The most recent diagnostic criteria for multiple sclerosis (MS) ascertain that findings from spinal cord MRI can be used to demonstrate dissemination in space. Because little is known about the prevalence and characteristics of cord lesions early in the disease, the authors studied the prevalence of spinal cord abnormalities in patients with early-stage MS and assessed their impact on diagnostic classification.
The brains and spinal cords of 104 recently diagnosed patients with MS were examined. Median interval between first symptom and diagnosis was 18.4 months. The brain MRI protocol included before and after gadolinium axial T1-weighted conventional spin-echo sequences and dual-echo spin-echo images. For spinal cord MRI, sagittal cardiac-triggered dual-echo T2-weighted and sagittal T1-weighted spin-echo images were included. Clinical assessment for each patient included age, sex, clinical signs for spinal cord involvement, and Expanded Disability Status Scale.
Abnormal cord MRIs were found in 83% of patients, usually with only focal lesions. Diffuse cord abnormalities were found in 13% of patients, although in isolation they were found in only three patients. Focal cord lesions were often multiple (median number, 3.0), small (median, 0.8 vertebral segments), and primarily (56.4%) situated in the cervical spinal cord. In 68 of 104 patients (65.4%), two or more focal lesions were visible on spinal cord images. The criteria for dissemination in space, as defined in the McDonald criteria for the brain, were met in only 66.3% of the patients. This percentage increased to 84.6% when spinal cord MRI abnormalities were also included.
Spinal cord abnormalities are prevalent in patients with early-stage MS, have distinct morphologic characteristics, and help to determine dissemination in space at time of diagnosis.
"Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that commonly results in disability (Noseworthy et al., 2000). Spinal cord involvement is common in MS, even early in disease (Bot et al., 2004a). Multiple sclerosis plaques contain marked pathologic heterogeneity, with variable demyelination, axonal damage, gliosis, remyelination and inflammation (Barnes et al., 1991). "
[Show abstract][Hide abstract] ABSTRACT: Correlation of diffusion tensor imaging (DTI) with histochemical staining for demyelination and axonal damage in multiple sclerosis (MS) ex vivo human cervical spinal cords.
In MS, demyelination, axonal degeneration, and inflammation contribute to disease pathogenesis to variable degrees. Based upon in vivo animal studies with acute injury and histopathologic correlation, we hypothesized that DTI can differentiate between axonal and myelin pathologies within humans.
DTI was performed at 4.7 T on 9 MS and 5 normal control fixed cervical spinal cord blocks following autopsy. Sections were then stained for Luxol fast blue (LFB), Bielschowsky silver, and hematoxylin and eosin (H&E). Regions of interest (ROIs) were graded semi-quantitatively as normal myelination, mild (<50%) demyelination, or moderate-severe (>50%) demyelination. Corresponding axonal counts were manually determined on Bielschowsky silver. ROIs were mapped to co-registered DTI parameter slices. DTI parameters evaluated included standard quantitative assessments of apparent diffusion coefficient (ADC), relative anisotropy (RA), axial diffusivity and radial diffusivity. Statistical correlations were made between histochemical gradings and DTI parameters using linear mixed models.
Within ROIs in MS subjects, increased radial diffusivity distinguished worsening severities of demyelination. Relative anisotropy was decreased in the setting of moderate-severe demyelination compared to normal areas and areas of mild demyelination. Radial diffusivity, ADC, and RA became increasingly altered within quartiles of worsening axonal counts. Axial diffusivity did not correlate with axonal density (p=0.091).
Increased radial diffusivity can serve as a surrogate for demyelination. However, radial diffusivity was also altered with axon injury, suggesting that this measure is not pathologically specific within chronic human MS tissue. We propose that radial diffusivity can serve as a marker of overall tissue integrity within chronic MS lesions. This study provides pathologic foundation for on-going in vivo DTI studies in MS.
"It is important to consider our results in light of histopathologic results. Because of the sensitivity of MT imaging to demyelination (Bot et al., 2004a, b), our results are consistent with evidence that demyelination plays an important role in generating clinical disability in multiple sclerosis. Histopathologic data also suggest that axon loss occurs independently of demyelination in areas of both focal and diffuse signal abnormality and is often present in normal appearing white matter (Bot and Barkhof, 2009). "
[Show abstract][Hide abstract] ABSTRACT: The human spinal cord contains segregated sensory and motor pathways that have been difficult to quantify using conventional magnetic resonance imaging (MRI) techniques. Multiple sclerosis is characterized by both focal and spatially diffuse spinal cord lesions with heterogeneous pathologies that have limited attempts at linking MRI and behaviour. We used a novel magnetization-transfer-weighted imaging approach to quantify damage to spinal white matter columns and tested its association with sensorimotor impairment. We studied 42 participants with multiple sclerosis who each underwent MRI at 3 Tesla and quantitative tests of sensorimotor function. We measured cerebrospinal-fluid-normalized magnetization-transfer signals in the dorsal and lateral columns and grey matter of the cervical cord. We also measured brain lesion volume, cervical spinal cord lesion number and cross-sectional area, vibration sensation, strength, walking velocity and standing balance. We used linear regression to assess the relationship between sensorimotor impairment and MRI abnormalities. We found that the dorsal column cerebrospinal-fluid-normalized magnetization-transfer signal specifically correlated with vibration sensation (R = 0.58, P < 0.001) and the lateral column signal with strength (R = -0.45, P = 0.003). Spinal cord signal measures also correlated with walking and balance dysfunction. A stepwise multiple regression showed that the dorsal column signal and diagnosis subtype alone explained a significant portion of the variance in sensation (R(2) = 0.54, P < 0.001), whereas the lateral column signal and diagnosis subtype explained a significant portion of the variance in strength (R(2) = 0.30, P < 0.001). These results help to understand the anatomic basis of sensorimotor disability in multiple sclerosis and have implications for testing the effects of neuroprotective and reparative interventions.
[Show abstract][Hide abstract] ABSTRACT: The diversity and heterogeneity of idiopathic central nervous system demyelinating disease in Asia has long been recognised, but there is a dearth of epidemiological work looking at this specific question. Existing data on demyelinating diseases from both the East and the West has been confounded by differences in case ascertainment, selection bias, differing study methodologies and the exclusion of so-called "atypical" cases. This is particularly so in Asia where the application of Western diagnostic criteria may not be appropriate. The RAPID Study is designed to identify the full spectrum of demyelinating disease presentations, including atypical forms, and those associated with other systemic diseases or other disease markers and it is not linked to any form of therapy or medical intervention. The time interval for data collection is finite at twelve months, at which stage the epidemiological data collected will be collated and analysed by the Central Steering Committee. The efforts of all contributors will be recognised in the planned publication derived from this study. Moreover, the data collected will be capable of forming the framework of subsequent clinically isolated syndrome follow up studies and may also form the basis of subsequent sub-studies such as in those centres which are in a position to perform serological and immunogenetic testing. Diagnostic criteria can only be established when a scientific evidence base has been established, and the criteria then tested prospectively. The RAPID data will be pivotal in helping to resolve current controversies surrounding immunological and radiological markers of demyelinating disease.
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