/CXCL10 levels than the pooled non-infectious CNS disorders (p = 0.0001). Within the infection group, elevated levels of MDC/CCL22 distinguished non-viral from viral infections (p = 0.0048). Each disease group of the non-infectious CNS disorders independently showed IP-10/CXCL10 levels that are significantly lower than the infection group [(autoimmune /demyelinating disorders (p = 0.0005), lymphomas (p = 0.0487), gliomas (p = 0.0294), and controls (p = 0.0001)]. Additionally, of the non-infectious diseases, gliomas can be distinguished from lymphomas by higher levels of GRO/CXCL1 (p = 0.0476), IL-7 (p = 0.0119), and IL-8 (p = 0.0460). Gliomas can also be distinguished from autoimmune/demyelinating disorders by higher levels of GRO/CXCL1 (p = 0.0044), IL-7 (p = 0.0035) and IL-8 (p = 0.0176). Elevated CSF levels of PDGF-AA distinguish lymphomas from autoimmune/demyelinating cases (p = 0.0130). Interrogation of the above comparisons using receiver operator characteristic analysis demonstrated area under the curve (AUC) values (ranging from 0.8636-1.0) that signify good to excellent utility as potential diagnostic discriminators. In conclusion, our work indicates that upon formal validation, measurement of CSF cytokine levels may have clinical utility in both identifying a CNS disorder as infectious in etiology and, furthermore, in distinguishing viral from non-viral CNS infections.

Immediate improvement of intraoperative monitoring signals following CSF release for cervical spine stenosis: Case report.

Cervical spondylotic myelopathy (CSM) is a degenerative pathology characterized by partial or complete conduction block on intraoperative neuromonitoring. We describe a case treated using osseoligamentous decompression and durotomy for cerebrospinal fluid (CSF) release. Intraoperative monitoring demonstrated immediate signal improvement with CSF release, suggesting that clinical improvement in CSM may result from resolution of CSF flow anomalies.

Heroin-induced acute myelopathy with extreme high levels of CSF glial fibrillar acidic protein indicating a toxic effect on astrocytes.

A man aged 33 years with previous heroin substance abuse was found unconscious lying in a bush. The patient had been without heroin for some time but had just started to use intravenous heroin again, 0.5-2 g daily. The patient had almost complete paraplegia and a sensory loss for all modalities below the mamillary level and a urine retention of 1.5 L. Acute MRI of the spine revealed an expanded spinal cord with increased intramedullary signal intensity, extending from C7-T9. The cerebrospinal fluid showed extremely high levels of nerve injury markers particularly glial fibrillar acidic protein (GFAP): 2 610 000/ng/L (ref. <750). The patient was empirically treated with intravenous 1 g methylprednisolone daily for 5 days and improved markedly. Very few diseases are known to produce such high levels of GFAP, indicating a toxic effect on astrocytes. Measuring GFAP could possibly aid in the diagnosis of heroin-induced myelopathy.

Cerebrospinal Fluid Analysis in Recumbent Adult Dairy Cows With or Without Spinal Cord Lesions.

BACKGROUND: Diagnosis of central nervous system (CNS) lesions in recumbent dairy cattle (RDC) is challenging because neurologic examination is limited and medical imaging often is challenging or unrewarding. Cerebrospinal fluid (CSF) analysis is useful in the diagnosis of CNS disorders in cattle. However, its utility in identifying spinal cord lesions in RDC remains to be evaluated. HYPOTHESIS/OBJECTIVES: We hypothesized that CSF analysis would discriminate between RDC with and without spinal cord lesions. ANIMALS: Twenty-one RDC with spinal cord lesions (RDC+) and 19 without (RDC-) were evaluated. METHODS: Spinal cord lesions were confirmed at necropsy. Signalment, clinical findings, and CSF results were compared retrospectively. Total nucleated cell count and differential, protein concentration, and red blood cell count in RDC+ and RDC- were compared. RESULTS: Neoplasia, trauma, and infectious processes were the most frequent spinal cord lesions identified. Cerebrospinal fluid protein concentrations and TNCC were significantly higher in RDC+ compared to RDC- (P = .0092 and P = .0103, respectively). Additionally, CSF protein concentrations and TNCC in RDC- were lower than previously published reference ranges. Using an interpretation rule based on CSF protein concentration and TNCC, it was possible to accurately identify 13 RDC with spinal cord lesions and 6 RDC without lesions. It was not possible to determine spinal cord status in the remaining 18 RDC. CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid analysis is valuable in the evaluation of spinal cord status in RDC. The prognosis associated with these findings remains to be determined.

Cerebrospinal Fluid Levels of Phosphorylated Neurofilament Heavy as a Diagnostic Marker of Canine Degenerative Myelopathy.

BACKGROUND: No definitive, antemortem diagnostic test for canine degenerative myelopathy (DM) is available. Phosphorylated neurofilament heavy (pNF-H) is a promising biomarker for nervous system diseases. HYPOTHESIS/OBJECTIVE: Cerebrospinal fluid (CSF) and serum pNF-H is a detectable biological marker for diagnosis of canine DM. ANIMALS: Fifty-three DM-affected, 27 neurologically normal, 7 asymptomatic at-risk, and 12 DM mimic dogs. METHODS: Archived CSF and serum pNF-H concentrations were determined by a commercially available ELISA. A receiver-operating characteristic (ROC) curve was generated with CSF values. RESULTS: Compared with old control dogs, median CSF pNF-H concentration was increased in all stages of DM; old dogs 5.1 ng/mL (interquartile range [IQR] 1.4-9.3) versus DM stage 1 23.9 ng/mL (IQR 20.8-29.6; P < .05) versus DM stage 2 36.8 ng/mL (IQR 22.9-51.2; P < .0001) versus DM stage 3 25.2 ng/mL (IQR 20.2-61.8; P < .001) versus DM stage 4 38.0 ng/mL (IQR 11.6-59.9; P < .01). Degenerative myelopathy stage 1 dogs had increased median CSF pNF-H concentrations compared with asymptomatic, at-risk dogs (3.4 ng/mL [IQR 1.5-10.9; P < .01]) and DM mimics (6.6 ng/mL [IQR 3.0-12.3; P < .01]). CSF pNF-H concentration >20.25 ng/mL was 80.4% sensitive (confidence interval [CI] 66.09-90.64%) and 93.6% specific (CI 78.58-99.21%) for DM. Area under the ROC curve was 0.9467 (CI 0.92-0.9974). No differences in serum pNF-H concentration were found between control and DM-affected dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: pNF-H concentration in CSF is a sensitive biomarker for diagnosis of DM. Although there was high specificity for DM in this cohort, further study should focus on a larger cohort of DM mimics, particularly other central and peripheral axonopathies.

Dorsal column myelopathy after intrathecal chemotherapy for leukemia.

Intrathecal chemotherapy with methotrexate, a folate antagonist, is widely used to treat central nervous system malignancies. The mechanisms underlying methotrexate-induced neurotoxicity are unclear but may be related to increased homocysteine levels. Intrathecal methotrexate-induced myelopathy mimicking subacute combined degeneration, with normal B12 levels, has been documented. We examined treatment and magnetic resonance imaging (MRI) characteristics of 13 patients with leukemia who received intrathecal methotrexate and developed urinary and bowel incontinence, ascending motor weakness, and sensory loss with dorsal column hyperintensity on MRI between 2000 and 2016. Cerebrospinal fluid evaluation was negative for leukemia in all patients and positive for elevated protein in 12 patients. Seven of eight patients with available data had reduced serum folate, increased serum homocysteine, or both, implicating methotrexate as the cause of neurotoxicity. Autopsy of one patient revealed loss of myelinated axons in the posterior columns. These findings suggest that methotrexate neurotoxicity may be mediated by folate antagonism. Awareness and a high index of suspicion of these characteristic clinical and radiographic features in patients who develop myelopathy after intrathecal methotrexate may help to avoid additional neurotoxic therapy in such patients.

Nested polymerase chain reaction in cerebrospinal fluid for diagnosing spinal cord schistosomiasis: A promising method.

INTRODUCTION: Spinal cord schistosomiasis is a neglected, disabling neurological disease commonly identified in patients from northeast Brazil. The methods currently available for its diagnosis need improvement. PCR in feces and urine is a sensitive diagnostic tool for diagnosis of schistosomiasis, but its value in the cerebrospinal fluid (CSF) is still unknown. OBJECTIVE: The objective of this study was to detect Schistosoma mansoni DNA in CSF from patients with spinal cord schistosomiasis, using the nested PCR (NPCR) assay. METHODS: This was a cross-sectional study carried out from March 2013 to January 2014 at the Aggeu Magalhães Research Center/FIOCRUZ (Pernambuco state, Brazil). NPCR was used to detect Schistosoma mansoni DNA in CSF samples from 20 patients with spinal cord schistosomiasis and 30 controls. RESULTS: NPCR was positive in 16 patients with spinal cord schistosomiasis and none from the control group (sensitivity 80%; specificity 100%, positive predictive value 100%; negative predictive value 88.2%). CONCLUSION: The NPCR technique is highly sensitive and specific for diagnosis of spinal cord schistosomiasis and can be an important diagnostic tool, particularly in cases with negative CSF serology.

Spinal Cord Stroke Presenting With Acute Monoplegia in a 17-Year-Old Tennis Player.

BACKGROUND: Acute monoplegia is a rare presentation for spinal cord stroke, which usually presents with paraplegia or paraparesis. PATIENT DESCRIPTION: We describe an athletic girl who presented after a week of heavy athletic activity complaining of back and left leg pain, followed by flaccid left leg paralysis. RESULTS: The prothrombotic evaluation was unremarkable. Cerebrospinal fluid studies demonstrated elevated myelin basic protein but no oligoclonal bands. Magnetic resonance imaging revealed a lesion in the anterior cord from T9 to T11 with T2 hyperintensity, contrast enhancement, and diffusion restriction, suggesting infarction. There was a herniated disc at T10-T11 contacting the spinal cord and Schmorl's nodes at T11 and T12. Magnetic resonance angiography of the spinal cord was limited by movement artifact. CONCLUSIONS: The combination of our patient's clinical presentation, imaging studies, and laboratory evaluation suggests that our patient had a spinal cord infarct. A fibrocartilaginous embolism was the likely mechanism of infarct due to the presence of Schmorl's nodes and disc herniation on imaging. In addition to spinal cord stroke, other possible mechanisms leading to presentation with monoplegia, such as transverse myelitis, neuromyelitis optica, and multiple sclerosis, are discussed.

Comparison of clinical characteristics between neuromyelitis optica spectrum disorders with and without spinal cord atrophy.

BACKGROUND: Spinal cord lesions is one of the predominant characteristics in patients with neuromyelitis optica spectrum disorders (NMOSD). Interestingly, mounting evidence indicates that spinal cord atrophy (SCA) is one of common clinical features in multiple sclerosis (MS) patients, and correlates closely with the neurological disability. However, Clinical studies related to the SCA aspects of NMOSD are still scarce. METHODS: We retrospectively analyzed 185 patients with NMOSD, including 23 patients with SCA and 162 patients without SCA. Data were collected regarding clinical characteristics, laboratory tests, and magnetic resonance imaging findings. RESULTS: 12.4% of patients had SCA in NMOSD. Patients with SCA had a longer disease duration and higher EDSS at clinical onset and last visit. More importantly, SCA patients were more prone to reach disability milestones (EDSS ≥ 6.0). Bowel or bladder dysfunction, movement disorders, and sensory disturbances symptoms were more common in patients with SCA. ESR and CRP were significantly higher in patients with SCA than those without SCA. Patients with SCA were more frequently complicated with cervical cord lesions. However, the ARR, progression index, seropositive rate of NMO-IgG and OCB were similar in the two groups. Futhermore, LETM did not differ significantly between patients with SCA and without SCA in NMOSD patients. CONCLUSIONS: Patients with SCA might have longer disease duration, more severe clinical disability, and more frequently complicated with cervical spinal cord lesions. SCA might be predictive of the more severe neurologic dysfunction and worse prognosis in NMOSD. Inflammation contributes to the development of SCA in NMOSD.

Intramedullary spinal cord mass presumptively associated with leishmaniasis in a dog.

CASE DESCRIPTION: A 9-year-old male Miniature Poodle was evaluated because of progressive severe right hemiparesis, right forelimb lameness, and signs of cervical pain. CLINICAL FINDINGS: A low body condition score (2/9) and popliteal lymphadenopathy were detected. Results of a CBC, serum biochemical analyses, urinalysis, cytologic examination of bone marrow and popliteal lymph node aspirates, and serum ELISA were consistent with systemic leishmaniasis. Magnetic resonance imaging of the cervical spinal cord revealed an intramedullary mass extending from the caudal aspect of the C5 vertebral body to the C5-6 intervertebral disk space with a contrast medium-enhanced pattern that had 3 zones (central contrast medium-enhanced core, intermediate isointense zone, and peripheral contrast medium-enhanced ring). Surgical biopsy of the mass was performed by means of a right C5-6 dorsal hemilaminectomy. Results of PCR assays for detection of Leishmania DNA in CSF and tissue biopsy samples were positive. TREATMENT AND OUTCOME: Treatment for systemic leishmaniasis was initiated. Two months later, body condition, neurologic signs, and gait of the dog had substantially improved; the dog had mild right forelimb paresis at that time. Results of follow-up MRI indicated resolution of the cervical spinal cord lesion. Four months after diagnosis, the dog's neurologic condition was stable. CLINICAL RELEVANCE: To the authors' knowledge, this report is the first in which clinical findings, clinicopathologic data, and MRI characteristics of an intramedullary inflammatory spinal cord lesion presumptively attributable to leishmaniasis in a dog have been reported, and the first report of CNS leishmaniasis in a dog with MRI resolution and a successful clinical response to treatment.

The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog.

Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p < 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent condition such as cIVDD.